CRYOPRESERVATION EFFECTS ON RECOMBINANT MYOBLASTS ENCAPSULATED IN ADHESIVE ALGINATE HYDROGELS

PubMed Central

Ahmad, Hajira F.; Sambanis, Athanassios

2013-01-01

Cell encapsulation in hydrogels is widely used in tissue engineering applications, including encapsulation of islets or other insulin-secreting cells in pancreatic substitutes. Use of adhesive, bio-functionalized hydrogels is receiving increasing attention, as cell-matrix interactions in 3-D can be important for various cell processes. With pancreatic substitutes, studies have indicated benefits of 3-D adhesion on the viability and/or function of insulin-secreting cells. As long-term storage of microencapsulated cells is critical for their clinical translation, cryopreservation of cells in hydrogels is actively being investigated. Previous studies have examined the cryopreservation response of cells encapsulated in non-adhesive hydrogels using conventional freezing and/or vitrification (ice-free cryopreservation), however, none have systematically compared the two cryopreservation methods with cells encapsulated within an adhesive 3-D environment. The latter would be significant, as evidence suggests adhesion influences cellular response to cryopreservation. Thus, the objective of this study was to determine the response to conventional freezing and vitrification of insulin-secreting cells encapsulated in an adhesive biomimetic hydrogel. Recombinant insulin-secreting C2C12 myoblasts were encapsulated in oxidized RGD-alginate and cultured 1 or 4 days post-encapsulation, cryopreserved, and assessed up to 3 days post-warming for metabolic activity and insulin secretion, and one day post-warming for cell morphology. Besides certain transient differences of the vitrified group relative to the Fresh control, both conventional freezing and vitrification maintained metabolism, secretion and morphology of the recombinant C2C12 cells. Thus, due to a simpler procedure and slightly superior results, conventional freezing is recommended over vitrification for the cryopreservation of C2C12 cells in oxidized RGD-modified alginate. PMID:23499987

Novel preparation of PLGA/HP55 nanoparticles for oral insulin delivery

NASA Astrophysics Data System (ADS)

Wu, Zhi Min; Ling, Li; Zhou, Li Ying; Guo, Xin Dong; Jiang, Wei; Qian, Yu; Luo, Kathy Qian; Zhang, Li Juan

2012-06-01

The aim of the present study was to develop the PLGA/HP55 nanoparticles with improved hypoglycemic effect for oral insulin delivery. The insulin-loaded PLGA/HP55 nanoparticles were produced by a modified multiple emulsion solvent evaporation method. The physicochemical characteristics, in vitro release of insulin, and in vivo efficacy in diabetic rats of the nanoparticles were evaluated. The insulin encapsulation efficiency was up to 94%, and insulin was released in a pH-dependent manner under simulated gastrointestinal conditions. When administered orally (50 IU/kg) to diabetic rats, the nanoparticles can decrease rapidly the blood glucose level with a maximal effect between 1 and 8 h. The relative bioavailability compared with subcutaneous injection (5 IU/kg) in diabetic rats was 11.3% ± 1.05%. This effect may be explained by the fast release of insulin in the upper intestine, where it is better absorbed by the high gradient concentration of insulin than other regions. These results show that the PLGA/HP55 nanoparticles developed in the study might be employed as a potential method for oral insulin delivery.

Three-dimensional printed polymeric system to encapsulate human mesenchymal stem cells differentiated into islet-like insulin-producing aggregates for diabetes treatment.

PubMed

Sabek, Omaima M; Farina, Marco; Fraga, Daniel W; Afshar, Solmaz; Ballerini, Andrea; Filgueira, Carly S; Thekkedath, Usha R; Grattoni, Alessandro; Gaber, A Osama

2016-01-01

Diabetes is one of the most prevalent, costly, and debilitating diseases in the world. Pancreas and islet transplants have shown success in re-establishing glucose control and reversing diabetic complications. However, both are limited by donor availability, need for continuous immunosuppression, loss of transplanted tissue due to dispersion, and lack of vascularization. To overcome the limitations of poor islet availability, here, we investigate the potential of bone marrow-derived mesenchymal stem cells differentiated into islet-like insulin-producing aggregates. Islet-like insulin-producing aggregates, characterized by gene expression, are shown to be similar to pancreatic islets and display positive immunostaining for insulin and glucagon. To address the limits of current encapsulation systems, we developed a novel three-dimensional printed, scalable, and potentially refillable polymeric construct (nanogland) to support islet-like insulin-producing aggregates' survival and function in the host body. In vitro studies showed that encapsulated islet-like insulin-producing aggregates maintained viability and function, producing steady levels of insulin for at least 4 weeks. Nanogland-islet-like insulin-producing aggregate technology here investigated as a proof of concept holds potential as an effective and innovative approach for diabetes cell therapy.

Three-dimensional printed polymeric system to encapsulate human mesenchymal stem cells differentiated into islet-like insulin-producing aggregates for diabetes treatment

PubMed Central

Sabek, Omaima M; Farina, Marco; Fraga, Daniel W; Afshar, Solmaz; Ballerini, Andrea; Filgueira, Carly S; Thekkedath, Usha R; Grattoni, Alessandro; Gaber, A Osama

2016-01-01

Diabetes is one of the most prevalent, costly, and debilitating diseases in the world. Pancreas and islet transplants have shown success in re-establishing glucose control and reversing diabetic complications. However, both are limited by donor availability, need for continuous immunosuppression, loss of transplanted tissue due to dispersion, and lack of vascularization. To overcome the limitations of poor islet availability, here, we investigate the potential of bone marrow–derived mesenchymal stem cells differentiated into islet-like insulin-producing aggregates. Islet-like insulin-producing aggregates, characterized by gene expression, are shown to be similar to pancreatic islets and display positive immunostaining for insulin and glucagon. To address the limits of current encapsulation systems, we developed a novel three-dimensional printed, scalable, and potentially refillable polymeric construct (nanogland) to support islet-like insulin-producing aggregates’ survival and function in the host body. In vitro studies showed that encapsulated islet-like insulin-producing aggregates maintained viability and function, producing steady levels of insulin for at least 4 weeks. Nanogland—islet-like insulin-producing aggregate technology here investigated as a proof of concept holds potential as an effective and innovative approach for diabetes cell therapy. PMID:27152147

Biochemical consequences of alginate encapsulation: a NMR study of insulin-secreting cells.

PubMed

Simpson, Nicholas E; Grant, Samuel C; Gustavsson, Lenita; Peltonen, Vilje-Mia; Blackband, Stephen J; Constantinidis, Ioannis

2006-04-01

In this study we explore the biochemical consequences of alginate encapsulation on betaTC3 cells. (13)C NMR spectroscopy and isotopomer analysis were used to investigate the effects of encapsulation on several enzymatic processes associated with the TCA cycle. Our data show statistically significant differences in various enzymatic fluxes related to the TCA cycle and insulin secretion between monolayer and alginate-encapsulated cultures. The principal cause for these effects was the process of trypsinization. Embedding the trypsinized cells in alginate beads did not have a compounded effect on the enzymatic fluxes of entrapped cells. However, an additional small but statistically significant decrease in insulin secretion was measured in encapsulated cells. Finally, differences in either enzymatic fluxes or glucose consumption as a function of bead diameter were not observed. However, differences in T(2), assessed by (1)H NMR microimaging, were observed as a function of bead diameter, suggesting that smaller beads became more organized with time in culture, while larger beads displayed a looser organization.

Poly(lactic-co-glycolic) acid loaded nano-insulin has greater potentials of combating arsenic induced hyperglycemia in mice: Some novel findings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Samadder, Asmita; Das, Jayeeta; Das, Sreemanti

Diabetes is a menacing problem, particularly to inhabitants of groundwater arsenic contaminated areas needing new medical approaches. This study examines if PLGA loaded nano-insulin (NIn), administered either intraperitoneally (i.p.) or through oral route, has a greater cost-effective anti-hyperglycemic potential than that of insulin in chronically arsenite-fed hyperglycemic mice. The particle size, morphology and zeta potential of nano-insulin were determined using dynamic light scattering method, scanning electronic and atomic force microscopies. The ability of the nano-insulin (NIn) to cross the blood–brain barrier (BBB) was also checked. Circular dichroic spectroscopic (CD) data of insulin and nano-insulin in presence or absence of arsenicmore » were compared. Several diabetic markers in different groups of experimental and control mice were assessed. The mitochondrial functioning through indices like cytochrome c, pyruvate-kinase, glucokinase, ATP/ADP ratio, mitochondrial membrane potential, cell membrane potential and calcium-ion level was also evaluated. Expressions of the relevant marker proteins and mRNAs like insulin, GLUT2, GLUT4, IRS1, IRS2, UCP2, PI3, PPARγ, CYP1A1, Bcl2, caspase3 and p38 for tracking-down the signaling cascade were also analyzed. Results revealed that i.p.-injected nano-encapsulated-insulin showed better results; NIn, due to its smaller size, faster mobility, site-specific release, could cross BBB and showed positive modulation in mitochondrial signaling cascades and other downstream signaling molecules in reducing arsenic-induced-hyperglycemia. CD data indicated that nano-insulin had less distorted secondary structure as compared with that of insulin in presence of arsenic. Thus, overall analyses revealed that PLGA nano-insulin showed better efficacy in combating arsenite-induced-hyperglycemia than that of insulin and therefore, has greater potentials for use in nano-encapsulated form. - Highlights: ► PLGA encapsulated nano-insulin attenuates arsenic-induced diabetes in mice. ► Encapsulated insulin acts effectively at nearly 10 fold lesser dose than insulin. ► Injection route is more effective than oral administration route. ► Nano-insulin can cross blood–brain barrier with added physiological implications. ► Nano-insulin acts mainly through regulation of mitochondrial signaling cascade.« less

Retention of gene expression in porcine islets after agarose encapsulation and long-term culture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dumpala, Pradeep R., E-mail: pdumpala@rixd.org; Holdcraft, Robert W.; Martis, Prithy C.

Agarose encapsulation of porcine islets allows extended in vitro culture, providing ample time to determine the functional capacity of the islets and conduct comprehensive microbiological safety testing prior to implantation as a treatment for type 1 diabetes mellitus. However, the effect that agarose encapsulation and long-term culture may have on porcine islet gene expression is unknown. The aim of the present study was to compare the transcriptome of encapsulated porcine islets following long-term in vitro culture against free islets cultured overnight. Global gene expression analysis revealed no significant change in the expression of 98.47% of genes. This indicates that the gene expressionmore » profile of free islets is highly conserved following encapsulation and long-term culture. Importantly, the expression levels of genes that code for critical hormones secreted by islets (insulin, glucagon, and somatostatin) as well as transcripts encoding proteins involved in their packaging and secretion are unchanged. While a small number of genes known to play roles in the insulin secretion and insulin signaling pathways are differentially expressed, our results show that overall gene expression is retained following islet isolation, agarose encapsulation, and long-term culture. - Highlights: • Effect of agarose encapsulation and 8 week culture on porcine islets was analyzed. • Transcriptome analysis revealed no significant change in a majority (98%) of genes. • Agarose encapsulation allows for long-term culture of porcine islets. • Islet culture allows for functional and microbial testing prior to clinical use.« less

pH-sensitive poly(lactide-co-glycolide) nanoparticle composite microcapsules for oral delivery of insulin.

PubMed

Sun, Shaoping; Liang, Na; Yamamoto, Hiromitsu; Kawashima, Yoshiaki; Cui, Fude; Yan, Pengfei

2015-01-01

This study proposes a new concept of pH-sensitive poly(lactide-co-glycolide) (PLGA) nanoparticle composite microcapsules for oral delivery of insulin. Firstly, insulin-sodium oleate complex was prepared by the hydrophobic ion pairing method and then encapsulated into PLGA nanoparticles by the emulsion solvent diffusion method. In order to reduce the burst release of insulin from PLGA nanoparticles and deliver insulin to specific gastrointestinal regions, hence to enhance bioavailability of insulin, the PLGA nanoparticles were further encapsulated into Eudragit(®) FS 30D to prepare PLGA nanoparticle composite microcapsules by organic spray-drying method. The preparation was evaluated in vitro and in vivo, and the absorption mechanism was discussed. The in vitro drug release studies revealed that the drug release was pH dependent, and the in vivo results demonstrated that the formulation of PLGA nanoparticle composite microcapsules was an effective candidate for oral insulin delivery.

Structure and dynamics of spin-labeled insulin entrapped in a silica matrix by the sol-gel method.

PubMed

Vanea, E; Gruian, C; Rickert, C; Steinhoff, H-J; Simon, V

2013-08-12

The structure and conformational dynamics of insulin entrapped into a silica matrix was monitored during the sol to maturated-gel transition by electron paramagnetic resonance (EPR) spectroscopy. Insulin was successfully spin-labeled with iodoacetamide and the bifunctional nitroxide reagent HO-1944. Room temperature continuous wave (cw) EPR spectra of insulin were recorded to assess the mobility of the attached spin labels. Insulin conformation and its distribution within the silica matrix were studied using double electron-electron resonance (DEER) and low-temperature cw-EPR. A porous oxide matrix seems to form around insulin molecules with pore diameters in the order of a few nanometers. Secondary structure of the encapsulated insulin investigated by Fourier transform infrared spectroscopy proved a high structural integrity of insulin even in the dried silica matrix. The results show that silica encapsulation can be used as a powerful tool to effectively isolate and functionally preserve biomolecules during preparation, storage, and release.

IGF-1 Release Kinetics from Chitosan Microparticles Fabricated Using Environmentally Benign Conditions

PubMed Central

Mantripragada, Venkata P.; Jayasuriya, Ambalangodage C.

2014-01-01

The main objective of this study is to maximize growth factor encapsulation efficiency into microparticles. The novelty of this study is to maximize the encapsulated growth factors into microparticles by minimizing the use of organic solvents and using relatively low temperatures. The microparticles were fabricated using chitosan biopolymer as a base polymer and cross-linked with tripolyphosphate (TPP). Insulin like-growth factor-1 (IGF-1) was encapsulated into microparticles to study release kinetics and bioactivity. In order to authenticate the harms of using organic solvents like hexane and acetone during microparticle preparation, IGF-1 encapsulated microparticles prepared by the emulsification and coacervation methods were compared. The microparticles fabricated by emulsification method have shown a significant decrease (p<0.05) in IGF-1 encapsulation efficiency, and cumulative release during the two-week period. The biocompatibility of chitosan microparticles and the bioactivity of the released IGF-1 were determined in vitro by live/dead viability assay. The mineralization data observed with Von Kossa assay, was supported by mRNA expression levels of osterix and runx2, which are transcription factors necessary for osteoblasts differentiation. Real time RT-PCR data showed an increased expression of runx 2 and a decreased expression of osterix over time, indicating differentiating osteoblasts. Chitosan microparticles prepared in optimum environmental conditions are a promising controlled delivery system for cells to attach, proliferate, differentiate and mineralize, thereby acting as a suitable bone repairing material. PMID:25063148

Cryopreservation of human insulin expressing cells macro-encapsulated in a durable therapeutic immunoisolating device theracyte.

PubMed

Yakhnenko, Ilya; Wong, Wallace K; Katkov, Igor I; Itkin-Ansari, Pamela

2012-01-01

Encapsulating insulin producing cells (INPCs) in an immunoisolation device have been shown to cure diabetes in rodents without the need for immunosuppression. However, micro-encapsulation in semi-solid gels raises longevity and safety concerns for future use of stem cell derived INPCs. We have focused on a durable and retrievable macro-encapsulation (> 10(6) cells) device (TheraCyte). Cryopreservation (CP) of cells preloaded into the device is highly desirable but may require prolonged exposure to cryoprotectants during loading and post-thaw manipulations. Here, we are reporting survival and function of a human islet cell line frozen as single cells or as islet-like cell clusters. The non-clusterized cells exhibited high cryosurvival after prolonged pre-freeze or post-thaw exposure to 10 percent DMSO. However, both clusterization and especially loading INPCs into the device reduced viable yield even without CP. The survived cryopreserved macro-encapsulated INPCs remained fully functional suggesting that CP of macro-encapsulated cells is a promising tool for cell based therapies.

pH-sensitive poly(lactide-co-glycolide) nanoparticle composite microcapsules for oral delivery of insulin

PubMed Central

Sun, Shaoping; Liang, Na; Yamamoto, Hiromitsu; Kawashima, Yoshiaki; Cui, Fude; Yan, Pengfei

2015-01-01

This study proposes a new concept of pH-sensitive poly(lactide-co-glycolide) (PLGA) nanoparticle composite microcapsules for oral delivery of insulin. Firstly, insulin–sodium oleate complex was prepared by the hydrophobic ion pairing method and then encapsulated into PLGA nanoparticles by the emulsion solvent diffusion method. In order to reduce the burst release of insulin from PLGA nanoparticles and deliver insulin to specific gastrointestinal regions, hence to enhance bioavailability of insulin, the PLGA nanoparticles were further encapsulated into Eudragit® FS 30D to prepare PLGA nanoparticle composite microcapsules by organic spray-drying method. The preparation was evaluated in vitro and in vivo, and the absorption mechanism was discussed. The in vitro drug release studies revealed that the drug release was pH dependent, and the in vivo results demonstrated that the formulation of PLGA nanoparticle composite microcapsules was an effective candidate for oral insulin delivery. PMID:25999713

Formulation Optimization of Human Insulin Loaded Microspheres for Controlled Oral Delivery Using Response Surface Methodology.

PubMed

Agrawal, Gauravkuma; Wakte, Pravin; Shelke, Santosh

2017-01-01

The objectives of the present investigation were to prepare recombinant human insulin entrapped Eudragit-S100 microspheres containing protease inhibitors and to precisely analyze the outcome of different formulation variables on the microspheres properties using a response surface methodology to develop an optimized formulation with desirable features. A central composite design was employed to produce microspheres of therapeutic protein by w/o/w multiple emulsion solvent evaporation technique using Eudragit S-100 as coating material and polyvinyl alcohol as a stabilizer. The effect of formulation variables (independent variables) that is levels of Eudragit S-100 (X1), therapeutic protein (X2), volumes of inner aqueous phase (X3) and external aqueous phase (X4) on dependant variables, that are encapsulation efficiency (Y1), drug release at pH 1.2 after 2 h (Y2) and drug release at pH 7.4 after of 2 h (Y3) were evaluated. The significant terms in the mathematical models were generated for each response parameter using multiple linear regression analysis and analysis of variance. All the formulation variables except the volume of external aqueous phase (X4) exerted a significant effect (P <0.05) on drug encapsulation efficiency (Y1) whereas first two variables, namely the levels of Eudragit S-100 (X1) and therapeutic protein (X2) materialized as the determining factors which significantly influenced drug release at pH 1.2 after 2 h (Y2) and drug release at pH 7.4 after of 2 h (Y3). The formulation was numerically optimized by framing the constraints on the dependent and independent variables using the desirability approach. The experimental values for Y1 and Y2 of optimized formulation were found to be 77.65% and 3.64%, respectively which were quite closer to results suggested by software. The results recorded indicate that the recombinant human insulin loaded Eudragit S-100 microspheres containing aprotinin have the benefits of higher loading efficiency, pH responsive and prolonged release characteristics, which may help to carry insulin to the optimum site of absorption. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Microspheres for the oral delivery of insulin: preparation, evaluation and hypoglycaemic effect in streptozotocin-induced diabetic rats.

PubMed

Zhang, Huan; Wang, Weimei; Li, Haoran; Peng, Yi; Zhang, Zhiqing

2018-01-01

Insulin-loaded microspheres were prepared by alternating deposition film layers that were composed of insulin and poly(vinyl sulfate) potassium on the surface of poly(lactic acid) (PLA) microspheres. The preparation of the insulin-loaded microspheres was optimized by an orthogonal test design, and the relationship between drug loading (DL) and film layers was studied. The particle size, DL and encapsulation efficiency of the obtained insulin-loaded microspheres with 10 films were 5.25 ± 0.15 µm, 111.33 ± 1.15 mg/g and 33.7 ± 0.19%, respectively. Following this, the physical characteristics of the insulin-loaded microspheres were investigated. The results from scanning electron microscopy and a laser particle size analyzer (LPSA) indicated the spherical morphology, rough surface and increasing particle sizes of the insulin-loaded microspheres, which were compared to those of PLA microspheres. An in vitro release study showed that the insulin-loaded microspheres were stable in HCl solution (pH 1.0) and released insulin slowly in phosphate-buffered solution (pH 6.8). Finally, the drug efficacy of the prepared insulin-loaded microspheres via oral administration was evaluated in rats with diabetes induced by streptozotocin, and an obvious dose-dependent hypoglycemic effect was observed. This preliminary data could illustrate the prospect of using microspheres for the oral delivery of insulin.

Development of glucose-responsive 'smart' insulin systems.

PubMed

Rege, Nischay K; Phillips, Nelson F B; Weiss, Michael A

2017-08-01

The complexity of modern insulin-based therapy for type I and type II diabetes mellitus and the risks associated with excursions in blood-glucose concentration (hyperglycemia and hypoglycemia) have motivated the development of 'smart insulin' technologies (glucose-responsive insulin, GRI). Such analogs or delivery systems are entities that provide insulin activity proportional to the glycemic state of the patient without external monitoring by the patient or healthcare provider. The present review describes the relevant historical background to modern GRI technologies and highlights three distinct approaches: coupling of continuous glucose monitoring (CGM) to deliver devices (algorithm-based 'closed-loop' systems), glucose-responsive polymer encapsulation of insulin, and molecular modification of insulin itself. Recent advances in GRI research utilizing each of the three approaches are illustrated; these include newly developed algorithms for CGM-based insulin delivery systems, glucose-sensitive modifications of existing clinical analogs, newly developed hypoxia-sensitive polymer matrices, and polymer-encapsulated, stem-cell-derived pancreatic β cells. Although GRI technologies have yet to be perfected, the recent advances across several scientific disciplines that are described in this review have provided a path towards their clinical implementation.

Development and characterization of lipid-polymeric nanoparticles for oral insulin delivery.

PubMed

Sgorla, Débora; Lechanteur, Anna; Almeida, Andreia; Sousa, Flávia; Melo, Eduardo; Bunhak, Élcio; Mainardes, Rubiana; Khalil, Najeh; Cavalcanti, Osvaldo; Sarmento, Bruno

2018-03-01

The oral route is widely accepted as the most physiological path for exogenous administration of insulin, as it closely mimic the endogenous insulin pathway. Thus, in this work it is proposed an innovative lipid-polymeric nanocarrier to delivery insulin orally. Areas covered: Nanoparticles were produced through a modified solvent emulsification-evaporation method, using ethyl palmitate and hydroxypropylmethylcellulose acetate succinate as matrix. Lipid-polymeric nanoparticles were around 300 nm in size, negatively charged (-20 mV) and associated insulin with efficiency higher than 80%. Differential scanning calorimetry suggested thermal stability of nanoparticles. In vitro release assays under simulated gastrointestinal conditions resulted in 9% and 14% of insulin released at pH 1.2 during 2 h and at pH 6.8 for 6 h, respectively, demonstrating the ability of those nanoparticles to protect insulin against premature degradation. Importantly, nanoparticles were observed to be safe at potential therapeutic concentrations as did not originate cytotoxicity to intestinal epithelial cells. Lastly, the permeability of nanoencapsulated insulin through Caco-2 monolayers and a triple Caco-2/HT29-MTX/Raji B cell model correlated well with slow release kinetics, and fosters the effectiveness of nanoparticles to promote intestinal absorption of peptidic drugs. Expert opinion: Lipid-polymeric nanoparticles were developed to encapsulate and carry insulin through intestine. Overall, nanoparticles provide insulin stability and intestinal permeability.

Effects of poly (lactic-co-glycolic acid) as a co-emulsifier on the preparation and hypoglycaemic activity of insulin-loaded solid lipid nanoparticles.

PubMed

Wang, S L; Xie, S Y; Zhu, L Y; Wang, F H; Zhou, W Z

2009-12-01

Poly (lactic-co-glycolic acid) (PLGA) was used as a co-emulsifier in the preparation of insulin-loaded solid lipid nanoparticles (SLN) with hydrogenated castor oil as lipid matrix and lecithin as surfactant by double-emulsion technique. The effects of PLGA on the preparation and hypoglycaemic activity of insulin-loaded SLN were studied. The results showed that with the supplement of PLGA, the encapsulation efficiency and loading capacity were increased significantly from 79.08 +/- 1.62 to 85.57 +/- 3.21% and 1.58 +/- 0.03 to 1.71 +/- 0.06%, whereas the surface charge and particle size were changed insignificantly from -25.87 +/- 2.65 to -22.67 +/- 1.19 mv and 431.0 +/- 16.1 to 397.0 +/- 68.0 nm, respectively. In vivo studies demonstrated that PLGA increased the sustained hypoglycaemic activity from 12 to 36 h and 24 to 120 h in normal and steptozotocin-induced diabetic mice after a single intramuscular injection of the insulin-loaded SLN. These results demonstrated that PLGA could enhance the entrapment of insulin in the nanoparticles, and more importantly, prolong the time of hypoglycaemic activity of the insulin-loaded SLN.

Acute Ischemia Induced by High-Density Culture Increases Cytokine Expression and Diminishes the Function and Viability of Highly Purified Human Islets of Langerhans.

PubMed

Smith, Kate E; Kelly, Amy C; Min, Catherine G; Weber, Craig S; McCarthy, Fiona M; Steyn, Leah V; Badarinarayana, Vasudeo; Stanton, J Brett; Kitzmann, Jennifer P; Strop, Peter; Gruessner, Angelika C; Lynch, Ronald M; Limesand, Sean W; Papas, Klearchos K

2017-11-01

Encapsulation devices have the potential to enable cell-based insulin replacement therapies (such as human islet or stem cell-derived β cell transplantation) without immunosuppression. However, reasonably sized encapsulation devices promote ischemia due to high β cell densities creating prohibitively large diffusional distances for nutrients. It is hypothesized that even acute ischemic exposure will compromise the therapeutic potential of cell-based insulin replacement. In this study, the acute effects of high-density ischemia were investigated in human islets to develop a detailed profile of early ischemia induced changes and targets for intervention. Human islets were exposed in a pairwise model simulating high-density encapsulation to normoxic or ischemic culture for 12 hours, after which viability and function were measured. RNA sequencing was conducted to assess transcriptome-wide changes in gene expression. Islet viability after acute ischemic exposure was reduced compared to normoxic culture conditions (P < 0.01). Insulin secretion was also diminished, with ischemic β cells losing their insulin secretory response to stimulatory glucose levels (P < 0.01). RNA sequencing revealed 657 differentially expressed genes following ischemia, with many that are associated with increased inflammatory and hypoxia-response signaling and decreased nutrient transport and metabolism. In order for cell-based insulin replacement to be applied as a treatment for type 1 diabetes, oxygen and nutrient delivery to β cells will need to be maintained. We demonstrate that even brief ischemic exposure such as would be experienced in encapsulation devices damages islet viability and β cell function and leads to increased inflammatory signaling.

A rapid-acting, long-acting insulin formulation based on a phospholipid complex loaded PHBHHx nanoparticles.

PubMed

Peng, Qiang; Zhang, Zhi-Rong; Gong, Tao; Chen, Guo-Qiang; Sun, Xun

2012-02-01

The application of poly(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) for sustained and controlled delivery of hydrophilic insulin was made possible by preparing insulin phospholipid complex loaded biodegradable PHBHHx nanoparticles (INS-PLC-NPs). The INS-PLC-NPs produced by a solvent evaporation method showed a spherical shape with a mean particle size, zeta potential and entrapment efficiency of 186.2 nm, -38.4 mv and 89.73%, respectively. In vitro studies demonstrated that only 20% of insulin was released within 31 days with a burst release of 5.42% in the first 8 h. The hypoglycaemic effect in STZ induced diabetic rats lasted for more than 3 days after the subcutaneous injection of INS-PLC-NPs, which significantly prolonged the therapeutic effect compared with the administration of insulin solution. The pharmacological bioavailability (PA) of INS-PLC-NPs relative to insulin solution was over 350%, indicating that the bioavailability of insulin was significantly enhanced by INS-PLC-NPs. Therefore, the INS-PLC-NPs system is promising to serve as a long lasting insulin release formulation, by which the patient compliance can be enhanced significantly. This study also showed that phospholipid complex loaded biodegradable nanoparticles (PLC-NPs) have a great potential to be used as a sustained delivery system for hydrophilic proteins to be encapsulated in hydrophobic polymers. Copyright © 2011 Elsevier Ltd. All rights reserved.

Thiol functionalized polymethacrylic acid-based hydrogel microparticles for oral insulin delivery.

PubMed

Sajeesh, S; Vauthier, C; Gueutin, C; Ponchel, G; Sharma, Chandra P

2010-08-01

In the present study thiol functionalized polymethacrylic acid-polyethylene glycol-chitosan (PCP)-based hydrogel microparticles were utilized to develop an oral insulin delivery system. Thiol modification was achieved by grafting cysteine to the activated surface carboxyl groups of PCP hydrogels (Cys-PCP). Swelling and insulin loading/release experiments were conducted on these particles. The ability of these particles to inhibit protease enzymes was evaluated under in vitro experimental conditions. Insulin transport experiments were performed on Caco-2 cell monolayers and excised intestinal tissue with an Ussing chamber set-up. Finally, the efficacy of insulin-loaded particles in reducing the blood glucose level in streptozotocin-induced diabetic rats was investigated. Thiolated hydrogel microparticles showed less swelling and had a lower insulin encapsulation efficiency as compared with unmodified PCP particles. PCP and Cys-PCP microparticles were able to inhibit protease enzymes under in vitro conditions. Thiolation was an effective strategy to improve insulin absorption across Caco-2 cell monolayers, however, the effect was reduced in the experiments using excised rat intestinal tissue. Nevertheless, functionalized microparticles were more effective in eliciting a pharmacological response in diabetic animal, as compared with unmodified PCP microparticles. From these studies thiolation of hydrogel microparticles seems to be a promising approach to improve oral delivery of proteins/peptides. Copyright 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Integrity and stability of oral liposomes containing bile salts studied in simulated and ex vivo gastrointestinal media.

PubMed

Hu, Shunwen; Niu, Mengmeng; Hu, Fuqiang; Lu, Yi; Qi, Jianping; Yin, Zongning; Wu, Wei

2013-01-30

The objective of this study was to investigate the integrtity and stability of oral liposomes containing glycocholate (SGC-Lip) in simulated gastrointestinal (GI) media and ex vivo GI media from rats in comparison with conventional liposomes (CH-Lip) composed of soybean phosphatidylcholine and cholesterol. Membrane integrity of liposomes was evaluated by monitoring calcein release, particle size and distribution in different simulated GI media. The stability of liposomes encapsulating insulin was investigated in simulated GI fluids containing pepsin or pancreatin and ex vivo GI enzyme fluids. Simulated GI media with low pH or physiological bile salts resulted in significant increase in calcein release, but dynamic laser scattering data showed that the size and distribution were generally stable. SGC-Lip retained the major amount of the initially encapsulated insulin as compared with CH-Lip in simulated GI fluids (SGF, FaSSGF, SIF and FeSSIF-V2). SGC-Lip retained respectively 17.1% and 20.5% of the initially encapsulated insulin in ex vivo GI fluid, which were also significantly more than CH-Lip. These results suggested that SGC-Lip could protect insulin from degradation to some degree during their transit through the gastrointestinal tract and contributed to enhanced oral absorption. Copyright © 2012 Elsevier B.V. All rights reserved.

Pancreatic Tissue Transplanted in TheraCyte Encapsulation Devices Is Protected and Prevents Hyperglycemia in a Mouse Model of Immune-Mediated Diabetes.

PubMed

Boettler, Tobias; Schneider, Darius; Cheng, Yang; Kadoya, Kuniko; Brandon, Eugene P; Martinson, Laura; von Herrath, Matthias

2016-01-01

Type 1 diabetes (T1D) is characterized by destruction of glucose-responsive insulin-producing pancreatic β-cells and exhibits immune infiltration of pancreatic islets, where CD8 lymphocytes are most prominent. Curative transplantation of pancreatic islets is seriously hampered by the persistence of autoreactive immune cells that require high doses of immunosuppressive drugs. An elegant approach to confer graft protection while obviating the need for immunosuppression is the use of encapsulation devices that allow for the transfer of oxygen and nutrients, yet prevent immune cells from making direct contact with the islet grafts. Here we demonstrate that macroencapsulation devices (TheraCyte) loaded with neonatal pancreatic tissue and transplanted into RIP-LCMV.GP mice prevented disease onset in a model of virus-induced diabetes mellitus. Histological analyses revealed that insulin-producing cells survived within the device in animal models of diabetes. Our results demonstrate that these encapsulation devices can protect from an immune-mediated attack and can contain a sufficient amount of insulin-producing cells to prevent overt hyperglycemia.

Human beta-cell precursors mature into functional insulin-producing cells in an immunoisolation device: implications for diabetes cell therapies.

PubMed

Lee, Seung-Hee; Hao, Ergeng; Savinov, Alexei Y; Geron, Ifat; Strongin, Alex Y; Itkin-Ansari, Pamela

2009-04-15

Islet transplantation is limited by the need for chronic immunosuppression and the paucity of donor tissue. As new sources of human beta-cells are developed (e.g., stem cell-derived tissue), transplanting them in a durable device could obviate the need for immunosuppression, while also protecting the patient from any risk of tumorigenicity. Here, we studied (1) the survival and function of encapsulated human beta-cells and their progenitors and (2) the engraftment of encapsulated murine beta-cells in allo- and autoimmune settings. Human islets and human fetal pancreatic islet-like cell clusters were encapsulated in polytetrafluorethylene devices (TheraCyte) and transplanted into immunodeficient mice. Graft survival and function was measured by immunohistochemistry, circulating human C-peptide levels, and blood glucose levels. Bioluminescent imaging was used to monitor encapsulated neonatal murine islets. Encapsulated human islet-like cell clusters survived, replicated, and acquired a level of glucose responsive insulin secretion sufficient to ameliorate hyperglycemia in diabetic mice. Bioluminescent imaging of encapsulated murine neonatal islets revealed a dynamic process of cell death followed by regrowth, resulting in robust long-term allograft survival. Further, in the non-obese diabetic (NOD) mouse model of type I diabetes, encapsulated primary beta-cells ameliorated diabetes without stimulating a detectable T-cell response. We demonstrate for the first time that human beta-cells function is compatible with encapsulation in a durable, immunoprotective device. Moreover, our study suggests that encapsulation of beta-cells before terminal differentiation will be a successful approach for new cell-based therapies for diabetes, such as those derived from stem cells.

VB12-coated Gel-Core-SLN containing insulin: Another way to improve oral absorption.

PubMed

He, Haibing; Wang, Puxiu; Cai, Cuifang; Yang, Rui; Tang, Xing

2015-09-30

To improve the oral absorption of insulin, a novel carrier of Vitamin B12 (VB12) gel core solid lipid nanopaticles (Gel-Core-SLN, GCSLN) was designed with a gel core, lipid matrix and VB12-coated surface. VB12-stearate was synthesized and characterized by infrared spectroscopy (IR), nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). Sol-gel conversion following ultrasonic heating and double emulsion technology were combined to implant the insulin-containing gel into solid lipid nanoparticles (SLN). The influence of the mode of administration, food, the amount of VB12-stearate and the particle size on the oral absorption of insulin incorporated in the VB12-GCSLN was investigated. The determined partition coefficient (LogP) of VB12-stearate in a dichloromethane (DCM)-water system was 3.4. This new structure of VB12-GCSLN had higher insulin encapsulation efficiency (EE) of 55.9%, a lower burst release of less than 10% in the first 2h. In vivo studies demonstrated that stronger absorption of insulin with a relative pharmacological availability (PA) of 9.31% compared with the normal insulin-loaded SLN and GCSLN and fairly stable blood glucose levels up to 12h were maintained without any sharp fluctuations. This study suggests that VB12-GCSLN containing insulin appears to be a promising nano carrier for oral delivery of biomacromolecules with relatively high pharmacological availability. Copyright © 2015 Elsevier B.V. All rights reserved.

Simultant encapsulation of vitamin C and beta-carotene in sesame (Sesamum indicum l.) liposomes

NASA Astrophysics Data System (ADS)

Hudiyanti, D.; Fawrin, H.; Siahaan, P.

2018-04-01

In this study sesame liposomes were used to encapsulate both vitamin C and beta-carotene simultaneously. Liposomes were prepared with addition of cholesterol. The encapsulation efficiency (EE) of sesame liposomes for vitamin C in the present of beta-carotene was 77%. The addition of cholesterol increased the encapsulation efficiency. The highest encapsulation efficiency was 89% obtained in liposomes with 10% and 20% cholesterol. Contrary to that, the highest beta-carotene encapsulation efficiency of 78%, was found in the sesame liposomes prepared without the added cholesterol. Results showed that sesame liposomes can be used to encapsulate beta-carotene and vitamin C simultaneously. When beta-carotene and vitamin C were encapsulated concurrently, cholesterol intensified the efficiency of vitamin C encapsulation on the contrary it diminished the efficiency of beta-carotene encapsulation.

Using selective withdrawal to encapsulate pancreatic islets for immunoisolation

NASA Astrophysics Data System (ADS)

Wyman, Jason; Murphy, William; Mrksich, Milan

2005-11-01

We apply selective-withdrawal for encapsulating insulin-producing pancreatic islets within thin poly(ethylene glycol) (PEG) coats. Islets placed in an aqueous PEG solution are drawn into the selective-withdrawal spout which then breaks up, leaving the islets surrounded by a thin, 20μm, polymer coat. These coats, whose thickness is independent of the size of the encapsulated islet, are photo-crosslinked to form hydrogel capsules. We can apply multiple coats of varying chemical composition. These coats provide a semi-permeable membrane which allows the islets to respond to changes in glucose concentration by producing insulin in a manner similar to that of unencapsulated islets. Furthermore, the hydrogel capsules exclude large molecules the size of the smallest antibodies. Our results suggest that this microencapsulation technique may be useful for the transplantation of islets for treatment of Type I diabetes.

Can natural polymers assist in delivering insulin orally?

PubMed

Nur, Mokhamad; Vasiljevic, Todor

2017-10-01

Diabetes mellitus is one of the most grave and lethal non communicable diseases. Insulin is normally used to medicate diabetes. Due to bioavailability issues, the most regular route of administration is through injection, which may pose compliance problems to treatment. The oral administration thus appears as a suitable alternative, but with several important problems. Low stability of insulin in the gastrointestinal tract and low intestinal permeation are some of the issues. Encapsulation of insulin into polymer-based particles emerges as a plausible strategy. Different encapsulation approaches and polymers have been used in this regard. Polymers with different characteristics from natural or synthetic origin have been assessed to attain this goal, with natural polymers being preferable. Natural polymers studied so far include chitosan, alginate, carrageenan, starch, pectin, casein, tragacanth, dextran, carrageenan, gelatine and cyclodextrin. While some promising knowledge and results have been gained, a polymeric-based particle system to deliver insulin orally has not been introduced onto the market yet. In this review, effectiveness of different natural polymer materials developed so far along with fabrication techniques are evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

Drug permeability and mucoadhesion properties of thiolated trimethyl chitosan nanoparticles in oral insulin delivery.

PubMed

Yin, Lichen; Ding, Jieying; He, Chunbai; Cui, Liming; Tang, Cui; Yin, Chunhua

2009-10-01

Trimethyl chitosan-cysteine conjugate (TMC-Cys) was synthesized in an attempt to combine the mucoadhesion and the permeation enhancing effects of TMC and thiolated polymers related to different mechanisms for oral absorption. TMC-Cys with various molecular weights (30, 200, and 500 kDa) and quaternization degrees (15 and 30%) was allowed to form polyelectrolyte nanoparticles with insulin through self-assembly, which demonstrated particle size of 100-200 nm, zeta potential of +12 to +18 mV, and high encapsulation efficiency. TMC-Cys/insulin nanoparticles (TMC-Cys NP) showed a 2.1-4.7-fold increase in mucoadhesion compared to TMC/insulin nanoparticles (TMC NP), which might be partly attributed to disulfide formation between TMC-Cys and mucin as evidenced by DSC measurement. Compared to insulin solution and TMC NP, TMC-Cys NP induced increased insulin transport through rat intestine by 3.3-11.7 and 1.7-2.6 folds, promoted Caco-2 cell internalization by 7.5-12.7 and 1.7-3.0 folds, and augmented uptake in Peyer's patches by 14.7-20.9 and 1.7-5.0 folds, respectively. Such results were further confirmed by in vivo experiment with the optimal TMC-Cys NP. Biocompatibility assessment revealed lack of toxicity of TMC-Cys NP. Therefore, self-assembled nanoparticles between TMC-Cys and protein drugs could be an effective and safe oral delivery system.

Human β-cell Precursors Mature Into Functional Insulin-producing Cells in an Immunoisolation Device: Implications for Diabetes Cell Therapies

PubMed Central

Lee, Seung-Hee; Hao, Ergeng; Savinov, Alexei Y.; Geron, Ifat; Strongin, Alex Y.; Itkin-Ansari, Pamela

2009-01-01

Background Islet transplantation is limited by the need for chronic immunosuppression and the paucity of donor tissue. As new sources of human β-cells are developed (e.g., stem cell-derived tissue), transplanting them in a durable device could obviate the need for immunosuppression, while also protecting the patient from any risk of tumorigenicity. Here, we studied (1) the survival and function of encapsulated human β-cells and their progenitors and (2) the engraftment of encapsulated murine β-cells in allo- and autoimmune settings. Methods Human islets and human fetal pancreatic islet-like cell clusters were encapsulated in polytetrafluorethylene devices (TheraCyte) and transplanted into immunodeficient mice. Graft survival and function was measured by immunohistochemistry, circulating human C-peptide levels, and blood glucose levels. Bioluminescent imaging was used to monitor encapsulated neonatal murine islets. Results Encapsulated human islet-like cell clusters survived, replicated, and acquired a level of glucose responsive insulin secretion sufficient to ameliorate hyperglycemia in diabetic mice. Bioluminescent imaging of encapsulated murine neonatal islets revealed a dynamic process of cell death followed by regrowth, resulting in robust long-term allograft survival. Further, in the non-obese diabetic (NOD) mouse model of type I diabetes, encapsulated primary β-cells ameliorated diabetes without stimulating a detectable T-cell response. Conclusions We demonstrate for the first time that human β-cells function is compatible with encapsulation in a durable, immunoprotective device. Moreover, our study suggests that encapsulation of β-cells before terminal differentiation will be a successful approach for new cell-based therapies for diabetes, such as those derived from stem cells. PMID:19352116

Stimuli sensitive polymethacrylic acid microparticles (PMAA)--oral insulin delivery.

PubMed

Victor, Sunita Prem; Sharma, Chandra P

2002-10-01

This study investigated polymethacrylic acid (PMAA) microparticles for controlled release of Insulin in oral administration. The microparticles were characterised by scanning electron microscopy (SEM) for morphological studies. The swelling behaviour and drug release profile in various pH media were studied. The % swelling of gels was found to be inversely related to the amount of crosslinker added. Inclusion complex of betaCD and Insulin was studied using polyacrylamide gel electrophoresis (PAGE). Optimum complexation was obtained in the ratio 100 mg betaCD: 200 IU Insulin. The release pattern of Insulin from Insulin-betaCD complex encapsulated PMAA microparticles showed release of Insulin for more than seven hours.

Subconjunctivally Implanted Hydrogels for Sustained Insulin Release to Reduce Retinal Cell Apoptosis in Diabetic Rats.

PubMed

Imai, Hisanori; Misra, Gauri P; Wu, Linfeng; Janagam, Dileep R; Gardner, Thomas W; Lowe, Tao L

2015-12-01

Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients that involves early-onset retinal cell loss. Here, we report our recent work using subconjunctivally implantable hydrogels for sustained insulin release to the retina to prevent retinal degeneration. The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide and a dextran macromer containing oligolactate-(2-hydroxyetheyl methacrylate) units. Insulin was loaded into the hydrogels during the synthesis. The ex vivo bioactivity of insulin released from the hydrogels was tested on fresh rat retinas using immunoprecipitation and immunoblotting to measure insulin receptor tyrosine and Akt phosphorylation. The biosafety and the effect on the blood glucose of the hydrogels were evaluated in rats 2 months after subconjunctival implantation. The release of insulin from the hydrogels was studied both in vitro in PBS (pH 7.4), and in vivo using confocal microscopy and RIA kit. The in vivo bioactivity of the released insulin was investigated in diabetic rats using DNA fragmentation method. The hydrogels could load insulin with approximately 98% encapsulation efficiency and continuously release FITC-insulin in PBS (pH = 7.4) at 37°C for at least 5 months depending on their composition. Insulin lispro released from the hydrogels was biologically active by increasing insulin receptor tyrosine and Akt serine phosphorylation of ex vivo retinas. In vivo studies showed normal retinal histology 2 months post subconjunctival implantation. Insulin released from subconjunctivally implanted hydrogels could be detected in the retina by using confocal microscopy and RIA kit for 1 week. The implanted hydrogels with insulin lispro did not change the blood glucose level of normal and diabetic rats, but significantly reduced the DNA fragmentation of diabetic retinas for 1 week. The developed hydrogels have great potential to sustain release of insulin to the retina via subconjunctival implantation to minimize DR without the risk of hypoglycemia.

Subconjunctivally Implanted Hydrogels for Sustained Insulin Release to Reduce Retinal Cell Apoptosis in Diabetic Rats

PubMed Central

Imai, Hisanori; Misra, Gauri P.; Wu, Linfeng; Janagam, Dileep R.; Gardner, Thomas W.; Lowe, Tao L.

2015-01-01

Purpose Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients that involves early-onset retinal cell loss. Here, we report our recent work using subconjunctivally implantable hydrogels for sustained insulin release to the retina to prevent retinal degeneration. Methods The hydrogels are synthesized by UV photopolymerization of N-isopropylacrylamide and a dextran macromer containing oligolactate-(2-hydroxyetheyl methacrylate) units. Insulin was loaded into the hydrogels during the synthesis. The ex vivo bioactivity of insulin released from the hydrogels was tested on fresh rat retinas using immunoprecipitation and immunoblotting to measure insulin receptor tyrosine and Akt phosphorylation. The biosafety and the effect on the blood glucose of the hydrogels were evaluated in rats 2 months after subconjunctival implantation. The release of insulin from the hydrogels was studied both in vitro in PBS (pH 7.4), and in vivo using confocal microscopy and RIA kit. The in vivo bioactivity of the released insulin was investigated in diabetic rats using DNA fragmentation method. Results The hydrogels could load insulin with approximately 98% encapsulation efficiency and continuously release FITC-insulin in PBS (pH = 7.4) at 37°C for at least 5 months depending on their composition. Insulin lispro released from the hydrogels was biologically active by increasing insulin receptor tyrosine and Akt serine phosphorylation of ex vivo retinas. In vivo studies showed normal retinal histology 2 months post subconjunctival implantation. Insulin released from subconjunctivally implanted hydrogels could be detected in the retina by using confocal microscopy and RIA kit for 1 week. The implanted hydrogels with insulin lispro did not change the blood glucose level of normal and diabetic rats, but significantly reduced the DNA fragmentation of diabetic retinas for 1 week. Conclusions The developed hydrogels have great potential to sustain release of insulin to the retina via subconjunctival implantation to minimize DR without the risk of hypoglycemia. PMID:26658505

Islet Transplantation and Encapsulation: An Update on Recent Developments

PubMed Central

Vaithilingam, Vijayaganapathy; Tuch, Bernard E.

2011-01-01

Human islet transplantation can provide good glycemic control in diabetic recipients without exogenous insulin. However, a major factor limiting its application is the recipient's need to adhere to life-long immunosuppression, something that has serious side effects. Microencapsulating human islets is a strategy that should prevent rejection of the grafted tissue without the need for anti-rejection drugs. Despite promising studies in various animal models, the encapsulated human islets so far have not made an impact in the clinical setting. Many non-immunological and immunological factors such as biocompatibility, reduced immunoprotection, hypoxia, pericapsular fibrotic overgrowth, effects of the encapsulation process and post-transplant inflammation hamper the successful application of this promising technology. In this review, strategies are discussed to overcome the above-mentioned factors and to enhance the survival and function of encapsulated insulin-producing cells, whether in islets or surrogate β-cells. Studies at our center show that barium alginate microcapsules are biocompatible in rodents, but not in humans, raising concerns over the use of rodents to predict outcomes. Studies at our center also show that the encapsulation process had little or no effect on the cellular transcriptome of human islets and on their ability to function either in vitro or in vivo. New approaches incorporating further modifications to the microcapsule surface to prevent fibrotic overgrowth are vital, if encapsulated human islets or β-cell surrogates are to become a viable therapy option for type 1 diabetes in humans. PMID:21720673

Novel PLGA-based nanoparticles for the oral delivery of insulin.

PubMed

Malathi, Sampath; Nandhakumar, Perumal; Pandiyan, Velayudham; Webster, Thomas J; Balasubramanian, Sengottuvelan

2015-01-01

Insulin is the drug therapy for patients with insulin-dependent diabetes mellitus. A number of attempts have been made in the past to overcome the problems associated with the oral delivery of insulin, but with little success. Orally administered insulin has encountered with many difficulties such as rapid degradation and poor intestinal absorption. The potential use of D-α-tocopherol poly(ethylene glycol) 1000 succinate (TPGS)-emulsified poly(ethylene glycol) (PEG)-capped poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was investigated for sustained delivery of insulin (IS). To investigate the efficacy of TPGS-emulsified PEG-capped PLGA NPs (TPPLG NPs) as a potential drug carrier for the oral delivery of insulin. A series of biodegradable low-molecular-weight PLGA (80/20 [PLG4] and 70/30 [PLG6]) copolymers were synthesized by melt polycondensation. The commercial insulin-loaded TPGS-emulsified PEG-capped PLGA NPs (ISTPPLG NPs) were synthesized by water-oil-water emulsion solvent evaporation method. The physical and chemical properties of PLGA copolymers, particle size, zeta potential, and morphology of the NPs were examined. The in vivo studies of ISTPPLG NPs were carried out in diabetic rats by oral administration. The maximum encapsulation efficiency of ISTPPLG6 NPs was 78.6% ± 1.2%, and the mean diameter of the NPs was 180 ± 20 nm. The serum glucose level was significantly (twofold) decreased on treatment with ISTPPLG NPs, and there was a threefold decrease with insulin-loaded PLGA (70/30) NPs when compared to that of free insulin-treated diabetic rats. The results show that the oral administration of ISTPPLG6 NPs is an effective method of reducing serum glucose level for a period of 24 hours. Histopathological studies reveal that ISTPPLG NPs could restore the damage caused by streptozotocin in the liver, kidneys, and pancreas, indicating its biocompatibility and regenerative effects. ISTPPLG6 NPs can act as potential drug carriers for the oral delivery of insulin.

Novel PLGA-based nanoparticles for the oral delivery of insulin

PubMed Central

Malathi, Sampath; Nandhakumar, Perumal; Pandiyan, Velayudham; Webster, Thomas J; Balasubramanian, Sengottuvelan

2015-01-01

Background Insulin is the drug therapy for patients with insulin-dependent diabetes mellitus. A number of attempts have been made in the past to overcome the problems associated with the oral delivery of insulin, but with little success. Orally administered insulin has encountered with many difficulties such as rapid degradation and poor intestinal absorption. The potential use of D-α-tocopherol poly(ethylene glycol) 1000 succinate (TPGS)-emulsified poly(ethylene glycol) (PEG)-capped poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was investigated for sustained delivery of insulin (IS). Objective To investigate the efficacy of TPGS-emulsified PEG-capped PLGA NPs (TPPLG NPs) as a potential drug carrier for the oral delivery of insulin. Methods A series of biodegradable low-molecular-weight PLGA (80/20 [PLG4] and 70/30 [PLG6]) copolymers were synthesized by melt polycondensation. The commercial insulin-loaded TPGS-emulsified PEG-capped PLGA NPs (ISTPPLG NPs) were synthesized by water–oil–water emulsion solvent evaporation method. The physical and chemical properties of PLGA copolymers, particle size, zeta potential, and morphology of the NPs were examined. The in vivo studies of ISTPPLG NPs were carried out in diabetic rats by oral administration. Results The maximum encapsulation efficiency of ISTPPLG6 NPs was 78.6%±1.2%, and the mean diameter of the NPs was 180±20 nm. The serum glucose level was significantly (twofold) decreased on treatment with ISTPPLG NPs, and there was a threefold decrease with insulin-loaded PLGA (70/30) NPs when compared to that of free insulin-treated diabetic rats. The results show that the oral administration of ISTPPLG6 NPs is an effective method of reducing serum glucose level for a period of 24 hours. Histopathological studies reveal that ISTPPLG NPs could restore the damage caused by streptozotocin in the liver, kidneys, and pancreas, indicating its biocompatibility and regenerative effects. Conclusion ISTPPLG6 NPs can act as potential drug carriers for the oral delivery of insulin. PMID:25848248

[Influence of wall polymer and preparation process on the particle size and encapsulation of hemoglobin microcapsules].

PubMed

Qiu, Wei; Ma, Guang-Hui; Meng, Fan-Tao; Su, Zhi-Guo

2004-03-01

Methoxypoly (ethylene glycol)- block-poly (DL-lactide) (PELA) microcapsules containing bovine hemoglobin (BHb) were prepared by a W/O/W double emulsion-solvent diffusion process. The P50 and Hill coeffcient were 3466 Pa and 2.4 respectively, which were near to the natural bioactivity of bovine hemoglobin. The results suggested that polymer composition had significant influence on encapsulation efficiency and particle size of microcapsules. The encapsulation efficiency could reach 90% and the particle size 3 - 5 microm when the PELA copolymer containing MPEG 2000 block was used. The encapsulation efficiency and particle size increased with the concentration of PELA. Increasing the concentrations of NaCl in outer aqueous solution resulted in the increase of encapsulation efficiency and the decrease of particle size. As the concentration of stabilizer in outer aqueous solution increased in the range of 10 g/L to 20 g/L, the particle size reduced while encapsulation efficiency was increased, further increase of the stabilizer concentration would decrease encapsulation efficiency. Increasing of primary emulsion stirring rate was advantageous to the improvement of encapsulation efficiency though it had little influence on the particle size. The influence of re-emulsion stirring rate was complicated, which was not apparent in the case of large volume of re-emulsion solution. When the wall polymer and primary emulsion stirring rate were fixed, the encapsulation efficiency decreased as the particle size reduced.

Microfabricated biocapsules for the immunoisolation of pancreatic islets of Langerhans

NASA Astrophysics Data System (ADS)

Desai, Tejal Ashwin

1998-08-01

A silicon-based microfabricated biocapsule was developed and evaluated for use in the immunoisolation of transplanted cells, specifically pancreatic islets of Langerhans for the treatment of Type I diabetes. The transplantation of cells with specific functions is a promising therapy for a wide variety of pathologies including diabetes, Parkinson's, and hemophilia. Such transplanted cells, however, are sensitive to both cellular and humoral immune rejection as well as damage by autoimmune activity, without chronic immunosuppression. The research presented in this dissertation investigated whether microfabricated silicon-based biocapsules, with uniform membrane pore sizes in the tens of nanometer range, could provide an immunoprotective environment for pancreatic islets and other insulin-secreting cell lines, while maintaining cell viability and functionality. By utilizing fabrication techniques commonly employed in the microelectronics industry (MEMS), membranes were fabricated with precisely controlled and uniform pore sizes, allowing the optimization of biocapsule membrane parameters for the encapsulation of specific hormone-secreting cell types. The biocapsule-forming process employed bulk micromachining to define cell-containing chambers within single crystalline silicon wafers. These chambers interface with the surrounding biological environment through polycrystalline silicon filter membranes, which were surface micromachined to present a high density of uniform pores to allow sufficient permeability to oxygen, glucose, and insulin. Both in vitro and in vivo experiments established the biocompatibility of the microfabricated biocapsule, and demonstrated that encapsulated cells could live and function normally in terms of insulin-secretion within microfabricated environments for extended periods of time. This novel research shows the potential of using microfabricated biocapsules for the encapsulation of several different cell xenografts. The semipermeability of microfabricated biocapsules, their biocompatibility, along with their thermal and chemical stability, may provide an improved encapsulation device for the immunoisolation of cell xenografts in hormone-replacement and cell-based therapies.

Protein-Containing Multilayer Capsules by Templating on Mesoporous CaCO3 Particles: POST- and PRE-Loading Approaches.

PubMed

Balabushevich, Nadezhda G; Lopez de Guerenu, Anna V; Feoktistova, Natalia A; Skirtach, Andre G; Volodkin, Dmitry

2016-01-01

Encapsulation of model proteins (catalase, insulin, aprotinin) into multilayer dextran sulphate/protamin capsules by templating on CaCO3 microparticles is investigated employing: (i) PRE-loading into CaCO3 particles by adsorption or co-synthesis and (ii) POST-loading into performed capsules. Protein encapsulation is governed by both its size and electrostatic interactions with the carbonate microparticles and multilayer shell. PRE-loading enables improved encapsulation compared to POST-loading (catalase content in capsules 630 and 70 mg · g(-1)). Bioactivity of encapsulated protein is not affected by interaction with multilayers but may be reduced at slightly alkaline pH due to CaCO3 hydrolysis. This study might help to successfully encapsulate fragile bio-macromolecules into multilayer capsules. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Production of solid lipid submicron particles for protein delivery using a novel supercritical gas-assisted melting atomization process.

PubMed

Salmaso, Stefano; Elvassore, Nicola; Bertucco, Alberto; Caliceti, Paolo

2009-02-01

A supercritical carbon dioxide micronization technique based on gas-assisted melting atomization has been designed to prepare protein-loaded solid lipid submicron particles. The supercritical process was applied to homogeneous dispersions of insulin in lipid mixtures: (1) tristearin, Tween-80, phosphatidylcholine and 5 kDa PEG (1:0.1:0.9:1 and 1:0.1:0.9:2 weight ratio); and (2) tristearin, dioctyl sulfosuccinate and phosphatidylcholine (1:1:0.5 weight ratio). Optimized process conditions yielded dry nonagglomerated powders with high product recovery (70%, w/w). Dynamic light scattering and transmission electron microscopy showed that two size fractions of particles, with 80-120 and 200-400 nm diameters, were produced. In all final products, dimethylsulfoxide used to prepare the insulin/lipid mixture was below 20 ppm. Protein encapsulation efficiency increased up to 80% as the DMSO content in the insulin/lipid mixture increased. Compared to the particles without PEG, the polymer-containing particles dispersed rapidly in water, and the dispersions were more stable under centrifugation as less than 20% of suspended particles precipitated after extensive centrifugation. In vitro, the protein was slowly released from the formulation without PEG, while a burst and faster release were obtained from the formulations containing PEG. Subcutaneous injection to diabetic mice of insulin extracted from the particles showed that the supercritical process did not impair the protein hypoglycemic activity.

Current and Future Perspectives on Alginate Encapsulated Pancreatic Islet.

PubMed

Strand, Berit L; Coron, Abba E; Skjak-Braek, Gudmund

2017-04-01

Transplantation of pancreatic islets in immune protective capsules holds the promise as a functional cure for type 1 diabetes, also about 40 years after the first proof of principal study. The concept is simple in using semipermeable capsules that allow the ingress of oxygen and nutrients, but limit the access of the immune system. Encapsulated human islets have been evaluated in four small clinical trials where the procedure has been evaluated as safe, but lacking long-term efficacy. Host reactions toward the biomaterials used in the capsules may be one parameter limiting the long-term function of the graft in humans. The present article briefly discusses important capsule properties such as stability, permeability and biocompatibility, as well as possible strategies to overcome current challenges. Also, recent progress in capsule development as well as the production of insulin-producing cells from human stem cells that gives promising perspectives for the transplantation of encapsulated insulin-producing tissue is briefly discussed. Stem Cells Translational Medicine 2017;6:1053-1058. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Microencapsulation techniques to develop formulations of insulin for oral delivery: a review.

PubMed

Cárdenas-Bailón, Fernando; Osorio-Revilla, Guillermo; Gallardo-Velázquez, Tzayhrí

2013-01-01

Oral insulin delivery represents one of the most challenging goals for pharmaceutical industry. In general, it is accepted that oral administration of insulin would be more accepted by patients and insulin would be delivered in a more physiological way than the parenteral route. From all strategies to deliverer insulin orally, microencapsulation or nanoencapsulation of insulin are the most promising approaches because these techniques protect insulin from enzymatic degradation in stomach, show a good release profile at intestine pH values, maintain biological activity during formulation and enhance intestinal permeation at certain extent. From different microencapsulation techniques, it seems that complex coacervation, multiple emulsion and internal gelation are the most appropriate techniques to encapsulate insulin due to their relative ease of preparation. Besides that, the use of organic solvents is not required and can be scaled up at low cost; however, relative oral bioavailability still needs to be improved.

Chitosan-sodium lauryl sulfate nanoparticles as a carrier system for the in vivo delivery of oral insulin.

PubMed

Elsayed, Amani; Al-Remawi, Mayyas; Qinna, Nidal; Farouk, Asim; Al-Sou'od, Khaldoun A; Badwan, Adnan A

2011-09-01

The present work explores the possibility of formulating an oral insulin delivery system using nanoparticulate complexes made from the interaction between biodegradable, natural polymer called chitosan and anionic surfactant called sodium lauryl sulfate (SLS). The interaction between chitosan and SLS was confirmed by Fourier transform infrared spectroscopy. The nanoparticles were prepared by simple gelation method under aqueous-based conditions. The nanoparticles were stable in simulated gastric fluids and could protect the encapsulated insulin from the GIT enzymes. Additionally, the in vivo results clearly indicated that the insulin-loaded nanoparticles could effectively reduce the blood glucose level in a diabetic rat model. However, additional formulation modifications are required to improve insulin oral bioavailability.

Preparation of insulin-containing microcapsules by a layer-by-layer deposition of concanavalin A and glycogen.

PubMed

Sato, Katsuhiko; Kodama, Daisuke; Endo, Yoshihiro; Anzai, Jun-ichi

2009-01-01

The sugar sensitive microcapsules were prepared by a layer-by-layer deposition of concanavalin A (Con A) and glycogen on a calcium carbonate particle containing fluorescein-labeled insulin (F-insulin). The Con A/glycogen multilayer capsules were formed through sugar-lectin interactions by using inner and outer poly(ethyleneimine)/poly(vinyl sulfate) multilayers as supports, while without the supports the microcapsules could not be formed. Fluorescent microscope observations revealed that the capsules thus prepared are spherical in shape with 3-10 microm diameter. The microcapsules released encapsulated F-insulin upon addition of sugars. This is because the added sugars replace glycogen in the binding site of Con A, resulting in the enhanced permeability of the microcapsules to insulin.

Ibuprofen-in-cyclodextrin-in-W/O/W emulsion - Improving the initial and long-term encapsulation efficiency of a model active ingredient.

PubMed

Hattrem, Magnus N; Kristiansen, Kåre A; Aachmann, Finn L; Dille, Morten J; Draget, Kurt I

2015-06-20

A challenge in formulating water-in-oil-in-water (W/O/W) emulsions is the uncontrolled release of the encapsulated compound prior to application. Pharmaceuticals and nutraceuticals usually have amphipathic nature, which may contribute to leakage of the active ingredient. In the present study, cyclodextrins (CyDs) were used to impart a change in the relative polarity and size of a model compound (ibuprofen) by the formation of inclusion complexes. Various inclusion complexes (2-hydroxypropyl (HP)-β-CyD-, α-CyD- and γ-CyD-ibuprofen) were prepared and presented within W/O/W emulsions, and the initial and long-term encapsulation efficiency was investigated. HP-β-CyD-ibuprofen provided the highest encapsulation of ibuprofen in comparison to a W/O/W emulsion with unassociated ibuprofen confined within the inner water phase, with a four-fold increase in the encapsulation efficiency. An improved, although lower, encapsulation efficiency was obtained for the inclusion complex γ-CyD-ibuprofen in comparison to HP-β-CyD-ibuprofen, whereas α-CyD-ibuprofen had a similar encapsulation efficiency to that of unassociated ibuprofen. The lower encapsulation efficiency of ibuprofen in combination with α-CyD and γ-CyD was attributed to a lower association constant for the γ-CyD-ibuprofen inclusion complex and the ability of α-CyD to form inclusion complexes with fatty acids. For the W/O/W emulsion prepared with HP-β-CyD-ibuprofen, the highest encapsulation of ibuprofen was obtained at hyper- and iso-osmotic conditions and by using an excess molar ratio of CyD to ibuprofen. In the last part of the study, it was suggested that the chemical modification of the HP-β-CyD molecule did not influence the encapsulation of ibuprofen, as a similar encapsulation efficiency was obtained for an inclusion complex prepared with mono-1-glucose-β-CyD. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of an encapsulated stem cell-based therapy for diabetes.

PubMed

Tomei, Alice Anna; Villa, Chiara; Ricordi, Camillo

2015-01-01

Islet transplantation can treat the most severe cases of type 1 diabetes but it currently requires deceased donor pancreata as an islet source and chronic immunosuppression to prevent rejection and recurrence of autoimmunity. Stem cell-derived insulin-producing cells may address the shortage of organ donors, whereas cell encapsulation may reduce or eliminate the requirement for immunosuppression, minimizing the risks associated with the islet transplantation procedure, and potentially prolonging graft survival. This review focuses on the design principles for immunoisolation devices and on stem cell differentiation into insulin-producing cell products. The reader will gain understanding of the different types of immunoisolation devices and the key parameters that affect the outcome of the encapsulated graft. Progresses in stem cell differentiation towards mature endocrine islet cells, including the most recent clinical trials and the challenges associated with the application of immunoisolation devices designed for primary islets to stem-cell products, are also discussed. Recent advancements in the field of stem cell-derived islet cell products and immunoisolation strategies hold great promise for type 1 diabetes. However, a combination product including both cells and an immunoisolation strategy still needs to be optimized and tested for safety and efficacy.

Oral insulin delivery, the challenge to increase insulin bioavailability: Influence of surface charge in nanoparticle system.

PubMed

Czuba, Elodie; Diop, Mouhamadou; Mura, Carole; Schaschkow, Anais; Langlois, Allan; Bietiger, William; Neidl, Romain; Virciglio, Aurélien; Auberval, Nathalie; Julien-David, Diane; Maillard, Elisa; Frere, Yves; Marchioni, Eric; Pinget, Michel; Sigrist, Séverine

2018-05-05

Oral administration of insulin increases patient comfort and could improve glycemic control thanks to the hepatic first passage. However, challenges remain. The current approach uses poly (d, lactic-co-glycolic) acid (PLGA) nanoparticles (NPs), an effective drug carrier system with a long acting profile. However, this system presents a bioavailability of less than 20% for insulin encapsulation. In this context, physico-chemical parameters like surface charge could play a critical role in NP uptake by the intestinal barrier. Therefore, we developed a simple method to modulate NP surface charge to test its impact on uptake in vitro and finally on NP efficiency in vivo. Various NPs were prepared in the presence (+) or absence (-) of polyvinyl alcohol (PVA), sodium dodecyl sulfate (SDS), and/or coated with chitosan chloride. In vitro internalization was tested using epithelial culture of Caco-2 or using a co-culture (Caco-2/RevHT29MTX) by flow cytometry. NPs were then administered by oral route using a pharmaceutical complex vector (100 or 250 UI/kg) in a diabetic rat model. SDS-NPs (-42 ± 2 mV) were more negatively charged than -PVA-NPs (-22 ± 1 mV) and chitosan-coated NPs were highly positively charged (56 ± 2 mV) compared to +PVA particles (-2 ± 1 mV), which were uncharged. In the Caco-2 model, NP internalization was significantly improved by using negatively charged NPs (SDS NPs) compared to using classical NPs (+PVA NPs) and chitosan-coated NPs. Finally, the efficacy of insulin SDS-NPs was demonstrated in vivo (100 or 250 UI insulin/kg) with a reduction of blood glucose levels in diabetic rats. Formulation of negatively charged NPs represents a promising approach to improve NP uptake and insulin bioavailability for oral delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

Biomimetic silica encapsultation of living cells

NASA Astrophysics Data System (ADS)

Jaroch, David Benjamin

Living cells perform complex chemical processes on size and time scales that artificial systems cannot match. Cells respond dynamically to their environment, acting as biological sensors, factories, and drug delivery devices. To facilitate the use of living systems in engineered constructs, we have developed several new approaches to create stable protective microenvironments by forming bioinspired cell-membrane-specific silica-based encapsulants. These include vapor phase deposition of silica gels, use of endogenous membrane proteins and polysaccharides as a site for silica nucleation and polycondensation in a saturated environment, and protein templated ordered silica shell formation. We demonstrate silica layer formation at the surface of pluripotent stem-like cells, bacterial biofilms, and primary murine and human pancreatic islets. Materials are characterized by AFM, SEM and EDS. Viability assays confirm cell survival, and metabolite flux measurements demonstrate normal function and no major diffusion limitations. Real time PCR mRNA analysis indicates encapsulated islets express normal levels of genetic markers for β-cells and insulin production. The silica glass encapsulant produces a secondary bone like calcium phosphate mineral layer upon exposure to media. Such bioactive materials can improve device integration with surrounding tissue upon implantation. Given the favorable insulin response, bioactivity, and long-term viability observed in silica-coated islets, we are currently testing the encapsulant's ability to prevent immune system recognition of foreign transplants for the treatment of diabetes. Such hybrid silica-cellular constructs have a wide range of industrial, environmental, and medical applications.

Encapsulation system for the immunoisolation of living cells

NASA Technical Reports Server (NTRS)

Lacik, Igor (Inventor); Brissova, Marcela (Inventor); Wang, Taylor G. (Inventor); Anikumar, Amrutur V. (Inventor); Prokop, Ales (Inventor); Powers, Alvin C. (Inventor)

1999-01-01

The present invention is drawn to a composition of matter comprising high viscosity sodium alginate, cellulose sulfate and a multi-component polycation. Additionally, the present invention provides methods for making capsules, measuring capsule permeability to immunologically-relevant proteins and treating disease in an animal using encapsulated cells. Over one thousand combinations of polyanions and polycations were examined as polymer candidates suitable for encapsulation of living cells and thirty-three pairs were effective. The combination of sodium alginate, cellulose sulfate, poly(methylene-co-guanidine) hydrochloride, calcium chloride, and sodium chloride produced the most desirable results. Pancreatic islets encapsulated in this multicomponent capsule demonstrated glucose-stimulated insulin secretion in vitro and reversed diabetes without stimulating immune reaction in mice. The capsule formulation and system of the present invention allows independent adjustments of capsule size, wall thickness, mechanical strength and permeability, and offers distinct advantages for immunoisolating cells.

Oral Insulin Delivery: How Far Are We?

PubMed Central

Fonte, Pedro; Araújo, Francisca; Reis, Salette; Sarmento, Bruno

2013-01-01

Oral delivery of insulin may significantly improve the quality of life of diabetes patients who routinely receive insulin by the subcutaneous route. In fact, compared with this administration route, oral delivery of insulin in diabetes treatment offers many advantages: higher patient compliance, rapid hepatic insulinization, and avoidance of peripheral hyperinsulinemia and other adverse effects such as possible hypoglycemia and weight gain. However, the oral delivery of insulin remains a challenge because its oral absorption is limited. The main barriers faced by insulin in the gastrointestinal tract are degradation by proteolytic enzymes and lack of transport across the intestinal epithelium. Several strategies to deliver insulin orally have been proposed, but without much clinical or commercial success. Protein encapsulation into nanoparticles is regarded as a promising alternative to administer insulin orally because they have the ability to promote insulin paracellular or transcellular transport across the intestinal mucosa. In this review, different delivery systems intended to increase the oral bioavailability of insulin will be discussed, with a special focus on nanoparticulate carrier systems, as well as the efforts that pharmaceutical companies are making to bring to the market the first oral delivery system of insulin. The toxicological and safety data of delivery systems, the clinical value and progress of oral insulin delivery, and the future prospects in this research field will be also scrutinized. PMID:23567010

Enteric-coated capsules filled with mono-disperse micro-particles containing PLGA-lipid-PEG nanoparticles for oral delivery of insulin.

PubMed

Yu, Fei; Li, Yang; Liu, Chang Sheng; Chen, Qin; Wang, Gui Huan; Guo, Wei; Wu, Xue E; Li, Dong Hui; Wu, Winston Duo; Chen, Xiao Dong

2015-04-30

The success of the oral delivery of insulin (INS) as a therapeutic protein drug would significantly improve the quality of life of diabetic patients who would otherwise receive multiple daily INS injections. The oral delivery of INS, however, is still limited in its delivery efficiency, which could be due to the chemical, enzymatic, and adsorption barriers. In this work, in an attempt to improve the delivery efficiency, the INS-loaded polymer-lipid hybrid nanoparticles (INS-PLGA-lipid-PEG NPs) were designed and constructed through a double-emulsion solvent evaporation technique, followed by formulation of the spherical micro-particles using a spray freeze dryer (SFD). This kind of dryers has a uniquely designed microfluidic aerosol nozzle (MFAN), ensuring the formation of uniform particles. The resulted particles of ∼212 μm could easily be reverted to discrete INS-PLGA-lipid-PEG NPs in an aqueous solution. The INS-PLGA-lipid-PEG NPs created in this work showed a highly negative surface charge, excellent entrapment efficiency (92.3%) and a sustained drug release (∼24 h). Confocal laser scanning microscopy and flow cytometer were used to show that the cellular uptake efficiency for the INS-PLGA-lipid-PEG NPs was more effective than the INS in Caco-2 cells. More importantly, the in vivo pharmacodynamics demonstrated that the orally delivered system induced a prolonged decrease in blood glucose levels among diabetic rats. The relative bioavailability of INS compared with subcutaneous injection in diabetic rats was found to be approximately 12%. These results suggested that the encapsulated INS-PLGA-lipid-PEG NPs are promising and should be investigated further in the near future as an effective INS oral delivery system. Copyright © 2015. Published by Elsevier B.V.

Comparative studies on osmosis based encapsulation of sodium diclofenac in porcine and outdated human erythrocyte ghosts.

PubMed

Bukara, Katarina; Drvenica, Ivana; Ilić, Vesna; Stančić, Ana; Mišić, Danijela; Vasić, Borislav; Gajić, Radoš; Vučetić, Dušan; Kiekens, Filip; Bugarski, Branko

2016-12-20

The objective of our study was to develop controlled drug delivery system based on erythrocyte ghosts for amphiphilic compound sodium diclofenac considering the differences between erythrocytes derived from two readily available materials - porcine slaughterhouse and outdated transfusion human blood. Starting erythrocytes, empty erythrocyte ghosts and diclofenac loaded ghosts were compared in terms of the encapsulation efficiency, drug releasing profiles, size distribution, surface charge, conductivity, surface roughness and morphology. The encapsulation of sodium diclofenac was performed by an osmosis based process - gradual hemolysis. During this process sodium diclofenac exerted mild and delayed antihemolytic effect and increased potassium efflux in porcine but not in outdated human erythrocytes. FTIR spectra revealed lack of any membrane lipid disorder and chemical reaction with sodium diclofenac in encapsulated ghosts. Outdated human erythrocyte ghosts with detected nanoscale damages and reduced ability to shrink had encapsulation efficiency of only 8%. On the other hand, porcine erythrocyte ghosts had encapsulation efficiency of 37% and relatively slow drug release rate. More preserved structure and functional properties of porcine erythrocytes related to their superior encapsulation and release performances, define them as more appropriate for the usage in sodium diclofenac encapsulation process. Copyright © 2016 Elsevier B.V. All rights reserved.

Design, characterisation and application of alginate-based encapsulated pig liver esterase.

PubMed

Pauly, Jan; Gröger, Harald; Patel, Anant V

2018-06-05

Encapsulation of hydrolases in biopolymer-based hydrogels often suffers from low activities and encapsulation efficiencies along with high leaching and unsatisfactory recycling properties. Exemplified for the encapsulation of pig liver esterase the coating of alginate and chitosan beads have been studied by creating various biopolymer hydrogel beads. Enzyme activity and encapsulation efficiency were notably enhanced by chitosan coating of alginate beads while leaching remained nearly unchanged. This was caused by the enzymatic reaction acidifying the matrix, which increased enzyme retention through enhanced electrostatic enzyme-alginate interaction but decreased activity through enzyme deactivation. A practical and ready-to-use method for visualising pH in beads during reaction by co-encapsulation of a conventional pH indicator was also found. Our method proves that pH control inside the beads can only be realised by buffering. The resulting beads provided a specific activity of 0.267 μmol ∙ min -1 ∙ mg -1 , effectiveness factor 0.88, encapsulation efficiency of 88%, 5% leaching and good recycling properties. This work will contribute towards better understanding and application of encapsulated hydrolases for enzymatic syntheses. Copyright © 2018 Elsevier B.V. All rights reserved.

A review of piscine islet xenotransplantation using wild-type tilapia donors and the production of transgenic tilapia expressing a “humanized” tilapia insulin

PubMed Central

Wright, James R; Yang, Hua; Hyrtsenko, Olga; Xu, Bao-You; Yu, Weiming; Pohajdak, Bill

2014-01-01

Most islet xenotransplantation laboratories have focused on porcine islets, which are both costly and difficult to isolate. Teleost (bony) fish, such as tilapia, possess macroscopically visible distinct islet organs called Brockmann bodies which can be inexpensively harvested. When transplanted into diabetic nude mice, tilapia islets maintain long-term normoglycemia and provide human-like glucose tolerance profiles. Like porcine islets, when transplanted into euthymic mice, they are rejected in a CD4 T-cell-dependent manner. However, unlike pigs, tilapia are so phylogenetically primitive that their cells do not express α(1,3)Gal and, because tilapia are highly evolved to live in warm stagnant waters nearly devoid of dissolved oxygen, their islet cells are exceedingly resistant to hypoxia, making them ideal for transplantation within encapsulation devices. Encapsulation, especially when combined with co-stimulatory blockade, markedly prolongs tilapia islet xenograft survival in small animal recipients, and a collaborator has shown function in diabetic cynomolgus monkeys. In anticipation of preclinical xenotransplantation studies, we have extensively characterized tilapia islets (morphology, embryologic development, cell biology, peptides, etc.) and their regulation of glucose homeostasis. Because tilapia insulin differs structurally from human insulin by 17 amino acids, we have produced transgenic tilapia whose islets stably express physiological levels of humanized insulin and have now bred these to homozygosity. These transgenic fish can serve as a platform for further development into a cell therapy product for diabetes. PMID:25040337

A review of piscine islet xenotransplantation using wild-type tilapia donors and the production of transgenic tilapia expressing a "humanized" tilapia insulin.

PubMed

Wright, James R; Yang, Hua; Hyrtsenko, Olga; Xu, Bao-You; Yu, Weiming; Pohajdak, Bill

2014-01-01

Most islet xenotransplantation laboratories have focused on porcine islets, which are both costly and difficult to isolate. Teleost (bony) fish, such as tilapia, possess macroscopically visible distinct islet organs called Brockmann bodies which can be inexpensively harvested. When transplanted into diabetic nude mice, tilapia islets maintain long-term normoglycemia and provide human-like glucose tolerance profiles. Like porcine islets, when transplanted into euthymic mice, they are rejected in a CD4 T-cell-dependent manner. However, unlike pigs, tilapia are so phylogenetically primitive that their cells do not express α(1,3)Gal and, because tilapia are highly evolved to live in warm stagnant waters nearly devoid of dissolved oxygen, their islet cells are exceedingly resistant to hypoxia, making them ideal for transplantation within encapsulation devices. Encapsulation, especially when combined with co-stimulatory blockade, markedly prolongs tilapia islet xenograft survival in small animal recipients, and a collaborator has shown function in diabetic cynomolgus monkeys. In anticipation of preclinical xenotransplantation studies, we have extensively characterized tilapia islets (morphology, embryologic development, cell biology, peptides, etc.) and their regulation of glucose homeostasis. Because tilapia insulin differs structurally from human insulin by 17 amino acids, we have produced transgenic tilapia whose islets stably express physiological levels of humanized insulin and have now bred these to homozygosity. These transgenic fish can serve as a platform for further development into a cell therapy product for diabetes. © 2014 The Authors. Xenotransplantation Published by John Wiley & Sons Ltd.

Effects of melamine formaldehyde resin and CaCO3 diffuser-loaded encapsulation on correlated color temperature uniformity of phosphor-converted LEDs.

PubMed

Yang, Liang; Lv, Zhicheng; Jiaojiao, Yuan; Liu, Sheng

2013-08-01

Phosphor-free dispensing is the most widely used LED packaging method, but this method results in poor quality in angular CCT uniformity. This study proposes a diffuser-loaded encapsulation to solve the problem; the effects of melamine formaldehyde (MF) resin and CaCO3 loaded encapsulation on correlated color temperature (CCT) uniformity and luminous efficiency reduction of the phosphor-converted LEDs are investigated. Results reveal that MF resin loaded encapsulation has better light diffusion performance compared to MF resin loaded encapsulation at the same diffuser concentration, but CaCO3 loaded encapsulation has better luminous efficiency maintenance. The improvements in angular color uniformity for the LEDs emitting with MF resin and CaCO3 loaded encapsulation can be explained by the increase in photon scattering. The utility of this low cost and controllable mineral diffuser packaging method provides a practical approach for enhancing the angular color uniformity of LEDs. The diffuser mass ratio of 1% MF resin or 10% CaCO3 is the optimum condition to obtain low angular CCT variance and high luminous efficiency.

Structural properties and release of insulin-loaded reverse hexagonal (HII) liquid crystalline mesophase.

PubMed

Mishraki-Berkowitz, Tehila; Aserin, Abraham; Garti, Nissim

2017-01-15

Insulin loading into the H II mesophases was examined as a function of its concentration, with addition of glycerol as a cosolvent and with addition of phosphatidylcholine (PC) as a structural stabilizer. The structural properties, the molecular interactions, the viscoelastic properties, and the dynamic behavior were investigated by SAXS, ATR-FTIR, and rheological measurements. Insulin release was then monitored and analyzed. Insulin incorporation into the H II systems shrank the cylinders as it competed with the lipids in water-bonding. Insulin interrupted the interface while increasing τ max and creating a more solid-like response. Upon addition of PC, cooperative flow behavior was detected, which is probably the reason for increase in insulin cumulative release from 28% to 52% after 300 min. In the presence of glycerol, the system was less cooperative but insulin was more compactly folded, resulting in a slight improvement in insulin release (up to 6%). Addition of both PC and glycerol caused the maximum release (55%). The addition of additives into the H II system demonstrates how structural modifications can improve insulin release, and influence future design of encapsulated drug delivery systems. Copyright © 2016 Elsevier Inc. All rights reserved.

Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats.

PubMed

Matveyenko, Aleksey V; Georgia, Senta; Bhushan, Anil; Butler, Peter C

2010-11-01

Embryonic stem cell therapy has been proposed as a therapeutic strategy to restore β-cell mass and function in T1DM. Recently, a group from Novocell (now ViaCyte) reported successful development of glucose-responsive islet-like structures after implantation of pancreatic endoderm (PE) derived from human embryonic stem cells (hESC) into immune-deficient mice. Our objective was to determine whether implantation of hESC-derived pancreatic endoderm from Novocell into athymic nude rats results in development of viable glucose-responsive pancreatic endocrine tissue. Athymic nude rats were implanted with PE derived from hESC either via implantation into the epididymal fat pads or by subcutaneous implantation into TheraCyte encapsulation devices for 20 wk. Blood glucose, weight, and human insulin/C-peptide secretion were monitored by weekly blood draws. Graft β-cell function was assessed by a glucose tolerance test, and graft morphology was assessed by immunohistochemistry and immunofluorescence. At 20 wk postimplantation, epididymal fat-implanted PE progressed to develop islet-like structures in 50% of implants, with a mean β-cell fractional area of 0.8 ± 0.3%. Human C-peptide and insulin were detectable, but at very low levels (C-peptide = 50 ± 26 pmol/l and insulin = 15 ± 7 pmol/l); however, there was no increase in human C-peptide/insulin levels after glucose challenge. There was no development of viable pancreatic tissue or meaningful secretory function when human PE was implanted in the TheraCyte encapsulation devices. These data confirm that islet-like structures develop from hESC differentiated to PE by the protocol developed by NovoCell. However, the extent of endocrine cell formation and secretory function is not yet sufficient to be clinically relevant.

Inconsistent formation and nonfunction of insulin-positive cells from pancreatic endoderm derived from human embryonic stem cells in athymic nude rats

PubMed Central

Matveyenko, Aleksey V.; Georgia, Senta; Bhushan, Anil

2010-01-01

Embryonic stem cell therapy has been proposed as a therapeutic strategy to restore β-cell mass and function in T1DM. Recently, a group from Novocell (now ViaCyte) reported successful development of glucose-responsive islet-like structures after implantation of pancreatic endoderm (PE) derived from human embryonic stem cells (hESC) into immune-deficient mice. Our objective was to determine whether implantation of hESC-derived pancreatic endoderm from Novocell into athymic nude rats results in development of viable glucose-responsive pancreatic endocrine tissue. Athymic nude rats were implanted with PE derived from hESC either via implantation into the epididymal fat pads or by subcutaneous implantation into TheraCyte encapsulation devices for 20 wk. Blood glucose, weight, and human insulin/C-peptide secretion were monitored by weekly blood draws. Graft β-cell function was assessed by a glucose tolerance test, and graft morphology was assessed by immunohistochemistry and immunofluorescence. At 20 wk postimplantation, epididymal fat-implanted PE progressed to develop islet-like structures in 50% of implants, with a mean β-cell fractional area of 0.8 ± 0.3%. Human C-peptide and insulin were detectable, but at very low levels (C-peptide = 50 ± 26 pmol/l and insulin = 15 ± 7 pmol/l); however, there was no increase in human C-peptide/insulin levels after glucose challenge. There was no development of viable pancreatic tissue or meaningful secretory function when human PE was implanted in the TheraCyte encapsulation devices. These data confirm that islet-like structures develop from hESC differentiated to PE by the protocol developed by NovoCell. However, the extent of endocrine cell formation and secretory function is not yet sufficient to be clinically relevant. PMID:20587750

Encapsulation of NF-κ B Decoy Oligonucleotides within Echogenic Liposomes and Ultrasound-Triggered Release

PubMed Central

Buchanan, Kyle D.; Huang, Shao-Ling; Kim, Hyunggun; McPherson, David D.; MacDonald, Robert C.

2011-01-01

Echogenic liposomes (ELIP) have additional promise, beyond diagnostic agents, as vehicles for delivering oligonucleotides (ODN), especially if the release of the agent can be triggered and its uptake can be enhanced by ultrasound application at a specific site. The purpose of this study was to co-encapsulate air and NF-κB decoy ODN within ELIP allowing ultrasound to release encapsulated ODN from ELIP, and to accurately quantify release of encapsulated ODN from ELIP upon ultrasound application. FITC-labeled sense ODN (2 mM) was incorporated within ELIP using freeze/thaw method. Encapsulation efficiency of FITC-ODN was spectrofluorometrically analyzed by quenching fluorescence of unencapsulated FITC-ODN using a complementary strand tagged with Iowa Black FQ-ODN. Quenching of FITC-ODN (0.05 μM) with Iowa Black FQ-ODN (0.1 μM) was found to be efficient (92.4 ± 0.2 %), allowing accurate determination of encapsulated ODN. Encapsulation efficiency of ODN was 14.2 ± 2.5 % in DPPC/DOPC/DPPG/CH liposomes and 29.6 ± 1.5 % in DPPC/DOPE/DPPG/CH liposomes. Application of ultrasound (1 MHz continuous wave, 0.26 MPa peak-to-peak pressure amplitude, 60 seconds.) to the latter formulation triggered 41.6 ± 4.3 % release of ODN from ODN-containing ELIP. We have thus demonstrated that ODN can be encapsulated into ELIP and released efficiently upon ultrasound application. These findings suggest potential applications for gene therapy in atherosclerosis treatment. PMID:19804805

Injectable Polyethylene Glycol Hydrogel for Islet Encapsulation: an in vitro and in vivo Characterization

PubMed Central

Knobeloch, Tracy; Abadi, Sakineh Esmaeili Mohsen; Bruns, Joseph; Zustiak, Silviya Petrova; Kwon, Guim

2017-01-01

An injection of hydrogel-encapsulated islets that controls blood glucose levels over long term would provide a much needed alternative treatment for type 1 diabetes mellitus (T1DM). To this end, we tested the feasibility of using an injectable polyethylene glycol (PEG) hydrogel as a scaffold for islet encapsulation. Encapsulated islets cultured in vitro for 6 days showed excellent cell viability and released insulin with higher basal and stimulated insulin secretion than control islets. Host responses to PEG hydrogels were studied by injecting PEG hydrogels (no treatment and vehicle controls used) into the peritoneal cavities of B6D2F1 mice and monitoring alterations in body weight, food and water intake, and blood glucose levels. After 2 weeks, peritoneal cavity cells were harvested, followed by hydrogel retrieval, and extraction of spleens. Body weights, food and water intake, and blood glucose levels were unaltered in mice injected with hydrogels compared to no treatment and vehicle-injected control mice. Frozen sections of a hydrogel showed the presence of tissues and small number of immune cells surrounding the hydrogel but no cell infiltration into the hydrogel bulk. Spleen sizes were not significantly different under the experimental conditions. Peritoneal cavity cells were slightly higher in mice injected with hydrogels compared to control mice but no statistical difference between vehicle- and hydrogel-injected mice was noted. As an in vivo feasibility study, streptozotocin-induced diabetic mice were injected with vehicle or hydrogels containing 50 islets each into two sites, the peritoneal cavity and a subcutaneous site on the back. Transient control of blood glucose levels were observed in mice injected with hydrogels containing islets. In summary, we developed an injectable PEG hydrogel that supported islet function and survival in vitro and in vivo and elicited only a mild host response. Our work illustrates the feasibility of using injectable PEG hydrogels for islet encapsulation. PMID:29527325

High-efficiency single cell encapsulation and size selective capture of cells in picoliter droplets based on hydrodynamic micro-vortices.

PubMed

Kamalakshakurup, Gopakumar; Lee, Abraham P

2017-12-05

Single cell analysis has emerged as a paradigm shift in cell biology to understand the heterogeneity of individual cells in a clone for pathological interrogation. Microfluidic droplet technology is a compelling platform to perform single cell analysis by encapsulating single cells inside picoliter-nanoliter (pL-nL) volume droplets. However, one of the primary challenges for droplet based single cell assays is single cell encapsulation in droplets, currently achieved either randomly, dictated by Poisson statistics, or by hydrodynamic techniques. In this paper, we present an interfacial hydrodynamic technique which initially traps the cells in micro-vortices, and later releases them one-to-one into the droplets, controlled by the width of the outer streamline that separates the vortex from the flow through the streaming passage adjacent to the aqueous-oil interface (d gap ). One-to-one encapsulation is achieved at a d gap equal to the radius of the cell, whereas complete trapping of the cells is realized at a d gap smaller than the radius of the cell. The unique feature of this technique is that it can perform 1. high efficiency single cell encapsulations and 2. size-selective capturing of cells, at low cell loading densities. Here we demonstrate these two capabilities with a 50% single cell encapsulation efficiency and size selective separation of platelets, RBCs and WBCs from a 10× diluted blood sample (WBC capture efficiency at 70%). The results suggest a passive, hydrodynamic micro-vortex based technique capable of performing high-efficiency single cell encapsulation for cell based assays.

Preparation and modification of N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride nanoparticle as a protein carrier.

PubMed

Xu, Yongmei; Du, Yumin; Huang, Ronghua; Gao, Leping

2003-12-01

N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) is water-soluble derivative of chitosan (CS), synthesized by the reaction between glycidyl-trimethyl-ammonium chloride and CS. HTCC nanoparticles have been formed based on ionic gelation process of HTCC and sodium tripolyphosphate (TPP). Bovine serum albumin (BSA), as a model protein drug, was incorporated into the HTCC nanoparticles. HTCC nanoparticles were 110-180 nm in size, and their encapsulation efficiency was up to 90%. In vitro release studies showed a burst effect and a slow and continuous release followed. Encapsulation efficiency was obviously increased with increase of initial BSA concentration. Increasing TPP concentration from 0.5 to 0.7 mg/ml promoted encapsulation efficiency from 46.7% to 90%, and delayed release. As for modified HTCC nanoparticles, adding polyethylene glycol (PEG) or sodium alginate obviously decreased the burst effect of BSA from 42% to 18%. Encapsulation efficiency was significantly reduced from 47.6% to 2% with increase of PEG from 1.0 to 20.0 mg/ml. Encapsulation efficiency was increased from 14.5% to 25.4% with increase of alginate from 0.3 to 1.0 mg/ml.

Encapsulation of adenovirus serotype 5 in anionic lecithin liposomes using a bead-based immunoprecipitation technique enhances transfection efficiency.

PubMed

Mendez, Natalie; Herrera, Vanessa; Zhang, Lingzhi; Hedjran, Farah; Feuer, Ralph; Blair, Sarah L; Trogler, William C; Reid, Tony R; Kummel, Andrew C

2014-11-01

Oncolytic viruses (OVs) constitute a promising class of cancer therapeutics which exploit validated genetic pathways known to be deregulated in many cancers. To overcome an immune response and to enhance its potential use to treat primary and metastatic tumors, a method for liposomal encapsulation of adenovirus has been developed. The encapsulation of adenovirus in non-toxic anionic lecithin-cholesterol-PEG liposomes ranging from 140 to 180 nm in diameter have been prepared by self-assembly around the viral capsid. The encapsulated viruses retain their ability to infect cancer cells. Furthermore, an immunoprecipitation (IP) technique has shown to be a fast and effective method to extract non-encapsulated viruses and homogenize the liposomes remaining in solution. 78% of adenovirus plaque forming units were encapsulated and retained infectivity after IP processing. Additionally, encapsulated viruses have shown enhanced transfection efficiency up to 4 × higher compared to non-encapsulated Ads. Extracting non-encapsulated viruses from solution may prevent an adverse in vivo immune response and may enhance treatment for multiple administrations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Encapsulation of Adenovirus Serotype 5 in Anionic Lecithin Liposomes using a Bead-Based Immunoprecipitation Technique Enhances Transfection Efficiency

PubMed Central

Mendez, N.; Herrera, V.; Zhang, L.; Hedjran, F.; Feuer, R.; Blair, S.; Trogler, W.; Reid, T.

2014-01-01

Oncolytic viruses (OVs) constitute a promising class of cancer therapeutics which exploit validated genetic pathways known to be deregulated in many cancers. To overcome an immune response and to enhance its potential use to treat primary and metastatic tumors, a method for liposomal encapsulation of adenovirus has been developed. The encapsulation of adenovirus in non-toxic anionic lecithin-cholesterol-PEG liposomes ranging from 140–180nm in diameter have been prepared by self-assembly around the viral capsid. The encapsulated viruses retain their ability to infect cancer cells. Furthermore, an immunoprecipitation (IP) technique has shown to be a fast and effective method to extract non-encapsulated viruses and homogenize the liposomes remaining in solution. 78% of adenovirus plaque forming units were encapsulated and retained infectivity after IP processing. Additionally, encapsulated viruses have shown enhanced transfection efficiency up to 4× higher compared to non-encapsulated Ads. Extracting non-encapsulated viruses from solution may prevent an adverse in vivo immune response and may enhance treatment for multiple administrations. PMID:25154663

Encapsulation optimization of lemon balm antioxidants in calcium alginate hydrogels.

PubMed

Najafi-Soulari, Samira; Shekarchizadeh, Hajar; Kadivar, Mahdi

2016-11-01

Calcium alginate hydrogel beads were used to encapsulate lemon balm extract. Chitosan layer was used to investigate the effect of hydrogel coating. To determine the interactions of antioxidant compounds of extract with encapsulation materials and its stability, microstructure of hydrogel beads was thoroughly monitored using scanning electron microscopy and Fourier transform infrared (FTIR). Total polyphenols content and antiradical activity of lemon balm extract were also evaluated before and after encapsulation. Three significant parameters (lemon balm extract, sodium alginate, and calcium chloride concentrations) were optimized by response surface methodology to obtain maximum encapsulation efficiency. The FTIR spectra showed no interactions between extract and polymers as there were no new band in spectra of alginate hydrogel after encapsulation of active compounds of lemon balm extract. The antioxidant activity of lemon balm extract did not change after encapsulation. Therefore, it was found that alginate is a suitable material for encapsulation of natural antioxidants. Sodium alginate solution concentration, 1.84%, lemon balm extract concentration, 0.4%, and calcium chloride concentration, 0.2% was determined to be the optimum condition to reach maximum encapsulation efficiency.

Encapsulated Islet Transplantation: Where Do We Stand?

PubMed

Vaithilingam, Vijayaganapathy; Bal, Sumeet; Tuch, Bernard E

2017-01-01

Transplantation of pancreatic islets encapsulated within immuno-protective microcapsules is a strategy that has the potential to overcome graft rejection without the need for toxic immunosuppressive medication. However, despite promising preclinical studies, clinical trials using encapsulated islets have lacked long-term efficacy, and although generally considered clinically safe, have not been encouraging overall. One of the major factors limiting the long-term function of encapsulated islets is the host's immunological reaction to the transplanted graft which is often manifested as pericapsular fibrotic overgrowth (PFO). PFO forms a barrier on the capsule surface that prevents the ingress of oxygen and nutrients leading to islet cell starvation, hypoxia and death. The mechanism of PFO formation is still not elucidated fully and studies using a pig model have tried to understand the host immune response to empty alginate microcapsules. In this review, the varied strategies to overcome or reduce PFO are discussed, including alginate purification, altering microcapsule geometry, modifying alginate chemical composition, co-encapsulation with immunomodulatory cells, administration of pharmacological agents, and alternative transplantation sites. Nanoencapsulation technologies, such as conformal and layer-by-layer coating technologies, as well as nanofiber, thin-film nanoporous devices, and silicone based NanoGland devices are also addressed. Finally, this review outlines recent progress in imaging technologies to track encapsulated cells, as well as promising perspectives concerning the production of insulin-producing cells from stem cells for encapsulation.

Effect of Over 10-Year Cryopreserved Encapsulated Pancreatic Islets Of Langerhans.

PubMed

Kinasiewicz, Joanna; Antosiak-Iwanska, Magdalena; Godlewska, Ewa; Sitarek, Elzbieta; Sabat, Marek; Fiedor, Piotr; Granicka, Ludomira

2017-08-28

Immunoisolation of pancreatic islets of Langerhans performed by the encapsulation process may be a method to avoid immunosuppressive therapy after transplant. The main problem related to islet transplant is shortage of human pancreata. Resolution of this obstacle may be cryopreservation of encapsulated islets, which enables collection of sufficient numbers of isolated islets required for transplant and long-term storage. Here, we assessed the ability of encapsulated islets to function after long-term banking at low temperature. Islets of Langerhans isolated from rat, pig, and human pancreata were encapsulated within alginate-poly-L-lysine-alginate microcapsules. Cryopreservation was carried out using a controlled method of freezing (Kriomedpol freezer; Kriomedpol, Warsaw, Poland), and samples were stored in liquid nitrogen. After 10 years, the samples were thawed with the rapid method (with 0.75 M of sucrose) and then cultured. We observed that microcapsules containing islets maintained their shape and integrity after thawing. During culture, free islets were defragmented into single cells, whereas encapsulated islets were still round in shape and compact. After 1, 4, and 7 days of culture of encapsulated islets, the use of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tests showed increased mitochondrial activity. After they were thawed, the insulin secretion capacity was comparable with that obtained with fresh islets. Cryopreservation and storage of free and microencapsulated islets were possible for about 10 years, although only encapsulated islets retained viability and secretory properties.

Encapsulation of Volatile Citronella Essential Oil by Coacervation: Efficiency and Release Study

NASA Astrophysics Data System (ADS)

Manaf, M. A.; Subuki, I.; Jai, J.; Raslan, R.; Mustapa, A. N.

2018-05-01

The volatile citronella essential oil was encapsulated by simple coacervation and complex coacervation using Arabic gum and gelatin as wall material. Glutaraldehyde was used in the methodology as crosslinking agent. The citronella standard calibration graph obtained with R2 of 0.9523 was used for the accurate determination of encapsulation efficiency and release study. The release kinetic was analysed based on Fick"s law of diffusion for polymeric system and linear graph of Log fraction release over Log time was constructed to determine the release rate constant, k and diffusion coefficient, n. Both coacervation methods in the present study produce encapsulation efficiency around 94%. The produced capsules for both coacervation processes were discussed based on the capsules morphology and release kinetic mechanisms.

Effect of PLGA as a polymeric emulsifier on preparation of hydrophilic protein-loaded solid lipid nanoparticles.

PubMed

Xie, ShuYu; Wang, SiLiang; Zhao, BaoKai; Han, Chao; Wang, Ming; Zhou, WenZhong

2008-12-01

Most proteins are hydrophilic and poorly encapsulated into the hydrophobic matrix of solid lipid nanoparticles (SLN). To solve this problem, poly (lactic-co-glycolic acid) (PLGA) was utilized as a lipophilic polymeric emulsifier to prepare hydrophilic protein-loaded SLN by w/o/w double emulsion and solvent evaporation techniques. Hydrogenated castor oil (HCO) was used as a lipid matrix and bovine serum albumin (BSA), lysozyme and insulin were used as model proteins to investigate the effect of PLGA on the formulation of the SLN. The results showed that PLGA was essential for the primary w/o emulsification. In addition, the stability of the w/o emulsion, the encapsulation efficiency and loading capacity of the nanoparticles were enhanced with the increase of PLGA concentration. Furthermore, increasing PLGA concentration decreased zeta potential significantly but had no influence on particle size of the SLN. In vitro release study showed that PLGA significantly affected the initial burst release, i.e. the higher the content of PLGA, the lower the burst release. The released proteins maintained their integrity and bioactivity as confirmed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and biological assay. These results demonstrated that PLGA was an effective emulsifier for the preparation of hydrophilic protein-loaded SLN.

Glucose-responsive microgels integrated with enzyme nanocapsules for closed-loop insulin delivery.

PubMed

Gu, Zhen; Dang, Tram T; Ma, Minglin; Tang, Benjamin C; Cheng, Hao; Jiang, Shan; Dong, Yizhou; Zhang, Yunlong; Anderson, Daniel G

2013-08-27

A glucose-responsive closed-loop insulin delivery system represents the ideal treatment of type 1 diabetes mellitus. In this study, we develop uniform injectable microgels for controlled glucose-responsive release of insulin. Monodisperse microgels (256 ± 18 μm), consisting of a pH-responsive chitosan matrix, enzyme nanocapsules, and recombinant human insulin, were fabricated through a one-step electrospray procedure. Glucose-specific enzymes were covalently encapsulated into the nanocapsules to improve enzymatic stability by protecting from denaturation and immunogenicity as well as to minimize loss due to diffusion from the matrix. The microgel system swelled when subjected to hyperglycemic conditions, as a result of the enzymatic conversion of glucose into gluconic acid and protonation of the chitosan network. Acting as a self-regulating valve system, microgels were adjusted to release insulin at basal release rates under normoglycemic conditions and at higher rates under hyperglycemic conditions. Finally, we demonstrated that these microgels with enzyme nanocapsules facilitate insulin release and result in a reduction of blood glucose levels in a mouse model of type 1 diabetes.

In vivo studies on insulin permeability of an immunoisolation device intended for islet transplantation using the microdialysis technique.

PubMed

Rafael, E; Wernerson, A; Arner, P; Tibell, A

1999-01-01

In this study, insulin was injected into Theracyte immunoisolation devices to analyze changes in the permeability of the device over time after implantation. The recovery of insulin was studied after subcutaneous implantation of the devices in rats, using the microdialysis technique. The area under the insulin concentration vs. time curves (AUC) after insulin injection in devices implanted 1 day previously did not differ significantly from the AUC after subcutaneous injection. At 1, 2 and 4 weeks after implantation, the recovery of insulin was significantly reduced, but at 3 months, the AUC was not significantly different from that in the control group. Histological examination showed that the number of vascular profiles within 15 microm of the device were significantly higher at 2, 4 weeks and 3 months after transplantation when compared to numbers at 1 week. The design of the device allows transplantation of cells at a chosen time point after its implantation. Delayed filling of the device would allow neovascularization of the device surface before graft implantation and we suggest that such a schedule might improve function of the encapsulated graft.

Effect of drug loading method against drug dissolution mechanism of encapsulated amoxicillin trihydrate in matrix of semi-IPN chitosan-poly(N-vinylpyrrolidone) hydrogel with KHCO3 as pore forming agent in floating drug delivery system

NASA Astrophysics Data System (ADS)

Fimantari, Khansa; Budianto, Emil

2018-04-01

Helicobacterpylori infection can be treated using trihydrate amoxicillin. However, this treatment is not effective enough, as the conventional dosage treatment has a relatively short retention time in the human stomach. In the present study, the amoxicillin trihydrate drug will be encapsulated into a semi-IPN K-PNVP hydrogel matrix with 7,5% KHCO3 as a pore-forming agent. The encapsulated drug is tested with in vitro method to see the efficiency of its encapsulation and dissolution. The hydrogel in situ loading produces an encapsulation efficiency value. The values of the encapsulation efficiency are 95% and 98%, while post loading hydrogel yields an encapsulation efficiency value is 77% and the dissolution is 84%. The study of drug dissolution mechanism was done by using mathematical equation model to know its kinetics and its mechanism of dissolution. The post loading hydrogel was done by using thefirst-order model, while hydrogel in situ loading used Higuchi model. The Korsmeyer-Peppas model shows that post loading hydrogel dissolution mechanism is a mixture of diffusion and erosion, and in situ loading hydrogel in the form of diffusion. It is supported by the results of hydrogel characterization, before and after dissolution test with an optical microscope. The results of the optical microscope show that the hydrogel surface before and after the dissolution tested for both methods shows the change becomes rougher.

Optofluidic encapsulation and manipulation of silicon microchips using image processing based optofluidic maskless lithography and railed microfluidics.

PubMed

Chung, Su Eun; Lee, Seung Ah; Kim, Jiyun; Kwon, Sunghoon

2009-10-07

We demonstrate optofluidic encapsulation of silicon microchips using image processing based optofluidic maskless lithography and manipulation using railed microfluidics. Optofluidic maskless lithography is a dynamic photopolymerization technique of free-floating microstructures within a fluidic channel using spatial light modulator. Using optofluidic maskless lithography via computer-vision aided image processing, polymer encapsulants are fabricated for chip protection and guiding-fins for efficient chip conveying within a fluidic channel. Encapsulated silicon chips with guiding-fins are assembled using railed microfluidics, which is an efficient guiding and heterogeneous self-assembly system of microcomponents. With our technology, externally fabricated silicon microchips are encapsulated, fluidically guided and self-assembled potentially enabling low cost fluidic manipulation and assembly of integrated circuits.

Characterization and Antilisterial Effect of Phosphatidylcholine Nanovesicles Containing the Antimicrobial Peptide Pediocin.

PubMed

de Mello, Michele Brauner; da Silva Malheiros, Patrícia; Brandelli, Adriano; Pesce da Silveira, Nádya; Jantzen, Márcia Monks; de Souza da Motta, Amanda

2013-03-01

Encapsulation may provide increased stability and antimicrobial efficiency to bacteriocins. In this work, the antilisterial peptide pediocin was encapsulated in nanovesicles prepared from partially purified soybean phosphatidylcholine. The maintenance of antimicrobial activity and properties of free and encapsulated pediocin was observed during 13 days at 4 °C, and after this period, the encapsulated pediocin retained 50 % its initial activity. The maintenance of the bioactive properties of free and encapsulated pediocin was observed against different species of Listeria, inhibiting Listeria monocytogenes, Listeria innocua and Listeria ivanovii. The size of vesicles containing pediocin was determined by dynamic light scattering as an average of 190 nm, with little change throughout the observation period. Polydispersity index values were around 0.201 and are considered satisfactory, indicating an adequate size distribution of liposomes. The efficiency of encapsulation was 80 %. Considering these results, the protocol used was appropriate for the encapsulation of this bacteriocin. Results demonstrate the production of stable nanoparticulate material. The maintenance of the properties of pediocin encapsulated in liposomes is fundamental to prospect the stability in different conditions of the food matrix.

A Comparative Cytotoxic Evaluation of Disulfiram Encapsulated PLGA Nanoparticles on MCF-7 Cells.

PubMed

Fasehee, Hamidreza; Ghavamzadeh, Ardeshir; Alimoghaddam, Kamran; Ghaffari, Seyed-Hamidollah; Faghihi, Shahab

2017-04-01

Background: Disulfiram is oral aldehyde dehydrogenase (ALDH) inhibitor that has been used in the treatment of alcoholism. Recent studies show that this drug has anticancer properties; however, its rapid degradation has limited its clinical application. Encapsulation of disulfiram polymeric nanoparticles (NPs) may improve its anticancer activities and protect rapid degradation of the drug. Materials and Methods: A poly (lactide-co-Glycolide) (PLGA) was developed for encapsulation of disulfiram and its delivery into breast cancer cells. Disulfiram encapsulated PLGA NPs were prepared by nanoprecipitation method and were characterized by Scanning Electron Microscopy (SEM). The loading and encapsulation efficiency of NPs were determined using UV-Visible spectroscopy. Cell cytotoxicity of free and encapsulated form of disulfiram is also determined using MTT assay. Results: Disulfiram encapsulated PLGA NPs had uniform size with 165 nm. Drug loading and entrapment efficiency were 5.35 ±0.03% and 58.85±1.01%. The results of MTT assay showed that disulfiram encapsulated PLGA NPs were more potent in induction of apoptosis compare to free disulfiram. Conclusion: Based on the results obtained in the present study it can be concluded that encapsulation of disulfiram with PLGA can protect its degradation in improve its cytotoxicity on breast cancer cells.

Preparation of a novel composite nanofiber gel-encapsulated human placental extract through layer-by-layer self-assembly

PubMed Central

LIU, GUOHUI; CHEN, XI; ZHOU, WU; YANG, SHUHUA; YE, SHUNAN; CAO, FAQI; LIU, YI; XIONG, YUAN

2016-01-01

Aqueous human placenta extract (HPE) has been previously used to treat chronic soft tissue ulcer; however, the optimal dosage of HPE has yet to be elucidated. The present study investigated a novel nanofiber gel composed through layer-by-layer (LbL) self-assembly, in which HPE was encapsulated. IKVAV, RGD, RAD16 and FGL-PA were screened and combined to produce an optimal vehicle nanofiber gel through LbL assembly. Subsequently, the aqueous HPE was encapsulated into this nanofiber at the appropriate concentration, and the morphology, particle size, drug loading efficacy, encapsulation rate, release efficiency and structure validation were detected. The encapsulation efficiency of all three HPE samples was >90%, the nanofiber gel exhibited a slow releasing profile, and the structure of HPE encapsulated in the nanofiber gel was unvaried. In conclusion, this type of novel composite nanocapsules may offer a promising delivery system for HPE. PMID:27073463

Stem Cell Therapies for Treating Diabetes: Progress and Remaining Challenges.

PubMed

Sneddon, Julie B; Tang, Qizhi; Stock, Peter; Bluestone, Jeffrey A; Roy, Shuvo; Desai, Tejal; Hebrok, Matthias

2018-06-01

Restoration of insulin independence and normoglycemia has been the overarching goal in diabetes research and therapy. While whole-organ and islet transplantation have become gold-standard procedures in achieving glucose control in diabetic patients, the profound lack of suitable donor tissues severely hampers the broad application of these therapies. Here, we describe current efforts aimed at generating a sustainable source of functional human stem cell-derived insulin-producing islet cells for cell transplantation and present state-of-the-art efforts to protect such cells via immune modulation and encapsulation strategies. Copyright © 2018. Published by Elsevier Inc.

PROGRESS IN CLINICAL ENCAPSULATED ISLET XENOTRANSPLANTATION

PubMed Central

Cooper, David K.C.; Matsumoto, Shinichi; Abalovich, Adrian; Itoh, Takeshi; Mourad, Nizar I.; Gianello, Pierre R; Wolf, Eckhard; Cozzi, Emanuele

2016-01-01

At the 2015 combined congress of the CTS, IPITA, and IXA, a symposium was held to discuss recent progress in pig islet xenotransplantation. The presentations focused on 5 major topics – (i) the results of 2 recent clinical trials of encapsulated pig islet transplantation, (ii) the inflammatory response to encapsulated pig islets, (iii) methods to improve the secretion of insulin by pig islets, (iv) genetic modifications to the islet-source pigs aimed to protect the islets from the primate immune and/or inflammatory responses, and (v) regulatory aspects of clinical pig islet xenotransplantation. Trials of microencapsulated porcine islet transplantation to treat unstable type 1 diabetic patients have been associated with encouraging preliminary results. Further advances to improve efficacy may include (i) transplantation into a site other than the peritoneal cavity, which might result in better access to blood, oxygen, and nutrients; (ii) the development of a more biocompatible capsule and/or the minimization of a foreign body reaction; (iii) pig genetic modification to induce a greater secretion of insulin by the islets, and/or to reduce the immune response to islets released from damaged capsules; and (iv) reduction of the inflammatory response to the capsules/islets by improvements in the structure of the capsules and/or in genetic-engineering of the pigs and/or in some form of drug therapy. Ethical and regulatory frameworks for islet xenotransplantation are already available in several countries, and there is now a wider international perception of the importance of developing an internationally-harmonized ethical and regulatory framework. PMID:27482959

Mass transfer of large molecules through collagen and collagen-silica hybrid membranes

NASA Astrophysics Data System (ADS)

Jofre-Lora, Pedro

Diabetes is a growing concern in the United States and around the world that must be addressed through new treatment options. Current standard treatment options of diabetes are limiting and have tremendous impacts on patient's lives. Emerging therapies, such as the implantation of encapsulated islets, are promising treatment options, but have not yet materialized due to unsolved problems with material properties. Hybrid silica-collagen membranes address some of these unsolved problems and are a promising material for cell encapsulation. However, the mass transfer properties of large molecules, such as insulin, TNF-alpha, IL1beta, and other important proteins in the etiology of diabetes, through these hybrid membranes are poorly characterized. In order to begin characterizing these properties, a device was constructed to accurately and efficiently measure the mass transfer of other similar large molecules, fluorescein isothiocyanate dextrans (FITC-dextran), through collagen-silica hybrid membranes. The device was used to measure diffusion coefficients of 4, 20, 40, and 150 kDa FITC-dextrans through non-silicified and silicified samples of 200 and 1000 Pa porcine skin collagen. Diffusion coefficients were found to be in the 10-7-10-6 cm2s -1 range, which is in agreement with previously published data for similar molecules through similar hydrogels. The effects of collagen stiffness, FITC-dextran molecular weight, and silicification treatment on diffusion were investigated. It was found that collagen stiffness and FITC-dextran molecular weight had a negative correlation with diffusion, whereas silicification treatment had no global impact on diffusion. The device created, and the results of this preliminary investigation, can be used to develop collagen-silica hybrid membranes as an alternative material for cell encapsulation in a forward-design manner.

A Comparative Cytotoxic Evaluation of Disulfiram Encapsulated PLGA Nanoparticles on MCF-7 Cells

PubMed Central

Fasehee, Hamidreza; Ghavamzadeh, Ardeshir; Alimoghaddam, Kamran; Ghaffari, Seyed-Hamidollah; Faghihi, Shahab

2017-01-01

Background: Disulfiram is oral aldehyde dehydrogenase (ALDH) inhibitor that has been used in the treatment of alcoholism. Recent studies show that this drug has anticancer properties; however, its rapid degradation has limited its clinical application. Encapsulation of disulfiram polymeric nanoparticles (NPs) may improve its anticancer activities and protect rapid degradation of the drug. Materials and Methods: A poly (lactide-co-Glycolide) (PLGA) was developed for encapsulation of disulfiram and its delivery into breast cancer cells. Disulfiram encapsulated PLGA NPs were prepared by nanoprecipitation method and were characterized by Scanning Electron Microscopy (SEM). The loading and encapsulation efficiency of NPs were determined using UV-Visible spectroscopy. Cell cytotoxicity of free and encapsulated form of disulfiram is also determined using MTT assay. Results: Disulfiram encapsulated PLGA NPs had uniform size with 165 nm. Drug loading and entrapment efficiency were 5.35 ±0.03% and 58.85±1.01%. The results of MTT assay showed that disulfiram encapsulated PLGA NPs were more potent in induction of apoptosis compare to free disulfiram. Conclusion: Based on the results obtained in the present study it can be concluded that encapsulation of disulfiram with PLGA can protect its degradation in improve its cytotoxicity on breast cancer cells. PMID:28875004

Encapsulation Efficiency and Micellar Structure of Solute-Carrying Block Copolymer Nanoparticles

PubMed Central

Woodhead, Jeffrey L.; Hall, Carol K.

2011-01-01

We use discontinuous molecular dynamics (DMD) computer simulation to investigate the encapsulation efficiency and micellar structure of solute-carrying block copolymer nanoparticles as a function of packing fraction, polymer volume fraction, solute mole fraction, and the interaction parameters between the hydrophobic head blocks and between the head and the solute. The encapsulation efficiency increases with increasing polymer volume fraction and packing fraction but decreases with increasing head-head interaction strength. The latter is due to an increased tendency for the solute to remain on the micelle surface. We compared two different nanoparticle assembly methods, one in which the solute and copolymer co-associate and the other in which the copolymer micelle is formed before the introduction of solute. The assembly method does not affect the encapsulation efficiency but does affect the solute uptake kinetics. Both head-solute interaction strength and head-head interaction strength affect the density profile of the micelles; increases in the former cause the solute to distribute more evenly throughout the micelle, while increases in the latter cause the solute to concentrate further from the center of the micelle. We explain our results in the context of a model of drug insertion into micelles formulated by Kumar and Prud’homme; as conditions become more conducive to micelle formation, a stronger energy barrier to solute insertion forms which in turn decreases the encapsulation efficiency of the system. PMID:21918582

Preparation of a nano emodin transfersome and study on its anti-obesity mechanism in adipose tissue of diet-induced obese rats

PubMed Central

2014-01-01

Objective To describe the preparation of nano emodin transfersome (NET) and investigate its effect on mRNA expression of adipose triglyceride lipase (ATGL) and G0/G1 switch gene 2 (G0S2) in adipose tissue of diet-induced obese rats. Methods NET was prepared by film-ultrasonic dispersion method. The effects of emodin components at different ratios on encapsulation efficiency were investigated.The NET envelopment rate was determined by ultraviolet spectrophotometry. The particle size and Zeta potential of NET were evaluated by Zetasizer analyzer. Sixty male SD rats were assigned to groups randomly. After 8-week treatment, body weight, wet weight of visceral fat and the percentage of body fat (PBF) were measured. Fasting blood glucose and serum lipid levels were determined. The adipose tissue section was HE stained, and the cellular diameter and quantity of adipocytes were evaluated by light microscopy. The mRNA expression of ATGL and G0S2 from the peri-renal fat tissue was assayed by RT-PCR. Results The appropriate formulation was deoxycholic acid sodium salt vs. phospholipids 1:8, cholesterol vs. phospholipids 1:3, vitamin Evs. phospholipids 1:20, and emodin vs. phospholipid 1:6. Zeta potential was −15.11 mV, and the particle size was 292.2 nm. The mean encapsulation efficiency was (69.35 ± 0.25)%. Compared with the obese model group, body weight, wet weight of visceral fat, PBF and mRNA expression of G0S2 from peri-renal fat tissue were decreased significantly after NET treatment (all P < 0.05), while high-density lipoprotein cholesterol (HDL-C), the diameter of adipocytes and mRNA expression of ATGL from peri-renal fat tissue were increased significantly (all P < 0.05). Conclusion The preparation method is simple and reasonable. NET with negative electricity was small and uniform in particle size, with high encapsulation efficiency and stability. NET could reduce body weight and adipocyte size, and this effect was associated with the up-regulation of ATGL, down-regulation of G0S2 expression in the adipose tissue, and improved insulin sensitivity. PMID:24641917

One step effective removal of Congo Red in chitosan nanoparticles by encapsulation

NASA Astrophysics Data System (ADS)

Alver, Erol; Bulut, Mehmet; Metin, Ayşegül Ülkü; Çiftçi, Hakan

2017-01-01

Chitosan nanoparticles (CNPs) were prepared with ionotropic gelation between chitosan and tripolyphosphate for the removal of Congo Red. The production of chitosan nanoparticles and the dye removal process was carried out in one-step. The removal efficiency of Congo Red by encapsulation within chitosan from the aqueous solution and its storage stability are examined at different pH values. The influence of some parameters such as the initial dye concentration, pH value of the dye solution, electrolyte concentration, tripolyphosphate concentration, mixing time and speed on the encapsulation is examined. Congo Red removal efficiency and encapsulation capacity of chitosan nanoparticles were determined as above 98% and 5107 mg Congo Red/g chitosan, respectively.

Development of alginate microspheres containing thyme essential oil using ionic gelation.

PubMed

Benavides, Sergio; Cortés, Pablo; Parada, Javier; Franco, Wendy

2016-08-01

Essential oils are a good antimicrobial and antioxidant agent alternative in human or animal feed. However, their direct use has several disadvantages such as volatilization or oxidation. The development of essential oil microspheres may help to avoid these problems. The objective of the present research was to microencapsulate thyme essential oil by generating emulsions with different dispersion degrees. The emulsions were encapsulated in calcium-alginate microspheres by ionic gelation. The microspheres were evaluated regarding size, shape, encapsulation efficiency, loading capacity and antimicrobial properties. The results indicate that encapsulation efficiency and loading capacity are dependent on concentration and degree of dispersion. The best encapsulation conditions were obtained at 2% v/v of thyme essential oil with a high dispersion degree (18,000rpm/5min), which was achieved with an efficiency of 85%. Finally, the microspheres obtained showed significant antimicrobial effect, especially in gram-positive bacteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of native and modified banana starch nanoparticles as vehicles for curcumin.

PubMed

Acevedo-Guevara, Leonardo; Nieto-Suaza, Leonardo; Sanchez, Leidy T; Pinzon, Magda I; Villa, Cristian C

2018-05-01

In recent years, starch nanoparticles have been of great interest for drug delivery due to their relatively easy synthesis, biocompatibility, and vast amount of botanical sources. Native and acetylated starch obtained from green bananas were used for synthesis of curcumin-loaded starch nanoparticles. Mean particle size, encapsulation efficiency, and curcumin release in simulated gastric and intestinal fluids were studied. Both nanosystems showed sizes lower than 250 nm and encapsulation efficiency above 80%, with acetylated banana starch nanoparticles having the capacity to encapsulate more curcumin molecules. Both FTIR and XRD analyses showed that starch acetylation allows stronger hydrogen bond interaction between curcumin and the starch matrix, thus, higher encapsulation efficiency. Finally, curcumin release studies showed that acetylated banana starch nanoparticles allowed more controlled release, probably due to their stronger hydrogen bond interaction with curcumin. Copyright © 2018. Published by Elsevier B.V.

Silicon nanopore membrane (SNM) for islet encapsulation and immunoisolation under convective transport

NASA Astrophysics Data System (ADS)

Song, Shang; Faleo, Gaetano; Yeung, Raymond; Kant, Rishi; Posselt, Andrew M.; Desai, Tejal A.; Tang, Qizhi; Roy, Shuvo

2016-03-01

Problems associated with islet transplantation for Type 1 Diabetes (T1D) such as shortage of donor cells, use of immunosuppressive drugs remain as major challenges. Immune isolation using encapsulation may circumvent the use of immunosuppressants and prolong the longevity of transplanted islets. The encapsulating membrane must block the passage of host’s immune components while providing sufficient exchange of glucose, insulin and other small molecules. We report the development and characterization of a new generation of semipermeable ultrafiltration membrane, the silicon nanopore membrane (SNM), designed with approximately 7 nm-wide slit-pores to provide middle molecule selectivity by limiting passage of pro-inflammatory cytokines. Moreover, the use of convective transport with a pressure differential across the SNM overcomes the mass transfer limitations associated with diffusion through nanometer-scale pores. The SNM exhibited a hydraulic permeability of 130 ml/hr/m2/mmHg, which is more than 3 fold greater than existing polymer membranes. Analysis of sieving coefficients revealed 80% reduction in cytokines passage through SNM under convective transport. SNM protected encapsulated islets from infiltrating cytokines and retained islet viability over 6 hours and remained responsive to changes in glucose levels unlike non-encapsulated controls. Together, these data demonstrate the novel membrane exhibiting unprecedented hydraulic permeability and immune-protection for islet transplantation therapy.

Aerobic TCE degradation by encapsulated toluene-oxidizing bacteria, Pseudomonas putida and Bacillus spp.

PubMed

Kim, Seungjin; Bae, Wookeun; Hwang, Jungmin; Park, Jaewoo

2010-01-01

The degradation rates of toluene and trichloroethylene (TCE) by Pseudomonas putida and Bacillus spp. that were encapsulated in polyethylene glycol (PEG) polymers were evaluated in comparison with the results of exposure to suspended cultures. PEG monomers were polymerized together with TCE-degrading microorganisms, such that the cells were encapsulated in and protected by the matrices of the PEG polymers. TCE concentrations were varied from 0.1 to 1.5 mg/L. In the suspended cultures of P. putida, the TCE removal rate decreased as the initial TCE concentration increased, revealing TCE toxicity or a limitation of reducing power, or both. When the cells were encapsulated, an initial lag period of about 10-20 h was observed for toluene degradation. Once acclimated, the encapsulated P. putida cultures were more tolerant to TCE at an experimental range of 0.6-1.0 mg/L and gave higher transfer efficiencies (mass TCE transformed/mass toluene utilized). When the TCE concentration was low (e.g., 0.1 mg/L) the removal of TCE per unit mass of cells (specific removal) was significantly lower, probably due to a diffusion limitation into the PEG pellet. Encapsulated Bacillus spp. were able to degrade TCE cometabolically. The encapsulated Bacillus spp. gave significantly higher values than did P. putida in the specific removal and the transfer efficiency, particularly at relatively high TCE concentration of approximately 1.0±0.5 mg/L. The transfer efficiency by encapsulated Bacillus spp. in this study was 0.27 mgTCE/mgToluene, which was one to two orders of magnitude greater than the reported values.

Efficient encapsulation of antisense oligonucleotides in lipid vesicles using ionizable aminolipids: formation of novel small multilamellar vesicle structures.

PubMed

Semple, S C; Klimuk, S K; Harasym, T O; Dos Santos, N; Ansell, S M; Wong, K F; Maurer, N; Stark, H; Cullis, P R; Hope, M J; Scherrer, P

2001-02-09

Typical methods used for encapsulating antisense oligodeoxynucleotides (ODN) and plasmid DNA in lipid vesicles result in very low encapsulation efficiencies or employ cationic lipids that exhibit unfavorable pharmacokinetic and toxicity characteristics when administered intravenously. In this study, we describe and characterize a novel formulation process that utilizes an ionizable aminolipid (1,2-dioleoyl-3-dimethylammonium propane, DODAP) and an ethanol-containing buffer system for encapsulating large quantities (0.15--0.25 g ODN/g lipid) of polyanionic ODN in lipid vesicles. This process requires the presence of up to 40% ethanol (v/v) and initial formulation at acidic pH values where the DODAP is positively charged. In addition, the presence of a poly(ethylene glycol)-lipid was required during the formulation process to prevent aggregation. The 'stabilized antisense-lipid particles' (SALP) formed are stable on adjustment of the external pH to neutral pH values and the formulation process allows encapsulation efficiencies of up to 70%. ODN encapsulation was confirmed by nuclease protection assays and (31)P NMR measurements. Cryo-electron microscopy indicated that the final particles consisted of a mixed population of unilamellar and small multilamellar vesicles (80--140 nm diameter), the relative proportion of which was dependent on the initial ODN to lipid ratio. Finally, SALP exhibited significantly enhanced circulation lifetimes in mice relative to free antisense ODN, cationic lipid/ODN complexes and SALP prepared with quaternary aminolipids. Given the small particle sizes and improved encapsulation efficiency, ODN to lipid ratios, and circulation times of this formulation compared to others, we believe SALP represent a viable candidate for systemic applications involving nucleic acid therapeutics.

Differential permeation of piroxicam-loaded PLGA micro/nanoparticles and their in vitro enhancement

NASA Astrophysics Data System (ADS)

Shankarayan, Raju; Kumar, Sumit; Mishra, Prashant

2013-03-01

Piroxicam is a non-steroidal anti-inflammatory drug used for the treatment of musculoskeletal pain. The main problem encountered when piroxicam is administered orally is its gastric side-effect (ulcer, bleeding and holes in the stomach). Transmucosal delivery and encapsulation of piroxicam in biodegradable particles offer potential advantages over conventional oral delivery. The present study was aimed to develop an alternative to piroxicam-delivery which could overcome the direct contact of the drug at the mucosal membrane and its permeation through the mucosal membrane was studied. To achieve this, the piroxicam was encapsulated in Poly (lactide- co-glycolide) (PLGA) microparticles (size 1-4 μm, encapsulation efficiency 80-85 %) and nanoparticles (size 151.6 ± 28.6 nm, encapsulation efficiency 92.17 ± 3.08 %). Various formulation process parameters were optimised for the preparation of piroxicam-loaded PLGA nanoparticles of optimal size and encapsulation efficiency. Transmucosal permeability of piroxicam-loaded PLGA micro- and nanoparticles through the porcine oesophageal mucosa was studied. Using fluorescently labelled PLGA micro- and nanoparticles, size-dependent permeation was demonstrated. Furthermore, the effect of different permeation enhancers on the flux rate and permeability coefficient for the permeation of nanoparticles was investigated. The results suggested that amongst the permeation enhancers used the most efficient enhancement of permeation was observed with 10 mM sodium dodecyl sulphate.

Optimization of gatifloxacin liposomal hydrogel for enhanced transcorneal permeation.

PubMed

Hosny, Khaled Mohamed

2010-03-01

The aim of this study was to prepare and characterize a topically effective prolonged-release ophthalmic gatifloxacin liposomal hydrogel formulation. Reverse-phase evaporation was used for the preparation of liposomes consisting of phosphatidylcholine (PC) and cholesterol (CH). The effect of PC:CH molar ratio on the percentage of drug encapsulated was investigated. The effect of additives, such as stearylamine (SA) or dicetyl phosphate (DP), as positive and negative charge inducers, respectively, was studied. Morphology, mean size, encapsulation efficiency, and in vitro release of gatifloxacin from liposomes were evaluated. For hydrogel preparation, carbopol 940 was applied. In vitro transcorneal permeation through excised albino rabbit cornea was also determined. Optimal encapsulation efficiency was found at the 5:3 PC:CH molar ratio; by increasing CH content above this limit, the encapsulation efficiency decreased. Positively charged liposomes showed superior entrapment efficiency over other liposomes. Hydrogel-containing liposomes with lipid content PC, CH, and SA in a molar ratio of 5:3:1, respectively, showed best release and transcorneal permeation. These results suggest that the encapsulation of gatifloxacin into liposomes prolonged the in vitro release, depending on composition of the vesicles. In addition, the polymer hydrogel used in the preparation ensured steady, prolonged transcorneal permeation. In conclusion, gatifloxacin liposomal hydrogel is a suitable delivery system for the improvement of the ocular bioavailability of gatifloxacin.

Preparation of uniform-sized PELA microspheres with high encapsulation efficiency of antigen by premix membrane emulsification.

PubMed

Wei, Qiang; Wei, Wei; Tian, Rui; Wang, Lian-Yan; Su, Zhi-Guo; Ma, Guang-Hui

2008-07-15

Relatively uniform-sized poly(lactide-co-ethylene glycol) (PELA) microspheres with high encapsulation efficiency were prepared rapidly by a novel method combining emulsion-solvent extraction and premix membrane emulsification. Briefly, preparation of coarse double emulsions was followed by additional premix membrane emulsification, and antigen-loaded microspheres were obtained by further solidification. Under the optimum condition, the particle size was about 1 mum and the coefficient of variation (CV) value was 18.9%. Confocal laser scanning microscope and flow cytometer analysis showed that the inner droplets were small and evenly dispersed and the antigen was loaded uniformly in each microsphere when sonication technique was occupied to prepare primary emulsion. Distribution pattern of PEG segment played important role on the properties of microspheres. Compared with triblock copolymer PLA-PEG-PLA, the diblock copolymer PLA-mPEG yielded a more stable interfacial layer at the interface of oil and water phase, and thus was more suitable to stabilize primary emulsion and protect coalescence of inner droplets and external water phase, resulting in high encapsulation efficiency (90.4%). On the other hand, solidification rate determined the time for coalescence during microspheres fabrication, and thus affected encapsulation efficiency. Taken together, improving the polymer properties and solidification rate are considered as two effective strategies to yield high encapsulation.

Storage of nuclear materials by encapsulation in fullerenes

DOEpatents

Coppa, Nicholas V.

1994-01-01

A method of encapsulating radioactive materials inside fullerenes for stable long-term storage. Fullerenes provide a safe and efficient means of disposing of nuclear waste which is extremely stable with respect to the environment. After encapsulation, a radioactive ion is essentially chemically isolated from its external environment.

The influence of immune system stimulation on encapsulated islet graft survival.

PubMed

Orłowski, Tadeusz M; Godlewska, Ewa; Tarchalska, Magda; Kinasiewicz, Joanna; Antosiak, Magda; Sabat, Marek

2005-01-01

The aim of this study was to determine the influence activating of the recipient immune system on the function of microencapsulated islet xenografts. The skin of WAG or Fisher rats and WAG free or encapsulated (APA) Langerhans islets were transplanted to healthy or to streptozotocin diabetic BALB/c mice. Skin grafts were performed following the method of Billingham and Medawar. Rat islets were isolated from pancreas by the Lacy and Kostianovsy method and encapsulated with calcium alginate-poly-L-lysine-alginate according to the 3-step coating method of Sun. The transplantation of encapsulated WAG islets, despite activation of the host immune system, restored euglycemia for over 180 +/-100 days. A subsequent skin graft taken from the same donor was rejected in the second set mode, but euglycemia persisted. In diabetic recipients, impaired immune response was corrected by successful encapsulated islet transplantation. In diabetic mice, strong stimulation with 2-fold skin transplantation induced primary non-function of grafted islets despite their encapsulation. The survival of an islet xenograft depends on the level of activation of the recipient immune system. The immune response of diabetic mice was impaired, but increased after post-transplant restitution of euglycemia. Microencapsulation sufficiently protected grafted islets, and remission of diabetes was preserved. However, after strong specific or non-specific stimulation of the host immune system, non-function of xenografted islets developed despite their encapsulation. Therefore, islet graft recipients should avoid procedures which could stimulate their immune systems. If absolutely necessary, the graft should be protected by exogenous insulin therapy at that time.

Encapsulation performance of layer-by-layer microcapsules for proteins.

PubMed

De Temmerman, Marie-Luce; Demeester, Jo; De Vos, Filip; De Smedt, Stefaan C

2011-04-11

This study reports on the encapsulation efficiency of proteins in dextran sulfate/poly-L-arginine-based microcapsules, fabricated via layer-by-layer assembly (LbL). For this purpose, radiolabeled proteins are entrapped in CaCO(3) microparticles, followed by LbL coating of the CaCO(3) cores and subsequent dissolving of the CaCO(3) using EDTA. To allow to improve protein encapsulation in LbL microcapsules, we studied all steps in the preparation of the microcapsules where loss of protein load might occur. The encapsulation efficiency of proteins in LbL microcapsules turns out to be strongly dependent on both the charge and molecular weight of the protein as well as on the number of polyelectrolyte bilayers the microcapsules consist of.

Hydrogel Microencapsulated Insulin-Secreting Cells Increase Keratinocyte Migration, Epidermal Thickness, Collagen Fiber Density, and Wound Closure in a Diabetic Mouse Model of Wound Healing.

PubMed

Aijaz, Ayesha; Faulknor, Renea; Berthiaume, François; Olabisi, Ronke M

2015-11-01

Wound healing is a hierarchical process of intracellular and intercellular signaling. Insulin is a potent chemoattractant and mitogen for cells involved in wound healing. Insulin's potential to promote keratinocyte growth and stimulate collagen synthesis in fibroblasts is well described. However, there currently lacks an appropriate delivery mechanism capable of consistently supplying a wound environment with insulin; current approaches require repeated applications of insulin, which increase the chances of infecting the wound. In this study, we present a novel cell-based therapy that delivers insulin to the wound area in a constant or glucose-dependent manner by encapsulating insulin-secreting cells in nonimmunogenic poly(ethylene glycol) diacrylate (PEGDA) hydrogel microspheres. We evaluated cell viability and insulin secretory characteristics of microencapsulated cells. Glucose stimulation studies verified free diffusion of glucose and insulin through the microspheres, while no statistical difference in insulin secretion was observed between cells in microspheres and cells in monolayers. Scratch assays demonstrated accelerated keratinocyte migration in vitro when treated with microencapsulated cells. In excisional wounds on the dorsa of diabetic mice, microencapsulated RIN-m cells accelerated wound closure by postoperative day 7; a statistically significant increase over AtT-20ins-treated and control groups. Histological results indicated significantly greater epidermal thickness in both microencapsulated RIN-m and AtT-20ins-treated wounds. The results suggest that microencapsulation enables insulin-secreting cells to persist long enough at the wound site for a therapeutic effect and thereby functions as an effective delivery vehicle to accelerate wound healing.

Comparative study of DNA encapsulation into PLGA microparticles using modified double emulsion methods and spray drying techniques.

PubMed

Oster, C G; Kissel, T

2005-05-01

Recently, several research groups have shown the potential of microencapsulated DNA as adjuvant for DNA immunization and in tissue engineering approaches. Among techniques generally used for microencapsulation of hydrophilic drug substances into hydrophobic polymers, modified WOW double emulsion method and spray drying of water-in-oil dispersions take a prominent position. The key parameters for optimized microspheres are particle size, encapsulation efficiency, continuous DNA release and stabilization of DNA against enzymatic and mechanical degradation. This study investigates the possibility to encapsulate DNA avoiding shear forces which readily degrade DNA during this microencapsulation. DNA microparticles were prepared with polyethylenimine (PEI) as a complexation agent for DNA. Polycations are capable of stabilizing DNA against enzymatic, as well as mechanical degradation. Further, complexation was hypothesized to facilitate the encapsulation by reducing the size of the macromolecule. This study additionally evaluated the possibility of encapsulating lyophilized DNA and lyophilized DNA/PEI complexes. For this purpose, the spray drying and double emulsion techniques were compared. The size of the microparticles was characterized by laser diffractometry and the particles were visualized by scanning electron microscopy (SEM). DNA encapsulation efficiencies were investigated photometrically after complete hydrolysis of the particles. Finally, the DNA release characteristics from the particles were studied. Particles with a size of <10 microm which represent the threshold for phagocytic uptake could be prepared with these techniques. The encapsulation efficiency ranged from 100-35% for low theoretical DNA loadings. DNA complexation with PEI 25?kDa prior to the encapsulation process reduced the initial burst release of DNA for all techniques used. Spray-dried particles without PEI exhibited high burst releases, whereas double emulsion techniques showed continuous release rates.

Biopolymer-prebiotic carbohydrate blends and their effects on the retention of bioactive compounds and maintenance of antioxidant activity.

PubMed

Silva, Eric Keven; Zabot, Giovani L; Cazarin, Cinthia B B; Maróstica, Mário R; Meireles, M Angela A

2016-06-25

The objective of this study was to evaluate the use of inulin (IN), a prebiotic carbohydrate without superficial activity, as an encapsulating matrix of lipophilic bioactive compounds. For achieving the encapsulation, IN was associated with biopolymers that present superficial activity: modified starch (HiCap), whey protein isolate (WPI) and gum acacia (GA). Encapsulation was performed through emulsification assisted by ultrasound followed by freeze-drying (FD) process to dry the emulsions. All blends retained geranylgeraniol. GA-IN blend yielded the highest geranylgeraniol retention (96±2wt.%) and entrapment efficiency (94±3wt.%), whilst WPI-IN blend yielded the highest encapsulation efficiency (88±2wt.%). After encapsulation, composition of geranylgeraniol in the annatto seed oil was maintained (23.0±0.5g/100g of oil). Such findings indicate that the method of encapsulation preserved the active compound. All blends were also effective for maintaining the antioxidant activity of the oil through ORAC and DPPH analyses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Optimization of encapsulation of a synthetic long peptide in PLGA nanoparticles: low-burst release is crucial for efficient CD8(+) T cell activation.

PubMed

Silva, A L; Rosalia, R A; Sazak, A; Carstens, M G; Ossendorp, F; Oostendorp, J; Jiskoot, W

2013-04-01

Overlapping synthetic long peptides (SLPs) hold great promise for immunotherapy of cancer. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are being developed as delivery systems to improve the potency of peptide-based therapeutic cancer vaccines. Our aim was to optimize PLGA NP for SLP delivery with respect to encapsulation and release, using OVA24, a 24-residue long synthetic antigenic peptide covering a CTL epitope of ovalbumin (SIINFEKL), as a model antigen. Peptide-loaded PLGA NPs were prepared by a double emulsion/solvent evaporation technique. Using standard conditions (acidic inner aqueous phase), we observed that either encapsulation was very low (1-30%), or burst release extremely high (>70%) upon resuspension of NP in physiological buffers. By adjusting formulation and process parameters, we uncovered that the pH of the first emulsion was critical to efficient encapsulation and controlled release. In particular, an alkaline inner aqueous phase resulted in circa 330 nm sized NP with approximately 40% encapsulation efficiency and low (<10%) burst release. These NP showed enhanced MHC class I restricted T cell activation in vitro when compared to high-burst releasing NP and soluble OVA24, proving that efficient entrapment of the antigen is crucial to induce a potent cellular immune response. Copyright © 2012 Elsevier B.V. All rights reserved.

Isolation, banking, encapsulation and transplantation of different types of Langerhans islets.

PubMed

Antosiak-Iwańska, Magdalena; Sitarek, Elzbieta; Sabat, Marek; Godlewska, Ewa; Kinasiewicz, Joanna; Weryński, Andrzej

2009-05-01

The discovery of a cure for diabetes is a dream of many medical researchers. The transplantation of Langerhans islets is a potential treatment of choice for patients with type 1 diabetes as a source of endogenous insulin for the recipient. The aim of the experiment was to transplant Langerhans islets without immunosuppression. To protect the grafts against transplant rejection, semipermeable membranes could be used. Langerhans islets were isolated from rats and pigs and immunoisolated by encapsulation in alginate-protamine-heparin (APH) or alginate-poly-L-lysine-alginate (APA) membranes. Islets were pooled in a controlled manner. Tests for cryopreservation and biocompatibility were also performed. The capsules coated with APH are more resistant than the capsules coated with APA. After transplantation of the islets immunoisolated with APA, euglycemia is maintained longer than after transplantation of the islets immunoisolated with APH. Microencapsulation protects the islets from destruction by the host. It is feasible to treat experimental diabetes by transplantation of encapsulated Langerhans islets without immunosuppression.

Cashew gum and inulin: New alternative for ginger essential oil microencapsulation.

PubMed

Fernandes, Regiane Victória de Barros; Botrel, Diego Alvarenga; Silva, Eric Keven; Borges, Soraia Vilela; Oliveira, Cassiano Rodrigues de; Yoshida, Maria Irene; Feitosa, Judith Pessoa de Andrade; de Paula, Regina Célia Monteiro

2016-11-20

This study aimed to evaluate the effect of partial replacement of cashew gum by inulin used as wall materials, on the characteristics of ginger essential oil microencapsulated by spray drying with ultrasound assisted emulsions. The characterization of particles was evaluated as encapsulation efficiency and particle size. In addition, the properties of the microcapsules were studied through FTIR analysis, adsorption isotherms, thermal gravimetric analysis, X-ray and scanning electron microscopy. It was found that the solubility of the treatments was affected by the composition of the wall material and reached higher values (89.80%) when higher inulin concentrations were applied. The encapsulation efficiency (15.8%) was lower at the highest inulin concentration. The particles presented amorphous characteristics and treatment with cashew gum as encapsulant exhibited the highest water absorption at high water activity. The cashew gum and inulin matrix (3:1(w/w) ratio) showed the best characteristics regarding the encapsulation efficiency and morphology, showing no cracks in the structure. Copyright © 2016 Elsevier Ltd. All rights reserved.

The therapeutic effect of nano-encapsulated and nano-emulsion forms of carvacrol on experimental liver fibrosis.

PubMed

Hussein, Jihan; El-Banna, Mona; Mahmoud, Khaled F; Morsy, Safaa; Abdel Latif, Yasmin; Medhat, Dalia; Refaat, Eman; Farrag, Abdel Razik; El-Daly, Sherien M

2017-06-01

The present study aimed to compare the therapeutic efficiency of nano-encapsulated and nano-emulsion carvacrol administration on liver injury in thioacetamide (TAA) treated rats. To fulfill our target, we used sixty male albino rats classified into six groups as follow: control, nano-encapsulated carvacrol, nano-emulsion carvacrol, thioacetamide, treated nano-encapsulated carvacrol and treated nano-emulsion carvacrol groups. Blood samples were collected from all groups and the separated serum was used for analysis of the following biochemical parameters; aspartate aminotransferase (AST), alanine aminotransferase (ALT), S100 B protein, alpha fetoprotein (AFP) and caspase-3. The levels of malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), monocyte chemoattractant protein-1(MCP-1) and hydroxyproline content were all evaluated in liver tissue homogenate. Histopathological examinations for liver tissues were also performed. Thioacetamide induced hepatic damage in rats as revealed by the significant increase in the levels of serum ALT, AST and produced oxidative stress as displayed by the significant elevation in the levels of hepatic MDA and NO concomitant with a significant decrease in GSH. In addition, thioacetamide significantly increased serum S100B protein, alpha fetoprotein and caspase-3 along with hepatic MCP-1 and hydroxyproline; these results were confirmed by the histopathological investigation. In contrast, nano-encapsulated and nano-emulsion carvacrol were able to ameliorate these negative changes in the thioacetamide injected rats. However, the effect of the nano-encapsulated form of carvacrol was more prominent than the nano-emulsion form. Nano-encapsulated and nano-emulsion carvacrol can ameliorate thioacetamide induced liver injury. These results could be attributed to the potential anti-inflammatory, antioxidant, and anti-apoptotic activities of carvacrol in addition to the effectiveness of the encapsulation technique that can protect carvacrol structure and increase its efficiency and stability. Moreover, nano-encapsulation of carvacrol is more efficient than nano-emulsion. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Exergy analysis of encapsulation of photochromic dye by spray drying

NASA Astrophysics Data System (ADS)

Çay, A.; Akçakoca Kumbasar, E. P.; Morsunbul, S.

2017-10-01

Application of exergy analysis methodology for encapsulation of photochromic dyes by spray drying was presented. Spray drying system was investigated considering two subsystems, the heater and the dryer sections. Exergy models for each subsystem were proposed and exergy destruction rate and exergy efficiency of each subsystem and the whole system were computed. Energy and exergy efficiency of the system were calculated to be 5.28% and 3.40%, respectively. It was found that 90% of the total exergy inlet was destroyed during encapsulation by spray drying and the exergy destruction of the heater was found to be higher.

Tracking hypoxic signaling within encapsulated cell aggregates.

PubMed

Skiles, Matthew L; Sahai, Suchit; Blanchette, James O

2011-12-16

In Diabetes mellitus type 1, autoimmune destruction of the pancreatic β-cells results in loss of insulin production and potentially lethal hyperglycemia. As an alternative treatment option to exogenous insulin injection, transplantation of functional pancreatic tissue has been explored. This approach offers the promise of a more natural, long-term restoration of normoglycemia. Protection of the donor tissue from the host's immune system is required to prevent rejection and encapsulation is a method used to help achieve this aim. Biologically-derived materials, such as alginate and agarose, have been the traditional choice for capsule construction but may induce inflammation or fibrotic overgrowth which can impede nutrient and oxygen transport. Alternatively, synthetic poly(ethylene glycol) (PEG)-based hydrogels are non-degrading, easily functionalized, available at high purity, have controllable pore size, and are extremely biocompatible. As an additional benefit, PEG hydrogels may be formed rapidly in a simple photo-crosslinking reaction that does not require application of non-physiological temperatures. Such a procedure is described here. In the crosslinking reaction, UV degradation of the photoinitiator, 1-[4-(2-Hydroxyethoxy)-phenyl]-2-hydroxy-2-methyl-1-propane-1-one (Irgacure 2959), produces free radicals which attack the vinyl carbon-carbon double bonds of dimethacrylated PEG (PEGDM) inducing crosslinking at the chain ends. Crosslinking can be achieved within 10 minutes. PEG hydrogels constructed in such a manner have been shown to favorably support cells, and the low photoinitiator concentration and brief exposure to UV irradiation is not detrimental to viability and function of the encapsulated tissue. While we methacrylate our PEG with the method described below, PEGDM can also be directly purchased from vendors such as Sigma. An inherent consequence of encapsulation is isolation of the cells from a vascular network. Supply of nutrients, notably oxygen, is therefore reduced and limited by diffusion. This reduced oxygen availability may especially impact β-cells whose insulin secretory function is highly dependent on oxygen. Capsule composition and geometry will also impact diffusion rates and lengths for oxygen. Therefore, we also describe a technique for identifying hypoxic cells within our PEG capsules. Infection of the cells with a recombinant adenovirus allows for a fluorescent signal to be produced when intracellular hypoxia-inducible factor (HIF) pathways are activated. As HIFs are the primary regulators of the transcriptional response to hypoxia, they represent an ideal target marker for detection of hypoxic signaling. This approach allows for easy and rapid detection of hypoxic cells. Briefly, the adenovirus has the sequence for a red fluorescent protein (Ds Red DR from Clontech) under the control of a hypoxia-responsive element (HRE) trimer. Stabilization of HIF-1 by low oxygen conditions will drive transcription of the fluorescent protein (Figure 1). Additional details on the construction of this virus have been published previously. The virus is stored in 10% glycerol at -80° C as many 150 μL aliquots in 1.5 mL centrifuge tubes at a concentration of 3.4 x 10(10) pfu/mL. Previous studies in our lab have shown that MIN6 cells encapsulated as aggregates maintain their viability throughout 4 weeks of culture in 20% oxygen. MIN6 aggregates cultured at 2 or 1% oxygen showed both signs of necrotic cells (still about 85-90% viable) by staining with ethidium bromide as well as morphological changes relative to cells in 20% oxygen. The smooth spherical shape of the aggregates displayed at 20% was lost and aggregates appeared more like disorganized groups of cells. While the low oxygen stress does not cause a pronounced drop in viability, it is clearly impacting MIN6 aggregation and function as measured by glucose-stimulated insulin secretion. Western blot analysis of encapsulated cells in 20% and 1% oxygen also showed a significant increase in HIF-1α for cells cultured in the low oxygen conditions which correlates with the expression of the DsRed DR protein.

Highly efficient enzyme encapsulation in a protein nanocage: towards enzyme catalysis in a cellular nanocompartment mimic

NASA Astrophysics Data System (ADS)

Schoonen, Lise; Nolte, Roeland J. M.; van Hest, Jan C. M.

2016-07-01

The study of enzyme behavior in small nanocompartments is crucial for the understanding of biocatalytic processes in the cellular environment. We have developed an enzymatic conjugation strategy to attach a model enzyme to the interior of a cowpea chlorotic mottle virus capsid. It is shown that with this methodology high encapsulation efficiencies can be achieved. Additionally, we demonstrate that the encapsulation does not affect the enzyme performance in terms of a decreased activity or a hampered substrate diffusion. Finally, it is shown that the encapsulated enzymes are protected against proteases. We believe that our strategy can be used to study enzyme kinetics in an environment that approaches physiological conditions.The study of enzyme behavior in small nanocompartments is crucial for the understanding of biocatalytic processes in the cellular environment. We have developed an enzymatic conjugation strategy to attach a model enzyme to the interior of a cowpea chlorotic mottle virus capsid. It is shown that with this methodology high encapsulation efficiencies can be achieved. Additionally, we demonstrate that the encapsulation does not affect the enzyme performance in terms of a decreased activity or a hampered substrate diffusion. Finally, it is shown that the encapsulated enzymes are protected against proteases. We believe that our strategy can be used to study enzyme kinetics in an environment that approaches physiological conditions. Electronic supplementary information (ESI) available: Experimental procedures for the cloning, expression, and purification of all proteins, as well as supplementary figures and calculations. See DOI: 10.1039/c6nr04181g

Effects of pore forming agents of potassium bicarbonate and drug loading method against dissolution mechanisms of amoxicillin drugs encapsulated in hydrogel full-Ipn chitosan-poly(N-vinylcaprolactam) as a floating drug delivery system

NASA Astrophysics Data System (ADS)

Aini, Nurul; Rahayu, Dyah Utami Cahyaning; Budianto, Emil

2018-04-01

The limitation of amoxicillin trihydrate in the treatment of H. pylori bacteria is relatively short retention time in the stomach. The FDDS (Floating Drug Delivery System) amoxicillin trihydrate into a chitosan-poly(N-vinylcaprolactam) full-Ipn hydrogel matrix using a pore-forming agent KHCO3 is expected to overcome these limitations. The pore-forming agent to be used is 15% KHCO3 compound. Chemical kinetics approach is performed to determine the dissolution mechanism of amoxicillin trihydrate from K-PNVCL hydrogel in vitro on gastric pH and characterization using SEM performed to confirm the dissolution mechanism. Hydrogels with the addition of pore-forming agents will be loading in situ loading and post loading. Fourier Transform Infra Red (FTIR) spectroscopy was used to characterize K-PNVCL and UV-Vis hydrogels used to calculate the efficiency of encapsulation and drug dissolution rate in K-PNVCL hydrogel. Hydrogel K-PNVCL / KHCO3 that encapsulated by in situ loading method resulted in an encapsulation efficiency of 93.5% and dissolution of 93.4%. While the Hydrogel K-PNVCL / KHCO3 which is drug encapsulation resulted in an encapsulation efficiency of 87.2% with dissolution of 81.5%. Chemical kinetics approach to in situ encapsulation of loading and post loading shows the dissolution mechanism occurring in the K-PNVCL / KHCO3 hydrogel matrix occurs by diffusion. Observation using optical microscope and SEM showed the mechanism of drug dissolution in Hydrogel K-PNVCL occurred by diffusion.

Formulation and evaluation of lidocaine base ethosomes for transdermal delivery.

PubMed

Zhu, Xiaoliang; Li, Fuli; Peng, Xuebiao; Zeng, Kang

2013-08-01

Although transdermal preparations of local anesthetics have been used to reduce pain caused by skin surgery, these preparations cannot effectively penetrate through the epidermis because of the barrier formed by the stratum corneum and the thick epidermis. Ethosomes can effectively transport drugs across the skin because of their thermodynamic stability, small size, high encapsulation efficiency, and percutaneous penetration. We evaluated lidocaine base ethosomes by measuring their loading efficiency, encapsulation efficiency, thermodynamic stability, and percutaneous penetration capability in vitro, and their effectiveness and cutaneous irritation in vivo. Lidocaine base ethosomes were prepared using the injection-sonication-filter method. Size, loading efficiency, encapsulation efficiency, and stability were evaluated using a Zetasizer and high performance liquid chromatography. Formulation was determined by measuring the maximum encapsulation efficiency in the orthogonal test. Percutaneous penetration efficiency in vitro was analyzed using a Franz-type diffusion cell experiment. In vivo effectiveness was analyzed using the pinprick test. Cutaneous irritancy tests were performed on white guinea pigs, followed by histopathologic analysis. The results were compared with lidocaine liposomes as well as lidocaine delivered in a hydroethanolic solution. Lidocaine base ethosomes composed of 5% (w/w) egg phosphatidyl choline, 35% (w/w) ethanol, 0.2% (w/w) cholesterol, 5% (w/w) lidocaine base, and ultrapure water had a mean maximum encapsulation of 51% ± 4%, a mean particle size of 31 ± 3 nm, and a mean loading efficiency of 95.0% ± 0.1%. The encapsulation efficiency of lidocaine base ethosomes remained stable for 60 days at 25°C ± 1°C (95% confidence interval [CI], -1.12% to 1.34%; P = 0.833). The transdermal flux of lidocaine base differed significantly for the 3 preparations (F = 120, P < 0.001), being significantly greater from ethosomes than from liposomes (95% corrected CI, 1129-1818 µg/(cm(2)·h); P < 0.001), and from hydroethanolic solution (95% corrected CI, 1468-2157 µg/(cm(2)·h); P < 0.001). Lidocaine base ethosomes had a shorter onset time and longer duration in vivo than did lidocaine base liposomes or lidocaine delivered in a hydroethanolic solution. Lidocaine base ethosomes showed no evidence of dermal irritation in guinea pigs. Ethosomes are potential carriers of local anesthetics across the skin and may have applicability for other percutaneous drugs that require rapid onset.

Insulin-producing Cells from Adult Human Bone Marrow Mesenchymal Stromal Cells Could Control Chemically Induced Diabetes in Dogs: A Preliminary Study.

PubMed

Gabr, Mahmoud M; Zakaria, Mahmoud M; Refaie, Ayman F; Ismail, Amani M; Khater, Sherry M; Ashamallah, Sylvia A; Azzam, Maha M; Ghoneim, Mohamed A

2018-01-01

Ten mongrel dogs were used in this study. Diabetes was chemically induced in 7 dogs, and 3 dogs served as normal controls. For each diabetic dog, 5 million human bone marrow-derived mesenchymal stem cells/kg were differentiated to form insulin-producing cells using a trichostatin-based protocol. Cells were then loaded in 2 TheraCyte capsules which were transplanted under the rectus sheath. One dog died 4 d postoperatively from pneumonia. Six dogs were followed up with for 6 to 18 mo. Euglycemia was achieved in 4 dogs. Their glucose tolerance curves exhibited a normal pattern demonstrating that the encapsulated cells were glucose sensitive and insulin responsive. In the remaining 2 dogs, the fasting blood sugar levels were reduced but did not reach normal values. The sera of all transplanted dogs contained human insulin and C-peptide with a negligible amount of canine insulin. Removal of the transplanted capsules was followed by prompt return of diabetes. Intracytoplasmic insulin granules were seen by immunofluorescence in cells from the harvested capsules. Furthermore, all pancreatic endocrine genes were expressed. This study demonstrated that the TheraCyte capsule or a similar device can provide adequate immunoisolation, an important issue when stem cells are considered for the treatment of type 1 diabetes mellitus.

Microfluidic approach for encapsulation via double emulsions.

PubMed

Wang, Wei; Zhang, Mao-Jie; Chu, Liang-Yin

2014-10-01

Double emulsions, with inner drops well protected by the outer shells, show great potential as compartmentalized systems to encapsulate multiple components for protecting actives, masking flavor, and targetedly delivering and controllably releasing drugs. Precise control of the encapsulation characteristics of each component is critical to achieve an optimal therapeutic efficacy for pharmaceutical applications. Such controllable encapsulation can be realized by using microfluidic approaches for producing monodisperse double emulsions with versatile and controllable structures as the encapsulation system. The size, number and composition of the emulsion drops can be accurately manipulated for optimizing the encapsulation of each component for pharmaceutical applications. In this review, we highlight the outstanding advantages of controllable microfluidic double emulsions for highly efficient and precisely controllable encapsulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

An integrated buccal delivery system combining chitosan films impregnated with peptide loaded PEG-b-PLA nanoparticles.

PubMed

Giovino, Concetta; Ayensu, Isaac; Tetteh, John; Boateng, Joshua S

2013-12-01

Peptide (insulin) loaded nanoparticles (NPs) have been embedded into buccal chitosan films (Ch-films-NPs). These films were produced by solvent casting and involved incorporating in chitosan gel (1.25% w/v), NPs-Insulin suspensions at three different concentrations (1, 3, and 5mg of NPs per film) using glycerol as plasticiser. Film swelling and mucoadhesion were investigated using 0.01M PBS at 37°C and texture analyzer, respectively. Formulations containing 3mg of NPs per film produced optimised films with excellent mucoadhesion and swelling properties. Dynamic laser scattering measurements showed that the erosion of the chitosan backbone controlled the release of NPs from the films, preceding in vitro drug (insulin) release from Ch-films-NPs after 6h. Modulated release was observed with 70% of encapsulated insulin released after 360h. The use of chitosan films yielded a 1.8-fold enhancement of ex vivo insulin permeation via EpiOral™ buccal tissue construct relative to the pure drug. Flux and apparent permeation coefficient of 0.1μg/cm(2)/h and 4×10(-2)cm(2)/h were respectively obtained for insulin released from Ch-films-NPs-3. Circular dichroism and FTIR spectroscopy demonstrated that the conformational structure of the model peptide drug (insulin) released from Ch-films-NPs was preserved during the formulation process. Copyright © 2013 Elsevier B.V. All rights reserved.

Nanospheres Encapsulating Anti-Leishmanial Drugs for Their Specific Macrophage Targeting, Reduced Toxicity, and Deliberate Intracellular Release

PubMed Central

Shukla, Anil Kumar; Patra, Sanjukta

2012-01-01

Abstract The current work focuses on the study of polymeric, biodegradable nanoparticles (NPs) for the encapsulation of doxorubicin and mitomycin C (anti-leishmanial drugs), and their efficient delivery to macrophages, the parasite's home. The biodegradable polymer methoxypoly-(ethylene glycol)-b-poly (lactic acid) (MPEG-PLA) was used to prepare polymeric NPs encapsulating doxorubicin and mitomycin C. The morphology, mean diameter, and surface area of spherical NPs were determined by transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), and BET surface area analysis. X-ray diffraction was performed to validate drug encapsulation. An in vitro release profile of the drugs suggested a fairly slow release. These polymeric NPs were efficiently capable of releasing drug inside macrophages at a slower pace than the free drug, which was monitored by epi-fluorescence microscopy. Encapsulation of doxorubicin and mitomycin C into NPs also decreases cellular toxicity in mouse macrophages (J774.1A). PMID:22925019

A biomimetic hybrid nanoplatform for encapsulation and precisely controlled delivery of therasnostic agents

NASA Astrophysics Data System (ADS)

Wang, Hai; Agarwal, Pranay; Zhao, Shuting; Yu, Jianhua; Lu, Xiongbin; He, Xiaoming

2015-12-01

Nanoparticles have demonstrated great potential for enhancing drug delivery. However, the low drug encapsulation efficiency at high drug-to-nanoparticle feeding ratios and minimal drug loading content in nanoparticle at any feeding ratios are major hurdles to their widespread applications. Here we report a robust eukaryotic cell-like hybrid nanoplatform (EukaCell) for encapsulation of theranostic agents (doxorubicin and indocyanine green). The EukaCell consists of a phospholipid membrane, a cytoskeleton-like mesoporous silica matrix and a nucleus-like fullerene core. At high drug-to-nanoparticle feeding ratios (for example, 1:0.5), the encapsulation efficiency and loading content can be improved by 58 and 21 times, respectively, compared with conventional silica nanoparticles. Moreover, release of the encapsulated drug can be precisely controlled via dosing near infrared laser irradiation. Ultimately, the ultra-high (up to ~87%) loading content renders augmented anticancer capacity both in vitro and in vivo. Our EukaCell is valuable for drug delivery to fight against cancer and potentially other diseases.

Preparation and in vitro evaluation of heparin-loaded polymeric nanoparticles.

PubMed

Jiao, Y Y; Ubrich, N; Marchand-Arvier, M; Vigneron, C; Hoffman, M; Maincent, P

2001-01-01

Nanoparticles of a highly soluble macromolecular drug, heparin, were formulated with two biodegradable polymers (poly-E-caprolactone [PCL] and poly (D, L-lactic-co-glycolic-acid) 50/50 [PLAGA]) and two nonbiodegradable positively charged polymers (Eudragit RS and RL) by the double emulsion and solvent evaporation method, using a high-pressure homogenization device. The encapsulation efficiency and heparin release profiles were studied as a function of the type of polymers employed (alone or in combination) and the concentration of heparin. Optimal encapsulation efficiency was observed when 5000 IU of heparin were incorporated in the first emulsion. High drug entrapment efficiency was observed in both Eudragit RS and RL nanoparticles (60% and 98%, respectively), compared with PLAGA and PCL nanoparticles (<14%). The use of the two types of Eudragit in combination with PCL and PLAGA increased the encapsulation efficiency compared with these two biodegradable polymers used alone; however, the in vitro drug release was not modified and remained low. On the other hand, the addition of esterase to the dissolution medium resulted in a significant increase in heparin release. The in vitro biological activity of released heparin, evaluated by measuring the anti-Xa activity by a colorimetric assay, was conserved after the encapsulation process.

High loading efficiency and sustained release of siRNA encapsulated in PLGA nanoparticles: quality by design optimization and characterization.

PubMed

Cun, Dongmei; Jensen, Ditte Krohn; Maltesen, Morten Jonas; Bunker, Matthew; Whiteside, Paul; Scurr, David; Foged, Camilla; Nielsen, Hanne Mørck

2011-01-01

Poly(DL-lactide-co-glycolide acid) (PLGA) is an attractive polymer for delivery of biopharmaceuticals owing to its biocompatibility, biodegradability and outstanding controlled release characteristics. The purpose of this study was to understand and define optimal parameters for preparation of small interfering RNA (siRNA)-loaded PLGA nanoparticles by the double emulsion solvent evaporation method and characterize their properties. The experiments were performed according to a 2(5-1) fractional factorial design based on five independent variables: The volume ratio between the inner water phase and the oil phase, the PLGA concentration, the sonication time, the siRNA load and the amount of acetylated bovine serum albumin (Ac-BSA) in the inner water phase added to stabilize the primary emulsion. The effects on the siRNA encapsulation efficiency and the particle size were investigated. The most important factors for obtaining an encapsulation efficiency as high as 70% were the PLGA concentration and the volume ratio whereas the size was mainly affected by the PLGA concentration. The viscosity of the oil phase was increased at high PLGA concentration, which explains the improved encapsulation by stabilization of the primary emulsion and reduction of siRNA leakage to the outer water phase. Addition of Ac-BSA increased the encapsulation efficiency at low PLGA concentrations. The PLGA matrix protected siRNA against nuclease degradation, provided a burst release of surface-localized siRNA followed by a triphasic sustained release for two months. These results enable careful understanding and definition of optimal process parameters for preparation of PLGA nanoparticles encapsulating high amounts of siRNA with immediate and long-term sustained release properties. Copyright © 2010 Elsevier B.V. All rights reserved.

The Poisson distribution and beyond: methods for microfluidic droplet production and single cell encapsulation.

PubMed

Collins, David J; Neild, Adrian; deMello, Andrew; Liu, Ai-Qun; Ai, Ye

2015-09-07

There is a recognized and growing need for rapid and efficient cell assays, where the size of microfluidic devices lend themselves to the manipulation of cellular populations down to the single cell level. An exceptional way to analyze cells independently is to encapsulate them within aqueous droplets surrounded by an immiscible fluid, so that reagents and reaction products are contained within a controlled microenvironment. Most cell encapsulation work has focused on the development and use of passive methods, where droplets are produced continuously at high rates by pumping fluids from external pressure-driven reservoirs through defined microfluidic geometries. With limited exceptions, the number of cells encapsulated per droplet in these systems is dictated by Poisson statistics, reducing the proportion of droplets that contain the desired number of cells and thus the effective rate at which single cells can be encapsulated. Nevertheless, a number of recently developed actively-controlled droplet production methods present an alternative route to the production of droplets at similar rates and with the potential to improve the efficiency of single-cell encapsulation. In this critical review, we examine both passive and active methods for droplet production and explore how these can be used to deterministically and non-deterministically encapsulate cells.

Cassia Cinnamon Supplementation Reduces Peak Blood Glucose Responses but Does Not Improve Insulin Resistance and Sensitivity in Young, Sedentary, Obese Women.

PubMed

Gutierrez, Jean L; Bowden, Rodney G; Willoughby, Darryn S

2016-01-01

Cassia cinnamon has been suggested to lower blood glucose (BG) and serum insulin (SI) due to an improvement in insulin resistance (IR) and sensitivity (IS). This study compared the effects Cassia cinnamon had on calculated IR and IS values and BG and SI in response to an oral glucose tolerance test (OGTT) in young, sedentary, and obese women. On three separate days, 10 women had a fasted venous blood sample obtained. Participants were given 5 g of encapsulated placebo (PLC) or 5 g of encapsulated Cassia cinnamon bark (CASS). Three hours after the initial blood sample, another blood sample was obtained to calculate values for IS and IR. The participants then completed an OGTT by consuming a 75 g glucose solution. Blood was obtained 30, 60, 90, and 120 min following glucose ingestion. IS and IR were not significantly different between placebo and Cassia (p > .05). The peak BG concentration in response to the OGTT was significantly lower at the 30 min time point for CASS, as compared to PLC (140 ± 5.8 and 156 ± 5.2 mg/dL, p = .025); however, there was no significant difference between treatments for SI (p > .05). The area-under-the-curve responses for BG and SI were not significantly different between PLC and CASS (p > .05). This study suggests that a 5 g dose of Cassia cinnamon may reduce the peak BG response and improve glucose tolerance following an OGTT, but with no improvement in IS and IR in young, sedentary, obese women.

Encapsulation of enzyme via one-step template-free formation of stable organic-inorganic capsules: A simple and efficient method for immobilizing enzyme with high activity and recyclability.

PubMed

Huang, Renliang; Wu, Mengyun; Goldman, Mark J; Li, Zhi

2015-06-01

Enzyme encapsulation is a simple, gentle, and general method for immobilizing enzyme, but it often suffers from one or more problems regarding enzyme loading efficiency, enzyme leakage, mechanical stability, and recyclability. Here we report a novel, simple, and efficient method for enzyme encapsulation to overcome these problems by forming stable organic-inorganic hybrid capsules. A new, facile, one-step, and template-free synthesis of organic-inorganic capsules in aqueous phase were developed based on PEI-induced simultaneous interfacial self-assembly of Fmoc-FF and polycondensation of silicate. Addition of an aqueous solution of Fmoc-FF and sodium silicate into an aqueous solution of PEI gave a new class of organic-inorganic hybrid capsules (FPSi) with multi-layered structure in high yield. The capsules are mechanically stable due to the incorporation of inorganic silica. Direct encapsulation of enzyme such as epoxide hydrolase SpEH and BSA along with the formation of the organic-inorganic capsules gave high yield of enzyme-containing capsules (∼1.2 mm in diameter), >90% enzyme loading efficiency, high specific enzyme loading (158 mg protein g(-1) carrier), and low enzyme leakage (<3% after 48 h incubation). FPSi-SpEH capsules catalyzed the hydrolysis of cyclohexene oxide to give (1R, 2R)-cyclohexane-1,2-diol in high yield and concentration, with high specific activity (6.94 U mg(-1) protein) and the same high enantioselectivity as the free enzyme. The immobilized SpEH demonstrated also excellent operational stability and recyclability: retaining 87% productivity after 20 cycles with a total reaction time of 80 h. The new enzyme encapsulation method is efficient, practical, and also better than other reported encapsulation methods. © 2015 Wiley Periodicals, Inc.

Encapsulation efficiency of CdSe/ZnS quantum dots by liposomes determined by thermal lens microscopy

PubMed Central

Batalla, Jessica; Cabrera, Humberto; San Martín-Martínez, Eduardo; Korte, Dorota; Calderón, Antonio; Marín, Ernesto

2015-01-01

In this study the encapsulation of core shell carboxyl CdSe/ZnS quantum dots (QDs) by phospholipids liposome complexes is presented. It makes the quantum dots water soluble and photo-stable. Fluorescence self-quenching of the QDs inside the liposomes was observed. Therefore, the thermal lens microscopy (TLM) was found to be an useful tool for measuring the encapsulation efficiency of the QDs by the liposomes, for which an optimum value of 36% was determined. The obtained limit of detection (LOD) for determining QDs concentration by TLM was 0.13 nM. Moreover, the encapsulated QDs showed no prominent cytotoxicity toward Breast cancer cells line MDA-MB-231. This study was supported by UV-visible spectroscopy, high resolution transmission electron microscopy (HRTEM) and dynamic light scattering measurements (DLS). PMID:26504640

Encapsulation of docetaxel into PEGylated gold nanoparticles for vectorization to cancer cells.

PubMed

François, Alison; Laroche, Audrey; Pinaud, Noël; Salmon, Lionel; Ruiz, Jaime; Robert, Jacques; Astruc, Didier

2011-11-04

Encapsulation of docetaxel and its solubilization in water was carried out in PEGylated gold nanoparticles (AuNPs) as shown by 1H NMR (600 MHz) and UV/Vis spectroscopy and dynamic light scattering. Vectorization of PEGylated AuNP-encapsulated docetaxel was probed in vitro toward human colon carcinoma (HCT15) and human breast cancer (MCF7) cells. AuNPs alone presented no cytotoxicity toward either MCF7 or HCT15 adenocarcinoma cells. AuNP-docetaxel was found to be 2.5-fold more efficient than docetaxel alone against MCF7 cells, and the IC50 value of AuNP-docetaxel against HCT15 cells was lower than that of free docetaxel; the increased efficiency brought about by AuNP drug encapsulation was ∼1.5-fold. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhanced encapsulation of metoprolol tartrate with carbon nanotubes as adsorbent

NASA Astrophysics Data System (ADS)

Garala, Kevin; Patel, Jaydeep; Patel, Anjali; Dharamsi, Abhay

2011-12-01

A highly water-soluble antihypertensive drug, metoprolol tartrate (MT), was selected as a model drug for preparation of multi-walled carbon nanotubes (MWCNTs)-impregnated ethyl cellulose (EC) microspheres. The present investigation was aimed to increase encapsulation efficiency of MT with excellent adsorbent properties of MWCNTs. The unique surface area, stiffness, strength and resilience of MWCNTs have drawn much anticipation as carrier for highly water-soluble drugs. Carbon nanotubes drug adsorbate (MWCNTs:MT)-loaded EC microspheres were further optimized by the central composite design of the experiment. The effects of independent variables (MWCNTs:MT and EC:adsorbate) were evaluated on responses like entrapment efficiency (EE) and t 50 (time required for 50% drug release). The optimized batch was compared with drug alone EC microspheres. The results revealed high degree of improvement in encapsulation efficiency for MWCNTs:MT-loaded EC microspheres. In vitro drug release study exhibited complete release form drug alone microspheres within 15 h, while by the same time only 50-60% drug was released for MWCNTs-impregnated EC microspheres. The optimized batch was further characterized by various instrumental analyses such as scanning electron microscopy, powder X-ray diffraction and differential scanning calorimetry. The results endorse encapsulation of MWCNTs:MT adsorbate inside the matrix of EC microspheres, which might have resulted in enhanced encapsulation and sustained effect of MT. Hence, MWCNTs can be utilized as novel carriers for extended drug release and enhanced encapsulation of highly water-soluble drug, MT.

Optimisation of preparation conditions and properties of phytosterol liposome-encapsulating nattokinase.

PubMed

Dong, Xu-Yan; Kong, Fan-Pi; Yuan, Gang-You; Wei, Fang; Jiang, Mu-Lan; Li, Guang-Ming; Wang, Zhan; Zhao, Yuan-Di; Chen, Hong

2012-01-01

Phytosterol liposomes were prepared using the thin film method and used to encapsulate nattokinase (NK). In order to obtain a high encapsulation efficiency within the liposome, an orthogonal experiment (L9 (3)(4)) was applied to optimise the preparation conditions. The molar ratio of lecithin to phytosterols, NK activity and mass ratio of mannite to lecithin were the main factors that influenced the encapsulation efficiency of the liposomes. Based on the results of a single-factor test, these three factors were chosen for this study. We determined the optimum extraction conditions to be as follows: a molar ratio of lecithin to phytosterol of 2 : 1, NK activity of 2500 U mL⁻¹ and a mass ratio of mannite to lecithin of 3 : 1. Under these optimised conditions, an encapsulation efficiency of 65.25% was achieved, which agreed closely with the predicted result. Moreover, the zeta potential, size distribution and microstructure of the liposomes prepared were measured, and we found that the zeta potential was -51 ± 3 mV and the mean diameter was 194.1 nm. From the results of the scanning electron microscopy, we observed that the phytosterol liposomes were round and regular in shape and showed no aggregation.

Effect of drug loading method against the dissolution mechanism of encapsulated amoxicillin trihidrate drug in matrix of semi-IPN chitosan-poly (N-vinyl pyrrolidone) hydrogel with pore forming agent CaCO3

NASA Astrophysics Data System (ADS)

Nurjannah, Yanah; Budianto, Emil

2018-04-01

Heliobacter pylori (H.pylori) is a type of bacteria that causes inflammation in the lining of the stomach. The treatment of the bacterial infection by using conventional medicine which is amoxicillin trihidrate has a very short retention time in the stomach which is about 1-1,5 hours. Floating drug delivery system is expected to have a long retention time in the stomach so the efficiency of drug can be achieved. In this study, has been synthesized matrix of semi-IPN chitosan-Poly(N-vinil pyrrolidone) hydrogel with a pore-forming agent of CaCO3 under optimum conditions. Amoxicillin is encapsulated in a matrix hydrogel to be applied as a floating drug delivery system by in situ loading and post loading methods. The encapsulation efficiency and dissolution of in situ loading and post loading hydrogels are performed in vitro on gastric pH. In situ loading hydrogel shows higer percentage of encapsulation efficiency and dissolution compared to post loading hydrogel. The encapsulation efficiency of in situ and post loading hydrogels were 92,1% and 89,4%, respectively. The aim of drug dissolution by mathematical equation model is to know kinetics and the mecanism of dissolution. The kinetics release of in situ hydrogel tends to follow first order kinetics, while the post loading hydrogel follow the Higuchi model. The dissolution mecanism of hydrogels is erosion.

Antibiotic release from biodegradable PHBV microparticles.

PubMed

Sendil, D; Gürsel, I; Wise, D L; Hasirci, V

1999-05-20

For the treatment of periodontal diseases, design of a controlled release system seemed very appropriate for an effective, long term result. In this study a novel, biodegradable microbial polyester, poly(3-hydroxybutyrate-co-3-hydroxyvalerate), PHBV of various valerate contents containing a well established antibiotic, tetracycline, known to be effective against many of the periodontal disease related microorganisms, was used in the construction of a controlled release system. Tetracycline was loaded in the PHBV microspheres and microcapsules both in its acidic (TC) and in neutral form (TCN). Microcapsules of PHBV were prepared under different conditions using w/o/w double emulsion and their properties such as encapsulation efficiency, loading, release characteristics, and morphological properties were investigated. It was found that concentration of emulsifiers polyvinyl alcohol (PVA) and gelatin (varied between 0-4%) influenced the encapsulation efficiency appreciably. In order to increase encapsulation efficiency (from the obtained range of 18.1-30.1%) and slow down the release of the highly soluble tetracycline.HCl, it was neutralized with NaOH. Encapsulation efficiency of neutralized tetracycline was much higher (51.9-65.3%) due to the insoluble form of the drug used during encapsulation. The release behaviour of neither of the drugs was found to be of zero order. Rather the trends fitted reasonably well to Higuchi's approach for release from spherical micropheres. Biodegradability was not an appreciable parameter in the release from microcapsules because release was complete before any signs of degradation were observed.

Efficiencies of Dye-Sensitized Solar Cells using Ferritin-Encapsulated Quantum Dots with Various Staining Methods

NASA Astrophysics Data System (ADS)

Perez, Luis

Dye-sensitized solar cells (DSSC) have the potential to replace traditional and cost-inefficient crystalline silicon or ruthenium solar cells. This can only be accomplished by optimizing DSSC's energy efficiency. One of the major components in a dye-sensitized solar cell is the porous layer of titanium dioxide. This layer is coated with a molecular dye that absorbs sunlight. The research conducted for this paper focuses on the different methods used to dye the porous TiO2 layer with ferritin-encapsulated quantum dots. Multiple anodes were dyed using a method known as SILAR which involves deposition through alternate immersion in two different solutions. The efficiencies of DSSCs with ferritin-encapsulated lead sulfide dye deposited using SILAR were subsequently compared against the efficiencies produced by cells using the traditional immersion method. It was concluded that both methods resulted in similar efficiencies (? .074%) however, the SILAR method dyed the TiO2 coating significantly faster than the immersion method. On a related note, our experiments concluded that conducting 2 SILAR cycles yields the highest possible efficiency for this particular binding method. National Science Foundation.

Fatty acid binding proteins 4 and 5 in overweight prepubertal boys: effect of nutritional counselling and supplementation with an encapsulated fruit and vegetable juice concentrate.

PubMed

Canas, Jose A; Damaso, L; Hossain, J; Balagopal, P Babu

2015-01-01

Elevated fatty acid binding proteins (FABP) may play a role in obesity and co-morbidities. The role of nutritional interventions in modulating these levels remains unclear. The aim of this post hoc study was to determine the effect of overweight (OW) on FABP4 and FABP5 in boys in relation to indices of adiposity, insulin resistance and inflammation, and to investigate the effects of a 6-month supplementation with an encapsulated fruit and vegetable juice concentrate (FVJC) plus nutritional counselling (NC) on FABP levels. A post hoc analysis of a double-blind, randomised, placebo-controlled study of children recruited from the general paediatric population was performed. A total of thirty age-matched prepubertal boys (nine lean and twenty-one OW; aged 6-10 years) were studied. Patients received NC by a registered dietitian and were randomised to FVJC or placebo capsules for 6 months. FABP4, FABP5, glucose, insulin, homeostasis model assessment-insulin resistance (HOMA-IR), glucose-induced acute insulin response (AIR), lipid-corrected β-carotene (LCβC), adiponectin, leptin, high-sensitivity C-reactive protein (hs-CRP), IL-6 and body composition by dual-energy X-ray absorptiometry were determined before and after the intervention. FABP were higher (P < 0·01) in the OW v. lean boys and correlated directly with HOMA-IR, abdominal fat mass (AFM), hs-CRP, IL-6, and LCβC (P < 0·05 for all). FABP4 was associated with adiponectin and AIR (P < 0·05). FVJC plus NC reduced FABP4, HOMA-IR and AFM (P < 0·05 for all) but not FABP5. OW boys showed elevated FABP4 and FABP5, but only FABP4 was lowered by the FVJC supplement.

Fabrication, characterization and bioevaluation of silibinin loaded chitosan nanoparticles.

PubMed

Pooja, Deep; Babu Bikkina, Dileep J; Kulhari, Hitesh; Nikhila, Nalla; Chinde, Srinivas; Raghavendra, Y M; Sreedhar, B; Tiwari, Ashok K

2014-08-01

Silibinin is reported to possess multiple biological activities. However, its hydrophobic nature limits its bioavailability compromising in vivo biological activities. Nanoparticles-based delivery of such molecules has emerged as new technique to resolve these issues. Bio-degradable, compatible and adhesive nature of chitosan has recently attracted its suitability as a carrier for biologically active molecules. This study presents fabrication and characterization of chitosan-tripolyphosphate based encapsulation of silibinin. Various preparations of silibinin encapsulated chitosan-tripolyphosphate nanoparticles were studied for particle size, morphology, zeta-potential, and encapsulation efficiencies. Preparations were also evaluated for cytotoxic activities in vitro. The optimized silibinin loaded chitosan nanoparticles were of 263.7±4.1nm in particle size with zeta potential 37.4±1.57mV. Nanoparticles showed high silibinin encapsulation efficiencies (82.94±1.82%). No chemical interactions between silibinin and chitosan were observed in FTIR analysis. Powder X-ray diffraction analysis revealed transformed physical state of silibinin after encapsulation. Surface morphology and thermal behaviour were determined using TEM and DSC analysis. Encapsulated silibinin displayed increased dissolution and better cytotoxicity against human prostate cancer cells (DU145) than silibinin alone. Copyright © 2014 Elsevier B.V. All rights reserved.

Microencapsulation of Garcinia fruit extract by spray drying and its effect on bread quality.

PubMed

Ezhilarasi, Perumal Natarajan; Indrani, Dasappa; Jena, Bhabani Sankar; Anandharamakrishnan, Chinnaswamy

2014-04-01

(-)-Hydroxycitric acid (HCA) is the major acid present in the fruit rinds of certain species of Garcinia. HCA has been reported to have several health benefits. As HCA is highly hygroscopic in nature and thermally sensitive, it is difficult to incorporate in foodstuffs. Hence, Garcinia cowa fruit extract was microencapsulated using three different wall materials such as whey protein isolate (WPI), maltodextrin (MD) and a combination of whey protein isolate and maltodextrin (WPI + MD) by spray drying. Further, these microencapsulated powders were evaluated for their impact on bread quality and HCA retention. Maltodextrin (MD) encapsulates had higher free (86%) and net HCA (90%) recovery. Microencapsulates incorporated breads had enhanced qualitative characteristics and higher HCA content than water extract incorporated bread due to efficient encapsulation during bread baking. Comparatively, bread with MD encapsulates showed softer crumb texture, desirable sensory attributes with considerable volume and higher HCA content. The higher HCA contents of encapsulate incorporated breads were sufficient to claim for functionality of HCA in bread. Comparatively, MD had efficiently encapsulated Garcinia fruit extract during spray drying and bread baking. Spray drying proved to be an excellent encapsulation technique for incorporation into the food system. © 2013 Society of Chemical Industry.

Impact of culture conditions on β-carotene encapsulation using Yarrowia lipolytica cells

NASA Astrophysics Data System (ADS)

Dang, Tran Hai; Minh, Ho Thi Thu; Van Nhi, Tran Nguyen; Ngoc, Ta Thi Minh

2017-09-01

Yeast cell was reported as an effective natural preformed material for use in encapsulation of hydrophobic compounds. The encapsulation process was normally considered as passive transfer through cellular wall and cellular membrane. Beside solubility of hydrophobic compound in phospholipid membrane or plasmolysis, membrane characteristics of yeast cell which are differed between strains and influenced by culture conditions are main factors involving the accumulation of hydrophobic compound into yeast cell. In this study, the oleaginous yeast Yarrowia lipolytica was used as micro-container shell to encapsulate a high hydrophobic compound - β-carotene. Yeast cell was cultured under different conditions and wet yeast biomass was incubated with β-carotene which was dissolved in soybean oil overnight. β-carotene accumulation was then extracted and evaluated by UV-VIS spectrometry. Optimization of culture condition was investigated using the Box-Behnken model. β-carotene encapsulation efficiency in Y. lipolytica was showed to be affected by both pH of medium and agitation conditions. The highest β-carotene encapsulation efficiency was optimized at 42.8 μg/g with Y. lipolytica cultured at pH 4.5, medium volume equal to 115 ml and agitation speed at 211 rpm.

Investigation on Physicochemical Characteristics of a Nanoliposome-Based System for Dual Drug Delivery

NASA Astrophysics Data System (ADS)

Nam, Jae Hyun; Kim, So-Yeon; Seong, Hasoo

2018-04-01

Synergistic effects of multiple drugs with different modes of action are utilized for combinatorial chemotherapy of intractable cancers. Translation of in vitro synergistic effects into the clinic can be realized using an efficient delivery system of the drugs. Despite a few studies on nano-sized liposomes containing erlotinib (ERL) and doxorubicin (DOX) in a single liposome vesicle, reliable and reproducible preparation methods as well as physicochemical characteristics of a non-PEGylated nanoliposome co-encapsulated with ERL and DOX have not been yet elucidated. In this study, ERL-encapsulated nanoliposomes were prepared using the lipid film-hydration method. By ultrasonication using a probe sonicator, the liposome diameter was reduced to less than 200 nm. DOX was loaded into the ERL-encapsulated nanoliposomes using ammonium sulfate (AS)-gradient or pH-gradient method. Effects of DOX-loading conditions on encapsulation efficiency (EE) of the DOX were investigated to determine an efficient drug-loading method. In the EE of DOX, AS-gradient method was more effective than pH gradient. The dual drug-encapsulated nanoliposomes had more than 90% EE of DOX and 30% EE of ERL, respectively. Transmission electron microscopy and selected area electron diffraction analyses of the dual drug-encapsulated nanoliposomes verified the highly oriented DOX-sulfate crystals inside the liposome as well as the less oriented small crystals of ERL in the outermost region of the nanoliposome. The nanoliposomes were stable at different temperatures without an increase of the nanoliposome diameter. The dual drug-encapsulated nanoliposomes showed a time-differential release of ERL and DOX, implying proper sequential releases for their synergism. The preparation methods and the physicochemical characteristics of the dual drug delivery system contribute to the development of the optimal process and more advanced systems for translational researches.

Investigation of drug loading and in vitro release mechanisms of insulin-lauryl sulfate complex loaded PLGA nanoparticles.

PubMed

Shi, K; Cui, F; Yamamoto, H; Kawashima, Y

2008-12-01

Insulin, a water soluble peptide hormone, was hydrophobically ion-paired with sodium lauryl sulfate (SDS) at the stoichiometric molar ratio of 6:1. The obtained insulin-SDS complex precipitation was subsequently formulated in biodegradable poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles by a modified spontaneous emulsion solvent diffusion method. Compared with a conventional method for free insulin encapsulation, direct dissolution of SDS-paired insulin in the non-aqueous organic phase led to an increase in drug recovery from 42.5% to 89.6%. The more hydrophobic complex contributes to the improved affinity of insulin to the polymer matrix, resulting in a higher drug content in the nanoparticles. The drug loading was investigated by determining initial burst release at the first 30 min. The results showed that 64.8% of recovered drug were preferentially surface bound on complex loaded nanoparticles. The in vitro drug release was characterized by an initial burst and subsequent delayed release in dissolution media of deionized water and phosphate buffer saline (PBS). Compared with that in PBS, nanoparticles in deionized water medium presented very low initial burst release (15% vs. 65%) and incomplete cumulative release (25% vs. 90%) of the drug. In addition, dialysis experiments were performed to clarify the form of the released insulin in the dissolution media. The results suggested that the ion-pair complex was sensitive to ionic strength, insulin was released from the particular matrix as complex form and subsequently suffered dissociation from SDS in buffer saline. Moreover, the in vivo bioactivity of the SDS-paired insulin and nanoparticulate formulations were evaluated in mice by estimation of their blood sugar levels. The results showed that the bioactivity of insulin was unaltered after the ion-pairing process.

Microencapsulation of Nigella sativa oleoresin by spray drying for food and nutraceutical applications.

PubMed

Edris, Amr E; Kalemba, Danuta; Adamiec, Janusz; Piątkowski, Marcin

2016-08-01

Oleoresin of Nigella sativa L. (Black cumin) was obtained from the seeds using hexane extraction at room temperature. The oleoresin was emulsified in an aqueous solution containing gum Arabic/maltodextrin (1:1 w/w) and then encapsulated in powder form by spray drying. The characteristics of the obtained powder including moisture content, bulk density, wettability, morphology, encapsulation efficiency were evaluated. The effect of the spray drying on the chemical composition of the volatile oil fraction of N. sativa oleoresin was also evaluated using gas chromatographic-mass spectroscopic analysis. Results indicated that the encapsulation efficiency of the whole oleoresin in the powder can range from 84.2±1.5% to 96.2±0.2% depending on the conditions of extracting the surface oil from the powder. On the other hand the encapsulation efficiency of the volatile oil fraction was 86.2% ±4.7. The formulated N. sativa L. oleoresin powder can be used in the fortification of processed food and nutraceuticals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nanomaterial Solutions for the Protection of Insulin Producing Beta Cells

NASA Astrophysics Data System (ADS)

Atchison, Nicole Ann

Islet transplantation is a promising treatment for type 1 diabetes. However, even with the many successes, islet transplantation has yet to reach its full potential. Limited islet sources, loss of cell viability during isolation and culture, and post-transplant graft loss are a few of the issues preventing extensive use of islet transplantation. The application of biomaterial systems to alleviate some of the stresses affecting islet viability has led to improvements in isolation and transplantation outcomes, but problems persist. In this work we approach two distinct issues affecting islet viability; ischemic conditions and immunological attack post-transplant. Ischemic conditions have been linked to a loss of islet graft function and occur during organ preservation, islet isolation and culture, and after islets are transplanted. We show that liposomal delivery of adenosine triphosphate (ATP) to beta cells can limit cell death and loss of function in ischemic conditions. We demonstrate that by functionalizing liposomes with the fibronectin-mimetic peptide PR_b, delivery of liposomes to porcine islets and rat beta cells is increased compared to nontargeted controls. Additionally, liposomes are shown to protect by providing both ATP and lipids to the ischemic cells. The delivery of ATP was investigated here but application of PR_b functionalized liposomes could be extended to other interesting cargos as well. The second area of investigation involves encapsulation of islets with silica nanoparticles to create a permselective barrier. Silica nanoparticles are an interesting material for encapsulation given their ability to be fine-tuned and further functionalized. We demonstrate that size-tunable, fluorescent silica nanoparticles can be assembled layer-by-layer on the surface of cells and that silica nanoparticle encapsulated islets are able to secrete insulin in response to a glucose challenge.

Needle-free injection of insulin powder: delivery efficiency and skin irritation assessment.

PubMed

Li, Chun-yu; Wang, Zhe-wei; Tu, Can; Wang, Jia-bo; Jiang, Bing-qian; Li, Qi; Zeng, Ling-na; Ma, Zhi-jie; Zhang, Ping; Zhao, Yan-ling; Zhang, Ya-ming; Yan, Dan; Tan, Rui; Xiao, Xiao-he

2014-10-01

Insulin is widely used in treating diabetes, but still needs to be administered by needle injection. This study investigated a new needle-free approach for insulin delivery. A portable powder needleless injection (PNI) device with an automatic mechanical unit was designed. Its efficiency in delivering insulin was evaluated in alloxan-induced diabetic rabbits. The skin irritation caused by the device was investigated and the results were analyzed in relation to aerodynamic parameters. Inorganic salt-carried insulin powders had hypoglycemic effects, while raw insulin powders were not effective when delivered by PNI, indicating that salt carriers play an important role in the delivery of insulin via PNI. The relative delivery efficiency of phosphate-carried insulin powder using the PNI device was 72.25%. A safety assessment test showed that three key factors (gas pressure, cylinder volume, and nozzle distance) were related to the amount of skin irritation caused by the PNI device. Optimized injection conditions caused minimal skin lesions and are safe to use in practice. The results suggest that PNI has promising prospects as a novel technology for delivering insulin and other biological drugs.

Needle-free injection of insulin powder: delivery efficiency and skin irritation assessment*

PubMed Central

Li, Chun-yu; Wang, Zhe-wei; Tu, Can; Wang, Jia-bo; Jiang, Bing-qian; Li, Qi; Zeng, Ling-na; Ma, Zhi-jie; Zhang, Ping; Zhao, Yan-ling; Zhang, Ya-ming; Yan, Dan; Tan, Rui; Xiao, Xiao-he

2014-01-01

Insulin is widely used in treating diabetes, but still needs to be administered by needle injection. This study investigated a new needle-free approach for insulin delivery. A portable powder needleless injection (PNI) device with an automatic mechanical unit was designed. Its efficiency in delivering insulin was evaluated in alloxan-induced diabetic rabbits. The skin irritation caused by the device was investigated and the results were analyzed in relation to aerodynamic parameters. Inorganic salt-carried insulin powders had hypoglycemic effects, while raw insulin powders were not effective when delivered by PNI, indicating that salt carriers play an important role in the delivery of insulin via PNI. The relative delivery efficiency of phosphate-carried insulin powder using the PNI device was 72.25%. A safety assessment test showed that three key factors (gas pressure, cylinder volume, and nozzle distance) were related to the amount of skin irritation caused by the PNI device. Optimized injection conditions caused minimal skin lesions and are safe to use in practice. The results suggest that PNI has promising prospects as a novel technology for delivering insulin and other biological drugs. PMID:25294378

Pancreatic cell immobilization in alginate beads produced by emulsion and internal gelation.

PubMed

Hoesli, Corinne A; Raghuram, Kamini; Kiang, Roger L J; Mocinecová, Dušana; Hu, Xiaoke; Johnson, James D; Lacík, Igor; Kieffer, Timothy J; Piret, James M

2011-02-01

Alginate has been used to protect transplanted pancreatic islets from immune rejection and as a matrix to increase the insulin content of islet progenitor cells. The throughput of alginate bead generation by the standard extrusion and external gelation method is limited by the rate of droplet formation from nozzles. Alginate bead generation by emulsion and internal gelation is a scaleable alternative that has been used with biological molecules and microbial cells, but not mammalian cells. We describe the novel adaptation of this process to mammalian cell immobilization. After optimization, the emulsion process yielded 90 ± 2% mouse insulinoma 6 (MIN6) cell survival, similar to the extrusion process. The MIN6 cells expanded at the same rate in both bead types to form pseudo-islets with increased glucose stimulation index compared to cells in suspension. The emulsion process was suitable for primary pancreatic exocrine cell immobilization, leading to 67 ± 32 fold increased insulin expression after 10 days of immobilized culture. Due to the scaleability and broad availability of stirred mixers, the emulsion process represents an attractive option for laboratories that are not equipped with extrusion-based cell encapsulators, as well as for the production of immobilized or encapsulated cellular therapeutics on a clinical scale. © 2010 Wiley Periodicals, Inc.

Encapsulation of black carrot juice using spray and freeze drying.

PubMed

Murali, S; Kar, Abhijit; Mohapatra, Debabandya; Kalia, Pritam

2015-12-01

Black carrot juice extracted using pectinase enzyme was encapsulated in three different carrier materials (maltodextrin 20DE, gum arabic and tapioca starch) using spray drying at four inlet temperatures (150, 175, 200 and 225 ℃) and freeze drying at a constant temperature of - 53 ℃ and vacuum of 0.22-0.11 mbar with the constant feed mixture. The products were analyzed for total anthocyanin content, antioxidant activity, water solubility index, encapsulation efficiency and total colour change. For both the drying methods followed in this study, maltodextrin 20DE as the carrier material has proven to be better in retaining maximum anthocyanin and antioxidant activity compared to gum arabic and tapioca starch. The best spray dried product, was obtained at 150 ℃. The most acceptable was the freeze dried product with maximum anthocyanin content, antioxidant activity, water solubility index, encapsulation efficiency and colour change. © The Author(s) 2014.

Preparation of inorganic/organic polymer hybrid microcapsules with high encapsulation efficiency by an electrospray technique.

PubMed

Yunoki, Ayumi; Tsuchiya, Eiko; Fukui, Yu; Fujii, Akihiro; Maruyama, Tatsuo

2014-08-13

Microcapsules composed of calcium phosphate and chitosan were prepared in a single step by electrospraying. An aqueous solution containing calcium chloride and chitosan was electrosprayed into a phosphate solution to form a calcium phosphate shell on the sprayed droplets. The resulting microcapsules were 350 μm in average diameter. Investigation using fluorescently labeled chitosan and XRD measurements revealed that the shells of the microcapsules were composed of calcium phosphate (mainly hydroxyapatite) and chitosan. Instead of chitosan, poly(diallyldimethylammonium chloride) and polyethylene glycol were also available for microcapsule production by electrospraying. Variations in the electrospraying conditions resulted in a variety of microcapsule shapes. Various types of substrates were successfully encapsulated in microcapsules with a high encapsulation efficiency (more than 80%). Finally, we succeeded in the encapsulation of living yeast cells in microcapsules, and observed their growth within these microcapsules.

Analysis of Thermal Energy Storage Tank by ANSYS and Comparison with Experimental Results to Improve its Thermal Efficiency

NASA Astrophysics Data System (ADS)

Beemkumar, N.; Karthikeyan, A.; Shiva Keshava Reddy, Kota; Rajesh, Kona; Anderson, A.

2017-05-01

The discontinuous temperament of the solar power forces to consider about the energy storage. This work is to analyze the tank, amount of energy stored and its storage time. The thermal and flow analysis has been done by ANSYS with different set temperature values. The experimentation is done for various encapsulating materials with different phase change material (PCM). Findings: The results obtained from experimental work are compared with ANSYS output. The competence of the TES is calculated and further improvements are made to enhance its performance. During charging process the temperature distribution from heat transfer fluid (HTF) to PCM is maximum in copper encapsulations followed by aluminium encapsulations and brass encapsulations. The comparison shows only when the electrical power as an input source. The efficient way of captivating solar energy could be a better replacement for electrical input.

Encapsulation of ethylhexyl methoxycinnamate, a light-sensitive UV filter, in lipid nanoparticles.

PubMed

Durand, L; Habran, N; Henschel, V; Amighi, K

2010-01-01

The aim of this study was to encapsulate ethylhexyl methoxycinnamate (EMC), a commonly used UVB filter, in a solid lipid matrix in order to obtain microparticles and then nanoparticles to reduce its photo-instability under UV light exposure. Glyceryl behenate, rice bran wax and ozokerite were investigated for encapsulating EMC. The suspensions of nanoparticles contained 70% encapsulated EMC (relative to the lipid mass). The absorbance level at 310 nm of suspensions containing nanoparticles was more than twice that of those containing microparticles. So, decreasing the size of particles improved the efficiency of light protection, regardless of the lipid material used. Moreover, free EMC presented a 30% loss of its efficiency after 2 h of irradiation, whereas the three NLC formulations showed a loss of absorbency between 10% and 21%. The in vitro cutaneous penetration test did not show a higher potential penetration for EMC contained in nanosuspensions compared to free EMC.

Nano-encapsulations liberated from barley protein microparticles for oral delivery of bioactive compounds.

PubMed

Wang, Ruoxi; Tian, Zhigang; Chen, Lingyun

2011-03-15

Novel microparticles (3-5 μm) were created by pre-emulsifying barley proteins with a homogenizer followed a microfluidizer system. These microparticles exhibited a high oil carrying capacity (encapsulation efficiency, 93-97%; loading efficiency, 46-49%). Microparticle degradation and bioactive compound release behaviours were studied in the simulated gastro-intestinal (GI) tract. The data revealed that nano-encapsulations (20-30 nm) were formed as a result of enzymatic degradation of barley protein microparticle bulk matrix in the simulated gastric tract. These nano-encapsulations delivered β-carotene to a simulated human intestinal tract intact, where they were degraded by pancreatic enzymes and steadily released the β-carotene. These uniquely structured microparticles may provide a new strategy for the nutraceutical and pharmaceutical industries to develop targeted delivery systems for lipophilic bioactive compounds. Copyright © 2011 Elsevier B.V. All rights reserved.

A novel system for water soluble protein encapsulation with high efficiency: "micelles enhanced" polyelectrolyte capsules.

PubMed

Li, Xiaodong; Li, Xiaohui; Zhang, Jianxiang; Zhao, Shifang; Shen, Jiacong

2008-06-01

Novel "micelles enhanced" polyelectrolyte (PE) capsules based on functional templates of hybrid calcium carbonate were fabricated. Evidences suggested that the structure of capsule wall was different from that of conventional PE capsules, and the wall permeability of these PE capsules changed significantly. Lysozyme, a positively charged protein in neutral solution, was studied as a model protein to be encapsulated into the "micelles enhanced" PE capsules. Confocal laser scanning microscope was used to observe the entrapping process in real time, while UV-Vis spectroscope and scanning force microscope measurements suggested the high efficiency of encapsulation. In addition, the fluorescence recovery after photobleaching technique was employed to determine the existence form of deposited molecules. Further studies showed even negatively charged water-soluble peptides or proteins can be encapsulated into these hybrid capsules by modulating the pH value in bulk solution under its isoelectronic point as well. Copyright 2007 Wiley Periodicals, Inc.

Encapsulation of basic fibroblast growth factor by polyelectrolyte multilayer microcapsules and its controlled release for enhancing cell proliferation.

PubMed

She, Zhen; Wang, Chunxia; Li, Jun; Sukhorukov, Gleb B; Antipina, Maria N

2012-07-09

Basic fibroblast growth factor (FGF2) is an important protein for cellular activity and highly vulnerable to environmental conditions. FGF2 protected by heparin and bovine serum albumin was loaded into the microcapsules by a coprecipitation-based layer-by-layer encapsulation method. Low cytotoxic and biodegradable polyelectrolytes dextran sulfate and poly-L-arginine were used for capsule shell assembly. The shell thickness-dependent encapsulation efficiency was measured by enzyme-linked immunosorbent assay. A maximum encapsulation efficiency of 42% could be achieved by microcapsules with a shell thickness of 14 layers. The effects of microcapsule concentration and shell thickness on cytotoxicity, FGF2 release kinetics, and L929 cell proliferation were evaluated in vitro. The advantage of using microcapsules as the carrier for FGF2 controlled release for enhancing L929 cell proliferation was analyzed.

β-Cell–Specific Protein Kinase A Activation Enhances the Efficiency of Glucose Control by Increasing Acute-Phase Insulin Secretion

PubMed Central

Kaihara, Kelly A.; Dickson, Lorna M.; Jacobson, David A.; Tamarina, Natalia; Roe, Michael W.; Philipson, Louis H.; Wicksteed, Barton

2013-01-01

Acute insulin secretion determines the efficiency of glucose clearance. Moreover, impaired acute insulin release is characteristic of reduced glucose control in the prediabetic state. Incretin hormones, which increase β-cell cAMP, restore acute-phase insulin secretion and improve glucose control. To determine the physiological role of the cAMP-dependent protein kinase (PKA), a mouse model was developed to increase PKA activity specifically in the pancreatic β-cells. In response to sustained hyperglycemia, PKA activity potentiated both acute and sustained insulin release. In contrast, a glucose bolus enhanced acute-phase insulin secretion alone. Acute-phase insulin secretion was increased 3.5-fold, reducing circulating glucose to 58% of levels in controls. Exendin-4 increased acute-phase insulin release to a similar degree as PKA activation. However, incretins did not augment the effects of PKA on acute-phase insulin secretion, consistent with incretins acting primarily via PKA to potentiate acute-phase insulin secretion. Intracellular calcium signaling was unaffected by PKA activation, suggesting that the effects of PKA on acute-phase insulin secretion are mediated by the phosphorylation of proteins involved in β-cell exocytosis. Thus, β-cell PKA activity transduces the cAMP signal to dramatically increase acute-phase insulin secretion, thereby enhancing the efficiency of insulin to control circulating glucose. PMID:23349500

Preparation and Evaluation of Multiple Nanoemulsions Containing Gadolinium (III) Chelate as a Potential Magnetic Resonance Imaging (MRI) Contrast Agent.

PubMed

Sigward, Estelle; Corvis, Yohann; Doan, Bich-Thuy; Kindsiko, Kadri; Seguin, Johanne; Scherman, Daniel; Brossard, Denis; Mignet, Nathalie; Espeau, Philippe; Crauste-Manciet, Sylvie

2015-09-01

The objective was to develop, characterize and assess the potentiality of W1/O/W2 self-emulsifying multiple nanoemulsions to enhance signal/noise ratio for Magnetic Resonance Imaging (MRI). For this purpose, a new formulation, was designed for encapsulation efficiency and stability. Various methods were used to characterize encapsulation efficiency ,in particular calorimetric methods (Differential Scanning Calorimetry (DSC), thermogravimetry analysis) and ultrafiltration. MRI in vitro relaxivities were assessed on loaded DTPA-Gd multiple nanoemulsions. Characterization of the formulation, in particular of encapsulation efficiency was a challenge due to interactions found with ultrafiltration method. Thanks to the specifically developed DSC protocol, we were able to confirm the formation of multiple nanoemulsions, differentiate loaded from unloaded nanoemulsions and measure the encapsulation efficiency which was found to be quite high with a 68% of drug loaded. Relaxivity studies showed that the self-emulsifying W/O/W nanoemulsions were positive contrast agents, exhibiting higher relaxivities than those of the DTPA-Gd solution taken as a reference. New self-emulsifying multiple nanoemulsions that were able to load satisfactory amounts of contrasting agent were successfully developed as potential MRI contrasting agents. A specific DSC protocol was needed to be developed to characterize these complex systems as it would be useful to develop these self-formation formulations.

Preparation, characterization, and in vitro release study of albendazole-encapsulated nanosize liposomes

PubMed Central

Panwar, Preety; Pandey, Bhumika; Lakhera, P C; Singh, K P

2010-01-01

The purpose of the present study was to formulate effective and controlled release albendazole liposomal formulations. Albendazole, a hydrophobic drug used for the treatment of hydatid cysts, was encapsulated in nanosize liposomes. Rapid evaporation method was used for the preparation of albendazole-encapsulated conventional and PEGylated liposomes consisting of egg phosphatidylcholine (PC) and cholesterol (CH) in the molar ratios of (6:4) and PC:CH: polyethylene glycol (PEG) (5:4:1), respectively. In this study, PEGylated and conventional liposomes containing albendazole were prepared and their characteristics, such as particle size, encapsulation efficiency, and in vitro drug release were investigated. The drug encapsulation efficiency of PEGylated and conventional liposomes was 81% and 72%, respectively. The biophysical characterization of both conventional and PEG-coated liposomes were done by transmission electron microscopy and UV-vis spectrophotometry. Efforts were made to study in vitro release of albendazole. The drug release rate showed decrease in albendazole release in descending order: free albendazole, albendazole-loaded conventional liposomes, and least with albendazole-loaded PEG-liposomes. Biologically relevant vesicles were prepared and in vitro release of liposome-entrapped albendazole was determined. PMID:20309396

Factors influencing the properties and performance of microcapsules for immunoprotection of pancreatic islets.

PubMed

van Schilfgaarde, R; de Vos, P

1999-01-01

There are several approaches of immunoprotection of pancreatic islets for the purpose of successful allo- or xenotransplantation in the absence of immunosuppressive medication. Extravascular approaches are either macroencapsulation (large numbers of islets together in one device) or microencapsulation. The latter approach is to envelop each individual islet in a semipermeable immunoprotective capsule. Quite promising results have been achieved with polylysine-alginate microencapsulated islet grafts in rodents, but clinical application is still restricted to a very small number of cases. Relevant considerations regard the following aspects. The biocompatibility of the microcapsules is influenced by the chemical composition of the materials applied and by mechanical factors related to the production process. With purified instead of crude alginates, the percentage of capsules with fibrotic overgrowth is reduced to approximately ten percent, and the remaining overgrowth is mainly explained by mechanical factors, i.e. inadequate encapsulation of individual islets. Even with purified alginates, however, the duration of encapsulated graft function is limited to a period of six to twenty weeks. Obviously, other factors than bioincompatibility play a role, which factors have to be identified. The limited duration of graft survival cannot be explained by rejection since, in rats, survival times of encapsulated isografts are similar, if not identical, to those of encapsulated allografts. An important factor is probably insufficient nutrition as a consequence of insufficient blood supply of the encapsulated and thus isolated islet. This also influences the functional performance of encapsulated islet grafts. Although normoglycemia can be readily obtained in streptozotocin diabetic rat recipients, glucose tolerance remains severely impaired, as a consequence of an insufficient increase of insulin levels in response to intravenous or oral glucose challenge. Important factors are the characteristics of the capsules applied in view of optimal diffusion kinetics, and the fact that an encapsulated islet graft can only be implanted in the peritoneal cavity because of its volume. Further studies should focus on finding a practically applicable method to reduce the barrier between encapsulated islets and the bloodstream, in order to improve both the functional performance and the survival of encapsulated islet grafts.

Comparison of Different Encapsulating Adhesives to Enhance the Efficiencies and Lifetimes of Polymeric Solar Cells

NASA Astrophysics Data System (ADS)

Chung, Ming-Hua; Chen, Chen-Ming; Hsieh, Tsung-Eong; Tang, Rong-Ming; Tsai, Yu Sheng; Chu, Wei-Ping; Liu, Mark O.; Juang, Fuh-Shyang

2009-04-01

Polymeric solar cells (PSCs) with a derivative of C60 [[6,6]-phenyl C61-butyric acid methyl ester (PCBM)], and 3-hexylthiophene (P3HT) as active layers have been fabricated. The PSC devices were also packaged with glass and novel UV glues to improve their lifetimes and power conversion efficiencies (PCEs). After encapsulation with UV glue I, II, and III, the PCEs of PSCs reached 4, 4.82, and 6%, respectively, and their half-lifetimes increased to 16-18, 26-28, and 90 h, respectively, while the PCEs and half-lifetimes of PSCs without encapsulation were 3.76% and 2.5 h, respectively.

High hydrostatic pressure encapsulation of doxorubicin in ferritin nanocages with enhanced efficiency.

PubMed

Wang, Qi; Zhang, Chun; Liu, Liping; Li, Zenglan; Guo, Fangxia; Li, Xiunan; Luo, Jian; Zhao, Dawei; Liu, Yongdong; Su, Zhiguo

2017-07-20

Human ferritin (HFn) nanocaging is becoming an appealing platform for anticancer drugs delivery. However, protein aggregation always occurs during the encapsulation process, resulting in low production efficiency. A new approach using high hydrostatic pressure (HHP) was explored in this study to overcome the problem of loading doxorubicin (DOX) in HFn. At the pressure of 500MPa and pH 5.5, DOX molecules were found to be encapsulated into HFn. Meanwhile, combining it with an additive of 20mM arginine completely inhibited precipitation and aggregation, resulting in highly monodispersed nanoparticles with almost 100% protein recovery. Furthermore, stepwise decompression and incubation of the complex in atmospheric pressure at pH 7.4 for another period could further increase the DOX encapsulation ratio. The HFn-DOX nanoparticles (NPs) showed similar morphology and structural features to the hollow cage and no notable drug leakage occurred for HFn-DOX NPs when stored at 4°C and pH 7.4 for two weeks. HFn-DOX NPs prepared through HHP also showed significant cytotoxicity in vitro and higher antitumor bioactivity in vivo than naked DOX. Moreover, This HHP encapsulation strategy could economize on DOX that was greatly wasted during the conventional preparation process simply through a desalting column. These results indicated that HHP could offer a feasible approach with high efficiency for the production of HFn-DOX NPs. Copyright © 2017 Elsevier B.V. All rights reserved.

Immunological Challenges Facing Translation of Alginate Encapsulated Porcine Islet Xenotransplantation to Human Clinical Trials.

PubMed

Krishnan, Rahul; Ko, David; Foster, Clarence E; Liu, Wendy; Smink, A M; de Haan, Bart; De Vos, Paul; Lakey, Jonathan R T

2017-01-01

Transplantation of alginate-encapsulated islets has the potential to treat patients suffering from type I diabetes, a condition characterized by an autoimmune attack against insulin-secreting beta cells. However, there are multiple immunological challenges associated with this procedure, all of which must be adequately addressed prior to translation from trials in small animal and nonhuman primate models to human clinical trials. Principal threats to graft viability include immune-mediated destruction triggered by immunogenic alginate impurities, unfavorable polymer composition and surface characteristics, and release of membrane-permeable antigens, as well as damage associated molecular patterns (DAMPs) by the encapsulated islets themselves. The lack of standardization of significant parameters of bioencapsulation device design and manufacture (i.e., purification protocols, surface-modification grafting techniques, alginate composition modifications) between labs is yet another obstacle that must be overcome before a clinically effective and applicable protocol for encapsulating islets can be implemented. Nonetheless, substantial progress is being made, as is evident from prolonged graft survival times and improved protection from immune-mediated graft destruction reported by various research groups, but also with regard to discoveries of specific pathways involved in explaining observed outcomes. Progress in the latter is essential for a comprehensive understanding of the mechanisms responsible for the varying levels of immunogenicity of certain alginate devices. Successful translation of encapsulated islet transplantation from in vitro and animal model testing to human clinical trials hinges on application of this knowledge of the pathways and interactions which comprise immune-mediated rejection. Thus, this review not only focuses on the different factors contributing to provocation of the immune reaction by encapsulated islets, but also on the defining characteristics of the response itself.

Novel chitosan film embedded with liposome-encapsulated phage for biocontrol of Escherichia coli O157:H7 in beef.

PubMed

Cui, Haiying; Yuan, Lu; Lin, Lin

2017-12-01

In recent years, phages used for the reduction of pathogenic bacteria have fostered many attentions, but they are liable to lost bioactivity in food due to the presence of acidic compounds, enzymes and evaporite materials. To improve the stability of phages, a chitosan edible film containing liposome-encapsulated phage was engineered in the present study. The characteristics of liposome-encapsulated phage and the chitosan film containing liposome-encapsulated phage were investigated. The encapsulation efficiency of phages in liposome reached 57.66±0.12%. Besides, the desirable physical properties of chitosan film were obtained. The chitosan film embedded with liposome-encapsulated phage exhibited high antibacterial activity against Escherichia coli O157:H7, without the impact on the sensory properties of beef. Hence, chitosan film containing liposome-encapsulated phage could be a promising antibacterial packaging for beef preservation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Production of Methanol from Methane by Encapsulated Methylosinus sporium.

PubMed

Patel, Sanjay K S; Jeong, Jae-Hoon; Mehariya, Sanjeet; Otari, Sachin V; Madan, Bharat; Haw, Jung Rim; Lee, Jung-Kul; Zhang, Liaoyuan; Kim, In-Won

2016-12-28

Massive reserves of methane (CH₄) remain unexplored as a feedstock for the production of liquid fuels and chemicals, mainly because of the lack of economically suitable and sustainable strategies for selective oxidation of CH₄ to methanol. The present study demonstrates the bioconversion of CH₄ to methanol mediated by Type I methanotrophs, such as Methylomicrobium album and Methylomicrobium alcaliphilum . Furthermore, immobilization of a Type II methanotroph, Methylosinus sporium , was carried out using different encapsulation methods, employing sodium-alginate (Na-alginate) and silica gel. The encapsulated cells demonstrated higher stability for methanol production. The optimal pH, temperature, and agitation rate were determined to be pH 7.0, 30°C, and 175 rpm, respectively, using inoculum (1.5 mg of dry cell mass/ml) and 20% of CH₄ as a feed. Under these conditions, maximum methanol production (3.43 and 3.73 mM) by the encapsulated cells was recorded. Even after six cycles of reuse, the Na-alginate and silica gel encapsulated cells retained 61.8% and 51.6% of their initial efficiency for methanol production, respectively, in comparison with the efficiency of 11.5% observed in the case of free cells. These results suggest that encapsulation of methanotrophs is a promising approach to improve the stability of methanol production.

Prolonged survival and improved glycemia in BioBreeding diabetic rats after early sustained exposure to glucagon-like peptide 1.

PubMed

Yanay, Ofer; Moralejo, Daniel; Kernan, Kelly; Brzezinski, Margaret; Fuller, Jessica M; Barton, Randall W; Lernmark, Ake; Osborne, William R

2010-06-01

Type 1 diabetes (T1D) in both humans and BioBreeding (BB) rats is an autoimmune disease that results in complete destruction of islets and insulin dependency for life. Glucagon-like peptide 1 (GLP-1) promotes beta cell proliferation and neogenesis and has a potent insulinotropic effect. We hypothesized that the expression of GLP-1 before disease onset would increase islet mass, delay diabetes and prolong survival of BB rats. Vascular smooth muscle cells retrovirally transduced to secrete GLP-1 were seeded into TheraCyte encapsulation devices, implanted subcutaneously, and rats were monitored for diabetes. In untreated control rats, plasma GLP-1 levels were 34.5-39.5 pmol/l, whereas, in treated rats, plasma levels were elevated, in the range 90-250.4 pmol/l. Hypoglycemia was not detected and this was anticipated from the glucose-regulated action of GLP-1. Diabetes onset (mean + or - SEM) in untreated rats occurred at 56.5 + or - 0.6 days (n = 6) and, in GLP-1-treated rats, was delayed until 76.4 + or - 3.3 days (n = 5) (p < 0.001). After disease onset, untreated control rats showed a rapid weight loss and elevated blood glucose (>650 mg/dl) and did not survive beyond 11 days. At 5 days after diabetes onset, insulin-secreting islets were absent in untreated rats. By contrast, treated rats maintained weight for up to 143 days of age and showed insulin-secreting beta cells. Sustained GLP-1 expression delivered by encapsulated cells before diabetes onset in BB rats showed an improved clinical outcome, suggesting the potential for treating patients using long lasting GLP-1 analogs.

Self-assembled lecithin/chitosan nanoparticles for oral insulin delivery: preparation and functional evaluation.

PubMed

Liu, Liyao; Zhou, Cuiping; Xia, Xuejun; Liu, Yuling

2016-01-01

Here, we investigated the formation and functional properties of self-assembled lecithin/chitosan nanoparticles (L/C NPs) loaded with insulin following insulin-phospholipid complex preparation, with the aim of developing a method for oral insulin delivery. Using a modified solvent-injection method, insulin-loaded L/C NPs were obtained by combining insulin-phospholipid complexes with L/C NPs. The nanoparticle size distribution was determined by dynamic light scattering, and morphologies were analyzed by cryogenic transmission electron microscopy. Fourier transform infrared spectroscopy analysis was used to disclose the molecular mechanism of prepared insulin-loaded L/C NPs. Fast ultrafiltration and a reversed-phase high-performance liquid chromatography assay were used to separate free insulin from insulin entrapped in the L/C NPs, as well as to measure the insulin-entrapment and drug-loading efficiencies. The in vitro release profile was obtained, and in vivo hypoglycemic effects were evaluated in streptozotocin-induced diabetic rats. Our results indicated that insulin-containing L/C NPs had a mean size of 180 nm, an insulin-entrapment efficiency of 94%, and an insulin-loading efficiency of 4.5%. Cryogenic transmission electron microscopy observations of insulin-loaded L/C NPs revealed multilamellar structures with a hollow core, encircled by several bilayers. In vitro analysis revealed that insulin release from L/C NPs depended on the L/C ratio. Insulin-loaded L/C NPs orally administered to streptozotocin-induced diabetic rats exerted a significant hypoglycemic effect. The relative pharmacological bioavailability following oral administration of L/C NPs was 6.01%. With the aid of phospholipid-complexation techniques, some hydrophilic peptides, such as insulin, can be successfully entrapped into L/C NPs, which could improve oral bioavailability, time-dependent release, and therapeutic activity.

Vacuum-free laminated top electrode with conductive tapes for scalable manufacturing of efficient perovskite solar cells

DOE PAGES

Shao, Yuchuan; Wang, Qi; Dong, Qingfeng; ...

2015-06-25

The efficiency of organometal trihalide perovskites (OTP) solar cells have reached that parity of single crystal silicon, and its nature abundant raw material and solution-process capability promise a bright future for commercialization. However, the vacuum based techniques for metal electrode deposition and additional encapsulation layer increase the cost of the perovskite solar cells dramatically and impede their commercialization process. Here, we report a vacuum-free low temperature lamination technique to fabricate the top electrode by commercial conductive tapes (C-tape). The simple fabrication method yields good quality contact and high efficiency device of 12.7%. The C-tapes also encapsulated the devices effectively, resultingmore » in greatly improved device stability. As a result, the combination of lamination of electrodes and encapsulation layers into a single step significantly reduce the cost of device fabrication.« less

Antiproliferative effect of Antrodia camphorata polysaccharides encapsulated in chitosan-silica nanoparticles strongly depends on the metabolic activity type of the cell line

NASA Astrophysics Data System (ADS)

Kong, Zwe-Ling; Chang, Jenq-Sheng; Chang, Ke Liang B.

2013-09-01

Chitosan molecules interact with silica and encapsulate the Antrodia camphorata extract (ACE) polysaccharides to form composite nanoparticles. The nanoparticle suspensions of ACE polysaccharides encapsulated in silica-chitosan and silica nanoparticles approach an average particle size of 210 and 294 nm in solution, respectively. The encapsulation efficiencies of ACE polysaccharides are 66 and 63.5 %, respectively. Scanning electron micrographs confirm the formation of near-spherical nanoparticles. ACE polysaccharides solution had better antioxidative capability than ACE polysaccharides encapsulated in silica or silica-chitosan nanoparticles suspensions. The antioxidant capacity of nanoparticles increases with increasing dissolution time. The antitumor effects of ACE polysaccharides, ACE polysaccharides encapsulated in silica, or silica-chitosan nanoparticles increased with increasing concentration of nanoparticles. This is the first report demonstrating the potential of ACE polysaccharides encapsulated in chitosan-silica nanoparticles for cancer chemoprevention. Furthermore, this study suggests that antiproliferative effect of nanoparticle-encapsulated bioactive could significantly depend on the metabolic activity type of the cell line.

Quality by design: optimization of a liquid filled pH-responsive macroparticles using Draper-Lin composite design.

PubMed

Rafati, Hasan; Talebpour, Zahra; Adlnasab, Laleh; Ebrahimi, Samad Nejad

2009-07-01

In this study, pH responsive macroparticles incorporating peppermint oil (PO) were prepared using a simple emulsification/polymer precipitation technique. The formulations were examined for their properties and the desired quality was then achieved using a quality by design (QBD) approach. For this purpose, a Draper-Lin small composite design study was employed in order to investigate the effect of four independent variables, including the PO to water ratio, the concentration of pH sensitive polymer (hydroxypropyl methylcellulose phthalate), acid and plasticizer concentrations, on the encapsulation efficiency and PO loading. The analysis of variance showed that the polymer concentration was the most important variable on encapsulation efficiency (p < 0.05). The multiple regression analysis of the results led to equations that adequately described the influence of the independent variables on the selected responses. Furthermore, the desirability function was employed as an effective tool for transforming each response separately and encompassing all of these responses in an overall desirability function for global optimization of the encapsulation process. The optimized macroparticles were predicted to yield 93.4% encapsulation efficiency and 72.8% PO loading, which were remarkably close to the experimental values of 89.2% and 69.5%, consequently.

Characteristics of Artemether-Loaded Poly(lactic-co-glycolic) Acid Microparticles Fabricated by Coaxial Electrospray: Validation of Enhanced Encapsulation Efficiency and Bioavailability.

PubMed

Mangrio, Farhana Akbar; Dwivedi, Pankaj; Han, Shuya; Zhao, Gang; Gao, Dayong; Si, Ting; Xu, Ronald X

2017-12-04

Artemether is one of the most effective drugs for the treatment of chloroquine-resistant and Plasmodium falciparum strains of malaria. However, its therapeutic potency is hindered by its poor bioavailability. To overcome this limitation, we have encapsulated artemether in poly(lactic-co-glycolic) acid (PLGA) core-shell microparticles (MPs) using the coaxial electrospray method. With optimized process parameters including liquid flow rates and applied electric voltages, experiments are systematically carried out to generate a stable cone-jet mode to produce artemether-loaded PLGA-MPs with an average size of 2 μm, an encapsulation efficiency of 78 ± 5.6%, and a loading efficiency of 11.7%. The in vitro release study demonstrates the sustained release of artemether from the core-shell structure in comparison with that of plain artemether and that of MPs produced by single-axial electrospray without any relevant cytotoxicity. The in vivo studies are performed to evaluate the pharmacokinetic characteristics of the artemether-loaded PLGA-MPs. Our study implies that artemether can be effectively encapsulated in a protective shell of PLGA for controlled release kinetics and enhanced oral bioavailability.

Facile Preparation of Drug-Loaded Tristearin Encapsulated Superparamagnetic Iron Oxide Nanoparticles Using Coaxial Electrospray Processing.

PubMed

Rasekh, Manoochehr; Ahmad, Zeeshan; Cross, Richard; Hernández-Gil, Javier; Wilton-Ely, James D E T; Miller, Philip W

2017-06-05

Naturally occurring polymers are promising biocompatible materials that have many applications for emerging therapies, drug delivery systems, and diagnostic agents. The handling and processing of such materials still constitutes a major challenge, which can limit the full exploitation of their properties. This study explores an ambient environment processing technique: coaxial electrospray (CO-ES) to encapsulate genistein (an isoflavonoid and model drug), superparamagnetic iron oxide nanoparticles (SPIONs, 10-15 nm), and a fluorophore (BODIPY) into a layered (triglyceride tristearin shell) particulate system, with a view to constructing a theranostic agent. Mode mapping of CO-ES led to an optimized atomization engineering window for stable jetting, leading to encapsulation of SPIONs within particles of diameter 0.65-1.2 μm and drug encapsulation efficiencies of around 92%. Electron microscopy was used to image the encapsulated SPIONs and confirm core-shell triglyceride encapsulation in addition to further physicochemical characterization (AFM, FTIR, DSC, and TGA). Cell viability assays (MTT, HeLa cells) were used to determine optimal SPION loaded particles (∼1 mg/mL), while in vitro release profile experiments (PBS, pH = 7.4) demonstrate a triphasic release profile. Further cell studies confirmed cell uptake and internalization at selected time points (t = 1, 2, and 4 h). The results suggest potential for using the CO-ES technique as an efficient way to encapsulate SPIONs together with sensitive drugs for the development of multimodal particles that have potential application for combined imaging and therapy.

Clinical application of microencapsulated islets: actual prospectives on progress and challenges.

PubMed

Calafiore, Riccardo; Basta, Giuseppe

2014-04-01

After 25 years of intense pre-clinical work on microencapsulated intraperitoneal islet grafts into non-immunosuppressed diabetic recipients, the application of this procedure to patients with type 1 diabetes mellitus has been a significant step forward. This result, achieved in a few centers worldwide, underlies the safety of biopolymers used for microencapsulation. Without this advance, no permission for human application of microcapsules would have ever been obtained after years of purification technologies applied to the raw alginates. To improve safety of the encapsulated islet graft system, renewed efforts on the capsules' bioengineering, as well as on insulin-producing cells within the capsular membranes, are in progress. It is hoped that advances in these two critical aspects of the cell encapsulation technology will result in wider human application of this system. Copyright © 2013 Elsevier B.V. All rights reserved.

Dual-coating of liposomes as encapsulating matrix of antimicrobial peptides: Development and characterization

NASA Astrophysics Data System (ADS)

Gomaa, Ahmed I.; Martinent, Cynthia; Hammami, Riadh; Fliss, Ismail; Subirade, Muriel

2017-11-01

Abstract Antimicrobial peptides have been proposed as a potential biopreservatives in pharmaceutical research and agribusiness. However, many limitations hinder their utilization, such as their vulnerability to proteolytic digestion and their potential interaction with other food ingredients in complex food systems. One approach to overcome such problems is developing formulations entrapping and thereby protecting the antimicrobial peptides. Liposome encapsulation is a strategy that could be implemented to combine protection of the antimicrobial activity of the peptides from proteolytic enzymes and the controlled release of the encapsulated active ingredients. The objective of this study was to develop dual-coated food grade liposome formulations for oral administration of bacteriocins. The formulations were developed from anionic and cationic phospholipids as models of negatively and positively charged liposomes, respectively. Liposomes were prepared by the hydration of lipid films. Subsequently, the liposomes were coated with two layers comprising a biopolymer network (pectin) and whey proteins (WPI) in order to further improve their stability and enable the gradual release of the developed liposomes. Liposomes were characterized for their size, charge, molecular structure, morphology, encapsulation efficiency and release. The results of FTIR, zeta potential, size distribution and transmission electron microscopy confirmed that the liposomes were efficiently coated. Ionic interactions were involved in the stabilization of the positively charged liposome formulations. Negatively charge liposome formulations were stabilized through weak interactions. The release study proved the efficiency of dual coating on the protection of liposomes against gastrointestinal digestion. This work is the first to study the encapsulation of antimicrobial peptides in dual-coated liposomes. Furthermore, the work successfully encapsulated MccJ25 in both negative and positive liposome models.

Determination of size distribution and encapsulation efficiency of liposome-encapsulated hemoglobin blood substitutes using asymmetric flow field-flow fractionation coupled with multi-angle static light scattering.

PubMed

Arifin, Dian R; Palmer, Andre F

2003-01-01

In this study, we investigated the size distribution, encapsulation efficiency, and oxygen affinity of liposome-encapsulated tetrameric hemoglobin (LEHb) dispersions and correlated the data with the variation in extruder membrane pore size, ionic strength of the extrusion buffer, and hemoglobin (Hb) concentration. Asymmetric flow field-flow fractionation (AFFF) in series with multi-angle static light scattering (MASLS) was used to study the LEHb size distribution. We also introduced a novel method to measure the encapsulation efficiency using a differential interferometric refractive index (DIR) detector coupled to the AFFF-MASLS system. This technique was nondestructive toward the sample and easy to implement. LEHbs were prepared by extrusion using a lipid combination of dimyristoyl-phosphatidylcholine, cholesterol, and dimyristoyl-phosphatidylglycerol in a 10:9:1 molar ratio. Five initial Hb concentrations (50, 100, 150, 200, and 300 mg Hb per mL of buffer) extruded through five different membrane pore diameters (400, 200, 100, 80, and 50 nm) were studied. Phosphate buffered saline (PBS) and phosphate buffer (PB) both at pH 7.3 were used as extrusion buffers. Despite the variation, extrusion through 400-nm pore diameter membranes produced LEHbs smaller than the pore size, extrusion through 200-nm membranes produced LEHbs with diameters close to the pore diameter, and extrusion through 100-, 80-, and 50-nm membranes produced LEHbs larger than the pore sizes. We found that the choice of extrusion buffer had the greatest effect on the LEHb size distribution compared to either Hb concentration or extruder membrane pore size. Extrusion in PBS produced larger LEHbs and more monodisperse LEHb dispersions. However, LEHbs extruded in PB generally had higher Hb encapsulation efficiencies and lower methemoglobin (metHb) levels. The choice of extrusion buffer also affected how the encapsulation efficiency correlated with Hb concentration, extruder pore size, and the metHb level. The most optimum encapsulation efficiency and amount of Hb entrapped were achieved at the highest Hb concentration and the largest pore size for both extrusion buffers (62.38% and 187.14 mg Hb/mL of LEHb dispersion extruded in PBS, and 69.98% and 209.94 mg Hb/mL of LEHb dispersion extruded in PB). All LEHbs displayed good oxygen-carrying properties as indicated by their P(50) and cooperativity coefficients. LEHbs extruded in PB had an average P(50) of 23.04 mmHg and an average Hill number of 2.29, and those extruded in PBS had average values of 27.25 mmHg and 2.49. These oxygen-binding properties indicate that LEHbs possess strong potential as artificial blood substitutes. In addition, the metHb levels in PB-LEHb dispersions are significantly low even in the absence of antioxidants such as N-acetyl-L-cysteine.

Self-assembled lecithin/chitosan nanoparticles for oral insulin delivery: preparation and functional evaluation

PubMed Central

Liu, Liyao; Zhou, Cuiping; Xia, Xuejun; Liu, Yuling

2016-01-01

Purpose Here, we investigated the formation and functional properties of self-assembled lecithin/chitosan nanoparticles (L/C NPs) loaded with insulin following insulin–phospholipid complex preparation, with the aim of developing a method for oral insulin delivery. Methods Using a modified solvent-injection method, insulin-loaded L/C NPs were obtained by combining insulin–phospholipid complexes with L/C NPs. The nanoparticle size distribution was determined by dynamic light scattering, and morphologies were analyzed by cryogenic transmission electron microscopy. Fourier transform infrared spectroscopy analysis was used to disclose the molecular mechanism of prepared insulin-loaded L/C NPs. Fast ultrafiltration and a reversed-phase high-performance liquid chromatography assay were used to separate free insulin from insulin entrapped in the L/C NPs, as well as to measure the insulin-entrapment and drug-loading efficiencies. The in vitro release profile was obtained, and in vivo hypoglycemic effects were evaluated in streptozotocin-induced diabetic rats. Results Our results indicated that insulin-containing L/C NPs had a mean size of 180 nm, an insulin-entrapment efficiency of 94%, and an insulin-loading efficiency of 4.5%. Cryogenic transmission electron microscopy observations of insulin-loaded L/C NPs revealed multilamellar structures with a hollow core, encircled by several bilayers. In vitro analysis revealed that insulin release from L/C NPs depended on the L/C ratio. Insulin-loaded L/C NPs orally administered to streptozotocin-induced diabetic rats exerted a significant hypoglycemic effect. The relative pharmacological bioavailability following oral administration of L/C NPs was 6.01%. Conclusion With the aid of phospholipid-complexation techniques, some hydrophilic peptides, such as insulin, can be successfully entrapped into L/C NPs, which could improve oral bioavailability, time-dependent release, and therapeutic activity. PMID:26966360

Oral insulin delivery by means of solid lipid nanoparticles

PubMed Central

Sarmento, Bruno; Martins, Susana; Ferreira, Domingos; Souto, Eliana B

2007-01-01

The aim of this work was to produce and characterize cetyl palmitate-based solid lipid nanoparticles (SLN) containing insulin, and to evaluate the potential of these colloidal carriers for oral administration. SLN were prepared by a modified solvent emulsification-evaporation method based on a w/o/w double emulsion. The particle size, zeta potential and association efficiency of unloaded and insulin-loaded SLN were determined and were found to be around 350 nm, negatively charged and the insulin association efficiency was over 43%. After oral administration of insulin-loaded SLN to diabetic rats, a considerable hypoglycemic effect was observed during 24 hours. These results demonstrated that SLN promote the oral absorption of insulin. PMID:18203440

How efficient is sliding-scale insulin therapy? Problems with a 'cookbook' approach in hospitalized patients.

PubMed

Katz, C M

1991-04-01

Sliding-scale insulin therapy is seldom the best way to treat hospitalized diabetic patients. In the few clinical situations in which it is appropriate, close attention to details and solidly based scientific principles is absolutely necessary. Well-organized alternative approaches to insulin therapy usually offer greater efficiency and effectiveness.

Photosensitive function of encapsulated dye in carbon nanotubes.

PubMed

Yanagi, Kazuhiro; Iakoubovskii, Konstantin; Matsui, Hiroyuki; Matsuzaki, Hiroyuki; Okamoto, Hiroshi; Miyata, Yasumitsu; Maniwa, Yutaka; Kazaoui, Said; Minami, Nobutsugu; Kataura, Hiromichi

2007-04-25

Single-wall carbon nanotubes (SWCNTs) exhibit resonant absorption localized in specific spectral regions. To expand the light spectrum that can be utilized by SWCNTs, we have encapsulated squarylium dye into SWCNTs and clarified its microscopic structure and photosensitizing function. X-ray diffraction and polarization-resolved optical absorption measurements revealed that the encapsulated dye molecules are located at an off center position inside the tubes and aligned to the nanotube axis. Efficient energy transfer from the encapsulated dye to SWCNTs was clearly observed in the photoluminescence spectra. Enhancement of transient absorption saturation in the S1 state of the semiconducting SWCNTs was detected after the photoexcitation of the encapsulated dye, which indicates that ultrafast (<190 fs) energy transfer occurred from the dye to the SWCNTs.

Single cell kinase signaling assay using pinched flow coupled droplet microfluidics.

PubMed

Ramji, Ramesh; Wang, Ming; Bhagat, Ali Asgar S; Tan Shao Weng, Daniel; Thakor, Nitish V; Teck Lim, Chwee; Chen, Chia-Hung

2014-05-01

Droplet-based microfluidics has shown potential in high throughput single cell assays by encapsulating individual cells in water-in-oil emulsions. Ordering cells in a micro-channel is necessary to encapsulate individual cells into droplets further enhancing the assay efficiency. This is typically limited due to the difficulty of preparing high-density cell solutions and maintaining them without cell aggregation in long channels (>5 cm). In this study, we developed a short pinched flow channel (5 mm) to separate cell aggregates and to form a uniform cell distribution in a droplet-generating platform that encapsulated single cells with >55% encapsulation efficiency beating Poisson encapsulation statistics. Using this platform and commercially available Sox substrates (8-hydroxy-5-(N,N-dimethylsulfonamido)-2-methylquinoline), we have demonstrated a high throughput dynamic single cell signaling assay to measure the activity of receptor tyrosine kinases (RTKs) in lung cancer cells triggered by cell surface ligand binding. The phosphorylation of the substrates resulted in fluorescent emission, showing a sigmoidal increase over a 12 h period. The result exhibited a heterogeneous signaling rate in individual cells and showed various levels of drug resistance when treated with the tyrosine kinase inhibitor, gefitinib.

Nanoencapsulation of Insulin into Zirconium Phosphate for Oral Delivery Applications

PubMed Central

Díaz, Agustín; David, Amanda; Pérez, Riviam; González, Millie L.; Báez, Adriana; Wark, Stacey E.; Zhang, Paul; Clearfield, Abraham; Colón, Jorge L.

2010-01-01

The encapsulation of insulin into different kinds of materials for non-invasive delivery is an important field of study because of the many drawbacks of painful needle and syringe delivery such as physiological stress, infection, and local hypertrophy, among others.1 A stable, robust, non-toxic, and viable non-invasive carrier for insulin delivery is needed. We present a new approach for protein nanoencapsulation using layered zirconium phosphate (ZrP) nanoparticles produced without any preintercalator present. The use of ZrP without preintercalators produces a highly pure material, without any kinds of contaminants, such as the preintercalator, which can be noxious. Cytotoxicity cell viability in vitro experiments for the ZrP nanoparticles show that ZrP is not toxic, or harmful, in a biological environment, as previously reported for rats.2 Contrary to previous preintercalator-based methods, we show that insulin can be nanoencapsulated in ZrP if a highly hydrate phase of ZrP with an interlayer distance of 10.3 Å (10.3 Å-ZrP or θ-ZrP) is used as precursor. The intercalation of insulin into ZrP produced a new insulin-intercalated ZrP phase with a ca. 27 Å interlayer distance, as determined by X-ray powder diffraction, demonstrating a successful nanoencapsulation of the hormone. The in vitro release profile of the hormone after the intercalation was determined and circular dichroism was used to study the hormone stability upon intercalation and release. The insulin remains stable in the layered material, at room temperature, for a considerable amount of time, improving the shell life of the peptidic hormone. This type of materials represents a strong candidate to develop a non-invasive insulin carrier for the treatment of diabetes mellitus. PMID:20707305

Hydroxypropyl-β-cyclodextrin for Delivery of Baicalin via Inclusion Complexation by Supercritical Fluid Encapsulation.

PubMed

Li, Ying; He, Zhen-Dan; Zheng, Qian-En; Hu, Chengshen; Lai, Wing-Fu

2018-05-14

Over the years, various methods have been developed to enhance the solubility of insoluble drugs; however, most of these methods are time-consuming and labor intensive or involve the use of toxic materials. A method that can safely and effectively enhance the solubility of insoluble drugs is lacking. This study adopted baicalin as an insoluble drug model, and used hydroxypropyl-β-cyclodextrin for the delivery of baicalin via the inclusion complexation by supercritical fluid encapsulation. Different parameters for the complex preparation as well as the physicochemical properties of the complex have been investigated. Our results showed that when compared to the conventional solution mixing approach, supercritical fluid encapsulation enables a more precise control of the properties of the complex, and gives higher loading and encapsulation efficiency. It is anticipated that our reported method can be useful in enhancing the preparation efficiency of inclusion complexes, and can expand the application potential of insoluble herbal ingredients in treatment development and pharmaceutical formulation.

Stability of niosomes with encapsulated vitamin D3 and ferrous sulfate generated using a novel supercritical carbon dioxide method.

PubMed

Wagner, Michael E; Spoth, Katherine A; Kourkoutis, Lena F; Rizvi, Syed S H

2016-12-01

Niosomes were prepared using a novel supercritical carbon dioxide based method to simultaneously encapsulate ferrous sulfate and vitamin D3 as hydrophilic and hydrophobic cargo, respectively. Vesicle particle size was determined to be bimodal with peak diameters of 1.44 ± 0.16 μm and 7.21 ± 0.64 μm, with the smaller peak comprising 98.8% of the total niosomal volume. Encapsulation efficiency of ferrous sulfate was 25.1 ± 0.2% and encapsulation efficiency of vitamin D3 was 95.9 ± 1.47%. Physical stability of the produced niosomes was assessed throughout a storage period of 21 days. Niosomes showed good physical stability at 20 °C, but storage at 4 °C showed an initial burst release, indicating possible rupture of the niosomal membrane. The Korsmeyer-Peppas equation was used to model the release of ferrous sulfate over time at both storage temperatures.

Preparation and characterization of microparticles of β-cyclodextrin/glutathione and chitosan/glutathione obtained by spray-drying.

PubMed

Webber, Vanessa; de Siqueira Ferreira, Daniel; Barreto, Pedro Luis Manique; Weiss-Angeli, Valeria; Vanderlinde, Regina

2018-03-01

Reduced glutathione (GSH) is an efficient antioxidant on limitation of browning, of the loss of aromas and off-flavor formation in white wines. The encapsulation of GSH in a polymer system to be added in white wines may prolong its antioxidant action. The aim of this work was to prepare and characterize spray-dried microparticles using β-cyclodextrin (β-CD) or chitosan as polymers for encapsulation of GSH for its addition to wine to prevent oxidation. The microparticles obtained after the drying process were characterized regarding morphology, chemical interaction between GSH and polymers, thermal stability, microstructure, encapsulation efficiency and in vitro GSH release. SEM showed spherical microparticles, with wrinkled surfaces for β-CD/GSH and smooth surfaces for chitosan/GSH. A wide distribution of particle size was observed. In general, β-CD/GSH showed an average diameter smaller than the chitosan/GSH microparticles. FT-IR showed a possible interaction between GSH and both polymers. DSC and DRX showed that encapsulation process produced a marked decrease in GSH crystallinity. The encapsulation efficiency was 25.0% for chitosan/GSH and 62.4% for β-CD/GSH microparticles. The GSH release profiles from microparticles showed that β-CD can control the release behaviors of GSH better than chitosan in a model wine. Cumulative release data were fitted to an empirical equation to compute diffusional exponent (n), which indicates a trend the non-Fickian release of GSH. Copyright © 2017 Elsevier Ltd. All rights reserved.

Polymeric nano-encapsulation of 5-fluorouracil enhances anti-cancer activity and ameliorates side effects in solid Ehrlich Carcinoma-bearing mice.

PubMed

Haggag, Yusuf A; Osman, Mohamed A; El-Gizawy, Sanaa A; Goda, Ahmed E; Shamloula, Maha M; Faheem, Ahmed M; McCarron, Paul A

2018-05-29

Biodegradable PLGA nanoparticles, loaded with 5-fluorouracil (5FU), were prepared using a double emulsion method and characterised in terms of mean diameter, zeta potential, entrapment efficiency and in vitro release. Poly (vinyl alcohol) was used to modify both internal and external aqueous phases and shown have a significant effect on nanoparticulate size, encapsulation efficiency and the initial burst release. Addition of poly (ethylene glycol) to the particle matrix, as part of the polymeric backbone, improved significantly the encapsulation efficiency. 5FU-loaded NPs were spherical in shape and negatively charged with a size range of 185-350 nm. Biological evaluation was performed in vivo using a solid Ehrlich carcinoma (SEC) murine model. An optimised 5FU-loaded formulation containing PEG as part of a block copolymer induced a pronounced reduction in tumour volume and tumour weight, together with an improved percentage tumour growth inhibition. Drug-loaded nanoparticles showed no significant toxicity or associated changes on liver and kidney function in tested animals, whereas increased alanine aminotransferase, aspartate aminotransferase and serum creatinine were observed in animals treated with free 5FU. Histopathological examination demonstrated enhanced cytotoxic action of 5FU-loaded nanoparticles when compared to the free drug. Based on these findings, it was concluded that nano-encapsulation of 5FU using PEGylated PLGA improved encapsulation and sustained in vitro release. This leads to increased anti-tumour efficacy against SEC, with a reduction in adverse effects. Published by Elsevier Masson SAS.

Ciprofloxacin as ocular liposomal hydrogel.

PubMed

Hosny, Khaled Mohamed

2010-03-01

The purpose of this study was to prepare and characterize an ocular effective prolonged-release liposomal hydrogel formulation containing ciprofloxacin. Reverse-phase evaporation was used for preparation of liposomes consisting of soybean phosphatidylcholine (PC) and cholesterol (CH). The effect of PC/CH molar ratio on the percentage drug encapsulation was investigated. The effect of additives such as stearylamine (SA) or dicetyl phosphate (DP) as positive and negative charge inducers, respectively, were studied. Morphology, mean size, encapsulation efficiency, and in vitro release of ciprofloxacin from liposomes were evaluated. For hydrogel preparation, Carbopol 940 was applied. In vitro transcorneal permeation through excised albino rabbit cornea was also determined. Optimal encapsulation efficiency of 73.04 +/- 3.06% was obtained from liposomes formulated with PC/CH at molar ratio of 5:3 and by increasing CH content above this limit, the encapsulation decreased. Positively charged liposomes showed superior entrapment efficiency (82.01 +/- 0.52) over the negatively charged and the neutral liposomes. Hydrogel containing liposomes with lipid content PC, CH, and SA in molar ratio 5:3:1, respectively, showed the best release and transcorneal permeation with the percentage permeation of 30.6%. These results suggest that the degree of encapsulation of ciprofloxacin into liposomes and prolonged in vitro release depend on composition of the vesicles. In addition, the polymer hydrogel used in preparation ensure steady and prolonged transcorneal permeation. In conclusion, ciprofloxacin liposomal hydrogel is a suitable delivery system for improving the ocular bioavailability of ciprofloxacin.

Survival of Free and Encapsulated Human and Rat Islet Xenografts Transplanted into the Mouse Bone Marrow

PubMed Central

Meier, Raphael P. H.; Seebach, Jörg D.; Morel, Philippe; Mahou, Redouan; Borot, Sophie; Giovannoni, Laurianne; Parnaud, Geraldine; Montanari, Elisa; Bosco, Domenico; Wandrey, Christine; Berney, Thierry; Bühler, Leo H.; Muller, Yannick D.

2014-01-01

Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow) and 10 days (kidney capsule). Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation. PMID:24625569

Effects of Different End-Point Cooking Temperatures on the Efficiency of Encapsulated Phosphates on Lipid Oxidation Inhibition in Ground Meat.

PubMed

Kılıç, B; Şimşek, A; Claus, J R; Atılgan, E; Aktaş, N

2015-10-01

Effects of 0.5% encapsulated (e) phosphates (sodium tripolyphosphate, STP; sodium hexametaphosphate, HMP; sodium pyrophosphate, SPP) on lipid oxidation during storage (0, 1, and 7 d) of ground meat (chicken, beef) after being cooked to 3 end-point cooking temperatures (EPCT; 71, 74, and 77 °C) were evaluated. The use of STP or eSTP resulted in lower (P < 0.05) cooking loss (CL) compared to encapsulated or unencapsulated forms of HMP and SPP. Increasing EPCT led to a significant increase in CL (P < 0.05). Both STP and eSTP increased pH, whereas SPP and eSPP decreased pH (P < 0.05). The higher orthophosphate (OP) was obtained with STP or SPP compared to their encapsulated counterparts (P < 0.05). The lowest OP was determined in samples with HMP or eHMP (P < 0.05). A 77 °C EPCT resulted in lower OP in chicken compared to 74 and 71 °C (P < 0.05), dissimilar to beef, where EPCT did not affect OP. In encapsulated or unencapsulated form, using STP and SPP enhanced reduction in TBARS and lipid hydroperoxides (LPO) compared with HMP (P < 0.05). Regardless of the phosphate type, more effective lipid oxidation inhibition was achieved by the use of encapsulated forms (P < 0.05). Increasing EPCT resulted in lower TBARS in beef and higher LPO values in both beef and chicken samples (P < 0.05). Findings suggest that encapsulated phosphates can be a strategy to inhibit lipid oxidation for meat industry and the efficiency of encapsulated phosphates on lipid oxidation inhibition can be enhanced by lowering EPCT. © 2015 Institute of Food Technologists®

Influence of charge on encapsulation and release behavior of small molecules in self-assembled layer-by-layer microcapsules.

PubMed

Mandapalli, Praveen K; Labala, Suman; Vanamala, Deekshith; Koranglekar, Manali P; Sakimalla, Lakshmi A; Venuganti, Venkata Vamsi K

2014-12-01

The objective of this study is to investigate the influence of charge of model small molecules on their encapsulation and release behavior in layer-by-layer microcapsules (LbL-MC). Poly(styrene sulfonate) and poly(ethylene imine) were sequentially adsorbed on calcium carbonate sacrificial templates to prepare LbL-MC. Model molecules with varying charge, anionic - ascorbic acid, cationic - imatinib mesylate (IM) and neutral - 5-fluorouracil were encapsulated in LbL-MC. Free and encapsulated LbL-MC were characterized using zetasizer, FTIR spectroscope and differential scanning calorimeter. The influence of IM-loaded LbL-MC on cell viability was studied in B16F10 murine melanoma cells. Furthermore, biodistribution of IM-loaded LbL-MC with and without PEGylation was studied in BALB/c mice. Results showed spherical LbL-MC of 3.0 ± 0.4 μm diameter. Encapsulation efficiency of LbL-MC increased linearly (R(2 )= 0.89-0.99) with the increase in solute concentration. Increase in pH from 2 to 6 increased the encapsulation of charged molecules in LbL-MC. Charged molecules showed greater encapsulation efficiency in LbL-MC compared with neutral molecule. In vitro release kinetics showed Fickian and non-Fickian diffusion of small molecules, depending on the nature of molecular interactions with LbL-MC. At 50 μM concentration, free IM showed significantly (p < 0.05) more cytotoxicity compared with IM-loaded LbL-MC. Biodistribution studies showed that PEGylation of LbL-MC decreased the liver and spleen uptake of IM-encapsulated LbL-MC. In conclusion, LbL-MC can be developed as a potential carrier for small molecules depending on their physical and chemical properties.

Effects of two commercially available feline diets on glucose and insulin concentrations, insulin sensitivity and energetic efficiency of weight gain.

PubMed

Coradini, M; Rand, J S; Morton, J M; Rawlings, J M

2011-10-01

A low-carbohydrate, high-protein (LCHP) diet is often recommended for the prevention and management of diabetes in cats; however, the effect of macronutrient composition on insulin sensitivity and energetic efficiency for weight gain is not known. The present study compared the effect in adult cats (n 32) of feeding a LCHP (23 and 47 % metabolisable energy (ME)) and a high-carbohydrate, low-protein (HCLP) diet (51 and 21 % ME) on fasting and postprandial glucose and insulin concentrations, and on insulin sensitivity. Tests were done in the 4th week of maintenance feeding and after 8 weeks of ad libitum feeding, when weight gain and energetic efficiency of each diet were also measured. When fed at maintenance energy, the HCLP diet resulted in higher postprandial glucose and insulin concentrations. When fed ad libitum, the LCHP diet resulted in greater weight gain (P < 0.01), and was associated with higher energetic efficiency. Overweight cats eating the LCHP diet had similar postprandial glucose concentrations to lean cats eating the HCLP diet. Insulin sensitivity was not different between the diets when cats were lean or overweight, but glucose effectiveness was higher after weight gain in cats fed the HCLP diet. According to the present results, LCHP diets fed at maintenance requirements might benefit cats with multiple risk factors for developing diabetes. However, ad libitum feeding of LCHP diets is not recommended as they have higher energetic efficiency and result in greater weight gain.

Enhanced cavitation and heating of flowing polymer- and lipid-shelled microbubbles and phase-shift nanodroplets during focused ultrasound exposures

NASA Astrophysics Data System (ADS)

Zhang, Siyuan; Cui, Zhiwei; Li, Chong; Zhou, Fanyu; Zong, Yujin; Wang, Supin; Wan, Mingxi

2017-03-01

Cavitation and heating are the primary mechanisms of numerous therapeutic applications of ultrasound. Various encapsulated microbubbles (MBs) and phase-shift nanodroplets (NDs) have been used to enhance local cavitation and heating, creating interests in developing ultrasound therapy using these encapsulated MBs and NDs. This work compared the efficiency of flowing polymer- and lipid-shelled MBs and phase-shift NDs in cavitation and heating during focused ultrasound (FUS) exposures. Cavitation activity and temperature were investigated when the solution of polymer- and lipid-shelled MBs and NDs flowed through the vessel in a tissue-mimicking phantom with varying flow velocities when exposed to FUS at various acoustic power levels. The inertial cavitation dose (ICD) for the encapsulated MBs and NDs were higher than those for the saline. Temperature initially increased with increasing flow velocities of the encapsulated MBs, followed by a decrease of the temperature with increasing flow velocities when the velocity was much higher. Meanwhile, ICD showed a trend of increases with increasing flow velocity. For the phase-shift NDs, ICD after the first FUS exposure was lower than those after the second FUS exposure. For the encapsulated MBs, ICD after the first FUS exposure was higher than those after the second FUS exposure. Further studies are necessary to investigate the treatment efficiency of different encapsulated MBs and phase-shift NDs in cavitation and heating.

Minireview: Directed Differentiation and Encapsulation of Islet β-Cells—Recent Advances and Future Considerations

PubMed Central

Tse, Hubert M.; Kozlovskaya, Veronika; Kharlampieva, Eugenia

2015-01-01

Diabetes mellitus has rapidly become a 21st century epidemic with the promise to create vast economic and health burdens, if left unchecked. The 2 major forms of diabetes arise from unique causes, with outcomes being an absolute (type 1) or relative (type 2) loss of functional pancreatic islet β-cell mass. Currently, patients rely on exogenous insulin and/or other pharmacologies that restore glucose homeostasis. Although these therapies have prolonged countless lives over the decades, the striking increases in both type 1 and type 2 diabetic diagnoses worldwide suggest a need for improved treatments. To this end, islet biologists are developing cell-based therapies by which a patient's lost insulin-producing β-cell mass is replenished. Pancreatic or islet transplantation from cadaveric donors into diabetic patients has been successful, yet the functional islet demand far surpasses supply. Thus, the field has been striving toward transplantation of renewable in vitro-derived β-cells that can restore euglycemia. Challenges have been numerous, but progress over the past decade has generated much excitement. In this review we will summarize recent findings that have placed us closer than ever to β-cell replacement therapies. With the promise of cell-based diabetes therapies on the horizon, we will also provide an overview of cellular encapsulation technologies that will deliver critical protection of newly implanted cells. PMID:26340406

Structural and oxidative stabilization of spray dried fish oil microencapsulates with gum arabic and sage polyphenols: Characterization and release kinetics.

PubMed

Binsi, P K; Nayak, Natasha; Sarkar, P C; Jeyakumari, A; Muhamed Ashraf, P; Ninan, George; Ravishankar, C N

2017-03-15

The synergistic efficacy of gum arabic and sage polyphenols in stabilising capsule wall and protecting fish oil encapsulates from heat induced disruption and oxidative deterioration during spray drying was assessed. The emulsions prepared with sodium caseinate as wall polymer, gum arabic as wall co-polymer and sage extract as wall stabiliser was spray dried using a single fluid nozzle. Fish oil encapsulates stabilised with gum arabic and sage extract (SOE) exhibited significantly higher encapsulation efficiency compared to encapsulates containing gum arabic alone (FOE). Scanning electron microscopic and atomic force microscopic images revealed uniform encapsulates with good sphericity and smooth surface for SOE, compared to FOE powder. In vitro oil release of microencapsulates indicated negligible oil release in buffered saline whereas more than 80% of the oil loaded in encapsulates were released in simulated GI fluids. The encapsulates containing sage extract showed a lower rate of lipid oxidation during storage. Copyright © 2016 Elsevier Ltd. All rights reserved.

Encapsulation-free controlled release: Electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles

PubMed Central

Pakulska, Malgosia M.; Elliott Donaghue, Irja; Obermeyer, Jaclyn M.; Tuladhar, Anup; McLaughlin, Christopher K.; Shendruk, Tyler N.; Shoichet, Molly S.

2016-01-01

Encapsulation of therapeutic molecules within polymer particles is a well-established method for achieving controlled release, yet challenges such as low loading, poor encapsulation efficiency, and loss of protein activity limit clinical translation. Despite this, the paradigm for the use of polymer particles in drug delivery has remained essentially unchanged for several decades. By taking advantage of the adsorption of protein therapeutics to poly(lactic-co-glycolic acid) (PLGA) nanoparticles, we demonstrate controlled release without encapsulation. In fact, we obtain identical, burst-free, extended-release profiles for three different protein therapeutics with and without encapsulation in PLGA nanoparticles embedded within a hydrogel. Using both positively and negatively charged proteins, we show that short-range electrostatic interactions between the proteins and the PLGA nanoparticles are the underlying mechanism for controlled release. Moreover, we demonstrate tunable release by modifying nanoparticle concentration, nanoparticle size, or environmental pH. These new insights obviate the need for encapsulation and offer promising, translatable strategies for a more effective delivery of therapeutic biomolecules. PMID:27386554

Enhanced skeletal muscle lipid oxidative efficiency in insulin-resistant vs insulin-sensitive nondiabetic, nonobese humans.

PubMed

Galgani, Jose E; Vasquez, Karla; Watkins, Guillermo; Dupuy, Aude; Bertrand-Michel, Justine; Levade, Thierry; Moro, Cedric

2013-04-01

Skeletal muscle insulin resistance is proposed to result from impaired skeletal muscle lipid oxidative capacity. However, there is no evidence indicating that muscle lipid oxidative capacity is impaired in healthy otherwise insulin-resistant individuals. The objective of the study was to assess muscle lipid oxidative capacity in young, nonobese, glucose-tolerant, insulin-resistant vs insulin-sensitive individuals. In 13 insulin-sensitive [by Matsuda index (MI) (22.6 ± 0.6 [SE] kg/m(2)); 23 ± 1 years; MI 5.9 ± 0.1] and 13 insulin-resistant (23.2 ± 0.6 kg/m(2); 23 ± 3 years; MI 2.2 ± 0.1) volunteers, skeletal muscle biopsy, blood extraction before and after an oral glucose load, and dual-energy x-ray absorptiometry were performed. Skeletal muscle mitochondrial to nuclear DNA ratio, oxidative phosphorylation protein content, and citrate synthase and β-hydroxyacyl-CoA dehydrogenase activities were assessed. Muscle lipids and palmitate oxidation ((14)CO2 and (14)C-acid soluble metabolites production) at 4 [1-(14)C]palmitate concentrations (45-520 μM) were also measured. None of the muscle mitochondrial measures showed differences between groups, except for a higher complex V protein content in insulin-resistant vs insulin-sensitive volunteers (3.5 ± 0.4 vs 2.2 ± 0.4; P = .05). Muscle ceramide content was significantly increased in insulin-resistant vs insulin-sensitive individuals (P = .04). Total palmitate oxidation showed a similar concentration-dependent response in both groups (P = .69). However, lipid oxidative efficiency (CO2 to (14)C-acid soluble metabolites ratio) was enhanced in insulin-resistant vs insulin-sensitive individuals, particularly at the highest palmitate concentration (0.24 ± 0.04 vs 0.12 ± 0.02; P = .02). We found no evidence of impaired muscle mitochondrial oxidative capacity in young, nonobese, glucose-tolerant, otherwise insulin-resistant vs insulin-sensitive individuals. Enhanced muscle lipid oxidative efficiency in insulin resistance could be a potential mechanism to prevent further lipotoxicity.

Insulin acutely improves mitochondrial function of rat and human skeletal muscle by increasing coupling efficiency of oxidative phosphorylation.

PubMed

Nisr, Raid B; Affourtit, Charles

2014-02-01

Insulin is essential for the regulation of fuel metabolism and triggers the uptake of glucose by skeletal muscle. The imported glucose is either stored or broken down, as insulin stimulates glycogenesis and ATP synthesis. The mechanism by which ATP production is increased is incompletely understood at present and, generally, relatively little functional information is available on the effect of insulin on mitochondrial function. In this paper we have exploited extracellular flux technology to investigate insulin effects on the bioenergetics of rat (L6) and human skeletal muscle myoblasts and myotubes. We demonstrate that a 20-min insulin exposure significantly increases (i) the cell respiratory control ratio, (ii) the coupling efficiency of oxidative phosphorylation, and (iii) the glucose sensitivity of anaerobic glycolysis. The improvement of mitochondrial function is explained by an insulin-induced immediate decrease of mitochondrial proton leak. Palmitate exposure annuls the beneficial mitochondrial effects of insulin. Our data improve the mechanistic understanding of insulin-stimulated ATP synthesis, and reveal a hitherto undisclosed insulin sensitivity of cellular bioenergetics that suggests a novel way of detecting insulin responsiveness of cells. © 2013.

Insulin acutely improves mitochondrial function of rat and human skeletal muscle by increasing coupling efficiency of oxidative phosphorylation☆

PubMed Central

Nisr, Raid B.; Affourtit, Charles

2014-01-01

Insulin is essential for the regulation of fuel metabolism and triggers the uptake of glucose by skeletal muscle. The imported glucose is either stored or broken down, as insulin stimulates glycogenesis and ATP synthesis. The mechanism by which ATP production is increased is incompletely understood at present and, generally, relatively little functional information is available on the effect of insulin on mitochondrial function. In this paper we have exploited extracellular flux technology to investigate insulin effects on the bioenergetics of rat (L6) and human skeletal muscle myoblasts and myotubes. We demonstrate that a 20-min insulin exposure significantly increases (i) the cell respiratory control ratio, (ii) the coupling efficiency of oxidative phosphorylation, and (iii) the glucose sensitivity of anaerobic glycolysis. The improvement of mitochondrial function is explained by an insulin-induced immediate decrease of mitochondrial proton leak. Palmitate exposure annuls the beneficial mitochondrial effects of insulin. Our data improve the mechanistic understanding of insulin-stimulated ATP synthesis, and reveal a hitherto undisclosed insulin sensitivity of cellular bioenergetics that suggests a novel way of detecting insulin responsiveness of cells. PMID:24212054

Synthesis of poly(N-isopropylacrylamide)-co-poly(phenylboronate ester) acrylate and study on their glucose-responsive behavior.

PubMed

Yao, Yuan; Shen, Heyun; Zhang, Guanghui; Yang, Jing; Jin, Xu

2014-10-01

We introduced thermo-sensitive poly(N-isopropylacrylamide) (PNIPAM) into the polymer structure of poly(ethylene glycol)-block-poly(phenylboronate ester) acrylate (MPEG-block-PPBDEMA) by block and random polymerization pathways in order to investigate the effect of polymer architecture on the glucose-responsiveness and enhance their insulin release controllability. By following the structure, the continuous PNIPAM shell of the triblock polymer MPEG-block-PNIPAM-block-PPBDEMA collapsing on the glucose-responsive PPBDEMA core formed the polymeric micelles with a core-shell-corona structure, and MPEG-block-(PNIPAM-rand-PPBDEMA) exhibited core-corona micelles in which the hydrophobic core consisted of PNIPAM and PPBDEMA segments when the environmental temperature was increased above low critical solution temperature (LCST) of PNIPAM. The micellar morphologies can be precisely controlled by temperature change between 15 and 37°C. As a result, the introduction of PNIPAM greatly enhanced the overall stability of insulin encapsulated in the polymeric micelles in the absence of glucose over incubation 80 h at 37°C. Comparing to MPEG-block-PNIPAM-block-PPBDEMA, the nanocarriers from MPEG-block-(PNIPAM-rand-PPBDEMA) showed great insulin release behavior which is zero insulin release without glucose, low release at normal blood glucose concentration (1.0 mg/mL). Therefore, these nanocarriers may be served as promising self-regulated insulin delivery system for diabetes treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Encapsulation of Anticancer Drugs (5-Fluorouracil and Paclitaxel) into Polycaprolactone (PCL) Nanofibers and In Vitro Testing for Sustained and Targeted Therapy

PubMed Central

Iqbal, Sakib; Rashid, Mohammad H.; Arbab, Ali S.; Khan, Mujibur

2017-01-01

We report a continuous nanoscale encapsulation of cancer drugs 5-Fluorouracil (FU) and Paclitaxel into biocompatible polycaprolactone (PCL) nanofibers (NFs) using core-sheath electrospinning process. A high potential electric field of 19–23.2 kV was used to draw a compound solution jet from a specialized coaxial spinneret. Using of DMF in both core and Sheath resulted in NFs within 50–160 nm along with large beaded structures. Addition of Trichloromethane (TCM) or Trifluoroethanol (TFE) in sheath turned NFs in more uniform and thin fiber structure. The diameter range for paclitaxel encapsulated fibers was 22–90 nm with encapsulation efficiency of 77.5% and the amount of drug was only 4 to 5% of sheath polymer. Addition of PVA within core resulted drug nanocrystal formation outside of sheath and poor encapsulation efficiency (52%) with rapid initial release (52–53%) in first 3 days. Drug release test of NFs in different pH exhibited increase of release rate with the decrease of media pH. In-vitro cell viability test with FU encapsulated NFs in human prostatic cancer PC3 cells exhibited 38% alive cells at 5 μM concentration while in pristine FU 43% cells were alive. Paclitaxel encapsulated NFs with breast cancer cells also exhibited increased efficacy in comparison to pristine anticancer drugs. Continuous decrease of cell density indicated the slow release of cancer drugs from the NFs. Both PCL+Paclitaxel and PCL+5FU treated conditions caused breast cancer cell death between 40% to 50%. PMID:28845137

Encapsulation of Anticancer Drugs (5-Fluorouracil and Paclitaxel) into Polycaprolactone (PCL) Nanofibers and In Vitro Testing for Sustained and Targeted Therapy.

PubMed

Iqbal, Sakib; Rashid, Mohammad H; Arbab, Ali S; Khan, Mujibur

2017-04-01

We report a continuous nanoscale encapsulation of cancer drugs 5-Fluorouracil (FU) and Paclitaxel into biocompatible polycaprolactone (PCL) nanofibers (NFs) using core-sheath electrospinning process. A high potential electric field of 19-23.2 kV was used to draw a compound solution jet from a specialized coaxial spinneret. Using of DMF in both core and Sheath resulted in NFs within 50-160 nm along with large beaded structures. Addition of Trichloromethane (TCM) or Trifluoroethanol (TFE) in sheath turned NFs in more uniform and thin fiber structure. The diameter range for paclitaxel encapsulated fibers was 22-90 nm with encapsulation efficiency of 77.5% and the amount of drug was only 4 to 5% of sheath polymer. Addition of PVA within core resulted drug nanocrystal formation outside of sheath and poor encapsulation efficiency (52%) with rapid initial release (52-53%) in first 3 days. Drug release test of NFs in different pH exhibited increase of release rate with the decrease of media pH. In-vitro cell viability test with FU encapsulated NFs in human prostatic cancer PC3 cells exhibited 38% alive cells at 5 μM concentration while in pristine FU 43% cells were alive. Paclitaxel encapsulated NFs with breast cancer cells also exhibited increased efficacy in comparison to pristine anticancer drugs. Continuous decrease of cell density indicated the slow release of cancer drugs from the NFs. Both PCL+Paclitaxel and PCL+5FU treated conditions caused breast cancer cell death between 40% to 50%.

Colorful Packages: Encapsulation of Fluorescent Proteins in Complex Coacervate Core Micelles

PubMed Central

Westphal, Adrie H.; Kleijn, J. Mieke; Borst, Jan Willem

2017-01-01

Encapsulation of proteins can be beneficial for food and biomedical applications. To study their biophysical properties in complex coacervate core micelles (C3Ms), we previously encapsulated enhanced green fluorescent protein (EGFP) and its monomeric variant, mEGFP, with the cationic-neutral diblock copolymer poly(2-methyl-vinyl-pyridinium)n-b-poly(ethylene-oxide)m (P2MVPn-b-PEOm) as enveloping material. C3Ms with high packaging densities of fluorescent proteins (FPs) were obtained, resulting in a restricted orientational freedom of the protein molecules, influencing their structural and spectral properties. To address the generality of this behavior, we encapsulated seven FPs with P2MVP41-b-PEO205 and P2MVP128-b-PEO477. Dynamic light scattering and fluorescence correlation spectroscopy showed lower encapsulation efficiencies for members of the Anthozoa class (anFPs) than for Hydrozoa FPs derived from Aequorea victoria (avFPs). Far-UV CD spectra of the free FPs showed remarkable differences between avFPs and anFPs, caused by rounder barrel structures for avFPs and more elliptic ones for anFPs. These structural differences, along with the differences in charge distribution, might explain the variations in encapsulation efficiency between avFPs and anFPs. Furthermore, the avFPs remain monomeric in C3Ms with minor spectral and structural changes. In contrast, the encapsulation of anFPs gives rise to decreased quantum yields (monomeric Kusabira Orange 2 (mKO2) and Tag red fluorescent protein (TagRFP)) or to a pKa shift of the chromophore (FP variant mCherry). PMID:28753915

Microencapsulation of superoxide dismutase into poly(epsilon-caprolactone) microparticles by reverse micelle solvent evaporation.

PubMed

Youan, Bi-Botti Célestin

2003-01-01

The aim of this work was to encapsulate superoxide dismutase (SOD) in poly(epsilon-caprolactone) (PCL) microparticles by reverse micelle solvent evaporation. The concentration of PCL, the hydrophile-lipophile balance (HLB), and concentration of the sucrose ester used as surfactant in the organic phase were investigated as formulation variables. Relatively higher encapsulation efficiency (approximately 48%) and retained enzymatic activity (>90%) were obtained with microparticle formulation made from the 20% (w/v) PCL and 0.05% (w/v) sucrose ester of HLB = 6. This formulation allowed the in vitro release of SOD for at least 72 hr. These results showed that reverse micelle solvent evaporation can be used to efficiently encapsulate SOD in PCL microparticles. Such formulations may improve the bioavailability of SOD.

Internalized compartments encapsulated nanogels for targeted drug delivery

NASA Astrophysics Data System (ADS)

Yu, Jicheng; Zhang, Yuqi; Sun, Wujin; Wang, Chao; Ranson, Davis; Ye, Yanqi; Weng, Yuyan; Gu, Zhen

2016-04-01

Drug delivery systems inspired by natural particulates hold great promise for targeted cancer therapy. An endosome formed by internalization of plasma membrane has a massive amount of membrane proteins and receptors on the surface, which is able to specifically target the homotypic cells. Herein, we describe a simple method to fabricate an internalized compartments encapsulated nanogel with endosome membrane components (EM-NG) from source cancer cells. Following intracellular uptake of methacrylated hyaluronic acid (m-HA) adsorbed SiO2/Fe3O4 nanoparticles encapsulating a crosslinker and a photoinitiator, EM-NG was readily prepared through in situ crosslinking initiated under UV irradiation after internalization. The resulting nanogels loaded with doxorubicin (DOX) displayed enhanced internalization efficiency to the source cells through a specific homotypic affinity in vitro. However, when treated with the non-source cells, the EM-NGs exhibited insignificant difference in therapeutic efficiency compared to a bare HA nanogel with DOX. This study illustrates the potential of utilizing an internalized compartments encapsulated formulation for targeted cancer therapy, and offers guidelines for developing a natural particulate-inspired drug delivery system.Drug delivery systems inspired by natural particulates hold great promise for targeted cancer therapy. An endosome formed by internalization of plasma membrane has a massive amount of membrane proteins and receptors on the surface, which is able to specifically target the homotypic cells. Herein, we describe a simple method to fabricate an internalized compartments encapsulated nanogel with endosome membrane components (EM-NG) from source cancer cells. Following intracellular uptake of methacrylated hyaluronic acid (m-HA) adsorbed SiO2/Fe3O4 nanoparticles encapsulating a crosslinker and a photoinitiator, EM-NG was readily prepared through in situ crosslinking initiated under UV irradiation after internalization. The resulting nanogels loaded with doxorubicin (DOX) displayed enhanced internalization efficiency to the source cells through a specific homotypic affinity in vitro. However, when treated with the non-source cells, the EM-NGs exhibited insignificant difference in therapeutic efficiency compared to a bare HA nanogel with DOX. This study illustrates the potential of utilizing an internalized compartments encapsulated formulation for targeted cancer therapy, and offers guidelines for developing a natural particulate-inspired drug delivery system. Electronic supplementary information (ESI) available: Synthesis of m-HA; synthesis of rhodamine-HA derivative; supplementary data on relative fluorescence intensity of DOX-EN-NGs on HeLa cells. See DOI: 10.1039/c5nr08895j

Performance Improvement of Energy Storage System with nano-additivesin HTF

NASA Astrophysics Data System (ADS)

Beemkumar, N.; Karthikeyan, A.; Saravanakumar, B.; Jayaprabakar, J.

2017-05-01

This paper is intended to improve the heat transfer rate of thermal energy storage system with copper oxide (CuO) as nano-additivesin heat transfer fluid (HTF) by varying encapsulation materials. The experimentation is done with different encapsulating materials like copper, brass and aluminium. The results are analysed for their thermal performance characteristics during charging and discharging processes. D-Sorbitol and therminol-66 with CuO is used as PCM and HTF respectively. A comparison was made between the different encapsulations and it was found that copper encapsulation has higher efficient, storing and recovering energy. However, its high thermal conductivity promotes larger heat losses and its cost is also high on other side. So the economical use of encapsulation material is aluminium compared to other two materials.

A "ship in a bottle" strategy to load a hydrophilic anticancer drug in porous metal organic framework nanoparticles: efficient encapsulation, matrix stabilization, and photodelivery.

PubMed

di Nunzio, Maria Rosaria; Agostoni, Valentina; Cohen, Boiko; Gref, Ruxandra; Douhal, Abderrazzak

2014-01-23

An essential challenge in the development of nanosized metal organic framework (nanoMOF) materials in biomedicine is to develop a strategy to stabilize their supramolecular structure in biological media while being able to control drug encapsulation and release. We have developed a method to efficiently encapsulate topotecan (TPT, 1), an important cytotoxic drug, in biodegradable nanoMOFs. Once inside the pores, 1 monomers aggregate in a "ship in a bottle" fashion, thus filling practically all of the nanoMOFs' available free volume and stabilizing their crystalline supramolecular structures. Highly efficient results have been found with the human pancreatic cell line PANC1, in contrast with free 1. We also demonstrate that one- and two-photon light irradiation emerges as a highly promising strategy to promote stimuli-dependent 1 release from the nanoMOFs, hence opening new standpoints for further developments in triggered drug delivery.

Preparation, characterization, and transport of dexamethasone-loaded polymeric nanoparticles across a human placental in vitro model

PubMed Central

Ali, Hazem; Kalashnikova, Irina; White, Mark Andrew; Sherman, Michael; Rytting, Erik

2013-01-01

The purpose of this study was to prepare dexamethasone-loaded polymeric nanoparticles and evaluate their potential for transport across human placenta. Statistical modeling and factorial design was applied to investigate the influence of process parameters on the following nanoparticle characteristics: particle size, polydispersity index, zeta potential, and drug encapsulation efficiency. Dexamethasone and nanoparticle transport was subsequently investigated using the BeWo b30 cell line, an in vitro model of human placental trophoblast cells, which represent the rate-limiting barrier for maternal-fetal transfer. Encapsulation efficiency and drug transport were determined using a validated high performance liquid chromatography method. Nanoparticle morphology and drug encapsulation were further characterized by cryo-transmission electron microscopy and X-ray diffraction, respectively. Nanoparticles prepared from poly(lactic-co-glycolic acid) were spherical, with particle sizes ranging from 140–298 nm, and encapsulation efficiency ranging from 52–89%. Nanoencapsulation enhanced the apparent permeability of dexamethasone from the maternal compartment to the fetal compartment more than 10-fold in this model. Particle size was shown to be inversely correlated with drug and nanoparticle permeability, as confirmed with fluorescently-labeled nanoparticles. These results highlight the feasibility of designing nanoparticles capable of delivering medication to the fetus, in particular, potential dexamethasone therapy for the prenatal treatment of congenital adrenal hyperplasia. PMID:23850397

Encapsulating gold nanoparticles or nanorods in graphene oxide shells as a novel gene vector.

PubMed

Xu, Cheng; Yang, Darong; Mei, Lin; Lu, Bingan; Chen, Libao; Li, Qiuhong; Zhu, Haizhen; Wang, Taihong

2013-04-10

Surface modification of inorganic nanoparticles (NPs) is extremely necessary for biomedical applications. However, the processes of conjugating ligands to NPs surface are complicated with low yield. In this study, a hydrophilic shell with excellent biocompatibility was successfully constructed on individual gold NPs or gold nanorods (NRs) by encapsulating NPs or NRs in graphene oxide (GO) nanosheets through electrostatic self-assembly. This versatile and facile approach remarkably decreased the cytotoxicity of gold NPs or NRs capping with surfactant cetyltrimethylammonium bromide (CTAB) and provided abundant functional groups on NPs surface for further linkage of polyethylenimine (PEI). The PEI-functionalized GO-encapsulating gold NPs (GOPEI-AuNPs) were applied to delivery DNA into HeLa cells as a novel gene vector. It exhibited high transfection efficiency of 65% while retaining 90% viability of HeLa cells. The efficiency was comparable to commercialized PEI 25 kDa with the cytotoxicity much less than PEI. Moreover, the results on transfection efficiency was higher than PEI-functionalized GO, which can be attributed to the small size of NPs/DNA complex (150 nm at the optimal w/w ratio) and the spherical structure facilitating the cellular uptake. Our work paves the way for future studies focusing on GO-encapsulating, NP-based nanovectors.

Process optimization by use of design of experiments: Application for liposomalization of FK506.

PubMed

Toyota, Hiroyasu; Asai, Tomohiro; Oku, Naoto

2017-05-01

Design of experiments (DoE) can accelerate the optimization of drug formulations, especially complexed formulas such as those of drugs, using delivery systems. Administration of FK506 encapsulated in liposomes (FK506 liposomes) is an effective approach to treat acute stroke in animal studies. To provide FK506 liposomes as a brain protective agent, it is necessary to manufacture these liposomes with good reproducibility. The objective of this study was to confirm the usefulness of DoE for the process-optimization study of FK506 liposomes. The Box-Behnken design was used to evaluate the effect of the process parameters on the properties of FK506 liposomes. The results of multiple regression analysis showed that there was interaction between the hydration temperature and the freeze-thaw cycle on both the particle size and encapsulation efficiency. An increase in the PBS hydration volume resulted in an increase in encapsulation efficiency. Process parameters had no effect on the ζ-potential. The multiple regression equation showed good predictability of the particle size and the encapsulation efficiency. These results indicated that manufacturing conditions must be taken into consideration to prepare liposomes with desirable properties. DoE would thus be promising approach to optimize the conditions for the manufacturing of liposomes. Copyright © 2017 Elsevier B.V. All rights reserved.

Structure of a Multilayer Nanofilm To Increase the Encapsulation Efficiency of Basic Fibroblast Growth Factor.

PubMed

Han, Uiyoung; Hong, Jinkee

2018-03-05

In this study, we established the structure of a multilayer nanofilm that more efficiently encapsulates basic fibroblast growth factor (bFGF). First, a positively charged layer material was selected from biocompatible polymers such as collagen (Col), poly(beta-amino ester) (Poly2), and chitosan (Chi), while considering the film thickness. We then investigated the change in bFGF encapsulation efficiency when the multilayer structure was changed from a tetralayer to a trilayer. As a result, we obtained a highly improved bFGF encapsulation efficiency in the nanofilm using a positively charged layer formed by a blend of Col and Poly2 and a negatively charged poly(acrylic acid) (PAA) layer within a trilayered structure. In particular, we found that a significant amount of adsorbed bFGF was desorbed again during the film fabrication process of a tetralayered nanofilm. In the conventional nanofilm, bFGF was regarded as a polycation and formed a multilayer nanofilm that was composed of a tetralayered structure and was represented as (polycation/polyanion/bFGF/polyanion) n where n = number of repeated tetralayers. Here, we suggested that bFGF should not be considered a polycation, rather it should be considered as a small quantity of molecule that exists between the polyanion and polycation layers. In this case, the nanofilm is composed of repeating units of (polycation/polyanion/bFGF/polycation/polyanion), because the amount of adsorbed bFGF is considerably lower than that of other building blocks.

Comparing the enhancement efficiency between liposomes and microbubbles for insulin pulmonary absorption.

PubMed

Xu, Yan-Yan; Lu, Cui-Tao; Fu, Hong-Xing; Zhao, Ying-Zheng; Yang, Wei; Li, Xing; Zhang, Lu; Li, Xiao-Kun; Zhang, Ming

2011-07-01

The present study investigated the enhancement efficiency between liposomes and microbubbles for insulin pulmonary absorption. Two types of phospholipid-based vesicle-liposomes and microbubbles-were prepared, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cytotoxicity test was used to evaluate their in vitro toxicity in A549 cells. Cellular uptake of insulin combined with liposomes or microbubbles was determined using A549 cells. With intratracheal insufflation of Sprague-Dawley rats, an insulin mixture with liposomes or microbubbles was administered to assess its potential for promoting drug pulmonary absorption. Both liposomes and microbubbles had a narrow and monodispersed size distribution with average diameter of 3.1 μm and 1.0 μm, respectively. From the MTT cytotoxicity test, a phospholipid-based vesicle concentration of <25% (vol/vol) in the final volume was the safe dosage range that could avoid severe cytotoxic effects. The intracellular uptake amount of insulin in the insulin-microbubble mixture was significantly higher than that in the insulin-liposome mixture. The minimum reductions of the blood glucose concentration produced by insulin-microbubble and insulin-liposome mixtures were 60.8% and 35.0% of the initial glucose levels, respectively, and their bioavailabilities relative to subcutaneous injection were 48.6% and 30.8%, respectively. Microbubbles have much better efficiency than liposomes in the rate and extent of insulin pulmonary absorption. Microbubbles might be recommended as a potential agent for enhancing protein intrapulmonary absorption.

Delivery of kinesin spindle protein targeting siRNA in solid lipid nanoparticles to cellular models of tumor vasculature

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ying, Bo; Campbell, Robert B., E-mail: robert.campbell@mcphs.edu

2014-04-04

Highlights: • siRNA-lipid nanoparticles are solid particles not lipid bilayers with aqueous core. • High, but not low, PEG content can prevent nanoparticle encapsulation of siRNA. • PEG reduces cellular toxicity of cationic nanoparticles in vitro. • PEG reduces zeta potential while improving gene silencing of siRNA nanoparticles. • Kinesin spindle protein can be an effective target for tumor vascular targeting. - Abstract: The ideal siRNA delivery system should selectively deliver the construct to the target cell, avoid enzymatic degradation, and evade uptake by phagocytes. In the present study, we evaluated the importance of polyethylene glycol (PEG) on lipid-based carriermore » systems for encapsulating, and delivering, siRNA to tumor vessels using cellular models. Lipid nanoparticles containing different percentage of PEG were evaluated based on their physical chemical properties, density compared to water, siRNA encapsulation, toxicity, targeting efficiency and gene silencing in vitro. siRNA can be efficiently loaded into lipid nanoparticles (LNPs) when DOTAP is included in the formulation mixture. However, the total amount encapsulated decreased with increase in PEG content. In the presence of siRNA, the final formulations contained a mixed population of particles based on density. The major population which contains the majority of siRNA exhibited a density of 4% glucose, and the minor fraction associated with a decreased amount of siRNA had a density less than PBS. The inclusion of 10 mol% PEG resulted in a greater amount of siRNA associated with the minor fraction. Finally, when kinesin spindle protein (KSP) siRNA was encapsulated in lipid nanoparticles containing a modest amount of PEG, the proliferation of endothelial cells was inhibited due to the efficient knock down of KSP mRNA. The presence of siRNA resulted in the formation of solid lipid nanoparticles when prepared using the thin film and hydration method. LNPs with a relatively modest amount of PEG can sufficiently encapsulate siRNA, improve cellular uptake and the efficiency of gene silencing.« less

Thin Film Packaging Solutions for High Efficiency OLED Lighting Products

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2008-06-30

The objective of the 'Thin Film Packaging Solutions for High Efficiency OLED Lighting Products' project is to demonstrate thin film packaging solutions based on SiC hermetic coatings that, when applied to glass and plastic substrates, support OLED lighting devices by providing longer life with greater efficiency at lower cost than is currently available. Phase I Objective: Demonstrate thin film encapsulated working phosphorescent OLED devices on optical glass with lifetime of 1,000 hour life, CRI greater than 75, and 15 lm/W. Phase II Objective: Demonstrate thin film encapsulated working phosphorescent OLED devices on plastic or glass composite with 25 lm/W, 5,000more » hours life, and CRI greater than 80. Phase III Objective: Demonstrate 2 x 2 ft{sup 2} thin film encapsulated working phosphorescent OLED with 40 lm/W, 10,000 hour life, and CRI greater than 85. This report details the efforts of Phase III (Budget Period Three), a fourteen month collaborative effort that focused on optimization of high-efficiency phosphorescent OLED devices and thin-film encapsulation of said devices. The report further details the conclusions and recommendations of the project team that have foundation in all three budget periods for the program. During the conduct of the Thin Film Packaging Solutions for High Efficiency OLED Lighting Products program, including budget period three, the project team completed and delivered the following achievements: (1) a three-year marketing effort that characterized the near-term and longer-term OLED market, identified customer and consumer lighting needs, and suggested prototype product concepts and niche OLED applications lighting that will give rise to broader market acceptance as a source for wide area illumination and energy conservation; (2) a thin film encapsulation technology with a lifetime of nearly 15,000 hours, tested by calcium coupons, while stored at 16 C and 40% relative humidity ('RH'). This encapsulation technology was characterized as having less than 10% change in transmission during the 15,000 hour test period; (3) demonstrated thin film encapsulation of a phosphorescent OLED device with 1,500 hours of lifetime at 60 C and 80% RH; (4) demonstrated that a thin film laminate encapsulation, in addition to the direct thin film deposition process, of a polymer OLED device was another feasible packaging strategy for OLED lighting. The thin film laminate strategy was developed to mitigate defects, demonstrate roll-to-roll process capability for high volume throughput (reduce costs) and to support a potential commercial pathway that is less dependent upon integrated manufacturing since the laminate could be sold as a rolled good; (5) demonstrated that low cost 'blue' glass substrates could be coated with a siloxane barrier layer for planarization and ion-protection and used in the fabrication of a polymer OLED lighting device. This study further demonstrated that the substrate cost has potential for huge cost reductions from the white borosilicate glass substrate currently used by the OLED lighting industry; (6) delivered four-square feet of white phosphorescent OLED technology, including novel high efficiency devices with 82 CRI, greater than 50 lm/W efficiency, and more than 1,000 hours lifetime in a product concept model shelf; (7) presented and or published more than twenty internal studies (for private use), three external presentations (OLED workshop-for public use), and five technology-related external presentations (industry conferences-for public use); and (8) issued five patent applications, which are in various maturity stages at time of publication. Delivery of thin film encapsulated white phosphorescent OLED lighting technology remains a challenging technical achievement, and it seems that commercial availability of thin, bright, white OLED light that meets market requirements will continue to require research and development effort. However, there will be glass encapsulated white OLED lighting products commercialized in niche markets during the 2008 calendar year. This commercialization effort, the project team believes, will lead to increasing market attention and broader demand for more efficient, wide area general purpose white OLED lighting in the coming years.« less

Nanoparticles Based on Chitosan as Carriers for the Combined Herbicides Imazapic and Imazapyr

PubMed Central

Maruyama, Cintia Rodrigues; Guilger, Mariana; Pascoli, Mônica; Bileshy-José, Natalia; Abhilash, P.C.; Fraceto, Leonardo Fernandes; de Lima, Renata

2016-01-01

The use of lower concentrations and fewer applications of herbicides is one of the prime objectives of the sustainable agriculture as it decreases the toxicity to non-targeted organisms and the risk of wider environmental contamination. In the present work, nanoparticles were developed for encapsulation of the herbicides imazapic and imazapyr. Alginate/chitosan and chitosan/tripolyphosphate nanoparticles were manufactured, and their physicochemical stability was evaluated. Determinations were made of the encapsulation efficiency and release kinetics, and the toxicity of the nanoparticles was evaluated using cytotoxicity and genotoxicity assays. The effects of herbicides and herbicide-loaded nanoparticles on soil microorganisms were studied in detail using real-time polymerase chain reactions. The nanoparticles showed an average size of 400 nm and remained stable during 30 days of storage at ambient temperature. Satisfactory encapsulation efficiencies of between 50 and 70% were achieved for both types of particles. Cytotoxicity assays showed that the encapsulated herbicides were less toxic, compared to the free compounds, and genotoxicity was decreased. Analyses of soil microbiota revealed changes in the bacteria of the soils exposed to the different treatments. Our study proves that encapsulation of the herbicides improved their mode of action and reduced their toxicity, indicating their suitability for use in future practical applications. PMID:26813942

Systemic delivery of insulin via the nasal route using a new microemulsion system: In vitro and in vivo studies.

PubMed

Sintov, Amnon C; Levy, Haim V; Botner, Shafir

2010-12-01

The main purpose of this study was to investigate the nasal absorption of insulin from a new microemulsion spray preparation in rabbits. The bioavailability of insulin lispro via the nasal route using a W/O microemulsion was found to reach 21.5% relative to subcutaneous administration, whereas the use of an inverse microemulsion as well as a plain solution yielded less than 1% bioavailability. The profile of plasma glucose levels obtained after nasal spray application of the microemulsion (1IU/kg lispro) was similar to the subcutaneous profile of 0.5IU/kg at the first 90min after application and resulted in a 30-40% drop in glucose levels. The microemulsion system was characterized by DLS, TEM, viscosity measurements, and by construction of pseudo-ternary phase diagram. The average droplet size of an insulin-unloaded and insulin-loaded microemulsions containing 20% aqueous phase (surfactants-to-oil ratio=87:13) was 2nm and 2.26nm in diameter, respectively. In addition, the effect of the microemulsion on FITC-labeled insulin permeation was examined across the porcine nasal mucosa in vitro. The permeability coefficient of FITC-insulin via the microemulsion was 0.210±0.048cm/h with a lag time of 10.9±6.5min, whereas the permeability coefficient from a plain solution was 0.082±0.043cm/h with a lag time of 36.3±10.1min. In view of the absorption differences of insulin between 20%, 50% water-containing microemulsions and an aqueous solution obtained in vitro and in vivo, it has been concluded that the acceleration in the intramucosal transport process is the result of encapsulating insulin within the nano-droplet clusters of a W/O microemulsion, while the microemulsion ingredients seems to have no direct role. Copyright © 2010 Elsevier B.V. All rights reserved.

Characterisation of the Poly-(Vinylpyrrolidone)-Poly-(Vinylacetate-Co-Crotonic Acid) (PVP:PVAc-CA) Interpolymer Complex Matrix Microparticles Encapsulating a Bifidobacterium lactis Bb12 Probiotic Strain.

PubMed

Mamvura, C I; Moolman, F S; Kalombo, L; Hall, A N; Thantsha, M S

2011-06-01

The method of producing poly-(vinylpyrrolidone)-poly-(vinylacetate-co-crotonic acid) (PVP:PVAc-CA) interpolymer complex matrix microparticles in supercritical carbon dioxide (scCO2), encapsulating bacteria, has recently been developed. This study was aimed at probing the external and internal structure of these microparticles, which can be used in food. The encapsulation efficiency and distribution of encapsulated Bifidobacterium lactis Bb12 within these microparticles were also investigated. Scanning electron microscopy (SEM) revealed irregular, mostly small, smooth microparticles with no visible bacterial cells on the surface. However, some of the microparticles appeared to have porous surfaces. The results of a Microtrac S3500 particle size analyzer showed that the PVP:PVAc-CA interpolymer complex matrix microparticles encapsulating B. lactis Bb12 had an average particle size of 166.1 μm (<350 μm designated standard size for microparticles). The D 10, D 50 and D 90 values for these microparticles were 48.16, 166.06 and 382.55 μm, respectively. Both SEM and confocal laser scanning microscopy showed a high density of bacterial cells within the microparticles. An average encapsulation efficiency of 96% was achieved. Consequently, the microparticles have the potential to be evenly distributed in foods, deliver adequate amounts of probiotics and produce minimal adverse effects on the texture and mouth feel of the foods into which they are incorporated.

Sol-gel encapsulation for controlled drug release and biosensing

NASA Astrophysics Data System (ADS)

Fang, Jonathan

The main focus of this dissertation is to investigate the use of sol-gel encapsulation of biomolecules for controlled drug release and biosensing. Controlled drug release has advantages over conventional therapies in that it maintains a constant, therapeutic drug level in the body for prolonged periods of time. The anti-hypertensive drug Captopril was encapsulated in sol-gel materials of various forms, such as silica xerogels and nanoparticles. The primary objective was to show that sol-gel silica materials are promising drug carriers for controlled release by releasing Captopril at a release rate that is within a therapeutic range. We were able to demonstrate desired release for over a week from Captopril-doped silica xerogels and overall release from Captopril-doped silica nanoparticles. As an aside, the antibiotic Vancomycin was also encapsulated in these porous silica nanoparticles and desired release was obtained for several days in-vitro. The second part of the dissertation focuses on immobilizing antibodies and proteins in sol-gel to detect various analytes, such as hormones and amino acids. Sol-gel competitive immunoassays on antibody-doped silica xerogels were used for hormone detection. Calibration for insulin and C-peptide in standard solutions was obtained in the nM range. In addition, NASA-Ames is also interested in developing a reagentless biosensor using bacterial periplasmic binding proteins (bPBPs) to detect specific biomarkers, such as amino acids and phosphate. These bPBPs were doubly labeled with two different fluorophores and encapsulated in silica xerogels. Ligand-binding experiments were performed on the bPBPs in solution and in sol-gel. Ligand-binding was monitored by fluorescence resonance energy transfer (FRET) between the two fluorophores on the bPBP. Titration data show that one bPBP has retained its ligand-binding properties in sol-gel.

Micro-Encapsulation of non-aqueous solvents for energy-efficient carbon capture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stolaroff, Joshua K; Ye, Congwang; Oakdale, James

Here, we demonstrate micro-encapsulation of several promising designer solvents: an IL, PCIL, and CO2BOL. We develop custom polymers that cure by UV light in the presence of each solvent while maintaining high CO2 permeability. We use several new process strategies to accommodate the viscosity and phase changes. We then measure and compare the CO2 absorption rate and capacity as well as the multi-cycle performance of the encapsulated solvents. These results are compared with previous work on encapsulated sodium carbonate solution. The prospects for designer solvents to reduce the cost of post-combustion capture and the implications for process design with encapsulatedmore » solvents are discussed.« less

Controlled-release of tea polyphenol from gelatin films incorporated with different ratios of free/nanoencapsulated tea polyphenols into fatty food simulants

USDA-ARS?s Scientific Manuscript database

Gelatin films having controlled-release properties were developed by incorporation of different free/encapsulated tea polyphenol (TP) ratios through modifying the encapsulation efficiency (EE) of TP-loaded chitosan nanoparticles. Different EEs were obtained by adjusting the chitosan hydrochloride (C...

Thermal Analysis of Fluidized Bed and Fixed Bed Latent Heat Thermal Storage System

NASA Astrophysics Data System (ADS)

Beemkumar, N.; Karthikeyan, A.; Shiva Keshava Reddy, Kota; Rajesh, Kona; Anderson, A.

2017-05-01

Thermal energy storage technology is essential because its stores available energy at low cost. Objective of the work is to store the thermal energy in a most efficient method. This work is deal with thermal analysis of fluidized bed and fixed bed latent heat thermal storage (LHTS) system with different encapsulation materials (aluminium, brass and copper). D-Mannitol has been used as phase change material (PCM). Encapsulation material which is in orbicular shape with 4 inch diameter and 2 mm thickness orbicular shaped product is used. Therminol-66 is used as a heat transfer fluid (HTF). Arrangement of encapsulation material is done in two ways namely fluidized bed and fixed bed thermal storage system. Comparison was made between the performance of fixed bed and fluidized bed with different encapsulation material. It is observed that from the economical point of view aluminium in fluidized bed LHTS System has highest efficiency than copper and brass. The thermal energy storage system can be analyzed with fixed bed by varying mass flow rate of oil paves a way to find effective heat energy transfer.

Formulation of chitosan-TPP-pDNA nanocapsules for gene therapy applications

NASA Astrophysics Data System (ADS)

Gaspar, V. M.; Sousa, F.; Queiroz, J. A.; Correia, I. J.

2011-01-01

The encapsulation of DNA inside nanoparticles meant for gene delivery applications is a challenging process where several parameters need to be modulated in order to design nanocapsules with specific tailored characteristics. The purpose of this study was to investigate and improve the formulation parameters of plasmid DNA (pDNA) loaded in chitosan nanocapsules using tripolyphosphate (TPP) as polyanionic crosslinker. Nanocapsule morphology and encapsulation efficiency were analyzed as a function of chitosan degree of deacetylation and chitosan-TPP ratio. The manipulation of these parameters influenced not only the particle size but also the encapsulation and release of pDNA. Consequently the transfection efficiency of the nanoparticulated systems was also enhanced with the optimization of the particle characteristics. Overall, the differently formulated nanoparticulated systems possess singular properties that can be employed according to the desired gene delivery application.

Geraniol encapsulated in chitosan/gum arabic nanoparticles: a promising system for pest management in sustainable agriculture.

PubMed

de Oliveira, Jhones Luiz; Campos, Estefania Vangelie Ramos; Pereira, Anderson E S; Nunes, Lucas E S; da Silva, Camila C L; Pasquoto, Tatiane; Lima, Renata; Smaniotto, Giovani; Polanczyk, Ricardo Antonio; Fraceto, Leonardo F

2018-05-07

The nanoencapsulation of botanical compounds (such as geraniol) is an important strategy that can be used to increase the stability and efficiency of these substances in integrated pest management. In this study, chitosan/gum arabic nanoparticles containing geraniol were prepared and characterized. In addition, evaluation was made of the biological activity of geraniol encapsulated in chitosan/gum arabic nanoparticles towards whitefly (Bemisia tabaci). The optimized formulation showed a high encapsulation efficiency (>90%) and remained stable for about 120 days. The formulation protected the geraniol against degradation by UV radiation, and the in vitro release was according to a diffusion mechanism that was influenced by temperature. An attraction effect was observed for Bemisia tabaci, indicating the potential of this type of system for use in pest management, especially in trap devices.

Low Hysteresis Carbon Nanotube Transistors Constructed via a General Dry-Laminating Encapsulation Method on Diverse Surfaces.

PubMed

Yang, Yi; Wang, Zhongwu; Xu, Zeyang; Wu, Kunjie; Yu, Xiaoqin; Chen, Xiaosong; Meng, Yancheng; Li, Hongwei; Qiu, Song; Jin, Hehua; Li, Liqiang; Li, Qingwen

2017-04-26

Electrical hysteresis in carbon nanotube thin-film transistor (CNTTFT) due to surface adsorption of H 2 O/O 2 is a severe obstacle for practical applications. The conventional encapsulation methods based on vacuum-deposited inorganic materials or wet-coated organic materials have some limitations. In this work, we develop a general and highly efficient dry-laminating encapsulation method to reduce the hysteresis of CNTTFTs, which may simultaneously realize the construction and encapsulation of CNTTFT. Furthermore, by virtue of dry procedure and wide compatibility of PMMA, this method is suitable for the construction of CNTTFT on diverse surface including both inorganic and organic dielectric materials. Significantly, the dry-encapsulated CNTTFT exhibits very low or even negligible hysteresis with good repeatability and air stability, which is greatly superior to the nonencapsulated and wet-encapsulated CNTTFT with spin-coated PMMA. The dry-laminating encapsulation strategy, a kind of technological innovation, resolves a significant problem of CNTTFT and therefore will be promising in facile transferring and packaging the CNT films for high-performance optoelectronic devices.

Long-term Efficacy and Biocompatibility of Encapsulated Islet Transplantation With Chitosan-Coated Alginate Capsules in Mice and Canine Models of Diabetes.

PubMed

Yang, Hae Kyung; Ham, Dong-Sik; Park, Heon-Seok; Rhee, Marie; You, Young Hye; Kim, Min Jung; Shin, Juyoung; Kim, On-You; Khang, Gilson; Hong, Tae Ho; Kim, Ji-Won; Lee, Seung-Hwan; Cho, Jae-Hyoung; Yoon, Kun-Ho

2016-02-01

Clinical application of encapsulated islet transplantation is hindered by low biocompatibility of capsules leading to pericapsular fibrosis and decreased islet viability. To improve biocompatibility, we designed a novel chitosan-coated alginate capsules and compared them to uncoated alginate capsules. Alginate capsules were formed by crosslinking with BaCl2, then they were suspended in chitosan solution for 10 minutes at pH 4.5. Xenogeneic islet transplantation, using encapsulated porcine islets in 1,3-galactosyltransferase knockout mice, and allogeneic islet transplantation, using encapsulated canine islets in beagles, were performed without immunosuppressants. The chitosan-alginate capsules showed similar pore size, islet viability, and insulin secretory function compared to alginate capsules, in vitro. Xenogeneic transplantation of chitosan-alginate capsules demonstrated a trend toward superior graft survival (P = 0.07) with significantly less pericapsular fibrosis (cell adhesion score: 3.77 ± 0.41 vs 8.08 ± 0.05; P < 0.001) compared to that of alginate capsules up to 1 year after transplantation. Allogeneic transplantation of chitosan-alginate capsules normalized the blood glucose level up to 1 year with little evidence of pericapsular fibrotic overgrowth on graft explantation. The efficacy and biocompatibility of chitosan-alginate capsules were demonstrated in xenogeneic and allogeneic islet transplantations using small and large animal models of diabetes. This capsule might be a potential candidate applicable in the treatment of type 1 diabetes mellitus patients, and further studies in nonhuman primates are required.

Design of a vascularized synthetic poly(ethylene glycol) macroencapsulation device for islet transplantation.

PubMed

Weaver, Jessica D; Headen, Devon M; Hunckler, Michael D; Coronel, Maria M; Stabler, Cherie L; García, Andrés J

2018-07-01

The use of immunoisolating macrodevices in islet transplantation confers the benefit of safety and translatability by containing transplanted cells within a single retrievable device. To date, there has been limited development and characterization of synthetic poly(ethylene glycol) (PEG)-based hydrogel macrodevices for islet encapsulation and transplantation. Herein, we describe a two-component synthetic PEG hydrogel macrodevice system, designed for islet delivery to an extrahepatic islet transplant site, consisting of a hydrogel core cross-linked with a non-degradable PEG dithiol and a vasculogenic outer layer cross-linked with a proteolytically sensitive peptide to promote degradation and enhance localized vascularization. Synthetic PEG macrodevices exhibited equivalent passive molecular transport to traditional microencapsulation materials (e.g., alginate) and long-term stability in the presence of proteases in vitro and in vivo, out to 14 weeks in rats. Encapsulated islets demonstrated high viability within the device in vitro and the incorporation of RGD adhesive peptides within the islet encapsulating PEG hydrogel improved insulin responsiveness to a glucose challenge. In vivo, the implementation of a vasculogenic, degradable hydrogel layer at the outer interface of the macrodevice enhanced vascular density within the rat omentum transplant site, resulting in improved encapsulated islet viability in a syngeneic diabetic rat model. These results highlight the benefits of the facile PEG platform to provide controlled presentation of islet-supportive ligands, as well as degradable interfaces for the promotion of engraftment and overall graft efficacy. Copyright © 2018 Elsevier Ltd. All rights reserved.

High-oil-load encapsulation of medium-chain triglycerides and D-limonene mixture in modified starch by spray drying.

PubMed

Paramita, Vita; Furuta, Takeshi; Yoshii, Hidefumi

2012-02-01

Oil mixtures of medium-chain triglycerides (MCT) and D-limonene in mixing ratios from 10 to 100 wt% were encapsulated in modified starch (wall material) by spray drying to produce oil-rich powders. The oil load (mass ratio of oil mixture to wall material) of the infeed emulsion markedly influenced the properties of the infeed liquid and the characteristics of the resulting powder. The viscosity of the infeed liquid and the particle size of the powder exponentially decreased with increasing oil load, while the emulsion droplet size in the infeed liquid increased. In addition, retention of D-limonene during spray drying also decreased markedly with increasing oil load. Irrespective of the different oil loads and concentrations of the wall material, D-limonene retention was well correlated with the emulsion droplet diameter of the infeed liquid. The encapsulation efficiency of the oil mixture exhibited a maximum value (almost 100%) at an oil load between 0.5 and 1.0, before decreasing at higher oil loads. At an oil load of 2.0, the encapsulation efficiency of D-limonene was reduced to almost zero, while around 40% of the initial MCT was encapsulated in the powder. The increase in oil load also led to increased amounts of surface oil of MCT and D-limonene in the resulting powder due to the increasing emulsion droplet diameter of the infeed liquids. This study proposes the microencapsulation of medium-chain triglycerides under high-oil-load conditions by spray drying. The powders prepared by this process provide significant benefits in terms of rapid energy conversion after consumption without accumulation in the body. Important quality factors of the powder products such as the encapsulation efficiency and the amount of surface oil were examined to understand the optimum process conditions for spray drying. © 2012 Institute of Food Technologists®

Cellular Trojan horse based polymer nanoreactors with light-sensitive activity.

PubMed

Baumann, Patric; Spulber, Mariana; Dinu, Ionel Adrian; Palivan, Cornelia G

2014-08-07

Stimulus-sensitive systems at the nanoscale represent ideal candidates for improving therapeutic and diagnostic approaches by producing rapid responses to the presence of specific molecules or conditions either by changing properties or by acting "on demand". Here we introduce an optimized light-sensitive nanoreactor based on encapsulation of a photosensitizer inside polymer vesicles to serve as an efficient source of reactive oxygen species (ROS) "on demand". Two types of amphiphilic block copolymers, poly(2-methyloxazoline)-block-poly(dimethylsiloxane)-block-poly(2-methyloxazoline), PMOXA-PDMS-PMOXA, and poly(N-vinylpyrrolidone)-block-poly(dimethylsiloxane)-block-poly(N-vinylpyrrolidone), PNVP-PDMS-PNVP, were used to encapsulate Rose Bengal-bovine serum albumin (RB-BSA) inside the cavity of vesicles. The difference of copolymers molecular properties (hydrophobic to hydrophilic ratio, different chemical nature of the hydrophilic block) influenced the encapsulation ability, and uptake by cells, allowing therefore a selection of the most efficient polymer system. Nanoreactors were optimized in terms of (i) size, (ii) stability, and (iii) encapsulation efficiency based on a combination of light scattering, TEM, and UV-vis spectroscopy. By illumination, encapsulated RB-BSA conjugates generated in situ ROS, which diffused through the polymer membrane to the environment of the vesicles, as proved by electron spin resonance spectroscopy (ESR). Optimum illumination conditions were obtained based on the effect of the illumination time on the amount of ROS produced in situ by the encapsulated RB-BSA conjugates. ROS diffusion monitored by ESR was dependent on the molecular weight of copolymer that influences the thickness of the polymer membrane. Upon uptake into HeLa cells our nontoxic nanoreactors acted as a Trojan horse: they produced illumination-controlled ROS in sufficient amounts to induce cell death under photodynamic therapy (PDT) conditions. Straightforward production, stability, and Trojan horse activity inside cells support our light-sensitive nanoreactors for medical applications which require ROS to be generated with precise time and space control.

Effect of lecithin and starch on alginate-encapsulated probiotic bacteria.

PubMed

Donthidi, A R; Tester, R F; Aidoo, K E

2010-01-01

The effect of lecithin and starch on viability of alginate encapsulated probiotics was determined at different temperatures. Probiotic organisms (1% v/v>10Log CFU ml(-1)) were encapsulated using alginate (2% w/v), gelatinized starches (2% w/v) and lecithin (0-4% w/v) and stored in sealed containers at 4, 23 and 37 degrees C (to simulate shelf storage conditions). Incorporation of lecithin improved the entrapment efficiency (p < 0.05) and the viability of encapsulated bacteria (p = 0.02). Encapsulated Lactobacillus, Bifidobacterium species and Lactococcus lactis in lecithin containing freeze-dried beads had good survival stability (above 6Log CFU ml(-1)) at 23 degrees C for 12 weeks. The bacteria in the beads showed 6Log survival by the end of 2 weeks at 37 degrees C. Encapsulated L. casei in the alginate beads containing lecithin were also more stable in the yoghurt than the beads without lecithin. SEM analysis of the beads showed an irregular surface for the beads without lecithin.

Encapsulation of antioxidant phenolic compounds extracted from spent coffee grounds by freeze-drying and spray-drying using different coating materials.

PubMed

Ballesteros, Lina F; Ramirez, Monica J; Orrego, Carlos E; Teixeira, José A; Mussatto, Solange I

2017-12-15

Freeze-drying and spray-drying techniques were evaluated for encapsulation of phenolic compounds (PC) extracted from spent coffee grounds. Additionally, the use of maltodextrin, gum arabic and a mixture of these components (ratio 1:1) as wall material to retain the PC and preserve their antioxidant activity was also assessed. The contents of PC and flavonoids (FLA), as well as the antioxidant activity of the encapsulated samples were determined in order to verify the efficiency of each studied condition. Additional analyses for characterization of the samples were also performed. Both the technique and the coating material greatly influenced the encapsulation of antioxidant PC. The best results were achieved when PC were encapsulated by freeze-drying using maltodextrin as wall material. Under these conditions, the amount of PC and FLA retained in the encapsulated sample corresponded to 62% and 73%, respectively, and 73-86% of the antioxidant activity present in the original extract was preserved. Copyright © 2017 Elsevier Ltd. All rights reserved.

Encapsulation of lycopene in Chlorella pyrenoidosa: Loading properties and stability improvement.

PubMed

Pu, Chuanfen; Tang, Wenting

2017-11-15

Aiming to improve the stability of lycopene and incorporate it into a complex nutraceutical, exogenous lycopene-loaded Chlorella pyrenoidosa cells (CPCs) were developed. The complex had an encapsulation yield of 13.06±0.89% and an encapsulation efficiency of 96.31±3.10%. Fluorescence analyses indicated that lycopene was encapsulated in the CPCs. X-ray diffraction, thermogravimetric and differential scanning calorimetric analyses were conducted and compared to those of the non-loaded CPCs, lycopene and their physical mixture. These studies demonstrated that lycopene was amorphous in the complex. The degradation kinetics indicated that encapsulation increased the stability of lycopene. The antioxidant activity of lycopene loaded CPCs against DPPH free radicals was higher than that of the unencapsulated lycopene after storage at 25°C for 25d. This study proved the feasibility of encapsulation of lycopene in the CPCs and combined the activities of both materials, which could be employed in the production of novel nutraceuticals to reduce oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

Encapsulation of Nucleic Acids into Giant Unilamellar Vesicles by Freeze-Thaw: a Way Protocells May Form

NASA Astrophysics Data System (ADS)

Qiao, Hai; Hu, Na; Bai, Jin; Ren, Lili; Liu, Qing; Fang, Liaoqiong; Wang, Zhibiao

2017-12-01

Protocells are believed to consist of a lipid membrane and encapsulated nucleic acid. As the lipid membrane is impermeable to macromolecules like nucleic acids, the processes by which nucleic acids become encapsulated inside lipid membrane compartments are still unknown. In this paper, a freeze-thaw method was modified and applied to giant unilamellar vesicles (GUVs) and deoxyribonucleic acid (DNA) in mixed solution resulting in the efficient encapsulation of 6.4 kb plasmid DNA and similar length linear DNA into GUVs. The mechanism of encapsulation was followed by observing the effect of freeze-thaw temperatures on GUV morphological change, DNA encapsulation and ice crystal formation, and analyzing their correlation. Following ice crystal formation, the shape of spherical GUVs was altered and membrane integrity was damaged and this was found to be a necessary condition for encapsulation. Heating alone had no effects on DNA encapsulation, but was helpful for restoring the spherical shape and membrane integrity of GUVs damaged during freezing. These results suggested that freeze-thaw could promote the encapsulation of DNA into GUVs by a mechanism: the vesicle membrane was breached by ice crystal formation during freezing, DNA entered into damaged GUVs through these membrane gaps and was encapsulated after the membrane was resealed during the thawing process. The process described herein therefore describes a simple way for the encapsulation of nucleic acids and potentially other macromolecules into lipid vesicles, a process by which early protocells might have formed.

Amidase encapsulated O-carboxymethyl chitosan nanoparticles for vaccine delivery.

PubMed

Smitha, K T; Sreelakshmi, M; Nisha, N; Jayakumar, R; Biswas, Raja

2014-02-01

This work reports the development of amidase encapsulated O-carboxymethyl chitosan nanoparticles (Ami-O-CMC NPs) of 300±50 nm size by ionic cross-linking method. The prepared Ami-O-CMC NPs had an encapsulation efficiency of 55.39%. Haemolysis assay and cytotoxicity studies proved the hemocompatibility and cytocompatibility of the prepared NPs. The sustained release of Ami from the NPs is expected to prolong its immunogenicity and in turn lead to development of better protective immunity against Staphylococcus aureus infections. Copyright © 2013 Elsevier B.V. All rights reserved.

PLGA nanoparticle-mediated delivery of tumor antigenic peptides elicits effective immune responses

PubMed Central

Ma, Wenxue; Chen, Mingshui; Kaushal, Sharmeela; McElroy, Michele; Zhang, Yu; Ozkan, Cengiz; Bouvet, Michael; Kruse, Carol; Grotjahn, Douglas; Ichim, Thomas; Minev, Boris

2012-01-01

The peptide vaccine clinical trials encountered limited success because of difficulties associated with stability and delivery, resulting in inefficient antigen presentation and low response rates in patients with cancer. The purpose of this study was to develop a novel delivery approach for tumor antigenic peptides in order to elicit enhanced immune responses using poly(DL-lactide-co-glycolide) nanoparticles (PLGA-NPs) encapsulating tumor antigenic peptides. PLGA-NPs were made using the double emulsion-solvent evaporation method. Artificial antigen-presenting cells were generated by human dendritic cells (DCs) loaded with PLGA-NPs encapsulating tumor antigenic peptide(s). The efficiency of the antigen presentation was measured by interferon-γ ELISpot assay (Vector Laboratories, Burlingame, CA). Antigen-specific cytotoxic T lymphocytes (CTLs) were generated and evaluated by CytoTox 96® Non-Radioactive Cytotoxicity Assay (Promega, Fitchburg, WI). The efficiency of the peptide delivery was compared between the methods of emulsification in incomplete Freund’s adjuvant and encapsulation in PLGA-NPs. Our results showed that most of the PLGA-NPs were from 150 nm to 500 nm in diameter, and were negatively charged at pH 7.4 with a mean zeta potential of −15.53 ± 0.71 mV; the PLGA-NPs could be colocalized in human DCs in 30 minutes of incubation. Human DCs loaded with PLGA-NPs encapsulating peptide induced significantly stronger CTL cytotoxicity than those pulsed with free peptide, while human DCs loaded with PLGA-NPs encapsulating a three-peptide cocktail induced a significantly greater CTL response than those encapsulating a two-peptide cocktail. Most importantly, the peptide dose encapsulated in PLGA-NPs was 63 times less than that emulsified in incomplete Freund’s adjuvant, but it induced a more powerful CTL response in vivo. These results demonstrate that the delivery of peptides encapsulated in PLGA-NPs is a promising approach to induce effective antitumor CTL responses in vivo. PMID:22619507

PLGA nanoparticle-mediated delivery of tumor antigenic peptides elicits effective immune responses.

PubMed

Ma, Wenxue; Chen, Mingshui; Kaushal, Sharmeela; McElroy, Michele; Zhang, Yu; Ozkan, Cengiz; Bouvet, Michael; Kruse, Carol; Grotjahn, Douglas; Ichim, Thomas; Minev, Boris

2012-01-01

The peptide vaccine clinical trials encountered limited success because of difficulties associated with stability and delivery, resulting in inefficient antigen presentation and low response rates in patients with cancer. The purpose of this study was to develop a novel delivery approach for tumor antigenic peptides in order to elicit enhanced immune responses using poly(DL-lactide-co-glycolide) nanoparticles (PLGA-NPs) encapsulating tumor antigenic peptides. PLGA-NPs were made using the double emulsion-solvent evaporation method. Artificial antigen-presenting cells were generated by human dendritic cells (DCs) loaded with PLGA-NPs encapsulating tumor antigenic peptide(s). The efficiency of the antigen presentation was measured by interferon-γ ELISpot assay (Vector Laboratories, Burlingame, CA). Antigen-specific cytotoxic T lymphocytes (CTLs) were generated and evaluated by CytoTox 96(®) Non-Radioactive Cytotoxicity Assay (Promega, Fitchburg, WI). The efficiency of the peptide delivery was compared between the methods of emulsification in incomplete Freund's adjuvant and encapsulation in PLGA-NPs. Our results showed that most of the PLGA-NPs were from 150 nm to 500 nm in diameter, and were negatively charged at pH 7.4 with a mean zeta potential of -15.53 ± 0.71 mV; the PLGA-NPs could be colocalized in human DCs in 30 minutes of incubation. Human DCs loaded with PLGA-NPs encapsulating peptide induced significantly stronger CTL cytotoxicity than those pulsed with free peptide, while human DCs loaded with PLGA-NPs encapsulating a three-peptide cocktail induced a significantly greater CTL response than those encapsulating a two-peptide cocktail. Most importantly, the peptide dose encapsulated in PLGA-NPs was 63 times less than that emulsified in incomplete Freund's adjuvant, but it induced a more powerful CTL response in vivo. These results demonstrate that the delivery of peptides encapsulated in PLGA-NPs is a promising approach to induce effective antitumor CTL responses in vivo.

Efficient gene transfection to the brain with ultrasound irradiation in mice using stabilized bubble lipopolyplexes prepared by the surface charge regulation method.

PubMed

Ogawa, Koki; Fuchigami, Yuki; Hagimori, Masayori; Fumoto, Shintaro; Miura, Yusuke; Kawakami, Shigeru

2018-01-01

We previously developed anionic ternary bubble lipopolyplexes, an ultrasound-responsive carrier, expecting safe and efficient gene transfection. However, bubble lipopolyplexes have a low capacity for echo gas (C 3 F 8 ) encapsulation (EGE) in nonionic solution such as 5% glucose. On the other hand, we were able to prepare bubble lipopolyplexes by inserting phosphate-buffered saline before C 3 F 8 encapsulation. Surface charge regulation (SCR) by electrolytes stabilizes liposome/plasmid DNA (pDNA) complexes by accelerated membrane fusion. Considering these facts, we hypothesized that SCR by electrolytes such as NaCl would promote C 3 F 8 encapsulation in bubble lipopolyplexes mediated by accelerated membrane fusion. We defined this hypothesis as SCR-based EGE (SCR-EGE). Bubble lipopolyplexes prepared by the SCR-EGE method (SCR-EGE bubble lipopolyplexes) are expected to facilitate the gene transfection because of the high amount of C 3 F 8 . Therefore, we applied these methods for gene delivery to the brain and evaluated the characteristics of transgene expression in the brain. First, we measured the encapsulation efficiency of C 3 F 8 in SCR-EGE bubble lipopolyplexes. Next, we applied these bubble lipopolyplexes to the mouse brain; then, we evaluated the transfection efficiency. Furthermore, three-dimensional transgene distribution was observed using multicolor deep imaging. SCR-EGE bubble lipopolyplexes had a higher C 3 F 8 content than conventional bubble lipopolyplexes. In terms of safety, SCR-EGE bubble lipopolyplexes possessed an anionic potential and showed no aggregation with erythrocytes. After applying SCR-EGE bubble lipopolyplexes to the brain, high transgene expression was observed by combining with ultrasound irradiation. As a result, transgene expression mediated by SCR-EGE bubble lipopolyplexes was observed mainly on blood vessels and partially outside of blood vessels. The SCR-EGE method may promote C 3 F 8 encapsulation in bubble lipopolyplexes, and SCR-EGE bubble lipopolyplexes may be potent carriers for efficient and safe gene transfection in the brain, especially to the blood vessels.

Lipid Encapsulation Provides Insufficient Total-Tract Digestibility to Achieve an Optimal Transfer Efficiency of Fatty Acids to Milk Fat

PubMed Central

Bainbridge, Melissa; Kraft, Jana

2016-01-01

Transfer efficiencies of rumen-protected n-3 fatty acids (FA) to milk are low, thus we hypothesized that rumen-protection technologies allow for biohydrogenation and excretion of n-3 FA. The objectives of this study were to i) investigate the ruminal protection and post-ruminal release of the FA derived from the lipid-encapsulated echium oil (EEO), and ii) assess the bioavailability and metabolism of the EEO-derived FA through measuring the FA content in plasma lipid fractions, feces, and milk. The EEO was tested for rumen stability using the in situ nylon bag technique, then the apparent total-tract digestibility was assessed in vivo using six Holstein dairy cattle. Diets consisted of a control (no EEO); 1.5% of dry matter (DM) as EEO and 1.5% DM as encapsulation matrix; and 3% DM as EEO. The EEO was rumen-stable and had no effect on animal production. EEO-derived FA were incorporated into all plasma lipid fractions, with the highest proportion of n-3 FA observed in cholesterol esters. Fecal excretion of EEO-derived FA ranged from 7–14%. Biohydrogenation products increased in milk, plasma, and feces with EEO supplementation. In conclusion, lipid-encapsulation provides inadequate digestibility to achieve an optimal transfer efficiency of n-3 FA to milk. PMID:27741299

Development and characterization of polymer-oil nanostructured carrier (PONC) for controlled delivery of all-trans retinoic acid (ATRA)

NASA Astrophysics Data System (ADS)

Narvekar, Mayuri M.

The commonly used PLGA-based delivery systems are often limited by their inadequate drug loading and release properties. This study reports the integration of oil into PLGA to form the prototype of a hybrid drug carrier PONC. Our primary goal is to confer the key strength of lipid-based drug carriers, i.e. efficient encapsulation of lipophilic compounds, to a PLGA system without taking away its various useful qualities. The PONC were formulated by emulsification solvent evaporation technique, which were then characterized for particle size, encapsulation efficiency, drug release and anticancer efficacy. The ATRA loaded PONC showed excellent encapsulation efficiency and release kinetics. Even after surface functionalization with PEG , controlled drug release kinetics was maintained, with 88.5% of the encapsulated ATRA released from the PEG-PONC in a uniform manner over 120 hours. It also showed favorable physicochemical properties and serum stability. PEG-PONC has demonstrated substantially superior activity over the free ATRA in ovarian cancer cells that are non-responsive to the standard chemotherapy. The newly developed PEG-PONC significantly reduced the IC50 values (p<0.05) in the chemoresistant cells in both MTT and colony formation assays. Hence, this new ATRA-nanoformulation may offer promising means for the delivery of lipophilic compounds like all-trans retinoic acid to treat highly resistant ovarian cancer.

Fabrication of composite poly(d,l-lactide)/montmorillonite nanoparticles for controlled delivery of acetaminophen by solvent-displacement method using glass capillary microfluidics.

PubMed

Othman, Rahimah; Vladisavljević, Goran T; Thomas, Noreen L; Nagy, Zoltan K

2016-05-01

Paracetamol (PCM)-loaded composite nanoparticles (NPs) composed of a biodegradable poly(d,l-lactide) (PLA) polymer matrix filled with organically modified montmorillonite (MMT) nanoparticles were fabricated by antisolvent nanoprecipitation in a microfluidic co-flow glass capillary device. The incorporation of MMT in the polymer improved both the drug encapsulation efficiency and the drug loading, and extended the rate of drug release in simulated intestinal fluid (pH 7.4). The particle size increased on increasing both the drug loading and the concentration of MMT in the polymer matrix, and decreased on increasing the aqueous to organic flow rate ratio. The drug encapsulation efficiency in the NPs was higher at higher aqueous to organic flow rate ratio due to faster formation of the NPs. The PCM-loaded PLA NPs containing 2 wt% MMT in PLA prepared at an aqueous to organic flow rate ratio of 10 with an orifice size of 200 μm exhibited a spherical shape with a mean size of 296 nm, a drug encapsulation efficiency of 38.5% and a drug loading of 5.4%. The encapsulation of MMT and PCM in the NPs was confirmed by transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis and attenuated total reflection-Fourier transform infrared spectroscopy. Copyright © 2016 Elsevier B.V. All rights reserved.

Durable Control of Autoimmune Diabetes in Mice Achieved by Intraperitoneal Transplantation of “Neo‐Islets,” Three‐Dimensional Aggregates of Allogeneic Islet and “Mesenchymal Stem Cells”

PubMed Central

Gooch, Anna; Hu, Zhuma; Ahlstrom, Jon; Zhang, Ping

2017-01-01

Abstract Novel interventions that reestablish endogenous insulin secretion and thereby halt progressive end‐organ damage and prolong survival of patients with autoimmune Type 1 diabetes mellitus (T1DM) are urgently needed. While this is currently accomplished with allogeneic pancreas or islet transplants, their utility is significantly limited by both the scarcity of organ donors and life‐long need for often‐toxic antirejection drugs. Coadministering islets with bone marrow‐derived mesenchymal stem cells (MSCs) that exert robust immune‐modulating, anti‐inflammatory, anti‐apoptotic, and angiogenic actions, improves intrahepatic islet survival and function. Encapsulation of insulin‐producing cells to prevent immune destruction has shown both promise and failures. Recently, stem cell‐derived insulin secreting β‐like cells induced euglycemia in diabetic animals, although their clinical use would still require encapsulation or anti‐rejection drugs. Instead of focusing on further improvements in islet transplantation, we demonstrate here that the intraperitoneal administration of islet‐sized “Neo‐Islets” (NIs), generated by in vitro coaggregation of allogeneic, culture‐expanded islet cells with high numbers of immuno‐protective and cyto‐protective MSCs, resulted in their omental engraftment in immune‐competent, spontaneously diabetic nonobese diabetic (NOD) mice. This achieved long‐term glycemic control without immunosuppression and without hypoglycemia. In preparation for an Food and Drug Administration‐approved clinical trial in dogs with T1DM, we show that treatment of streptozotocin‐diabetic NOD/severe combined immunodeficiency mice with identically formed canine NIs produced durable euglycemia, exclusively mediated by dog‐specific insulin. We conclude that this novel technology has significant translational relevance for canine and potentially clinical T1DM as it effectively addresses both the organ donor scarcity (>80 therapeutic NI doses/donor pancreas can be generated) and completely eliminates the need for immunosuppression. Stem Cells Translational Medicine 2017;6:1631–1643 PMID:28467694

Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo

NASA Astrophysics Data System (ADS)

Gou, Maling; Men, Ke; Shi, Huashan; Xiang, Mingli; Zhang, Juan; Song, Jia; Long, Jianlin; Wan, Yang; Luo, Feng; Zhao, Xia; Qian, Zhiyong

2011-04-01

Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 +/- 0.011) with a mean particle size of 27.3 +/- 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 +/- 1.02%, and drug loading of 12.95 +/- 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t1/2 and AUC of curcuminin vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesisin vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cellsin vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg-1curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p < 0.01), and induced a stronger anticancer effect than that of free curcumin (p < 0.05). In conclusion, Cur/MPEG-PCL micelles are an excellent intravenously injectable aqueous formulation of curcumin; this formulation can inhibit the growth of colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.

Phosphatidylcholine nanovesicles coated with chitosan or chondroitin sulfate as novel devices for bacteriocin delivery

NASA Astrophysics Data System (ADS)

da Silva, Indjara Mallmann; Boelter, Juliana Ferreira; da Silveira, Nádya Pesce; Brandelli, Adriano

2014-07-01

There is increased interest on the use of natural antimicrobial peptides in biomedicine and food preservation technologies. In this study, the antimicrobial activity of nisin encapsulated into nanovesicles containing polyanionic polysaccharides was investigated. Nisin was encapsulated in phosphatidylcholine (PC) liposomes containing chitosan or chondroitin sulfate by the thin-film hydration method and tested for antimicrobial activity against Listeria spp. The mean particle size of PC liposomes was 145 nm and varied to 210 and 134 nm with the incorporation of chitosan and chondroitin sulfate, respectively. Nisin-containing nanovesicles with and without incorporation of polysaccharides had a zeta potential values around -20 mV, showing mostly spherical structures when observed by transmission electron microscopy. Encapsulated nisin had similar efficiency as free nisin in inhibiting Listeria spp. isolated from bovine carcass, and greater efficiency in inhibiting Listeria monocytogenes. The formulation containing chitosan was more stable and more efficient in inhibiting L. monocytogenes when compared to the other nanovesicles tested. After 24 h, the viable cell counts were 2 log lower as compared with the other treatments and 7 log comparing to controls.

Microencapsulation of soybean oil by spray drying using oleosomes

NASA Astrophysics Data System (ADS)

Maurer, S.; Ghebremedhin, M.; Zielbauer, B. I.; Knorr, D.; Vilgis, T. A.

2016-02-01

The food industry has discovered that oleosomes are beneficial as carriers of bioactive ingredients. Oleosomes are subcellular oil droplets typically found in plant seeds. Within seeds, they exist as pre-emulsified oil high in unsaturated fatty acids, stabilised by a monolayer of phospholipids and proteins, called oleosins. Oleosins are anchored into the oil core with a hydrophobic domain, while the hydrophilic domains remain on the oleosome surface. To preserve the nutritional value of the oil and the function of oleosomes, microencapsulation by means of spray drying is a promising technique. For the microencapsulation of oleosomes, maltodextrin was used. To achieve a high oil encapsulation efficiency, optimal process parameters needed to be established. In order to better understand the mechanisms of drying behind powder formation and the associated powder properties, the findings obtained using different microscopic and spectroscopic measurements were correlated with each other. By doing this, it was found that spray drying of pure oleosome emulsions resulted in excessive component segregation and thus in a poor encapsulation efficiency. With the addition of maltodextrin, the oil encapsulation efficiency was significantly improved.

Antioxidant activity from encapsulated Cinnamaldehyde-Chitosan

NASA Astrophysics Data System (ADS)

Ariestiani, Bonita; Purbowatingrum; Ngadiwiyana; Ismiyarto; Fachriyah, Enny; Nurani, Khikmah

2018-05-01

Cinnamaldehyde compound is a powerful antioxidant agent that can effectively combat the free radicals referred to superoxide anions and hydroxy radicals, as well as other free radicals in in vitro testing. An antioxidant is an electron donor or reductant. antioxidants are also compounds that can inhibit oxidation reactions by binding to free radicals and highly reactive molecules. As a result, cell damage will be inhibited. However, the use of this compound still provides unsatisfactory results due to its degradation during the absorption process. The solution offered to solve the problem is by encapsulated it within chitosan nanoparticles that serve to protect the bioactive compound from degradation, increases of solubility and delivery of a bioactive compound to the target site by using freeze-drying technique. The value of encapsulation efficiency (EE) of cinnamaldyhde which encapsulated within chitosan nanoparticles is about 74,389% also antioxidant activity test showed that cinnamaldehyde encapsulated by nanochitosan could inhibit free radicals of 223.44 in IC50.

Stable metal-organic frameworks containing single-molecule traps for enzyme encapsulation.

PubMed

Feng, Dawei; Liu, Tian-Fu; Su, Jie; Bosch, Mathieu; Wei, Zhangwen; Wan, Wei; Yuan, Daqiang; Chen, Ying-Pin; Wang, Xuan; Wang, Kecheng; Lian, Xizhen; Gu, Zhi-Yuan; Park, Jihye; Zou, Xiaodong; Zhou, Hong-Cai

2015-01-19

Enzymatic catalytic processes possess great potential in chemical manufacturing, including pharmaceuticals, fuel production and food processing. However, the engineering of enzymes is severely hampered due to their low operational stability and difficulty of reuse. Here, we develop a series of stable metal-organic frameworks with rationally designed ultra-large mesoporous cages as single-molecule traps (SMTs) for enzyme encapsulation. With a high concentration of mesoporous cages as SMTs, PCN-333(Al) encapsulates three enzymes with record-high loadings and recyclability. Immobilized enzymes that most likely undergo single-enzyme encapsulation (SEE) show smaller Km than free enzymes while maintaining comparable catalytic efficiency. Under harsh conditions, the enzyme in SEE exhibits better performance than free enzyme, showing the effectiveness of SEE in preventing enzyme aggregation or denaturation. With extraordinarily large pore size and excellent chemical stability, PCN-333 may be of interest not only for enzyme encapsulation, but also for entrapment of other nanoscaled functional moieties.

Stable metal-organic frameworks containing single-molecule traps for enzyme encapsulation

NASA Astrophysics Data System (ADS)

Feng, Dawei; Liu, Tian-Fu; Su, Jie; Bosch, Mathieu; Wei, Zhangwen; Wan, Wei; Yuan, Daqiang; Chen, Ying-Pin; Wang, Xuan; Wang, Kecheng; Lian, Xizhen; Gu, Zhi-Yuan; Park, Jihye; Zou, Xiaodong; Zhou, Hong-Cai

2015-01-01

Enzymatic catalytic processes possess great potential in chemical manufacturing, including pharmaceuticals, fuel production and food processing. However, the engineering of enzymes is severely hampered due to their low operational stability and difficulty of reuse. Here, we develop a series of stable metal-organic frameworks with rationally designed ultra-large mesoporous cages as single-molecule traps (SMTs) for enzyme encapsulation. With a high concentration of mesoporous cages as SMTs, PCN-333(Al) encapsulates three enzymes with record-high loadings and recyclability. Immobilized enzymes that most likely undergo single-enzyme encapsulation (SEE) show smaller Km than free enzymes while maintaining comparable catalytic efficiency. Under harsh conditions, the enzyme in SEE exhibits better performance than free enzyme, showing the effectiveness of SEE in preventing enzyme aggregation or denaturation. With extraordinarily large pore size and excellent chemical stability, PCN-333 may be of interest not only for enzyme encapsulation, but also for entrapment of other nanoscaled functional moieties.

Encapsulated Hsp70 decreases endotoxin-induced production of ROS and TNFα in human phagocytes.

PubMed

Yurinskaya, M M; Kochetkova, O Yu; Shabarchina, L I; Antonova, O Yu; Suslikov, A V; Evgen'ev, M B; Vinokurov, M G

2017-01-01

Human heat shock protein Hsp70 was experimentally inserted into polyelectrolyte microcapsules. Encapsulated recombinant Hsp70 was studied in terms of its effects on neutrophil apoptosis, the production of reactive oxygen species, and the secretion of tumor necrosis factor alpha by promonocytic THP-1 cells. It was found that encapsulated Hsp70 effectively inhibits neutrophil apoptosis, unlike free exogenous protein used in solution. In THP-1 cells, encapsulated and free Hsp70 reduced LPS-induced tumor necrosis factor alpha production with a similar efficiency. Encapsulated Hsp70 reduces LPS-induced reactive oxygen species production by neutrophils in the course of its release from the microcapsules but not as much as free Hsp70. Thus, the polyelectrolyte microcapsules can be used as containers for the effective delivery of Hsp70 to neutrophils and monocytes to significantly improve the functioning of the innate immune system.

Encapsulation of Antifouling Organic Biocides in Poly(lactic acid) Nanoparticles

PubMed Central

Kamtsikakis, Aristotelis; Kavetsou, Eleni; Chronaki, Konstantina; Kiosidou, Evangelia; Pavlatou, Evangelia; Karana, Alexandra; Papaspyrides, Constantine; Detsi, Anastasia; Karantonis, Antonis; Vouyiouka, Stamatina

2017-01-01

The scope of the current research was to assess the feasibility of encapsulating three commercial antifouling compounds, Irgarol 1051, Econea and Zinc pyrithione, in biodegradable poly(lactic acid) (PLA) nanoparticles. The emulsification–solvent evaporation technique was herein utilized to manufacture nanoparticles with a biocide:polymer ratio of 40%. The loaded nanoparticles were analyzed for their size and size distribution, zeta potential, encapsulation efficiency and thermal properties, while the relevant physicochemical characteristics were correlated to biocide–polymer system. In addition, the encapsulation process was scaled up and the prepared nanoparticles were dispersed in a water-based antifouling paint in order to examine the viability of incorporating nanoparticles in such coatings. Metallic specimens were coated with the nanoparticles-containing paint and examined regarding surface morphology. PMID:28952560

Encapsulation of Antifouling Organic Biocides in Poly(lactic acid) Nanoparticles.

PubMed

Kamtsikakis, Aristotelis; Kavetsou, Eleni; Chronaki, Konstantina; Kiosidou, Evangelia; Pavlatou, Evangelia; Karana, Alexandra; Papaspyrides, Constantine; Detsi, Anastasia; Karantonis, Antonis; Vouyiouka, Stamatina

2017-09-26

The scope of the current research was to assess the feasibility of encapsulating three commercial antifouling compounds, Irgarol 1051, Econea and Zinc pyrithione, in biodegradable poly(lactic acid) (PLA) nanoparticles. The emulsification-solvent evaporation technique was herein utilized to manufacture nanoparticles with a biocide:polymer ratio of 40%. The loaded nanoparticles were analyzed for their size and size distribution, zeta potential, encapsulation efficiency and thermal properties, while the relevant physicochemical characteristics were correlated to biocide-polymer system. In addition, the encapsulation process was scaled up and the prepared nanoparticles were dispersed in a water-based antifouling paint in order to examine the viability of incorporating nanoparticles in such coatings. Metallic specimens were coated with the nanoparticles-containing paint and examined regarding surface morphology.

Microencapsulation of xylitol by double emulsion followed by complex coacervation.

PubMed

Santos, Milla G; Bozza, Fernanda T; Thomazini, Marcelo; Favaro-Trindade, Carmen S

2015-03-15

The objective of this study was to produce and characterise xylitol microcapsules for use in foods, in order to prolong the sweetness and cooling effect provided by this ingredient. Complex coacervation was employed as the microencapsulation method. A preliminary double emulsion step was performed due to the hydrophilicity of xylitol. The microcapsules obtained were characterised in terms of particle size and morphology (optical, confocal and scanning electron microscopy), solubility, sorption isotherms, FTIR, encapsulation efficiency and release study. The microcapsules of xylitol showed desirable characteristics for use in foods, such as a particle size below 109 μm, low solubility and complete encapsulation of the core by the wall material. The encapsulation efficiency ranged from 31% to 71%, being higher in treatments with higher concentrations of polymers. Release of over 70% of the microencapsulated xylitol in artificial saliva occurred within 20 min. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stable Formamidinium-Based Perovskite Solar Cells via In Situ Grain Encapsulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Kai; Li, Zhen; Yang, Ye

Formamidinium (FA)-based lead iodide perovskites have emerged as the most promising light-absorber materials in the prevailing perovskite solar cells (PSCs). However, they suffer from the phase-instability issue in the ambient atmosphere, which is holding back the realization of the full potential of FA-based PSCs in the context of high efficiency and stability. Herein, the tetraethylorthosilicate hydrolysis process is integrated with the solution crystallization of FA-based perovskites, forming a new film structure with individual perovskite grains encapsulated by amorphous silica layers that are in situ formed at the nanoscale. The silica not only protects perovskite grains from the degradation but alsomore » enhances the charge-carrier dynamics of perovskite films. The underlying mechanism is discussed using a joint experiment-theory approach. Through this in situ grain encapsulation method, PSCs show an efficiency close to 20% with an impressive 97% retention after 1000-h storage under ambient conditions.« less

Iridium Clusters Encapsulated in Carbon Nanospheres as Nanocatalysts for Methylation of (Bio)Alcohols.

PubMed

Liu, Qiang; Xu, Guoqiang; Wang, Zhendong; Liu, Xiaoran; Wang, Xicheng; Dong, Linlin; Mu, Xindong; Liu, Huizhou

2017-12-08

C-H methylation is an attractive chemical transformation for C-C bonds construction in organic chemistry, yet efficient methylation of readily available (bio)alcohols in water using methanol as sustainable C1 feedstock is limited. Herein, iridium nanocatalysts encapsulated in yolk-shell-structured mesoporous carbon nanospheres (Ir@YSMCNs) were synthesized for this transformation. Monodispersed Ir clusters (ca. 1.0 nm) were encapsulated in situ and spatially isolated within YSMCNs by a silica-assisted sol-gel emulsion strategy. A selection of (bio)alcohols (19 examples) was selectively methylated in aqueous phase with good-to-high yields over the developed Ir@YSMCNs. The improved catalytic efficiencies in terms of activity and selectivity together with the good stability and recyclability were contributable to the ultrasmall Ir clusters with oxidation chemical state as a consequence of the confinement effect of YSMCNs with interconnected nanostructures. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhanced in Vitro Anti-Tumor Activity of 5-Azacytidine by Entrapment into Solid Lipid Nanoparticles

PubMed Central

Jahanfar, Farhad; Hasani, Akbar; Shanebandi, Dariush; Rahmati, Mohammad; Hamishehkar, Hamed

2016-01-01

Purpose: In this study the effectiveness of encapsulating of 5-azacytidine into the lipid nanoparticles was investigated and in vitro effect of encapsulated 5-azacytidine studied on MCF-7 cell lines Methods: 5-azacytidine -loaded solid lipid nanoparticles were produced by double emulsification (w/o/w) method by using stearic acid as lipid matrix, soy lecithin and poloxamer 407 as surfactant and co-surfactant respectively. Particle size, zeta potential, surface morphology, entrapment efficiency and kinetic of drug release were studied. In vitro effect of 5-azacytidine on MCF-7 cell line studied by MTT assay, DAPI staining, Rhodamine B relative uptake, and also Real time RT-PCR was performed for studying difference effect of free and encapsulated drug on expression of RARß2 gene. Results: The formulation F5 with 55.84±0.46 % of entrapment efficiency shows zero order kinetic of drug release and selected for in vitro studies; the cytotoxicity of free drug and encapsulated drug in 48 h of incubation have significant difference. DAPI staining shows morphology of apoptotic nucleus in both free and encapsulated drug, Rhodamine B labeled SLNs show time dependency and accumulation of SLNs in cytoplasm. Real time qRT-PCR doesn’t show any significant difference (p>0.05) in expression of RARß2 gene in both cells treated with free or encapsulated drug. Conclusion: The results of the present study indicated that the entrapment of 5-azacytidine into SLNs enhanced its cytotoxicity performance and may pave a way for the future design of a desired dosage form for 5-azacytidine. PMID:27766220

Fully convergent chemical synthesis of ester insulin: determination of the high resolution X-ray structure by racemic protein crystallography.

PubMed

Avital-Shmilovici, Michal; Mandal, Kalyaneswar; Gates, Zachary P; Phillips, Nelson B; Weiss, Michael A; Kent, Stephen B H

2013-02-27

Efficient total synthesis of insulin is important to enable the application of medicinal chemistry to the optimization of the properties of this important protein molecule. Recently we described "ester insulin"--a novel form of insulin in which the function of the 35 residue C-peptide of proinsulin is replaced by a single covalent bond--as a key intermediate for the efficient total synthesis of insulin. Here we describe a fully convergent synthetic route to the ester insulin molecule from three unprotected peptide segments of approximately equal size. The synthetic ester insulin polypeptide chain folded much more rapidly than proinsulin, and at physiological pH. Both the D-protein and L-protein enantiomers of monomeric DKP ester insulin (i.e., [Asp(B10), Lys(B28), Pro(B29)]ester insulin) were prepared by total chemical synthesis. The atomic structure of the synthetic ester insulin molecule was determined by racemic protein X-ray crystallography to a resolution of 1.6 Å. Diffraction quality crystals were readily obtained from the racemic mixture of {D-DKP ester insulin + L-DKP ester insulin}, whereas crystals were not obtained from the L-ester insulin alone even after extensive trials. Both the D-protein and L-protein enantiomers of monomeric DKP ester insulin were assayed for receptor binding and in diabetic rats, before and after conversion by saponification to the corresponding DKP insulin enantiomers. L-DKP ester insulin bound weakly to the insulin receptor, while synthetic L-DKP insulin derived from the L-DKP ester insulin intermediate was fully active in binding to the insulin receptor. The D- and L-DKP ester insulins and D-DKP insulin were inactive in lowering blood glucose in diabetic rats, while synthetic L-DKP insulin was fully active in this biological assay. The structural basis of the lack of biological activity of ester insulin is discussed.

Fisetin yeast-based bio-capsules via osmoporation: effects of process variables on the encapsulation efficiency and internalized fisetin content.

PubMed

de Câmara, Antonio Anchieta; Dupont, Sébastien; Beney, Laurent; Gervais, Patrick; Rosenthal, Amauri; Correia, Roberta Targino Pinto; Pedrini, Márcia Regina da Silva

2016-06-01

Osmoporation is an innovative method that can be used with food-grade yeast cells of Saccharomyces cerevisiae as natural encapsulating matrices. This technique overcomes barriers that difficult encapsulation and enables the internalization of fragile bioactive molecules such as fisetin into yeasts. In the present study, we assessed the effects of concentration, osmotic pressure, and temperature on the encapsulation efficiency (EE) and internalized fisetin content (IF). Two different quantification strategies were investigated: direct extraction (DE) without cell washing or freeze-drying steps and indirect extraction (IE) performed after washings with ethanol and freeze-drying. Our results showed that osmoporation improved EE (33 %) and IF (1.199 mg). The best experimental conditions were found by using DE. High-resolution images showed that the yeast cell envelope was preserved during osmoporation at 30 MPa and 84 % of yeast cells remained viable after treatment. Washing cells with organic solvent led to decreased EE (0.65 %) and IF (0.023 mg). This was probably due to either damages caused to yeast cell envelope or fisetin dragged out of cell. Overall, the results demonstrated the adequacy and relevant biotechnological potential of yeasts as encapsulating matrices for hydrophobic compounds. This fresh biotechnological approach has proven to be a promising tool for the production of bioactive-rich food products.

Direct spray drying and microencapsulation of probiotic Lactobacillus reuteri from slurry fermentation with whey.

PubMed

Jantzen, M; Göpel, A; Beermann, C

2013-10-01

Formulations of dietary probiotics have to be robust against process conditions and have to maintain a sufficient survival rate during gastric transit. To increase efficiency of the encapsulation process and the viability of applied bacteria, this study aimed at developing spray drying and encapsulation of Lactobacillus reuteri with whey directly from slurry fermentation. Lactobacillus reuteri was cultivated in watery 20% (w/v) whey solution with or without 0·5% (w/v) yeast extract supplementation in a submerged slurry fermentation. Growth enhancement with supplement was observed. Whey slurry containing c. 10(9)  CFU g(-1) bacteria was directly spray-dried. Cell counts in achieved products decreased by 2 log cycles after drying and 1 log cycle during 4 weeks of storage. Encapsulated bacteria were distinctively released in intestinal milieu. Survival rate of encapsulated bacteria was 32% higher compared with nonencapsulated ones exposed to artificial digestive juice. Probiotic L. reuteri proliferate in slurry fermentation with yeast-supplemented whey and enable a direct spray drying in whey. The resulting microcapsules remain stable during storage and reveal adequate survival in simulated gastric juices and a distinct release in intestinal juices. Exploiting whey as a bacterial substrate and encapsulation matrix within a coupled fermentation and spray-drying process offers an efficient option for industrial production of vital probiotics. © 2013 The Society for Applied Microbiology.

Regulation of insulin preRNA splicing by glucose

PubMed Central

Wang, Juehu; Shen, Luping; Najafi, Habiba; Kolberg, Janice; Matschinsky, Franz M.; Urdea, Mickey; German, Michael

1997-01-01

Glucose tightly regulates the synthesis and secretion of insulin by β cells in the pancreatic islets of Langerhans. To investigate whether glucose regulates insulin synthesis at the level of insulin RNA splicing, we developed a method to detect and quantify a small amount of RNA by using the branched DNA (bDNA) signal-amplification technique. This assay is both sensitive and highly specific: mouse insulin II mRNA can be detected from a single β cell (βTC3 cells or mouse islets), whereas 1 million non-insulin-producing α cells (αTC1.6 cells) give no signal. By using intron and exon sequences, oligonucleotide probes were designed to distinguish the various unspliced and partially spliced insulin preRNAs from mature insulin mRNA. Insulin RNA splicing rates were estimated from the rate of disappearance of insulin preRNA signal from β cells treated with actinomycin D to block transcription. We found that the two introns in mouse insulin II are not spliced with the same efficiency. Intron 2 is spliced out more efficiently than intron 1. As a result, some mRNA retaining intron 1 enters the cytoplasm, making up ≈2-10% of insulin mRNA in the cell. This partially spliced cytoplasmic mRNA is quite stable, with a half-life similar to the completely spliced form. When islets grown in high glucose are shifted to low glucose medium, the level of insulin preRNA and the rate of splicing fall significantly. We conclude that glucose stimulates insulin gene transcription and insulin preRNA splicing. Previous estimates of insulin transcription rates based on insulin preRNA levels that did not consider the rate of splicing may have underestimated the effect of glucose on insulin gene transcription. PMID:9113994

Combining two technologies: multifunctional polymers and self-nanoemulsifying drug delivery system (SNEDDS) for oral insulin administration.

PubMed

Sakloetsakun, Duangkamon; Dünnhaupt, Sarah; Barthelmes, Jan; Perera, Glen; Bernkop-Schnürch, Andreas

2013-10-01

The aim of the study is to develop a self-nanoemulsifying drug delivery system (SNEDDS) based on thiolated chitosan for oral insulin administration. The preparations were characterized by particle size, entrapment efficiency, stability and drug release. Serum insulin concentrations were determined after oral administration of all formulations. Insulin SNEDDS formulation was served as control. The optimized SNEDDS consists of 65% (w/w) miglyol 840, 25% (w/w) cremophor EL, 10% (w/w) co-solvents (a mixture of DMSO and glycerol). The formulations in the presence or absence of insulin (5mg/mL) were spherical with the size range between 80 and 160 nm. Entrapment efficiency of insulin increased significantly when the thiolated chitosan was employed (95.14±2.96%), in comparison to the insulin SNEDDS (80.38±1.22%). After 30 min, the in vitro release profile of insulin from the nanoemulsions was markedly increased compared to the control. In vivo results showed that insulin/thiolated chitosan SNEDDS displayed a significant increase in serum insulin (p-value=0.02) compared to oral insulin solution. A new strategy to combine SNEDDS and thiolated chitosan described in the study would therefore be a promising and innovative approach to improve oral bioavailability of insulin. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Fully Convergent Chemical Synthesis of Ester Insulin: Determination of the High Resolution X-ray Structure by Racemic Protein Crystallography

PubMed Central

Avital-Shmilovici, Michal; Mandal, Kalyaneswar; Gates, Zachary P.; Phillips, Nelson B.; Weiss, Michael A.; Kent, Stephen B.H.

2013-01-01

Efficient total synthesis of insulin is important to enable the application of medicinal chemistry to the optimization of the properties of this important protein molecule. Recently we described ‘ester insulin’ – a novel form of insulin in which the function of the 35 residue C-peptide of proinsulin is replaced by a single covalent bond – as a key intermediate for the efficient total synthesis of insulin. Here we describe a fully convergent synthetic route to the ester insulin molecule from three unprotected peptide segments of approximately equal size. The synthetic ester insulin polypeptide chain folded much more rapidly than proinsulin, and at physiological pH. Both the D-protein and L-protein enantiomers of monomeric DKP ester insulin (i.e. [AspB10, LysB28, ProB29]ester insulin) were prepared by total chemical synthesis. The atomic structure of the synthetic ester insulin molecule was determined by racemic protein X-ray crystallography to a resolution of 1.6 Å. Diffraction quality crystals were readily obtained from the racemic mixture of {D-DKP ester insulin + L-DKP ester insulin}, whereas crystals were not obtained from the L-ester insulin alone even after extensive trials. Both the D-protein and L-protein enantiomers of monomeric DKP ester insulin were assayed for receptor binding and in diabetic rats, before and after conversion by saponification to the corresponding DKP insulin enantiomers. L-DKP ester insulin bound weakly to the insulin receptor, while synthetic L-DKP insulin derived from the L-DKP ester insulin intermediate was fully active in binding to the insulin receptor. The D- and L-DKP ester insulins and D-DKP insulin were inactive in lowering blood glucose in diabetic rats, while synthetic L-DKP insulin was fully active in this biological assay. The structural basis of the lack of biological activity of ester insulin is discussed. PMID:23343390

Using ß-cyclodextrin and Arabic Gum as Wall Materials for Encapsulation of Saffron Essential Oil

PubMed Central

Atefi, Mohsen; Nayebzadeh, Kooshan; Mohammadi, Abdorreza; Mortazavian, Amir Mohammad

2017-01-01

Saffron essential oil has a pleasant aroma and medicinal activities. However, it is sensible into the environmental condition. Therefore, it should be protected against unwanted changes during storage or processing. Encapsulation is introduced as a process by which liable materials are protected from unwanted changes. In the present study, different ratios (0:100, 25:75, 50:50, 75:25, and 100:0) of ß-cyclodextrin (ß-CD) and arabic gum (GA) were used as wall martial for encapsulation saffron essential oil. In order to calculate of loading capacity (LC) and encapsulation efficiency (EE), and release (RE), safranal was determined as indicator of saffron essential oil using GC. According to the results, the highest LC and EE were related to the mixture of ß-CD/GA at a 75:25 ratio. In contrast, the lowest encapsulate hygroscopicity (EH) and RE were observed when only ß-CD was applied as wall material (P≤0.05). Comparing the differential scanning calorimetry (DSC) thermograms of the control and encapsulate of ß-CD/GA (75:25) confirmed encapsulation of saffron essential oil. Scanning electron microscopy (SEM) images with high magnifications showed the rhombic structure that partially coated by GA. The mixture of ß-CD/GA at a 75:25 ratio can be recommended for saffron essential oil encapsulation. PMID:28496464

Using ß-cyclodextrin and Arabic Gum as Wall Materials for Encapsulation of Saffron Essential Oil.

PubMed

Atefi, Mohsen; Nayebzadeh, Kooshan; Mohammadi, Abdorreza; Mortazavian, Amir Mohammad

2017-01-01

Saffron essential oil has a pleasant aroma and medicinal activities. However, it is sensible into the environmental condition. Therefore, it should be protected against unwanted changes during storage or processing. Encapsulation is introduced as a process by which liable materials are protected from unwanted changes. In the present study, different ratios (0:100, 25:75, 50:50, 75:25, and 100:0) of ß-cyclodextrin (ß-CD) and arabic gum (GA) were used as wall martial for encapsulation saffron essential oil. In order to calculate of loading capacity (LC) and encapsulation efficiency (EE), and release (RE), safranal was determined as indicator of saffron essential oil using GC. According to the results, the highest LC and EE were related to the mixture of ß-CD/GA at a 75:25 ratio. In contrast, the lowest encapsulate hygroscopicity (EH) and RE were observed when only ß-CD was applied as wall material (P≤0.05). Comparing the differential scanning calorimetry (DSC) thermograms of the control and encapsulate of ß-CD/GA (75:25) confirmed encapsulation of saffron essential oil. Scanning electron microscopy (SEM) images with high magnifications showed the rhombic structure that partially coated by GA. The mixture of ß-CD/GA at a 75:25 ratio can be recommended for saffron essential oil encapsulation.

Modeling the Use of Mine Waste Rock as a Porous Medium Reservoir for Compressed Air Energy Storage

NASA Astrophysics Data System (ADS)

Donelick, R. A.; Donelick, M. B.

2016-12-01

We are studying the engineering and economic feasibilities of constructing Big Mass Battery (BiMBy) compressed air energy storage devices using some of the giga-tonnes of annually generated and historically produced mine waste rock/overburden/tailings (waste rock). This beneficial use of waste rock is based on the large mass (Big Mass), large pore volume, and wide range of waste rock permeabilities available at some large open pit metal mines and coal strip mines. Porous Big Mass is encapsulated and overlain by additional Big Mass; compressed air is pumped into the encapsulated pore space when renewable energy is abundant; compressed air is released from the encapsulated pore space to run turbines to generate electricity at the grid scale when consumers demand electricity. Energy storage capacity modeling: 1) Yerington Pit, Anaconda Copper Mine, Yerington, NV (inactive metal mine): 340 Mt Big Mass, energy storage capacity equivalent to 390k-710k home batteries of size 10 kW•h/charge, assumed 20% porosity, 50% overall efficiency. 2) Berkeley Pit, Butte Copper Mine, Butte, MT (inactive metal mine): 870 Mt Big Mass, energy storage capacity equivalent to 1.4M-2.9M home batteries of size 10 kW•h/charge, assumed 20% porosity, 50% overall efficiency. 3) Rosebud Mine, Colstrip, MT (active coal strip mine): 87 Mt over 2 years, energy storage capacity equivalent to 45k-67k home batteries of size 10 kW•h/charge, assumed 30% porosity, 50% overall efficiency. Encapsulating impermeable layer modeling: Inactive mine pits like Yerington Pit and Berkeley Pit, and similar active pits, have associated with them low permeability earthen material (silt and clay in Big Mass) at sufficient quantities to manufacture an encapsulating structure with minimal loss of efficiency due to leakage, a lifetime of decades or even centuries, and minimal need for the use of geomembranes. Active coal strip mines like Rosebud mine have associated with them low permeability earthen material such as coal combustion products (fly ash, bottom ash, boiler slag, other) that may be put to beneficial use as part of the encapsulating structure; however, coal strip mines have lower volume to surface ratios than mine pits increasing the potential need to use geomembranes.

Imaging efficiency of an X-ray contrast agent-incorporated polymeric microparticle.

PubMed

Ahn, Sungsook; Jung, Sung Yong; Lee, Jin Pyung; Lee, Sang Joon

2011-01-01

Biocompatible polymeric encapsulants have been widely used as a delivery vehicle for a variety of drugs and imaging agents. In this study, X-ray contrast agent (iopamidol) is encapsulated into a polymeric microparticle (polyvinyl alcohol) as a particulate flow tracer in synchrotron X-ray imaging system. The physical properties of the designed microparticles are investigated and correlated with enhancement in the imaging efficiency by experimental observation and theoretical interpretation. The X-ray absorption ability of the designed microparticle is assessed by Beer-Lambert-Bouguer law. Particle size, either in dried state or in solvent, primarily dominates the X-ray absorption ability under the given condition, thus affecting imaging efficiency of the designed X-ray contrast flow tracers. Copyright © 2011 John Wiley & Sons, Ltd.

Highly efficient one-step synthesis of carbon encapsulated nanocrystals by the oxidation of metal π-complexes

NASA Astrophysics Data System (ADS)

Liu, Boyang; Shao, Yingfeng; Xiang, Xin; Zhang, Fuhua; Yan, Shengchang; Li, Wenge

2017-08-01

Various carbon encapsulated nanocrystals, including MnS and MnO, Cr2O3, MoO2, Fe7S8 and Fe3O4, and ZrO2, are prepared in one step and in situ by a simple and highly efficient synthesis approach. The nanocrystals have an equiaxed morphology and a median size smaller than 30 nm. Tens and hundreds of these nanocrystals are entirely encapsulated by a wormlike amorphous carbon shell. The formation of a core-shell structure depends on the strongly exothermic reaction of metal π-complexes with ammonium persulfate in an autoclave at below 200 °C. During the oxidation process, the generated significant amounts of heat will destroy the molecular structure of the metal π-complex and cleave the ligands into small carbon fragments, which further transform into an amorphous carbon shell. The central metal atoms are oxidized to metal oxide/sulfide nanocrystals. The formation of a core-shell structure is independent of the numbers of ligands and carbon atoms as well as the metal types, implying that any metal π-complex can serve as a precursor and that various carbon encapsulated nanocrystals can be synthesized by this method.

Efficient in vitro encapsulation of protein cargo by an engineered protein container.

PubMed

Wörsdörfer, Bigna; Pianowski, Zbigniew; Hilvert, Donald

2012-01-18

An engineered variant of lumazine synthase, a nonviral capsid protein with a negatively charged luminal surface, is shown to encapsulate up to 100 positively supercharged green fluorescent protein (GFP) molecules in vitro. Packaging can be achieved starting either from intact, empty capsids or from capsid fragments by incubation with cargo in aqueous buffer. The yield of encapsulated GFP correlates directly with the host/guest mixing ratio, providing excellent control over packing density. Facile in vitro loading highlights the unusual structural dynamics of this novel nanocontainer and should facilitate diverse biotechnological and materials science applications. © 2011 American Chemical Society

Calcium alginate gel as encapsulation matrix for coimmobilized enzyme systems.

PubMed

Blandino, A; Macías, M; Cantero, D

2003-07-01

Encapsulation within calcium alginate gel capsules was used to produce a coimmobilized enzyme system. Glucose oxidase (GOD) and catalase (CAT) were chosen as model enzymes. The same values of Vmax and Km app for the GOD encapsulated system and for the GOD-CAT coencapsulated system were calculated. When gel beads and capsules were compared, the same catalyst deactivation sequence for the two enzymes was observed. However, when capsules were employed as immobilization support, GOD efficiencies were higher than for the gel beads. These results were explained in terms of the structure of the capsules.

Hybrid inorganic-organic capsules for efficient intracellular delivery of novel siRNAs against influenza A (H1N1) virus infection.

PubMed

Timin, Alexander S; Muslimov, Albert R; Petrova, Aleksandra V; Lepik, Kirill V; Okilova, Maria V; Vasin, Andrey V; Afanasyev, Boris V; Sukhorukov, Gleb B

2017-03-07

The implementation of RNAi technology into the clinical practice has been significantly postponing due to the issues regarding to the delivery of naked siRNA predominantly to target cells. Here we report the approach to enhance the efficiency of siRNA delivery by encapsulating the siRNA into new carrier systems which are obtained via the combination of widely used layer-by-layer technique and in situ modification by sol-gel chemistry. We used three types of siRNAs (NP-717, NP-1155 and NP-1496) in encapsulated form as new therapeutic agents against H1N1 influenza virus infection. By employing the hybrid microcontainers for the siRNA encapsulation we demonstrate the reduction of viral nucleoprotein (NP) level and inhibition of influenza virus production in infected cell lines (MDCK and A549). The obtained hybrid carriers based on assembled biodegradable polyelectrolytes and sol-gel coating possess several advantages such as a high cell uptake efficiency, low toxicity, efficient intracellular delivery of siRNAs and the protection of siRNAs from premature degradation before reaching the target cells. These findings underpin a great potential of versatile microencapsulation technology for the development of anti-viral RNAi delivery systems against influenza virus infection.

Inorganic Nanoporous Membranes for Immunoisolated Cell-Based Drug Delivery

PubMed Central

Mendelsohn, Adam; Desai, Tejal

2014-01-01

Materials advances enabled by nanotechnology have brought about promising approaches to improve the encapsulation mechanism for immunoisolated cell-based drug delivery. Cell-based drug delivery is a promising treatment for many diseases but has thus far achieved only limited clinical success. Treatment of insulin dependent diabetes mellitus (IDDM) by transplantation of pancreatic β-cells represents the most anticipated application of cell-based drug delivery technology. This review outlines the challenges involved with maintaining transplanted cell viability and discusses how inorganic nanoporous membranes may be useful in achieving clinical success. PMID:20384222

Characterization of Encapsulated Corrosion Inhibitors Containing Microparticles for Environmentally Friendly Smart Coatings

NASA Technical Reports Server (NTRS)

Pearman, Benjamin Pieter; Calle, Luz M.

2015-01-01

This poster presents the results obtained from experiments designed to evaluate the release properties, as well as the corrosion inhibition effectiveness, of several encapsulated corrosion inhibitors. Microencapsulation has been used in the development of environmentally friendly multifunctional smart coatings. This technique enables the incorporation of autonomous corrosion detection, inhibition and self-healing functionalities into many commercially available coating systems. Select environmentally friendly corrosion inhibitors were encapsulated in organic and inorganic pH-sensitive microparticles and their release in basic solutions was studied. The release rate results showed that the encapsulation can be tailored from fast, for immediate corrosion protection, to slow, which will provide continued long-term corrosion protection. The incorporation of several corrosion inhibitor release profiles into a coating provides effective corrosion protection properties. To investigate the corrosion inhibition efficiency of the encapsulated inhibitors, electrochemical techniques were used to obtain corrosion potential, polarization curve and polarization resistance data. These measurements were performed using the free as well as the encapsulated inhibitors singly or in combinations. Results from these electrochemical tests will be compared to those obtained from weight loss and other accelerated corrosion experiments.

Development of highly durable deep-ultraviolet AlGaN-based LED multichip array with hemispherical encapsulated structures using a selected resin through a detailed feasibility study

NASA Astrophysics Data System (ADS)

Nagai, Shoko; Yamada, Kiho; Hirano, Akira; Ippommatsu, Masamichi; Ito, Masahiro; Morishima, Naoki; Aosaki, Ko; Honda, Yoshio; Amano, Hiroshi; Akasaki, Isamu

2016-08-01

To replace mercury lamps with AlGaN-based deep-ultraviolet (DUV) LEDs, a simple and low-cost package with increased light extraction efficiency (LEE) is indispensable. Therefore, resin encapsulation is considered to be a key technology. However, the photochemical reactions induced by DUV light cause serious problems, and conventional resins cannot be used. In the former part of this study, a comparison of a silicone resin and fluorine polymers was carried out in terms of their suitability for encapsulation, and we concluded that only one of the fluorine polymers can be used for encapsulation. In the latter part, the endurance of encapsulation using the selected fluorine polymer was investigated, and we confirmed that the selected fluorine polymer can guarantee a lifetime of over 6,000 h at a wavelength of 265 nm. Furthermore, a 3 × 4 array module of encapsulated dies on a simple AlN submount was fabricated, demonstrating the possibility of W/cm2-class lighting.

Development of Hollow Steel Ball Macro-Encapsulated PCM for Thermal Energy Storage Concrete

PubMed Central

Dong, Zhijun; Cui, Hongzhi; Tang, Waiching; Chen, Dazhu; Wen, Haibo

2016-01-01

The application of thermal energy storage with phase change materials (PCMs) for energy efficiency of buildings grew rapidly in the last few years. In this research, octadecane paraffin was served as a PCM, and a structural concrete with the function of indoor temperature control was developed by using a macro-encapsulated PCM hollow steel ball (HSB). The macro-encapsulated PCM-HSB was prepared by incorporation of octadecane into HSBs through vacuum impregnation. Test results showed that the maximum percentage of octadecane carried by HSBs was 80.3% by mass. The macro-encapsulated PCM-HSB has a latent heat storage capacity as high as 200.5 J/g. The compressive strength of concrete with macro-encapsulated PCM-HSB at 28 days ranged from 22 to 40 MPa. The indoor thermal performance test revealed that concrete with macro-encapsulated octadecane-HSB was capable of reducing the peak indoor air temperature and the fluctuation of indoor temperature. It can be very effective in transferring the heating and cooling loads away from the peak demand times. PMID:28787859

Window encapsulation in car industry by using the 50 {Omega} RF technology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernard, J.P.; Barboteau, M.; Collet, L.

Throughout the world car industry has been using window encapsulation for a few years now. This technology is mainly used in production lines and is called RIM for polyurethane reaction injection moulding. This technology, however brings about some problems such as: glass breaking during mould closure, high production cost, systematic rough edges. The PSA Group (Peugeot-Citroen), a pioneer in this field, in collaboration with SAIREM has launched a new innovating process for window encapsulation by using the 50 {Omega} RF technology for gelling PVC Plastisol. The study was followed by an industrial prototype. Industrial equipment was then installed at WEBASTOmore » HEULIEZ for window encapsulation of the sunshine roof for the Citroen Xantia. The authors describe the principle of window encapsulation and the different existing processes. They describe the 50 {Omega} RF technology, an industrial installation and the constraints of this technology in order to get maximum efficiency. In the conclusion they present a technical and economical analysis of the different solutions for window encapsulation. They also present the advantages of the 50 {Omega} RF technology and the new opportunities it offers.« less

Application of modified-alginate encapsulated carbonate producing bacteria in concrete: a promising strategy for crack self-healing.

PubMed

Wang, Jianyun; Mignon, Arn; Snoeck, Didier; Wiktor, Virginie; Van Vliergerghe, Sandra; Boon, Nico; De Belie, Nele

2015-01-01

Self-healing concrete holds promising benefits to reduce the cost for concrete maintenance and repair as cracks are autonomously repaired without any human intervention. In this study, the application of a carbonate precipitating bacterium Bacillus sphaericus was explored. Regarding the harsh condition in concrete, B. sphaericus spores were first encapsulated into a modified-alginate based hydrogel (AM-H) which was proven to have a good compatibility with the bacteria and concrete regarding the influence on bacterial viability and concrete strength. Experimental results show that the spores were still viable after encapsulation. Encapsulated spores can precipitate a large amount of CaCO3 in/on the hydrogel matrix (around 70% by weight). Encapsulated B. sphaericus spores were added into mortar specimens and bacterial in situ activity was demonstrated by the oxygen consumption on the mimicked crack surface. While specimens with free spores added showed no oxygen consumption. This indicates the efficient protection of the hydrogel for spores in concrete. To conclude, the AM-H encapsulated carbonate precipitating bacteria have great potential to be used for crack self-healing in concrete applications.

Effect of alginate microencapsulation on the catalytic efficiency and in vitro enzyme-prodrug therapeutic efficacy of cytosine deaminase and of recombinant E. coli expressing cytosine deaminase.

PubMed

Funaro, Michael G; Nemani, Krishnamurthy V; Chen, Zhihang; Bhujwalla, Zaver M; Griswold, Karl E; Gimi, Barjor

2016-02-01

Cytosine deaminase (CD) catalyses the enzymatic conversion of the non-toxic prodrug 5-fluorocytosine (5-FC) to the potent chemotherapeutic form, 5-fluorouracil (5-FU). Intratumoral delivery of CD localises chemotherapy dose while reducing systemic toxicity. Encapsulation in biocompatible microcapsules immunoisolates CD and protects it from degradation. We report on the effect of alginate encapsulation on the catalytic and functional activity of isolated CD and recombinant E. coli engineered to express CD (E. coli(CD)). Alginate microcapsules containing either CD or Escherichia coli(CD) were prepared using ionotropic gelation. Conversion of 5-FC to 5-FU was quantitated in unencapsulated and encapsulated CD/E. coli(CD) using spectrophotometry, with a slower rate of conversion observed following encapsulation. Both encapsulated CD/5-FC and E. coli(CD)/5-FC resulted in cell kill and reduced proliferation of 9 L rat glioma cells, which was comparable to direct 5-FU treatment. Our results show that encapsulation preserves the therapeutic potential of CD and E. coli(CD) is equally effective for enzyme-prodrug therapy.

Development of Hollow Steel Ball Macro-Encapsulated PCM for Thermal Energy Storage Concrete.

PubMed

Dong, Zhijun; Cui, Hongzhi; Tang, Waiching; Chen, Dazhu; Wen, Haibo

2016-01-19

The application of thermal energy storage with phase change materials (PCMs) for energy efficiency of buildings grew rapidly in the last few years. In this research, octadecane paraffin was served as a PCM, and a structural concrete with the function of indoor temperature control was developed by using a macro-encapsulated PCM hollow steel ball (HSB). The macro-encapsulated PCM-HSB was prepared by incorporation of octadecane into HSBs through vacuum impregnation. Test results showed that the maximum percentage of octadecane carried by HSBs was 80.3% by mass. The macro-encapsulated PCM-HSB has a latent heat storage capacity as high as 200.5 J/g. The compressive strength of concrete with macro-encapsulated PCM-HSB at 28 days ranged from 22 to 40 MPa. The indoor thermal performance test revealed that concrete with macro-encapsulated octadecane-HSB was capable of reducing the peak indoor air temperature and the fluctuation of indoor temperature. It can be very effective in transferring the heating and cooling loads away from the peak demand times.

Application of modified-alginate encapsulated carbonate producing bacteria in concrete: a promising strategy for crack self-healing

PubMed Central

Wang, Jianyun; Mignon, Arn; Snoeck, Didier; Wiktor, Virginie; Van Vliergerghe, Sandra; Boon, Nico; De Belie, Nele

2015-01-01

Self-healing concrete holds promising benefits to reduce the cost for concrete maintenance and repair as cracks are autonomously repaired without any human intervention. In this study, the application of a carbonate precipitating bacterium Bacillus sphaericus was explored. Regarding the harsh condition in concrete, B. sphaericus spores were first encapsulated into a modified-alginate based hydrogel (AM-H) which was proven to have a good compatibility with the bacteria and concrete regarding the influence on bacterial viability and concrete strength. Experimental results show that the spores were still viable after encapsulation. Encapsulated spores can precipitate a large amount of CaCO3 in/on the hydrogel matrix (around 70% by weight). Encapsulated B. sphaericus spores were added into mortar specimens and bacterial in situ activity was demonstrated by the oxygen consumption on the mimicked crack surface. While specimens with free spores added showed no oxygen consumption. This indicates the efficient protection of the hydrogel for spores in concrete. To conclude, the AM-H encapsulated carbonate precipitating bacteria have great potential to be used for crack self-healing in concrete applications. PMID:26528254

Effect of spray-drying with organic solvents on the encapsulation, release and stability of fish oil.

PubMed

Encina, Cristian; Márquez-Ruiz, Gloria; Holgado, Francisca; Giménez, Begoña; Vergara, Cristina; Robert, Paz

2018-10-15

Fish-oil (FO) was encapsulated with hydroxypropylcelullose (HPC) by conventional spray-drying with water (FO-water) and solvent spray-drying with ethanol (FO-EtOH), methanol (FO-MeOH) and acetone (FO-Acet) in order to study the effect of the solvent on the encapsulation efficiency (EE), microparticle properties and stability of FO during storage at 40 °C. Results showed that FO-Acet presented the highest EE of FO (92.0%), followed by FO-EtOH (80.4%), FO-MeOH (75.0%) and FO-water (71.1%). A decrease of the dielectric constant increased the EE of FO, promoting triglyceride-polymer interactions instead of oil-in-water emulsion retention. FO release profile in aqueous model was similar for all FO-microparticles, releasing only the surface FO, according to Higuchi model. Oxidative stability of FO significantly improved by spray-drying with MeOH, both in surface and encapsulated oil fractions. In conclusion, encapsulation of FO by solvent spray-drying can be proposed as an alternative technology for encapsulation of hydrophobic molecules. Copyright © 2018 Elsevier Ltd. All rights reserved.

Preparation of hemoglobin-loaded nano-sized particles with porous structure as oxygen carriers.

PubMed

Zhao, Jian; Liu, Chang-Sheng; Yuan, Yuan; Tao, Xin-Yi; Shan, Xiao-Qian; Sheng, Yan; Wu, Fan

2007-03-01

Hb (hemoglobin)-loaded particles (HbP) encapsulated by a biodegradable polymer used as oxygen carrier were prepared. A modified double emulsion and solvent diffusion/evaporation method was adopted. All experiments were performed based on two types of biodegradable polymers, poly(epsilon-caprolactone) (PCL) and poly(epsilon-caprolactone-ethylene glycol) (PCL-PEG). The biodistribution and the survival time in blood of the particles were investigated in a mouse model. Encapsulation efficiency and pore-connecting efficiency were evaluated by a novel sulfocyanate potassium method. The influence of process parameters on the particle size and pore-connecting efficiency (PCE%) of nanoparticles have been discussed. The prepared conditions: solvent, external aqueous phase, pressure were discussed. The system utilizing dichloromethane (DCM)/ethyl acetate (EA) as a solvent with an unsaturated external aqueous phase yielded the highest encapsulation efficiency (87.35%) with a small mean particle size (153 nm). The formation of porous channels was attributed to the diffusion of solvent. The PCE% was more sensitive to the rate of solvent diffusion that was obviously affected by the preparation temperature. The PCE% reached 87.47% when PCL-PEG was employed at 25 degrees C. P(50) of HbP was 27 mmHg, which does not seem to be greatly affected by the encapsulation procedure. In vivo, following intravenous injection of 6-coumarin labeled HbP, the major organ accumulating Hb-loaded particles was the liver. The half-life of nano-sized PCL HbP was 3.1 times as long as the micro-sized PCL HbP. Also, Nano-sized as well as a PEGylated surface on HbP is beneficial for prolonged blood residence (7.2 fold increase).

Color-Tunable and High-Efficiency Dye-Encapsulated Metal-Organic Framework Composites Used for Smart White-Light-Emitting Diodes.

PubMed

Chen, Wenwei; Zhuang, Yixi; Wang, Le; Lv, Ying; Liu, Jianbin; Zhou, Tian-Liang; Xie, Rong-Jun

2018-05-25

Luminescent metal-organic frameworks (MOFs) (typically dye-encapsulated MOFs) are considered as one kind of interesting downconversion materials for white-light-emitting diodes (LEDs), but their quantum efficiency (QE) is not sufficient and thus needs to be significantly enhanced for practical applications. In this study, we successfully synthesized a series of Rh@bio-MOF-1 (Rh = rhodamine) with an internal QE as high as ∼79% via a solvothermal reaction followed by cation exchanges. The high efficiency of the Rh@bio-MOF-1 composites was attributable to the high intrinsic luminescent efficiency of the selected Rh dyes, the confinement effect in the bio-MOF-1 host, and the uniform particle morphology. The emission maximum could be continuously tuned from 550 to 610 nm by controlling the species and concentration of encapsulated dye molecules, showing great color tunability of the dye-encapsulated MOFs. The emission lifetime of ∼7 ns was 1 or 2 magnitude orders shorter than that of Ce 3+ - or Eu 2+ -doped inorganic phosphors, allowing for visible light communication (VLC). White LEDs, fabricated by using the synthesized Rh@bio-MOF-1 composite and inorganic phosphors of green (Ba,Sr) 2 SiO 4 :Eu 2+ and red CaAlSiN 3 :Eu 2+ , exhibited a high color rendering index of 80-94, a luminous efficacy of 94-156 lm/W, and an excellent stability in color point against drive current. The Rh@bio-MOF-1 composites with tunable colors, short emission lifetime, and high QE are expected to be used for smart white LEDs with multifunctions of both lighting and VLC.

Development of novel self-assembled DS-PLGA hybrid nanoparticles for improving oral bioavailability of vincristine sulfate by P-gp inhibition.

PubMed

Ling, Guixia; Zhang, Peng; Zhang, Wenping; Sun, Jin; Meng, Xiaoxue; Qin, Yimeng; Deng, Yihui; He, Zhonggui

2010-12-01

To improve the encapsulation efficiency and oral bioavailability of vincristine sulfate (VCR), novel self-assembled dextran sulphate-PLGA hybrid nanoparticles (DPNs) were successfully developed using self-assembly and nanoprecipitation method. By introducing the negative polymer of dextran sulphate sodium (DS), VCR was highly encapsulated (encapsulation efficiency up to 93.6%) into DPNs by forming electrostatic complex. In vitro release of VCR solution (VCR-Sol) and VCR-loaded DPNs (VCR-DPNs) in pH 7.4 PBS showed that about 80.4% of VCR released from VCR-DPNs after 96h and burst release was effectively reduced, indicating pronounced sustained-release characteristics. In vivo pharmacokinetics in rats after oral administration of VCR-Sol and VCR-DPNs indicated that the apparent bioavailability of VCR-DPNs was increased to approximate 3.3-fold compared to that of VCR-Sol. The cellular uptake experiments were conducted by quantitative assay of VCR cellular accumulation and fluorescence microscopy imaging of fluorescent labeled DPNs in two human breast cancer cells including MCF-7 and P-glycoprotein over-expressing MCF-7/Adr cells. The relative cellular uptake of VCR-DPNs was 12.4-fold higher than that of VCR-Sol in MCF-7/Adr cells implying that P-glycoprotein-mediated drug efflux was diminished by the introduction of DPNs. The new DPNs might provide an effective strategy for oral delivery of VCR with improved encapsulation efficiency and oral bioavailability. Copyright © 2010 Elsevier B.V. All rights reserved.

Encapsulating Immunostimulatory CpG Oligonucleotides in Listeriolysin O-Liposomes Promotes a Th1-Type Response and CTL Activity

PubMed Central

Andrews, Chasity D.; Huh, Myung-Sook; Patton, Kathryn; Higgins, Debbie; Van Nest, Gary; Ott, Gary; Lee, Kyung-Dall

2013-01-01

Immunostimulatory sequences (ISS) are short DNA sequences containing unmethylated CpG dimers that have multiple effects on the host immune system, including the ability to stimulate antigen-specific cytotoxic T lymphocytes (CTLs) and drive Th1-type immune responses. Listeriolysin O (LLO)-containing pH-sensitive liposomes have been shown to efficiently deliver macromolecules to the cytosol of APCs and efficiently stimulate CTLs. We hypothesized that encapsulating ISS-oligodeoxyribonucleotides (ODNs) in this delivery system would enhance the cell-mediated immune response and skew Th1-type responses in protein antigen-based vaccination utilizing LLO-liposomes. In vitro studies indicated that co-encapsulation of ISS in LLO-liposomes engendered activation of the NF-κB pathway while maintaining the efficient cytosolic delivery of antigen mediated by the co-encapsulated LLO. Antigen-specific CTL responses monitored by using the model antigen ovalbumin (OVA) in mice were enhanced when mice were immunized with OVA and ISS-ODN-containing LLO-liposomes compared with those immunized with either OVA-containing LLO-liposomes or OVA-ISS conjugates. The enhanced immune responses were of the Th1-type as monitored by the robust OVA-specific IgG2a induction and the OVA CD8 peptide-stimulated IFN-γ secretion. Our study suggests that including ISS-ODN in LLO-containing pH-sensitive liposomes yields a vaccine delivery system that enhances the cell-mediated immune response and skews this response toward the Th1-type. PMID:22376145

Excessive Cellular Proliferation Negatively Impacts Reprogramming Efficiency of Human Fibroblasts

PubMed Central

Gupta, Manoj K.; Teo, Adrian Kee Keong; Rao, Tata Nageswara; Bhatt, Shweta; Kleinridders, Andre; Shirakawa, Jun; Takatani, Tomozumi; Hu, Jiang; De Jesus, Dario F.; Windmueller, Rebecca; Wagers, Amy J.

2015-01-01

The impact of somatic cell proliferation rate on induction of pluripotent stem cells remains controversial. Herein, we report that rapid proliferation of human somatic fibroblasts is detrimental to reprogramming efficiency when reprogrammed using a lentiviral vector expressing OCT4, SOX2, KLF4, and cMYC in insulin-rich defined medium. Human fibroblasts grown in this medium showed higher proliferation, enhanced expression of insulin signaling and cell cycle genes, and a switch from glycolytic to oxidative phosphorylation metabolism, but they displayed poor reprogramming efficiency compared with cells grown in normal medium. Thus, in contrast to previous studies, our work reveals an inverse correlation between the proliferation rate of somatic cells and reprogramming efficiency, and also suggests that upregulation of proteins in the growth factor signaling pathway limits the ability to induce pluripotency in human somatic fibroblasts. Significance The efficiency with which human cells can be reprogrammed is of interest to stem cell biology. In this study, human fibroblasts cultured in media containing different concentrations of growth factors such as insulin and insulin-like growth factor-1 exhibited variable abilities to proliferate, with consequences on pluripotency. This occurred in part because of changes in the expression of proteins involved in the growth factor signaling pathway, glycolysis, and oxidative phosphorylation. These findings have implications for efficient reprogramming of human cells. PMID:26253715

Mesoporous silica nanoparticles as smart and safe devices for regulating blood biomolecule levels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Yan

2011-01-01

Stimuli-responsive end-capped MSN materials are promising drug carriers that securely deliver a large payload of drug molecules without degradation or premature release. A general review of the recent progress in this field is presented, including a summary of a series of hard and soft caps for drug encapsulation and a variety of internal and external stimuli for controlled release of different therapeutics, a discussion of the biocompatibility of MSN both in vitro and in vivo, and a description of the sophisticated stimuli-responsive systems with novel capping agents and controlled release mechanism. The unique internal and external surfaces of MSN weremore » utilized for the development of a glucose-responsive double delivery system end-capped with insulin. This unique system consists of functionalized MSNs capable of releasing insulin when the concentration of sugar in blood exceeds healthy levels. The insulin-free nanoparticles are then up taken by pancreatic cells, and release inside of them another biomolecule that stimulates the production of more insulin. The in vivo application of this system for the treatment of diabetes requires further understanding on the biological behaviors of these nanoparticles in blood vessels. The research presented in this dissertation demonstrated the size and surface effects on the interaction of MSNs with red blood cell membranes, and discovered how the surface of the nanoparticles can be modified to improve their compatibility with red blood cells and avoid their dangerous side effects. In order to optimize the properties of MSN for applying them as efficient intracellular drug carriers it is necessary to understand the factors that can regulate their internalization into and exocytosis out of the cells. The correlation between the particle morphology and aggregation of MSNs to the effectiveness of cellular uptake is discussed and compared with different cell lines. The differences in the degree of exocytosis of MSNs between healthy and cancer cells is reported and found to be responsible for the asymmetric transfer of the particles between both cell types. The fundamental studies on the hemocompatibility, endo- and exocytosis of MSN along with its ability to sequentially release multiple therapeutics in response to different stimuli, allow us to propose MSN as an intravascular vehicle with a great potential for various biomedical applications.« less

Self-healing Microencapsulation of Biomacromolecules without Organic Solvents**

PubMed Central

Reinhold, Samuel E.; Desai, Kashappa-Goud H.; Zhang, Li; Olsen, Karl F.

2012-01-01

Microencapsulation of biomacromolecules in PLGA is routinely performed with organic solvent through multiple complex steps deleterious to the biomacromolecule. The new self-healing based PLGA microencapsulation obviates micronization- and organic solvent-induced protein damage, provides very high encapsulation efficiency, exhibit stabilization and slow release of labile tetanus protein antigen, and provides long-term testosterone suppression in rats following a single injection of encapsulated leuprolide. PMID:23011773

Induced polymersome formation from a diblock PS-b-PAA polymer via encapsulation of positively charged proteins and peptides.

PubMed

Hvasanov, David; Wiedenmann, Jörg; Braet, Filip; Thordarson, Pall

2011-06-14

In contrast to simple salts or negatively charged macromolecules, positively charged proteins and peptides including cytochrome c (yeast) and poly-L-lysine are efficiently encapsulated while inducing the formation of polymersomes from polystyrene(140)-b-poly(acrylic acid)(48) (PS(140)-b-PAA(48)). This journal is © The Royal Society of Chemistry 2011

Encapsulation of albumin in self-assembled layer-by-layer microcapsules: comparison of co-precipitation and adsorption techniques.

PubMed

Labala, Suman; Mandapalli, Praveen Kumar; Bhatnagar, Shubhmita; Venuganti, Venkata Vamsi Krishna

2015-01-01

The objective of this study is to prepare and characterize polymeric self-assembled layer-by-layer microcapsules (LbL-MC) to deliver a model protein, bovine serum albumin (BSA). The aim is to compare the BSA encapsulation in LbL-MC using co-precipitation and adsorption methods. In co-precipitation method, BSA was co-precipitated with growing calcium carbonate particles to form a core template. Later, poly(styrene sulfonate) and poly(allylamine hydrochloride) were sequentially adsorbed onto the CaCO3 templates. In adsorption method, preformed LbL-MC were incubated with BSA and encapsulation efficiency is optimized for pH and salt concentration. Free and BSA-encapsulated LbL-MC were characterized using Zetasizer, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy and differential scanning calorimeter. Later, in vitro release studies were performed using dialysis membrane method at pH 4, 7.4 and 9. Results from Zetasizer and SEM showed free LbL-MC with an average size and zeta-potential of 2.0 ± 0.6 μm and 8.1 ± 1.9 mV, respectively. Zeta-potential of BSA-loaded LbL-MC was (-)7.4 ± 0.7 mV and (-)5.7 ± 1.0 mV for co-precipitation and adsorption methods, respectively. In adsorption method, BSA encapsulation in LbL-MC was found to be greater at pH 6.0 and 0.2 M NaCl. Co-precipitation method provided four-fold greater encapsulation efficiency (%) of BSA in LbL-MC compared with adsorption method. At pH 4, the BSA release from LbL-MC was extended up to 120 h. Polyacrylamide gel electrophoresis showed that BSA encapsulated in LBL-MC through co-precipitation is stable toward trypsin treatment. In conclusion, co-precipitation method provided greater encapsulation of BSA in LbL-MC. Furthermore, LbL-MC can be developed as carriers for pH-controlled protein delivery.

Effect of cryoprotectants on the porosity and stability of insulin-loaded PLGA nanoparticles after freeze-drying

PubMed Central

Fonte, Pedro; Soares, Sandra; Costa, Ana; Andrade, José Carlos; Seabra, Vítor; Reis, Salette; Sarmento, Bruno

2012-01-01

PLGA nanoparticles are useful to protect and deliver proteins in a localized or targeted manner, with a long-term systemic delivery pattern intended to last for a period of time, depending on polymer bioerosion and biodegradability. However, the principal concern regarding these carriers is the hydrolytic instability of polymer in aqueous suspension. Freeze-drying is a commonly used method to stabilize nanoparticles, and cryoprotectants may be also used, to even increase its physical stability. The aim of the present work was to analyze the influence of cryoprotectants on nanoparticle stability and porosity after freeze-drying, which may influence protein release and stability. It was verified that freeze-drying significantly increased the number of pores on PLGA-NP surface, being more evident when cryoprotectants are added. The presence of pores is important in a lyophilizate to facilitate its reconstitution in water, although this may have consequences to protein release and stability. The release profile of insulin encapsulated into PLGA-NP showed an initial burst in the first 2 h and a sustained release up to 48 h. After nanoparticles freeze-drying the insulin release increased about 18% in the first 2 h due to the formation of pores, maintaining a sustained release during time. After freeze-drying with cryoprotectants, the amount of insulin released was higher for trehalose and lower for sucrose, glucose, fructose and sorbitol comparatively to freeze-dried PLGA-NP with no cryoprotectant added. Besides the porosity, the ability of cryoprotectants to be adsorbed on the nanoparticles surface may also play an important role on insulin release and stability. PMID:23507897

Interactions between Surfactants in Solution and Electrospun Protein Fibers: Effects on Release Behavior and Fiber Properties.

PubMed

Stephansen, Karen; García-Díaz, María; Jessen, Flemming; Chronakis, Ioannis S; Nielsen, Hanne M

2016-03-07

Intermolecular interaction phenomena occurring between endogenous compounds, such as proteins and bile salts, and electrospun compounds are so far unreported, despite the exposure of fibers to such biorelevant compounds when applied for biomedical purposes, e.g., tissue engineering, wound healing, and drug delivery. In the present study, we present a systematic investigation of how surfactants and proteins, as physiologically relevant components, interact with insulin-loaded fish sarcoplasmic protein (FSP) electrospun fibers (FSP-Ins fibers) in solution and thereby affect fiber properties such as accessible surface hydrophilicity, physical stability, and release characteristics of an encapsulated drug. Interactions between insulin-loaded protein fibers and five anionic surfactants (sodium taurocholate, sodium taurodeoxycholate, sodium glycocholate, sodium glycodeoxycholate, and sodium dodecyl sulfate), a cationic surfactant (benzalkonium chloride), and a neutral surfactant (Triton X-100) were studied. The anionic surfactants increased the insulin release in a concentration-dependent manner, whereas the neutral surfactant had no significant effect on the release. Interestingly, only minute amounts of insulin were released from the fibers when benzalkonium chloride was present. The FSP-Ins fibers appeared dense after incubation with this cationic surfactant, whereas high fiber porosity was observed after incubation with anionic or neutral surfactants. Contact angle measurements and staining with the hydrophobic dye 8-anilino-1-naphthalenesulfonic acid indicated that the FSP-Ins fibers were hydrophobic, and showed that the fiber surface properties were affected differently by the surfactants. Bovine serum albumin also affected insulin release in vitro, indicating that also proteins may affect the fiber performance in an in vivo setting.

Depot formulation of vasoactive intestinal peptide by protamine-based biodegradable nanoparticles.

PubMed

Wernig, Karin; Griesbacher, Martin; Andreae, Fritz; Hajos, Franz; Wagner, Julian; Mosgoeller, Wilhelm; Zimmer, Andreas

2008-09-10

Drug delivery of protein and peptide-based drugs, which represent a growing and important therapeutic class, is hampered by these drugs' very short half-lives. High susceptibility towards enzymatic degradation necessitates frequent drug administration followed by poor adherence to therapy. Among these drugs is vasoactive intestinal peptide (VIP), a potent systemic and pulmonary vasodilator, which is a promising drug for the treatment of idiopathic pulmonary arterial hypertension (IPAH). Encapsulation of VIP into the nanoparticle matrix of biodegradable protamine-oligonucleotide nanoparticles (proticles) protects the peptide against rapid enzymatic degradation. Additionally, the nanoparticle matrix will be able to sustain drug release. Proticles consist of 18mer non-sense oligonucleotides and protamine, a polycationic arginine-rich peptide. VIP encapsulation occurs during self-assembly of the components. Within the present study, we evaluate nanoparticle size (hydrodynamic diameter) and zeta potential of VIP-loaded proticles as well as encapsulation efficiency and VIP release. Further, the pharmacological VIP response of "encapsulated VIP" is investigated using an ex vivo lung arterial model system. We found satisfying encapsulation efficiency (up to 80%), VIP release (77-87%), and an appropriate nanoparticle size (177-251 nm). Investigations on rat pulmonary arteries showed a modified VIP response of proticle-associated VIP. We noted differences in the profile of artery relaxation where VIP proticles lead to a 20-30% lower relaxation maximum than aqueous VIP solutions followed by prolonged vasodilatation. Our data indicate that proticles could be a feasible drug delivery system for a pulmonary VIP depot formulation.

Thin film photovoltaic cells having increased durability and operating life and method for making same

DOEpatents

Barnett, Allen M.; Masi, James V.; Hall, Robert B.

1980-12-16

A solar cell having a copper-bearing absorber is provided with a composite transparent encapsulating layer specifically designed to prevent oxidation of the copper sulfide. In a preferred embodiment, the absorber is a layer of copper sulfide and the composite layer comprises a thin layer of copper oxide formed on the copper sulfide and a layer of encapsulating glass formed on the oxide. It is anticipated that such devices, when exposed to normal operating conditions of various terrestrial applications, can be maintained at energy conversion efficiencies greater than one-half the original conversion efficiency for periods as long as thirty years.

Nanostructured polysaccharidic microcapsules for intracellular release of cisplatin.

PubMed

Vergaro, Viviana; Papadia, Paride; Petrini, Paola; Fanizzi, Francesco Paolo; De Pascali, Sandra A; Baldassarre, Francesca; Pastorino, Laura; Ciccarella, Giuseppe

2017-06-01

Carbohydrate polimeric microcapsules were assembled using a LbL approach onto a CaCO 3 core. The microcapsules were used to delivery the anticancer drug cisplatin into HeLa and MCF-7 cancer cell lines. Drug encapsulation, measured by ICP spectroscopy, was around 50% of the charging solution. Fluorimetric measurements showed an efficient cellular uptake of polysacchardic microcapsules in both cell lines. The drug-loaded capsules demonstrated a better efficiency against cell viability than the free drug. Specifically, the amount of platinum reaching genomic DNA was measured, showing that encapsulation improves the nuclear delivery of the drug for both cell lines. Copyright © 2017 Elsevier B.V. All rights reserved.

Entrapment of peptidoglycans and adamantyltripeptides into liposomes: an HPLC assay for determination of encapsulation efficiency.

PubMed

Frkanec, Ruza; Travas, Dijana; Krstanović, Marina; Spoljar, Beata Halassy; Ljevaković, Durdica; Vranesić, Branka; Frkanec, Leo; Tomasić, Jelka

2003-11-01

The encapsulation of different immunomodulating peptides, the peptidoglycan monomer, its semisynthetic derivatives (Adamant-1-yl)-acetyl-peptidoglycan monomer and Boc-Tyr-peptidoglycan monomer, respectively, and of two diastereoisomers of adamantyltripeptides into the large negatively charged multilamellar liposomes was investigated. The reproducible quantitative method using HPLC was established for the determination of the entrapped compounds. It was shown that the tested compounds could be efficiently incorporated into liposomes using either the film or modified film method. The results confirmed that the peptidoglycans with lipophilic substituents and particularly the adamantyltripeptides were incorporated into liposomes with higher efficiency than the peptidoglycan monomer using either of the described methods. Liposome preparations were stable at 4 degrees C up to seven days as shown by minimal leaking of the entrapped material.

Ordering and partitioning in vesicle forming block copolymer thin films

NASA Astrophysics Data System (ADS)

Parnell, Andrew; Kamata, Yohei; Jones, Richard

Cell biology routinely uses encapsulation processes to package a payload and transport it to a location where the payload can then be used. Synthetic polymer based liposomes (Polymersomes) are one possible way in which we can artificially contain a molecule of interest that is protected from its surrounding environment. Encapsulation technologies at present rely on forming a lipid vesicle and then extruding it in a solution containing the target molecule to be encapsulated. Only a small fraction is encapsulated in this process. This is because of the complex structural formation pathway in going from individual isolated amphiphilic molecules into vesicle aggregates. My talk will discuss strategies to overcome the formation pathways, by forming a block copolymer film with the target molecule and then solvent ordering prior to the formation of vesicles. By studying block copolymer thin films with neutron reflectivity and ellipsometry we are able to observe partitioning and ordering which is essential for high encapsulation efficiencies. We acknowledge funding from STFC for use of the ISIS spallation neutron source.

Multifunctional polymersomes for cytosolic delivery of gemcitabine and doxorubicin to cancer cells.

PubMed

Nahire, Rahul; Haldar, Manas K; Paul, Shirshendu; Ambre, Avinash H; Meghnani, Varsha; Layek, Buddhadev; Katti, Kalpana S; Gange, Kara N; Singh, Jagdish; Sarkar, Kausik; Mallik, Sanku

2014-08-01

Although liposomes are widely used as carriers of drugs and imaging agents, they suffer from a lack of stability and the slow release of the encapsulated contents at the targeted site. Polymersomes (vesicles of amphiphilic polymers) are considerably more stable compared to liposomes; however, they also demonstrate a slow release for the encapsulated contents, limiting their efficacy as a drug-delivery tool. As a solution, we prepared and characterized echogenic polymersomes, which are programmed to release the encapsulated drugs rapidly when incubated with cytosolic concentrations of glutathione. These vesicles encapsulated air bubbles inside and efficiently reflected diagnostic-frequency ultrasound. Folate-targeted polymersomes showed an enhanced uptake by breast and pancreatic-cancer cells in a monolayer as well as in three-dimensional spheroid cultures. Polymersomes encapsulated with the anticancer drugs gemcitabine and doxorubicin showed significant cytotoxicity to these cells. With further improvements, these vesicles hold the promise to serve as multifunctional nanocarriers, offering a triggered release as well as diagnostic ultrasound imaging. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of encapsulated Lactobacillus acidophilus along with pasteurized longan juice on the colon microbiota residing in a dynamic simulator of the human intestinal microbial ecosystem.

PubMed

Chaikham, Pittaya; Apichartsrangkoon, Arunee

2014-01-01

The effect of encapsulated Lactobacillus acidophilus LA5 along with pasteurized longan juice on the colon microbiota was investigated by applying a dynamic model of the human gastrointestinal tract. Encapsulated L. acidophilus LA5 in pasteurized longan juice or sole encapsulated L. acidophilus LA5 exhibited the efficiency of colonizing the colon and enabling the growth of colon lactobacilli as well as beneficial bifidobacteria but inhibited the growth of fecal coliforms and clostridia. Moreover, these treatments gave rise to a significant increase of lactic acid and short-chain fatty acids such as acetate, propionate, and butyrate. Although acetate displayed the highest quantity, it was likely that after incorporating encapsulated L. acidophilus LA5 plus pasteurized longan juice, quantity of butyrate exceed propionate, and acetate in comparison with their controls. Denaturant gradient gel electrophoresis patterns confirmed that various treatments affected the alteration of microbial community within the simulator of the human intestinal microbial ecosystem.

Facile fabrication of well-defined hydrogel beads with magnetic nanocomposite shells.

PubMed

Liu, Hongxia; Wang, Chaoyang; Gao, Quanxing; Chen, Jianxin; Ren, Biye; Liu, Xinxing; Tong, Zhen

2009-07-06

Well-defined magnetic nanocomposite beads with alginate gel cores and shells of iron oxide (gamma-Fe(2)O(3)) nanoparticles were prepared by self-assembly of colloidal particles at liquid-liquid interfaces and subsequent in situ gelation. Fe(2)O(3) nanoparticles could spontaneously adsorb onto the water droplet surfaces to stabilize water-in-hexane emulsions. Water droplets containing sodium alginate were in situ gelled by calcium cations, which were released from calcium-ethylenediamine tetraacetic acid (Ca-EDTA) chelate by decreasing pH value through slow hydrolysis of d-glucono-delta-lactone (GDL). The resulting hybrid beads with a core-shell structure were easily collected by removing hexane. This facile and high efficient fabrication had a 100% yield and could be carried out at room temperature. Insulin microcrystal was encapsulated into the hybrid beads by dispersing them in the aqueous solution of alginate sodium in the fabrication process. The sustained release could be obtained due to the dual barriers of the hydrogel core and the close-packed inorganic shell. The release curves were nicely fitted by the Weibull equation and the release followed Fickian diffusion. The hybrid beads may find applications as delivery vehicles for biomolecules, drugs, cosmetics, food supplements and living cells.

Anti-cancer vaccination by transdermal delivery of antigen peptide-loaded nanogels via iontophoresis.

PubMed

Toyoda, Mao; Hama, Susumu; Ikeda, Yutaka; Nagasaki, Yukio; Kogure, Kentaro

2015-04-10

Transdermal vaccination with cancer antigens is expected to become a useful anti-cancer therapy. However, it is difficult to accumulate enough antigen in the epidermis for effective exposure to Langerhans cells because of diffusion into the skin and muscle. Carriers, such as liposomes and nanoparticles, may be useful for the prevention of antigen diffusion. Iontophoresis, via application of a small electric current, is a noninvasive and efficient technology for transdermal drug delivery. Previously, we succeeded in the iontophoretic transdermal delivery of liposomes encapsulating insulin, and accumulation of polymer-based nanoparticle nanogels in the stratum corneum of the skin. Therefore, in the present study, we examined the use of iontophoresis with cancer antigen gp-100 peptide KVPRNQDWL-loaded nanogels for anti-cancer vaccination. Iontophoresis resulted in the accumulation of gp-100 peptide and nanogels in the epidermis, and subsequent increase in the number of Langerhans cells in the epidermis. Moreover, tumor growth was significantly suppressed by iontophoresis of the antigen peptide-loaded nanogels. Thus, iontophoresis of the antigen peptide-loaded nanogels may serve as an effective transdermal delivery system for anti-cancer vaccination. Copyright © 2015 Elsevier B.V. All rights reserved.

Sustained co-delivery of BIO and IGF-1 by a novel hybrid hydrogel system to stimulate endogenous cardiac repair in myocardial infarcted rat hearts.

PubMed

Fang, Rui; Qiao, Shupei; Liu, Yi; Meng, Qingyuan; Chen, Xiongbiao; Song, Bing; Hou, Xiaolu; Tian, Weiming

2015-01-01

Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization.

Sustained co-delivery of BIO and IGF-1 by a novel hybrid hydrogel system to stimulate endogenous cardiac repair in myocardial infarcted rat hearts

PubMed Central

Fang, Rui; Qiao, Shupei; Liu, Yi; Meng, Qingyuan; Chen, Xiongbiao; Song, Bing; Hou, Xiaolu; Tian, Weiming

2015-01-01

Dedifferentiation and proliferation of endogenous cardiomyocytes in situ can effectively improve cardiac repair following myocardial infarction (MI). 6-Bromoindirubin-3-oxime (BIO) and insulin-like growth factor 1 (IGF-1) are two potent factors that promote cardiomyocyte survival and proliferation. However, their delivery for sustained release in MI-affected areas has proved to be challenging. In the current research, we present a study on the sustained co-delivery of BIO and IGF-1 in a hybrid hydrogel system to simulate endogenous cardiac repair in an MI rat model. Both BIO and IGF-1 were efficiently encapsulated in gelatin nanoparticles, which were later cross-linked with the oxidized alginate to form a novel hybrid hydrogel system. The in vivo results indicated that the hybrid system could enhance the proliferation of cardiomyocytes in situ and could promote revascularization around the MI sites, allowing improved cardiac function. Taken together, we concluded that the hybrid hydrogel system can co-deliver BIO and IGF-1 to areas of MI and thus improve cardiac function by promoting the proliferation of cardiomyocytes and revascularization. PMID:26251592

Quality changes and shelf-life extension of ready-to-eat fish patties by adding encapsulated citric acid.

PubMed

Bou, Ricard; Claret, Anna; Stamatakis, Antonios; Martínez, Brigitte; Guerrero, Luis

2017-12-01

Citric acid is commonly used as a flavoring and preservative in food and beverages. The effect of adding citric acid directly or encapsulated (each at 1 and 2 g kg -1 ) on the quality and shelf-life of ready-to-eat sea bass patties was evaluated during storage at 4 °C in vacuum skin packaging. Microbial growth and total basic volatile nitrogen were maintained at relatively low levels up to 8 weeks of storage. With respect to oxidative stability, the addition of encapsulated citric acid minimized secondary oxidation values more efficiently than its direct addition, regardless of the concentration. This is in agreement with the decreased fishy odor observed in those patties containing encapsulated citric acid. Accordingly, sensory analysis showed that the addition of encapsulated citric acid at 1 g kg -1 resulted in lower scores in fish aroma compared to that of the control. Sourness is dependent on the amount of citric acid added, regardless of the form (direct or encapsulated). The form of citric acid addition, rather than the amount of citric acid added, caused changes in texture. Therefore, the use of encapsulated citric acid represents a suitable strategy that is of great interest in the seafood industry. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Asymmetric bioreduction of acetophenones by Baker's yeast and its cell-free extract encapsulated in sol-gel silica materials

NASA Astrophysics Data System (ADS)

Kato, Katsuya; Nakamura, Hitomi; Nakanishi, Kazuma

2014-02-01

Baker's yeast (BY) encapsulated in silica materials was synthesized using a yeast cell suspension and its cell-free extract during a sol-gel reaction of tetramethoxysilane with nitric acid as a catalyst. The synthesized samples were fully characterized using various methods, such as scanning electron microscopy, nitrogen adsorption-desorption, Fourier transform infrared spectroscopy, thermogravimetry, and differential thermal analysis. The BY cells were easily encapsulated inside silica-gel networks, and the ratio of the cells in the silica gel was approximately 75 wt%, which indicated that a large volume of BY was trapped with a small amount of silica. The enzyme activity (asymmetric reduction of prochiral ketones) of BY and its cell-free extract encapsulated in silica gel was investigated in detail. The activities and enantioselectivities of free and encapsulated BY were similar to those of acetophenone and its fluorine derivatives, which indicated that the conformation structure of BY enzymes inside silica-gel networks did not change. In addition, the encapsulated BY exhibited considerably better solvent (methanol) stability and recyclability compared to free BY solution. We expect that the development of BY encapsulated in sol-gel silica materials will significantly impact the industrial-scale advancement of high-efficiency and low-cost biocatalysts for the synthesis of valuable chiral alcohols.

Biodegradable polycaprolactone (PCL) nanosphere encapsulating superoxide dismutase and catalase enzymes.

PubMed

Singh, Sushant; Singh, Abhay Narayan; Verma, Anil; Dubey, Vikash Kumar

2013-12-01

Biodegradable polycaprolactone (PCL) nanosphere encapsulating superoxide dismutase (SOD) and catalase (CAT) were successfully synthesized using double emulsion (w/o/w) solvent evaporation technique. Characterization of the nanosphere using dynamic light scattering, field emission scanning electron microscope, and Fourier transform infrared spectroscopy revealed a spherical-shaped nanosphere in a size range of 812 ± 64 nm with moderate protein encapsulation efficiency of 55.42 ± 3.7 % and high in vitro protein release. Human skin HaCat cells were used for analyzing antioxidative properties of SOD- and CAT-encapsulated PCL nanospheres. Oxidative stress condition in HaCat cells was optimized with exposure to hydrogen peroxide (H2O2; 1 mM) as external stress factor and verified through reactive oxygen species (ROS) analysis using H2DCFDA dye. PCL nanosphere encapsulating SOD and CAT together indicated better antioxidative defense against H2O2-induced oxidative stress in human skin HaCat cells in comparison to PCL encapsulating either SOD or CAT alone as well as against direct supplement of SOD and CAT protein solution. Increase in HaCat cells SOD and CAT activities after treatment hints toward uptake of PCL nanosphere into the human skin HaCat cells. The result signifies the role of PCL-encapsulating SOD and CAT nanosphere in alleviating oxidative stress.

Droplet sorting based on the number of encapsulated particles using a solenoid valve.

PubMed

Cao, Zhenning; Chen, Fangyuan; Bao, Ning; He, Huacheng; Xu, Peisheng; Jana, Saikat; Jung, Sunghwan; Lian, Hongzhen; Lu, Chang

2013-01-07

Droplet microfluidics provides a high-throughput platform for screening subjects and conditions involved in biology. Droplets with encapsulated beads and cells have been increasingly used for studying molecular and cellular biology. Droplet sorting is needed to isolate and analyze the subject of interest during such screening. The vast majority of current sorting techniques use fluorescence intensity emitted by each droplet as the only criterion. However, due to the randomness and imperfections in the encapsulation process, typically a mixed population of droplets with an uneven number of encapsulated particles results and is used for screening. Thus droplet sorting based on the number of encapsulated particles becomes necessary for isolating or enriching droplets with a specific occupancy. In this work, we developed a fluorescence-activated microfluidic droplet sorter that integrated a simple deflection mechanism based on the use of a solenoid valve and a sophisticated signal processing system with a microcontroller as the core. By passing droplets through a narrow interrogation channel, the encapsulated particles were detected individually. The microcontroller conducted the computation to determine the number of encapsulated particles in each droplet and made the sorting decision accordingly that led to actuation of the solenoid valve. We tested both fluorescent beads and stained cells and our results showed high efficiency and accuracy for sorting and enrichment.

Silica sol-gel encapsulation of cyanobacteria: lessons for academic and applied research.

PubMed

Dickson, David J; Ely, Roger L

2013-03-01

Cyanobacteria inhabit nearly every ecosystem on earth, play a vital role in nutrient cycling, and are useful as model organisms for fundamental research in photosynthesis and carbon and nitrogen fixation. In addition, they are important for several established biotechnologies for producing food additives, nutritional and pharmaceutical compounds, and pigments, as well as emerging biotechnologies for biofuels and other products. Encapsulation of living cyanobacteria into a porous silica gel matrix is a recent approach that may dramatically improve the efficiency of certain production processes by retaining the biomass within the reactor and modifying cellular metabolism in helpful ways. Although encapsulation has been explored empirically in the last two decades for a variety of cell types, many challenges remain to achieving optimal encapsulation of cyanobacteria in silica gel. Recent evidence with Synechocystis sp. PCC 6803, for example, suggests that several unknown or uncharacterized proteins are dramatically upregulated as a result of encapsulation. Also, additives commonly used to ease stresses of encapsulating living cells, such as glycerol, have detrimental impacts on photosynthesis in cyanobacteria. This mini-review is intended to address the current status of research on silica sol-gel encapsulation of cyanobacteria and research areas that may further the development of this approach for biotechnology applications.

Random breakup of microdroplets for single-cell encapsulation

NASA Astrophysics Data System (ADS)

Um, Eujin; Lee, Seung-Goo; Park, Je-Kyun

2010-10-01

Microfluidic droplet-based technology enables encapsulation of cells in the isolated aqueous chambers surrounded by immiscible fluid but single-cell encapsulation efficiency is usually less than 30%. In this letter, we introduce a simple microgroove structure to break droplets into random sizes which further allows collecting of single-cell [Escherichia coli (E. coli)] containing droplets by their size differences. Pinched-flow separation method is integrated to sort out droplets of certain sizes which have high probability of containing one cell. Consequently, we were able to obtain more than 50% of droplets having single E. coli inside, keeping the proportion of multiple-cell containing droplets less than 16%.

Assessment of formulated amodiaquine microparticles in Leishmania donovani infected rats.

PubMed

Nettey, Henry; Allotey-Babington, Grace Lovia; Somuah, Isaac; Banga, N'guessan Benoit; Afrane, Barima; Amponsah, Seth Kwabena; Annor, Henrietta; Darko, Henry; Hanson, Kwame; Aidoo, Anoa; Broni, Marisa Nyarkoa; Sasu, Clement; Nyarko, Alexander

2017-02-01

The aim of this study was to formulate, characterise and evaluate the activity of amodiaquine microparticles against Leishmania donovani. Microparticles were formulated by encapsulating the drug in bovine serum albumin using the spray-dryer method. The microparticles were evaluated for size, zeta potential, drug content, encapsulation efficiency and in vitro release profile. The size range of the microparticles formulated was between 1.9 and 10 μm with an average zeta potential of -25.5 mV. Of the expected 20% drug loading, an average of 18.27% was obtained giving an encapsulation efficiency of 91.35%. Pharmacokinetic profile of amodiaquine improved with microencapsulation of the drug with C max , AUC 0→48 and t 1//2 all significantly higher than amodiaquine solution. Amodiaquine microparticles showed an overall higher bioavailability and hence were more effective in eliminating intra-tissue parasites than the drug solution. It would therefore be expected that the formulated microparticles will be more effective in treating visceral leishmaniasis.

Enhanced drug encapsulation and extended release profiles of calcium-alginate nanoparticles by using tannic acid as a bridging cross-linking agent.

PubMed

Abulateefeh, Samer R; Taha, Mutasem O

2015-01-01

Calcium alginate nanoparticles (NPs) suffer from sub-optimal stability in bio-relevant media leading to low drug encapsulation efficiency and uncontrolled release profiles. To sort out these drawbacks, a novel approach is proposed herein based on introducing tannic acid into these NPs to act as a bridging cross-linking aid agent. Calcium-alginate NPs were prepared by the ionotropic gelation method and loaded with diltiazem hydrochloride as a model drug. These NPs were characterized in terms of particle size, zeta potential, and morphology, and results were explained in accordance with Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The incorporation of tannic acid led to more than four folds increase in drug encapsulation efficiency (i.e. from 15.3% to 69.5%) and reduced burst drug release from 44% to around 10% within the first 30 min. These findings suggest the possibility of improving the properties of Ca-alginate NPs by incorporating cross-linking aid agents under mild conditions.

First evaluation of drug-in-cyclodextrin-in-liposomes as an encapsulating system for nerolidol.

PubMed

Azzi, Joyce; Auezova, Lizette; Danjou, Pierre-Edouard; Fourmentin, Sophie; Greige-Gerges, Hélène

2018-07-30

Nerolidol, a naturally occurring sesquiterpene with antimicrobial activities, is a promising candidate as a natural alternative for synthetic preservatives in food. However, its application is limited by low aqueous solubility and stability. In this study, conventional liposomes and drug-in-cyclodextrin-in-liposomes (DCLs) were evaluated for the first time as encapsulating materials for nerolidol. The size, encapsulation efficiency (EE%), loading rate (LR%), photo- and storage stabilities of both systems were characterized. Moreover, the in vitro release of nerolidol from liposomes and DCLs was investigated over time. Nerolidol was efficiently entrapped in both carriers with high EE% and LR% values. In addition, DCLs prolonged the release of nerolidol over one week and enhanced the photostability more effectively than conventional liposomes. Finally, all formulations were stable after 12 months of storage at 4 °C (>60% incorporated nerolidol). Therefore, DCLs are promising carriers for new applications of sesquiterpenes in the pharmaceutical and food industries. Copyright © 2018 Elsevier Ltd. All rights reserved.

Preparation and characterization of clove essential oil-loaded liposomes.

PubMed

Sebaaly, Carine; Jraij, Alia; Fessi, Hatem; Charcosset, Catherine; Greige-Gerges, Hélène

2015-07-01

In this study, suitable formulations of natural soybean phospholipid vesicles were developed to improve the stability of clove essential oil and its main component, eugenol. Using an ethanol injection method, saturated (Phospholipon 80H, Phospholipon 90H) and unsaturated soybean (Lipoid S100) phospholipids, in combination with cholesterol, were used to prepare liposomes at various eugenol and clove essential oil concentrations. Liposomal batches were characterized and compared for their size, polydispersity index, Zeta potential, loading rate, encapsulation efficiency and morphology. The liposomes were tested for their stability after storing them for 2 months at 4°C by monitoring changes in their mean size, polydispersity index and encapsulation efficiency (EE) values. It was found that liposomes exhibited nanometric oligolamellar and spherical shaped vesicles and protected eugenol from degradation induced by UV exposure; they also maintained the DPPH-scavenging activity of free eugenol. Liposomes constitute a suitable system for encapsulation of volatile unstable essential oil constituents. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Preparation and characterization of nanoemulsion].

PubMed

Sun, Yu-Jing; Wu, Dao-Cheng; Cao, Yun-Xin; Sui, Yan-Fang

2005-01-01

To prepare nanoemulsion-encapsulated BSA-FITC (NEBSA-FITC), study its characteristics, and measure its uptake by dendritic cells (DCs) and peritoneal macrophages. NEBSA-FITC was prepared by a method of interfacial polymerization.The encapsulation rate, drug-carrying capacity and stability of the nanoemulsion were determined by Sephadex-G100 chromatography. The shape and size of NEBSA-FITC were observed under electron microscope. The uptake of NEBSA-FITC by DCs and macrophage cells was detected by FACS and laser confocal microscopy. The mean size of NEBSA-FITC was (25+/-10) nm. The encapsulation rate was 91%, the drug-carrying capacity was 0.091 g/L and NEBSA-FITC had a good stability. The FACS analysis showed that DCs and macrophage cells could take in more NEBSA-FITC than free BSA. The observation under laser confocal microscope found that NEBSA-FITC was located in the cytoplasm of DCs. Nanoemulsion can be efficiently taken by DCs and macrophage cells, and therefore may be promising efficient carrier of APCs-targeted antitumor vaccine.

Alginate/cashew gum nanoparticles for essential oil encapsulation.

PubMed

de Oliveira, Erick F; Paula, Haroldo C B; de Paula, Regina C M

2014-01-01

Alginate/cashew gum nanoparticles were prepared via spray-drying, aiming at the development of a biopolymer blend for encapsulation of an essential oil. Nanoparticles were characterized regarding to their hydrodynamic volume, surface charge, Lippia sidoides essential oil content and release profile, in addition to being analyzed by infrared spectroscopy (FT-IR), thermal analysis (TGA/DSC) and X-ray diffractometry. Nanoparticles in solution were found to have averaged sizes in the range 223-399 nm, and zeta potential values ranging from -30 to -36 mV. Encapsulated oil levels varied from 1.9 to 4.4% with an encapsulation efficiency of up to 55%. The in vitro release profile showed that between 45 and 95% of oil was released within 30-50h. Kinetic studies revealed that release pattern follow a Korsmeyer-Peppas mechanism. Copyright © 2013 Elsevier B.V. All rights reserved.

An effective treatment approach of DPP-IV inhibitor encapsulated polymeric nanoparticles conjugated with anti-CD-4 mAb for type 1 diabetes.

PubMed

Thondawada, Mahesh; Wadhwani, Ashish Devidas; S Palanisamy, Dhanabal; Rathore, Hanumant Singh; Gupta, Ramesh C; Chintamaneni, Pavan Kumar; Samanta, Malay K; Dubala, Anil; Varma, Sameer; Krishnamurthy, Praveen T; Gowthamarajan, Kuppusamy

2018-07-01

Nanotechnology based biomedical approaches and surface modification techniques made it easier for targeting specific site and improving the treatment efficacy. The present study reports on targeted polymeric nanoparticles conjugated with antibody as a site-specific carrier system for effective treatment of type 1 diabetes. Sitagliptin (SP)-loaded Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP) were prepared by nanoprecipitation cum solvent evaporation method and were characterized in terms of morphology, size, surface charge, and entrapment efficiency. Optimized batch demonstrated a particle size of 105.24 nm, with significant entrapment efficacy. In vitro release studies exhibited a controlled release pattern of 67.76 ± 1.30% in 24 h, and a maximum of 96.59 ± 1.26% at the end of 48 h. Thiol groups were introduced on the surface of SP-NPs whose concentration on SP-NPs was 27 ± 2.6 mmol/mol PLGA-NPs, anti-CD4 antibody clone Q4120 was conjugated to the thiolated SP-NPs via a sulfo-MBS cross-linker, ∼70% conjugation was observed. The in vitro cytotoxicity studies performed on RIN-5 F cells for mAb-SP-NPs presented an IC 50 of 76 µg/mL, and the insulin release assay had revealed an increased release at 5.15 ± 0.16 IU/mL. The results indicate that mAb-SP-NPs allowed a controlled release of SP and thereby produced insulin levels comparable with control. Therefore, mAb-SP-NPs system appears to be effective in the treatment of auto immune diabetes, subject to further analysis.

Clinical porcine islet xenotransplantation under comprehensive regulation.

PubMed

Matsumoto, S; Tan, P; Baker, J; Durbin, K; Tomiya, M; Azuma, K; Doi, M; Elliott, R B

2014-01-01

Xenotransplantation with porcine islets is a promising approach to overcome the shortage of human donors. This is the first report of phase 1/2a xenotransplantation study of encapsulated neonatal porcine islets under the current framework of regulations for xenotransplantation in New Zealand. Newborn piglets were anesthetized and bled, and the pancreata were removed with the use of sterile technique and processed. Encapsulated neonatal porcine islets were implanted with the use of laparoscopy into the peritoneal cavity of 14 patients with unstable type 1 diabetes without any immunosuppressive drugs. The patients received encapsulated islets of 5,000 (n = 4; group 1), 10,000 (n = 4; group 2), 15,000 (n = 4; group 3), or 20,000 (n = 2; group 4) islet equivalents per kg body weight. Outcome was determined from adverse event reports, HbA1c, total daily insulin dose, and frequency of unaware hypoglycemic events. To assess graft function, transplant estimated function (TEF) scores were calculated. Sufficient or marginal numbers of encapsulated neonatal porcine islets were transplanted into streptozotocin-induced diabetic B6 mice as an in vivo functional assay. There were 4 serious adverse events, of which 3 were considered to be possibly related to the procedure. Tests for porcine endogenous retrovirus DNA and RNA were all negative. The numbers of unaware hypoglycemia events were reduced after transplantation in all groups. Four of 14 patients attained HbA1c <7% compared with 1 at baseline. The average TEF scores were 0.17, 0.02, -0.01, and 0.08 in groups 1, 2, 3, and 4 respectively. The in vivo study demonstrated that a sufficient number of the transplanted group reversed diabetes with positive porcine C-peptide. Transplantation of encapsulated neonatal porcine islets was safe and was followed by a reduction in unaware hypoglycemia events in unstable type 1 diabetic patients. The mouse in vivo assessment data demonstrated certain graft function. Copyright © 2014 Elsevier Inc. All rights reserved.

Plastic Encapsulation of Stabilized Escherichia coli and Pseudomonas putida

PubMed Central

Manzanera, M.; Vilchez, S.; Tunnacliffe, A.

2004-01-01

Escherichia coli and Pseudomonas putida dried in hydroxyectoine or trehalose are shown to be highly resistant to the organic solvents chloroform and acetone, and consequently, they can be encapsulated in a viable form in solid plastic materials. Bacteria are recovered by rehydration after physical disruption of the plastic. P. putida incorporated into a plastic coating of maize seeds was shown to colonize roots efficiently after germination. PMID:15128579

Ion-plating of solar cell arrays encapsulation task: LSA project 32

NASA Technical Reports Server (NTRS)

Volkers, J. C.

1983-01-01

An ion plating process by which solar cells can be metallized and AR coated, yielding efficiencies equal to or better than state-of-the-art cells, was developed. It was demonstrated that ion plated AR films may be used as an effective encapsulant, offering primary protection for the metallization. It was also shown that ion plated metallization and AR coatings can be consistent with the project cost goals.

Effect of Experimental Parameters on Alginate/Chitosan Microparticles for BCG Encapsulation

PubMed Central

Caetano, Liliana A.; Almeida, António J.; Gonçalves, Lídia M.D.

2016-01-01

The aim of the present study was to develop novel Mycobacterium bovis bacille Calmette-Guérin (BCG)-loaded polymeric microparticles with optimized particle surface characteristics and biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against Mycobacterium tuberculosis by the intranasal route. BCG was encapsulated in chitosan and alginate microparticles through three different polyionic complexation methods by high speed stirring. For comparison purposes, similar formulations were prepared with high shear homogenization and sonication. Additional optimization studies were conducted with polymers of different quality specifications in a wide range of pH values, and with three different cryoprotectors. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. Chitosan addition to BCG shifted the bacilli surface charge from negative zeta potential values to strongly positive ones. Chitosan of low molecular weight produced particle suspensions of lower size distribution and higher stability, allowing efficient BCG encapsulation and biocompatibility. Particle formulation consistency was improved when the availability of functional groups from alginate and chitosan was close to stoichiometric proportion. Thus, the herein described microparticulate system constitutes a promising strategy to deliver BCG vaccine by the intranasal route. PMID:27187418

Liposomes Size Engineering by Combination of Ethanol Injection and Supercritical Processing.

PubMed

Santo, Islane Espirito; Campardelli, Roberta; Albuquerque, Elaine Cabral; Vieira De Melo, Silvio A B; Reverchon, Ernesto; Della Porta, Giovanna

2015-11-01

Supercritical fluid extraction using a high-pressure packed tower is proposed not only to remove the ethanol residue from liposome suspensions but also to affect their size and distribution leading the production of nanosomes. Different operating pressures, temperatures, and gas to liquid ratios were explored and ethanol was successfully extracted up to a value of 400 ppm; liposome size and distribution were also reduced by the supercritical processing preserving their integrity, as confirmed by Z-potential data and Trasmission Electron Microscopy observations. Operating at 120 bar and 38°C, nanosomes with a mean diameter of about 180 ± 40 nm and good storage stability were obtained. The supercritical processing did not interfere on drug encapsulation, and no loss of entrapped drug was observed when the water-soluble fluorescein was loaded as a model compound. Fluorescein encapsulation efficiency was 30% if pure water was used during the supercritical extraction as processing fluid; whereas an encapsulation efficiency of 90% was obtained if the liposome suspension was processed in water/fluorescein solution. The described technology is easy to scale up to an industrial production and merge in one step the solvent extraction, liposome size engineering, and an excellent drug encapsulation in a single operation unit. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Spray-dried structured lipid containing long-chain polyunsaturated fatty acids for use in infant formulas.

PubMed

Nagachinta, Supakana; Akoh, Casimir C

2013-10-01

Human milk fat (HMF) analogs are structured lipids (SLs) modified to have palmitic acid content at the sn-2 position of the triacylglycerol (TAG) and fatty acid composition comparable to HMF. Some of these SLs are also designed to incorporate long-chain polyunsaturated fatty acids (LCPUFAs) because of their important role in infant development. In this study, Maillard reaction products (MRPs), obtained from heated whey protein isolates and corn syrup solids (CSS) solution, were used as encapsulants for microencapsulation of 2 enzymatically synthesized SLs for infant formula applications. The encapsulated SL powders were obtained through spray-drying and evaluated in terms of their microencapsulation efficiency, chemical and physical properties, oxidative stability, and dispersibility. The microencapsulation efficiency of the SLs was 90%. Dispersibility test using particle size measurement demonstrated that these powders dispersed quickly into a homogeneous suspension. The encapsulated SL powders had low peroxide and thiobarbituric acid-reactive substances values. Lower oxidative stability was obtained in the powder containing SL with a higher degree of unsaturation and a lower concentration of tocopherols. The results demonstrated that the degree of fatty acid unsaturation and concentration of endogenous antioxidant in starting oils influenced the oxidative stability of the encapsulated SLs. © 2013 Institute of Food Technologists®

Ni0 encapsulated in N-doped carbon nanotubes for catalytic reduction of highly toxic hexavalent chromium

NASA Astrophysics Data System (ADS)

Yao, Yunjin; Zhang, Jie; Chen, Hao; Yu, Maojing; Gao, Mengxue; Hu, Yi; Wang, Shaobin

2018-05-01

N-doped carbon nanotubes encapsulating Ni0 nanoparticles (Ni@N-C) were fabricated via thermal reduction of dicyandiamide and NiCl2·6H2O, and used to remove CrVI in polluted water. The resultant products present an excellent catalytic activity for CrVI reduction using formic acid under relatively mild conditions. The CrVI reduction efficiency of Ni@N-C was significantly affected by the preparation conditions including the mass of nickel salt and synthesis temperatures. The impacts of several reaction parameters, such as initial concentrations of CrVI and formic acid, solution pH and temperatures, as well as inorganic anions in solution on CrVI reduction efficiency were also evaluated in view of scalable industrial applications. Owing to the synergistic effects amongst tubes-coated Ni0, doped nitrogen, oxygen containing groups, and the configuration of carbon nanotubes, Ni@N-C catalysts exhibit excellent catalytic activity and recyclable capability for CrVI reduction. Carbon shell can efficiently protect inner Ni0 core and N species from corrosion and subsequent leaching, while Ni0 endows the Ni@N-C catalysts with ferromagnetism, so that the composites can be easily separated via a permanent magnet. This study opens up an avenue for design of N-doped carbon nanotubes encapsulating Ni0 nanoparticles with high CrVI removal efficiency and magnetic recyclability as low-cost catalysts for industrial applications.

Hydrophobic ion pairing of a minocycline/Ca(2+)/AOT complex for preparation of drug-loaded PLGA nanoparticles with improved sustained release.

PubMed

Holmkvist, Alexander Dontsios; Friberg, Annika; Nilsson, Ulf J; Schouenborg, Jens

2016-02-29

Polymeric nanoparticles is an established and efficient means to achieve controlled release of drugs. Incorporation of minocycline, an antibiotic with anti-inflammatory and neuroprotective properties, into biodegradable nanoparticles may therefore provide an efficient means to combat foreign body reactions to implanted electrodes in the brain. However, minocycline is commonly associated with poor encapsulation efficiencies and/or fast release rates due to its high solubility in water. Moreover, minocycline is unstable under conditions of low and high pH, heat and exposure to light, which exacerbate the challenges of encapsulation. In this work drug loaded PLGA nanoparticles were prepared by a modified emulsification-solvent-diffusion technique and characterized for size, drug encapsulation and in vitro drug release. A novel hydrophobic ion pair complex of minocycline, Ca(2+) ions and the anionic surfactant AOT was developed to protect minocycline from degradation and prolong its release. The optimized formulation resulted in particle sizes around 220 nm with an entrapment efficiency of 43% and showed drug release over 30 days in artificial cerebrospinal fluid. The present results constitute a substantial increase in release time compared to what has hitherto been achieved for minocycline and indicate that such particles might provide useful for sustained drug delivery in the CNS. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo.

PubMed

Gou, MaLing; Men, Ke; Shi, HuaShan; Xiang, MingLi; Zhang, Juan; Song, Jia; Long, JianLin; Wan, Yang; Luo, Feng; Zhao, Xia; Qian, ZhiYong

2011-04-01

Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 ± 0.011) with a mean particle size of 27.3 ± 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 ± 1.02%, and drug loading of 12.95 ± 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t(1/2) and AUC of curcumin in vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesis in vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cells in vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg(-1) curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p < 0.01), and induced a stronger anticancer effect than that of free curcumin (p < 0.05). In conclusion, Cur/MPEG-PCL micelles are an excellent intravenously injectable aqueous formulation of curcumin; this formulation can inhibit the growth of colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.

Double emulsion solvent evaporation techniques used for drug encapsulation.

PubMed

Iqbal, Muhammad; Zafar, Nadiah; Fessi, Hatem; Elaissari, Abdelhamid

2015-12-30

Double emulsions are complex systems, also called "emulsions of emulsions", in which the droplets of the dispersed phase contain one or more types of smaller dispersed droplets themselves. Double emulsions have the potential for encapsulation of both hydrophobic as well as hydrophilic drugs, cosmetics, foods and other high value products. Techniques based on double emulsions are commonly used for the encapsulation of hydrophilic molecules, which suffer from low encapsulation efficiency because of rapid drug partitioning into the external aqueous phase when using single emulsions. The main issue when using double emulsions is their production in a well-controlled manner, with homogeneous droplet size by optimizing different process variables. In this review special attention has been paid to the application of double emulsion techniques for the encapsulation of various hydrophilic and hydrophobic anticancer drugs, anti-inflammatory drugs, antibiotic drugs, proteins and amino acids and their applications in theranostics. Moreover, the optimized ratio of the different phases and other process parameters of double emulsions are discussed. Finally, the results published regarding various types of solvents, stabilizers and polymers used for the encapsulation of several active substances via double emulsion processes are reported. Copyright © 2015 Elsevier B.V. All rights reserved.

Investigation of test methods, material properties, and processes for solar cell encapsulants

NASA Technical Reports Server (NTRS)

1984-01-01

Photovoltaic (PV) modules consist of a string of electrically interconnected silicon solar cells capable of producing practical quantities of electrical power when exposed to sunlight. To insure high reliability and long term performance, the functional components of the solar cell module must be adequately protected from the environment by some encapsulation technique. The encapsulation system must provide mechanical support for the cells and corrosion protection for the electrical components. The goal of the program is to identify and develop encapsulation systems consistent with the PV module operating requirements of 30 year life and a target cost of $0.70 per peak watt ($70 per square meter) (1980 dollars). Assuming a module efficiency of ten percent, which is equivalent to a power output of 100 watts per square meter in midday sunlight, the capital cost of the modules may be calculated to be $70.00 per square meter. Out of this cost goal, only 20 percent is available for encapsulation due to the high cost of the cells, interconnects, and other related components. The encapsulation cost allocation may then be stated as $14.00 per square meter, included all coatings, pottant and mechanical supports for the cells.

The Effects of Insulin Resistance on Individual Tissues: An Application of a Mathematical Model of Metabolism in Humans.

PubMed

Pearson, Taliesin; Wattis, Jonathan A D; King, John R; MacDonald, Ian A; Mazzatti, Dawn J

2016-06-01

Whilst the human body expends energy constantly, the human diet consists of a mix of carbohydrates and fats delivered in a discontinuous manner. To deal with this sporadic supply of energy, there are transport, storage and utilisation mechanisms, for both carbohydrates and fats, around all tissues of the body. Insulin-resistant states such as type 2 diabetes and obesity are characterised by reduced efficiency of these mechanisms. Exactly how these insulin-resistant states develop, for example whether there is an order in which tissues become insulin resistant, is an active area of research with the hope of gaining a better overall understanding of insulin resistance. In this paper, we use a previously derived system of 12 first-order coupled differential equations that describe the transport between, and storage in, different tissues of the human body. We briefly revisit the derivation of the model before parametrising the model to account for insulin resistance. We then solve the model numerically, separately simulating each individual tissue as insulin resistant, and discuss and compare these results, drawing three main conclusions. The implications of these results are in accordance with biological intuition. First, insulin resistance in a tissue creates a knock-on effect on the other tissues in the body, whereby they attempt to compensate for the reduced efficiency of the insulin-resistant tissue. Second, insulin resistance causes a fatty liver, and the insulin resistance of tissues other than the liver can cause fat to accumulate in the liver. Finally, although insulin resistance in individual tissues can cause slightly reduced skeletal muscle metabolic flexibility, it is when the whole body is insulin resistant that the biggest effect on skeletal muscle flexibility is seen.

Sustained glucagon-like peptide 1 expression from encapsulated transduced cells to treat obese diabetic rats.

PubMed

Moralejo, Daniel; Yanay, Ofer; Kernan, Kelly; Bailey, Adam; Lernmark, Ake; Osborne, William

2011-04-01

Obesity and type 2 diabetes (T2D) are two prevalent chronic diseases that have become a major public health concern in industrialized countries. T2D is characterized by hyperglycemia and islet beta cell dysfunction. Glucagon-like peptide 1 (GLP-1) promotes β cell proliferation and neogenesis and has a potent insulinotropic effect. Leptin receptor deficient male rats are obese and diabetic and provide a model of T2D. We hypothesized that their treatment by sustained expression of GLP-1 using encapsulated cells may prevent or delay diabetes onset. Vascular smooth muscle cells (VSMC) retrovirally transduced to secrete GLP-1 were seeded into TheraCyte(TM) encapsulation devices, implanted subcutaneously and rats were monitored for diabetes. Rats that received cell implants showed mean plasma GLP-1 level of 119.3 ± 10.2pM that was significantly elevated over control values of 32.4 ± 2.9pM (P<0.001). GLP-1 treated rats had mean insulin levels of 45.9 ± 2.3ng/ml that were significantly increased over control levels of 7.3±1.5ng/ml (P<0.001). In rats treated before diabetes onset elevations in blood glucose were delayed and rats treated after onset became normoglycemic and showed improved glucose tolerance tests. Untreated diabetic rats possess abnormal islet structures characterized by enlarged islets with α-cell infiltration and multifocal vacuolization. GLP-1 treatment induced normalization of islet structures including a mantle of α-cells and increased islet mass. These data suggest that encapsulated transduced cells may offer a potential long term treatment of patients. Copyright © 2010 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Sustained glucagon-like peptide 1 expression from encapsulated transduced cells to treat obese diabetic rats

PubMed Central

Moralejo, Daniel; Yanay, Ofer; Kernan, Kelly; Bailey, Adam; Lernmark, Ake; Osborne, William

2011-01-01

Obesity and type 2 diabetes (T2D) are two prevalent chronic diseases that have become a major public health concern in industrialized countries. T2D is characterized by hyperglycemia and islet beta cell dysfunction. Glucagon-like peptide 1 (GLP-1) promotes β cell proliferation and neogenesis and has a potent insulinotropic effect. Leptin receptor deficient male rats are obese and diabetic and provide a model of T2D. We hypothesized that their treatment by sustained expression of GLP-1 using encapsulated cells may prevent or delay diabetes onset. Vascular smooth muscle cells (VSMC) retrovirally transduced to secrete GLP-1 were seeded into TheraCyteTM encapsulation devices, implanted subcutaneously and rats monitored for diabetes. Rats that received cell implants showed mean plasma GLP-1 level of 119.3±10.2 pM that was significantly elevated over control values of 32.4±2.9 pM (P<0.001). GLP-1 treated rats had mean insulin levels of 45.9±2.3 ng/ml that were significantly increased over control levels of 7.3±1.5 ng/ml (P<0.001). In rats treated before diabetes onset elevations in blood glucose were delayed and rats treated after onset became normoglycemic and showed improved glucose tolerance tests. Untreated diabetic rats possess abnormal islet structures characterized by enlarged islets with β-cell infiltration and multifocal vacuolization. GLP-1 treatment induced normalization of islet structures including a mantle of β-cells and increased islet mass. These data suggest encapsulated transduced cells may offer a potential long term treatment of patients. PMID:21216666

Development of an attract-and-kill co-formulation containing Saccharomyces cerevisiae and neem extract attractive towards wireworms.

PubMed

Humbert, Pascal; Vemmer, Marina; Mävers, Frauke; Schumann, Mario; Vidal, Stefan; Patel, Anant V

2018-07-01

Wireworms (Coleoptera: Elateridae) are major insect pests of worldwide relevance. Owing to the progressive phasing-out of chemical insecticides, there is great demand for innovative control options. This study reports on the development of an attract-and-kill co-formulation based on Ca-alginate beads, which release CO 2 and contain neem extract as a bioinsecticidal compound. The objectives of this study were to discover: (1) whether neem extract can be immobilized efficiently, (2) whether CO 2 -releasing Saccharomyces cerevisiae and neem extract are suitable for co-encapsulation, and (3) whether co-encapsulated neem extract affects the attractiveness of CO 2 -releasing beads towards wireworms. Neem extract was co-encapsulated together with S. cerevisiae, starch and amyloglucosidase with a high encapsulation efficiency of 98.6% (based on measurement of azadirachtin A as the main active ingredient). Even at enhanced concentrations, neem extract allowed growth of S. cerevisiae, and beads containing neem extract exhibited CO 2 -emission comparable with beads without neem extract. When applied to the soil, the beads established a CO 2 gradient of >15 cm. The co-formulation containing neem extract showed no repellent effects and was attractive for wireworms within the first 24 h after exposure. Co-encapsulation of S. cerevisiae and neem extract is a promising approach for the development of attract-and-kill formulations for the control of wireworms. This study offers new options for the application of neem extracts in soil. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Cinnamomum casia Extract Encapsulated Nanochitosan as Antihypercholesterol

NASA Astrophysics Data System (ADS)

Ngadiwiyana; Purbowatiningrum; Fachriyah, Enny; Ismiyarto

2017-02-01

Atherosclerosis vascular disease with clinical manifestations such as cardiovascular disease and stroke are the leading cause of death in Indonesia. One solution to these problems is a natural antihypercholesterol medicine by utilizing Cinnamomum casia extract. However, the use of natural extracts to lower blood cholesterol levels do not provide optimal results because it is possible that the active components of extract have been degraded/damaged during the absorption process. So that, we need to do the research to get a combination of chitosan nanoparticles-Cinnamomum casia. extract as a compound which has an antihypercholesterol activity through the in vitro study. Modification of natural extracts encapsulated nanochitosan be a freshness in this study, which were conducted using the method of inclusion. The combination of both has the dual function of protecting the natural extracts from degradation and deliver the natural extracts to the target site. Analysis of nanochitosan using the Particle Size Analyzer (PSA) shows the particle size of synthesis product that is equal to 64.9 nm. Encapsulation efficiency of Cinnamomum casia extract-Chitosan Nanoparticles known through UV-VIS spectrophotometry test and obtained the efficiency encapsulation percentage of 84.93%. Zeta Potential at 193,3 mv that chitosan appropriate for a delivery drug. Antihypercholesterol activity tested in vitro assay that showed the extract-nanoparticle chitosan in concentration 150 ppm gave the highest cholesterol decreasing level in the amount of 49.66% w/v. So it can be concluded that Cinnamomum casia extract can be encapsulated in nanoparticles of chitosan and proved that it has a cholesterol-lowering effect through the in vitro study.

Glucose and Insulin Secretory Response Patterns Following Diet and Tolazamide Therapy in Diabetes

PubMed Central

Turtle, J. R.

1970-01-01

Glucose and insulin secretory response patterns during glucose tolerance tests were determined in 28 maturity-onset diabetics, and the sequential effects of diet and a sulphonylurea, tolazamide, were assessed. Untreated diabetics showed hyperglycaemia, increased serum immunoreactive insulin response patterns, delayed insulin release, and relative insulin deficiency. Diet alone partially corrected the hyperglycaemia and serum immunoreactive insulin response but had no effect on the delayed insulin release or relative insulin deficiency. Tolazamide plus diet restored all values towards normal. The net effect of maintenance tolazamide therapy was to (1) restore the insulin secretory response pattern to normal, (2) reduce total pancreatic insulin output, and (3) improve the efficiency of insulin secretion. The results suggest that there is a rational basis for the use of sulphonylurea in all maturity-onset diabetics, including patients with mild carbohydrate intolerance and those who are apparently controlled by diet alone. PMID:5470087

Low Molecular Weight Chitosan–Insulin Polyelectrolyte Complex: Characterization and Stability Studies

PubMed Central

Al-Kurdi, Zakieh I.; Chowdhry, Babur Z.; Leharne, Stephen A.; Al Omari, Mahmoud M. H.; Badwan, Adnan A.

2015-01-01

The aim of the work reported herein was to investigate the effect of various low molecular weight chitosans (LMWCs) on the stability of insulin using USP HPLC methods. Insulin was found to be stable in a polyelectrolyte complex (PEC) consisting of insulin and LMWC in the presence of a Tris-buffer at pH 6.5. In the presence of LMWC, the stability of insulin increased with decreasing molecular weight of LMWC; 13 kDa LMWC was the most efficient molecular weight for enhancing the physical and chemical stability of insulin. Solubilization of insulin-LMWC polyelectrolyte complex (I-LMWC PEC) in a reverse micelle (RM) system, administered to diabetic rats, results in an oral delivery system for insulin with acceptable bioactivity. PMID:25830681

Review of world experience and properties of materials for encapsulation of terrestrial photovoltaic arrays

NASA Technical Reports Server (NTRS)

Carmichael, D. C.; Gaines, G. B.; Sliemers, F. A.; Kistler, C. W.; Igou, R. D.

1976-01-01

Published and unpublished information relating to encapsulation systems and materials properties was collected by searching the literature and appropriate data bases (over 1,300 documents were selected and reviewed) and by personal contacts including site and company visits. A data tabulation summarizing world experience with terrestrial photovoltaic arrays (50 installations) is presented in the report. Based on criteria of properties, processability, availability, and cost, candidate materials were identified which have potential for use in encapsulation systems for arrays with a lifetime of over 20 years high reliability, an efficiency greater than 10 percent, a total price less than $500/kW, and a production capacity of 500,000 kW/yr. The recommended materials (all commercially available) include, depending upon the device design, various borosilicate and soda-lime glasses and numerous polymerics suitable for specific encapsulation system functions.

Kinetics and Antioxidant Capacity of Proanthocyanidins Encapsulated in Zein Electrospun Fibers by Cyclic Voltammetry.

PubMed

Wang, Hualin; Hao, Lilan; Niu, Baicheng; Jiang, Suwei; Cheng, Junfeng; Jiang, Shaotong

2016-04-20

The proanthocyanidins encapsulated in zein (zein-PA) fibers was via electrospinning technique. The kinetics and antioxidant capacity of PA from zein fibers was investigated by cyclic voltammetry. Circular dichroism was used to investigate the secondary structure change of zein and its influence on the shape of fibers. The addition of PA caused a significant increase in viscosity and made fibers wider. These hydrogen bonds between zein and PA molecules would favor the α-helix change and decrease the β-folds of zein in electrospinning solutions, leading to a round-shaped tendency of fibers and enhancing the thermal properties slightly. Zein-PA fibers showed high encapsulation efficiency close to 100%, and the encapsulated PA retained its antioxidant capacity in fibers. Zein-PA fibers showed a good controlled release toward PA, and the predominant release of PA from fibers was Fickian diffusion, which could be well described by first-order model and Hixson-Crowell model.

Effect of insulin-coated trimethyl chitosan nanoparticles on IGF-1, IGF-2, and apoptosis in the hippocampus of diabetic male rats.

PubMed

Kalantarian, Giti; Ziamajidi, Nasrin; Mahjoub, Reza; Goodarzi, Mohammad Taghi; Saidijam, Massoud; Asl, Sara Soleimani; Abbasalipourkabir, Roghayeh

2018-06-06

Subcutaneous injection of insulin can lead to problems such as hypoglycemia and edema. The purpose of this research was to evaluate the effect of oral insulin-coated trimethyl chitosan nanoparticles on control of glycemic status, IGF-1 and IGF-2 levels, and apoptosis in the hippocampus of rats with diabetes mellitus. Insulin-coated trimethyl chitosan nanoparticles were prepared by the complex polyelectrolyte (PEC) method. Insulin loading content, loading efficiency, quantity and quality of particle size were evaluated. In vivo study was performed in different treatment groups of male Wistar rats with diabetes mellitus by insulin-coated trimethyl chitosan nanoparticles or subcutaneous injection of trade insulin. The duration of diabetes was eight weeks and the treatment was started after that time and continued for another two weeks. Body weight, fasting blood glucose (FBS), hippocampal apoptosis, and immunohistochemical (IHC) protein levels of IGF-1 and IGF-2 were assessed at the end of the experiments. The size and polydispersity indexes were 533 nanometers and 0.533, respectively. Insulin coated trimethyl chitosan nanoparticles showed high loading efficiency (97.67% ) and loading content (48.83% ). The spherical shape of nanoparticle was confirmed by transmission electron microscopic (TEM). The amine, amide, ether and aliphatic groups were evaluated using FT-IR spectrophotometer which represented the correctness of the insulin coated trimethyl chitosan nanoparticles. Although the apoptotic index was not changed either by insulin-coated nano-particles or commercial insulin in vivo results showed the efficacy of insulin-coated nanoparticles as well as commercial insulin in compensated weight loss, FBS and protein levels of IGF-1 and IGF-2. The present study showed the efficacy of insulin coated nanoparticle in oral route manner that can be tested in Phase I- III clinical trials. However, a behavioral study could reveal the efficacy of insulin-loaded nanoparticles in the improvement of cognitive changes through the modulation of IGF-1 and IGF-2 levels in the hippocampus.

An in silico method to identify computer-based protocols worthy of clinical study: An insulin infusion protocol use case

PubMed Central

Wong, Anthony F; Pielmeier, Ulrike; Haug, Peter J; Andreassen, Steen

2016-01-01

Objective Develop an efficient non-clinical method for identifying promising computer-based protocols for clinical study. An in silico comparison can provide information that informs the decision to proceed to a clinical trial. The authors compared two existing computer-based insulin infusion protocols: eProtocol-insulin from Utah, USA, and Glucosafe from Denmark. Materials and Methods The authors used eProtocol-insulin to manage intensive care unit (ICU) hyperglycemia with intravenous (IV) insulin from 2004 to 2010. Recommendations accepted by the bedside clinicians directly link the subsequent blood glucose values to eProtocol-insulin recommendations and provide a unique clinical database. The authors retrospectively compared in silico 18 984 eProtocol-insulin continuous IV insulin infusion rate recommendations from 408 ICU patients with those of Glucosafe, the candidate computer-based protocol. The subsequent blood glucose measurement value (low, on target, high) was used to identify if the insulin recommendation was too high, on target, or too low. Results Glucosafe consistently provided more favorable continuous IV insulin infusion rate recommendations than eProtocol-insulin for on target (64% of comparisons), low (80% of comparisons), or high (70% of comparisons) blood glucose. Aggregated eProtocol-insulin and Glucosafe continuous IV insulin infusion rates were clinically similar though statistically significantly different (Wilcoxon signed rank test P = .01). In contrast, when stratified by low, on target, or high subsequent blood glucose measurement, insulin infusion rates from eProtocol-insulin and Glucosafe were statistically significantly different (Wilcoxon signed rank test, P < .001), and clinically different. Discussion This in silico comparison appears to be an efficient nonclinical method for identifying promising computer-based protocols. Conclusion Preclinical in silico comparison analytical framework allows rapid and inexpensive identification of computer-based protocol care strategies that justify expensive and burdensome clinical trials. PMID:26228765

A 12-week randomized clinical trial investigating the potential for sucralose to affect glucose homeostasis.

PubMed

Grotz, V Lee; Pi-Sunyer, Xavier; Porte, Daniel; Roberts, Ashley; Richard Trout, J

2017-08-01

The discovery of gut sweet taste receptors has led to speculations that non-nutritive sweeteners, including sucralose, may affect glucose control. A double-blind, parallel, randomized clinical trial, reported here and previously submitted to regulatory agencies, helps to clarify the role of sucralose in this regard. This was primarily an out-patient study, with 4-week screening, 12-week test, and 4-week follow-up phases. Normoglycemic male volunteers (47) consumed ∼333.3 mg encapsulated sucralose or placebo 3x/day at mealtimes. HbA1c, fasting glucose, insulin, and C-peptide were measured weekly. OGTTs were conducted in-clinic overnight, following overnight fasting twice during screening phase, twice during test phase, and once at follow-up. Throughout the study, glucose, insulin, C-peptide and HbA1c levels were within normal range. No statistically significant differences between sucralose and placebo groups in change from baseline for fasting glucose, insulin, C-peptide and HbA1c, no clinically meaningful differences in time to peak levels or return towards basal levels in OGTTs, and no treatment group differences in mean glucose, insulin, or C-peptide AUC change from baseline were observed. The results of other relevant clinical trials and studies of gastrointestinal sweet taste receptors are compared to these findings. The collective evidence supports that sucralose has no effect on glycemic control. Copyright © 2017 Heartland Food Products Group. Published by Elsevier Inc. All rights reserved.

Thermo-responsive human α-elastin self-assembled nanoparticles for protein delivery.

PubMed

Kim, Jae Dong; Jung, Youn Jae; Woo, Chang Hee; Choi, Young Chan; Choi, Ji Suk; Cho, Yong Woo

2017-01-01

Self-assembled nanoparticles based on PEGylated human α-elastin were prepared as a potential vehicle for sustained protein delivery. The α-elastin was extracted from human adipose tissue and modified with methoxypolyethyleneglycol (mPEG) to control particle size and enhance the colloidal stability. The PEGylated human α-elastin showed sol-to-particle transition with a lower critical solution temperature (LCST) of 25°C-40°C in aqueous media. The PEGylated human α-elastin nanoparticles (PhENPs) showed a narrow size distribution with an average diameter of 330±33nm and were able to encapsulate significant amounts of insulin and bovine serum albumin (BSA) upon simple mixing at low temperature in water and subsequent heating to physiological temperature. The release profiles of insulin and BSA showed sustained release for 72h. Overall, the thermo-responsive self-assembled PhENPs provide a useful tool for a range of protein delivery and tissue engineering applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Platinum nanoparticles encapsulated metal-organic frameworks for the electrochemical detection of telomerase activity.

PubMed

Ling, Pinghua; Lei, Jianping; Jia, Li; Ju, Huangxian

2016-01-21

A simple and rapid electrochemical sensor is constructed for the detection of telomerase activity based on the electrocatalysis of platinum nanoparticle (Pt NP) encapsulated metal-organic frameworks (MOFs), which are synthesized by one-pot encapsulation of Pt NPs into prototypal MOFs, UiO-66-NH2. Integrating with the efficient electrocatalysis of Pt@MOFs towards NaBH4 oxidation, this biosensor shows the wide dynamic correlation of telomerase activity from 5 × 10(2) to 10(7) HeLa cells mL(-1) and the telomerase activity in a single HeLa cell was calculated to be 2.0 × 10(-11) IU, providing a powerful platform for detecting telomerase activity.

Low temperature oxidation synthesis of carbon encapsulated Cr2O3 nanocrystals and its lithium storage performance

NASA Astrophysics Data System (ADS)

Zhou, Yun; Liu, Boyang; Shao, Yingfeng; Fan, Chunhua; Fan, Runhua; Wen, Bosheng

A highly efficient and convenient strategy is developed for the one-step in-situ synthesis of carbon encapsulated Cr2O3 nanocrystals with core-shell structure (Cr2O3@C). The explosive reaction of chromocene with ammonium persulfate in an autoclave at 200∘C is crucial for the formation of this nanostructure. The Cr2O3 nanocrystals have a diameter of 5 to 20nm, which are entirely encapsulated by the amorphous carbon shell. The Cr2O3@C anode can retain a stable reversible capacity of 397mAhg-1 after 50 cycles at a current density of 119mA g-1.

Optical Properties of Hybrid Inorganic/Organic Thin Film Encapsulation Layers for Flexible Top-Emission Organic Light-Emitting Diodes.

PubMed

An, Jae Seok; Jang, Ha Jun; Park, Cheol Young; Youn, Hongseok; Lee, Jong Ho; Heo, Gi-Seok; Choi, Bum Ho; Lee, Choong Hun

2015-10-01

Inorganic/organic hybrid thin film encapsulation layers consist of a thin Al2O3 layer together with polymer material. We have investigated optical properties of thin film encapsulation layers for top-emission flexible organic light-emitting diodes. The transmittance of hybrid thin film encapsulation layers and the electroluminescent spectrum of organic light-emitting diodes that were passivated by hybrid organic/inorganic thin film encapsulation layers were also examined as a function of the thickness of inorganic Al203 and monomer layers. The number of interference peaks, their intensity, and their positions in the visible range can be controlled by varying the thickness of inorganic Al2O3 layer. On the other hand, changing the thickness of monomer layer had a negligible effect on the optical properties. We also verified that there is a trade-off between transparency in the visible range and the permeation of water vapor in hybrid thin film encapsulation layers. As the number of dyads decreased, optical transparency improved while the water vapor permeation barrier was degraded. Our study suggests that, in top-emission organic light-emitting diodes, the thickness of each thin film encapsulation layer, in particular that of the inorganic layer, and the number of dyads should be controlled for highly efficient top-emission flexible organic light-emitting diodes.

Surface functionalization of carbon nanotubes by direct encapsulation with varying dosages of amphiphilic block copolymers

NASA Astrophysics Data System (ADS)

Yao, Xueping; Li, Jie; Kong, Liang; Wang, Yong

2015-08-01

Encapsulation of carbon nanotubes (CNTs) by amphiphilic block copolymers is an efficient way to stabilize CNTs in solvents. However, the appropriate dosages of copolymers and the assembled structures are difficult to predict and control because of the insufficient understanding on the encapsulation process. We encapsulate multiwalled CNTs with polystyrene-block-poly (4-vinyl pyridine) (PS-b-P4VP) by directly mixing them in acetic acid under sonication. The copolymer forms a lamellar structure along the surface of CNTs with the PS blocks anchoring on the tube wall and the P4VP blocks exposed to the outside. The encapsulated CNTs achieve good dispersibility in polar solvents over long periods. To increase our understanding of the encapsulation process we investigate the assembled structures and stability of copolymer/CNTs mixtures with changing mass ratios. Stable dispersions are obtained at high mass ratios between the copolymer and CNTs, i.e. 2 or 3, with the presence of free spherical micelles. Transmission electron microscopy and thermal gravimetric analysis determine that the threshold for the complete coverage of CNTs by the copolymer occurs at the mass ratio of 1.5. The coated copolymer layer activates the surface of CNTs, enabling further functionalization of CNTs. For instance, atomic layer deposition of TiO2 produces conformal thin layers on the encapsulated CNTs while isolated TiO2 bumps are produced on the pristine, inert CNTs.

Effect of mucoadhesive polymers on the in vitro performance of insulin-loaded silica nanoparticles: Interactions with mucin and biomembrane models.

PubMed

Andreani, Tatiana; Miziara, Leonardo; Lorenzón, Esteban N; de Souza, Ana Luiza R; Kiill, Charlene P; Fangueiro, Joana F; Garcia, Maria L; Gremião, Palmira D; Silva, Amélia M; Souto, Eliana B

2015-06-01

The present paper focuses on the development and characterization of silica nanoparticles (SiNP) coated with hydrophilic polymers as mucoadhesive carriers for oral administration of insulin. SiNP were prepared by sol-gel technology under mild conditions and coated with different hydrophilic polymers, namely, chitosan, sodium alginate or poly(ethylene glycol) (PEG) with low and high molecular weight (PEG 6000 and PEG 20000) to increase the residence time at intestinal mucosa. The mean size and size distribution, association efficiency, insulin structure and insulin thermal denaturation have been determined. The mean nanoparticle diameter ranged from 289 nm to 625 nm with a PI between 0.251 and 0.580. The insulin association efficiency in SiNP was recorded above 70%. After coating, the association efficiency of insulin increased up to 90%, showing the high affinity of the protein to the hydrophilic polymer chains. Circular dichroism (CD) indicated that no conformation changes of insulin structure occurred after loading the peptide into SiNP. Nano-differential scanning calorimetry (nDSC) showed that SiNP shifted the insulin endothermic peak to higher temperatures. The influence of coating on the interaction of nanoparticles with dipalmitoylphosphatidylcholine (DPPC) biomembrane models was also evaluated by nDSC. The increase of ΔH values suggested a strong association of non-coated SiNP and those PEGylated nanoparticles coated with DPPC polar heads by forming hydrogen bonds and/or by electrostatic interaction. The mucoadhesive properties of nanoparticles were examined by studying the interaction with mucin in aqueous solution. SiNP coated with alginate or chitosan showed high contact with mucin. On the other hand, non-coated SiNP and PEGylated SiNP showed lower interaction with mucin, indicating that these nanoparticles can interdiffuse across mucus network. The results of the present work provide valuable data in assessing the in vitro performance of insulin-loaded SiNP coated with mucoadhesive polymers. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of AlGaN-based deep-ultraviolet (DUV) LEDs focusing on the fluorine resin encapsulation and the prospect of the practical applications

NASA Astrophysics Data System (ADS)

Hirano, Akira; Nagasawa, Yosuke; Ippommatsu, Masamichi; Aosaki, Ko; Honda, Yoshio; Amano, Hiroshi; Akasaki, Isamu

2016-09-01

AlGaN-based LEDs are expected to be useful for sterilization, deodorization, photochemical applications such as UV curing and UV printing, medical applications such as phototherapy, and sensing. Today, it has become clear that efficient AlGaN-based LED dies are producible between 355 and 250 nm with an external quantum efficiency (EQE) of 3% on flat sapphire. These dies were realized on flat sapphire without using a special technique, i.e., reduction in threading dislocation density or light extraction enhancement techniques such as the use of a photonic crystal or a patterned sapphire substrate. Despite the limited light extraction efficiency of about 8% owing to light absorption at a thick p-GaN contact layer, high EQEs of approximately 6% has been reproducible between 300 and 280 nm without using special techniques. Moreover, an EQE of 3.9% has been shown at 271 nm, despite the smaller current injection efficiency (CIE). The high EQEs are thought to correspond to the high internal quantum efficiency (IQE), indicating a small room for improving IQE. Accordingly, resin encapsulation on a simple submount is strongly desired. Recently, we have succeeded in demonstrating fluorine resin encapsulation on a ceramic sheet (chip-on-board, COB) that is massproducible. Furthermore, the molecular structure of a resin with a durability of more than 10,000 h is explained in this paper from the photochemical viewpoint. Thus, the key technologies of AlGaN-based DUV-LEDs having an EQE of 10% within a reasonable production cost have been established. The achieved efficiency makes AlGaN-based DUVLEDs comparable to high-pressure mercury lamps.

Curcumin liposomes prepared with milk fat globule membrane phospholipids and soybean lecithin.

PubMed

Jin, Hong-Hao; Lu, Qun; Jiang, Jian-Guo

2016-03-01

Using thin film ultrasonic dispersion method, the curcumin liposomes were prepared with milk fat globule membrane (MFGM) phospholipids and soybean lecithins, respectively, to compare the characteristics and stability of the 2 curcumin liposomes. The processing parameters of curcumin liposomes were investigated to evaluate their effects on the encapsulation efficiency. Curcumin liposomes were characterized in terms of size distribution, ζ-potential, and in vitro release behavior, and then their storage stability under various conditions was evaluated. The curcumin liposomes prepared with MFGM phospholipids had an encapsulation efficiency of about 74%, an average particle size of 212.3 nm, and a ζ-potential of -48.60 mV. The MFGM liposomes showed higher encapsulation efficiency, smaller particle size, higher absolute value of ζ-potential, and slower in vitro release than soybean liposomes. The retention rate of liposomal curcumin was significantly higher than that of free curcumin. The stability of the 2 liposomes under different pH was almost the same, but MFGM liposomes displayed a slightly higher stability than soybean liposomes under the conditions of Fe(3+), light, temperature, oxygen, and relative humidity. In conclusion, MFGM phospholipids have potential advantages in the manufacture of curcumin liposomes used in food systems. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Functionalized near-infrared quantum dots for in vivo tumor vasculature imaging

NASA Astrophysics Data System (ADS)

Hu, Rui; Yong, Ken-Tye; Roy, Indrajit; Ding, Hong; Law, Wing-Cheung; Cai, Hongxing; Zhang, Xihe; Vathy, Lisa A.; Bergey, Earl J.; Prasad, Paras N.

2010-04-01

In this paper, we report the use of near-infrared (NIR)-emitting alloyed quantum dots (QDs) as efficient optical probes for high contrast in vivo imaging of tumors. Alloyed CdTe1 - xSex/CdS QDs were prepared in the non-aqueous phase using the hot colloidal synthesis approach. Water dispersion of the QDs were accomplished by their encapsulation within polyethyleneglycol (PEG)-grafted phospholipid micelles. For tumor-specific delivery in vivo, the micelle-encapsulated QDs were conjugated with the cyclic arginine-glycine-aspartic acid (cRGD) peptide, which targets the αvβ3 integrins overexpressed in the angiogenic tumor vasculatures. Using in vivo NIR optical imaging of mice bearing pancreatic cancer xenografts, implanted both subcutaneously and orthotopically, we have demonstrated that systemically delivered cRGD-conjugated QDs, but not the unconjugated ones, can efficiently target and label the tumors with high signal-to-noise ratio. Histopathological analysis of major organs of the treated mice showed no evidence of systemic toxicity associated with these QDs. These experiments suggest that cRGD-conjugated NIR QDs can serve as safe and efficient probes for optical bioimaging of tumors in vivo. Furthermore, by co-encapsulating these QDs and anticancer drugs within these micelles, we have demonstrated a promising theranostic, nanosized platform for both cancer imaging and therapy.

Solar receiver with integrated optics

NASA Astrophysics Data System (ADS)

Jiang, Lun; Winston, Roland

2012-10-01

The current challenge for PV/Thermal (PV/T) systems is the reduction of radiation heat loss. Compared to solar thermal selective coating, the solar cells cannot be used as an efficient thermal absorber due to their large emissivity of the encapsulation material. Many commercial PV/T products therefore require a high concentration (more than 10x) to reach an acceptable thermal efficiency for their receivers. Such a concentration system inevitably has to track or semi-track, which induces additional cost and collects only the direct radiation from the sun. We propose a new PV/T design using a vacuum encapsulated thin film cell to solve this problem. The proposed design also collects the diffuse sun light efficiently by using an external compound parabolic concentrator (XCPC). Since the transparent electrode (TCO) of thin film cell is inherently transparent in visible light and reflective beyond infrared, this design uses this layer instead of the conventional solar cell encapsulation as the outmost heat loss surface. By integrating such a vacuum design with a tube shaped absorber, we reduce the complexity of conducting the heat energy and electricity out of the device. A low concentration standalone non-tracking solar collector is proposed in this paper. We also analyzed the thermosyphon system configuration using heat transfer and ray tracing models. The economics of such a receiver are presented.

Antidiabetic Activity from Gallic Acid Encapsulated Nanochitosan

NASA Astrophysics Data System (ADS)

Purbowatiningrum; Ngadiwiyana; Ismiyarto; Fachriyah, E.; Eviana, I.; Eldiana, O.; Amaliyah, N.; Sektianingrum, A. N.

2017-02-01

Diabetes mellitus (DM) has become a health problem in the world because it causes death. One of the phenolic compounds that have antidiabetic activity is gallic acid. However, the use of this compound still provides unsatisfactory results due to its degradation during the absorption process. The solution offered to solve the problem is by encapsulated it within chitosan nanoparticles that serve to protect the bioactive compound from degradation, increases of solubility and delivery of a bioactive compound to the target site by using freeze-drying technique. The result of chitosan nanoparticle’s Scanning Electron Microscopy (SEM) showed that chitosan nanoparticle’s size is uniform and it is smaller than chitosan. The value of encapsulation efficiency (EE) of gallic acid which encapsulated within chitosan nanoparticles is about 50.76%. Inhibition test result showed that gallic acid-chitosan nanoparticles at 50 ppm could inhibite α-glucosidase activity in 28.87% with 54.94 in IC50. So it can be concluded that gallic acid can be encapsulated in nanoparticles of chitosan and proved that it could inhibit α-glucosidase.

Submicron polycaprolactone particles as a carrier for imaging contrast agent for in vitro applications.

PubMed

Iqbal, Muhammad; Robin, Sophie; Humbert, Philippe; Viennet, Céline; Agusti, Geraldine; Fessi, Hatem; Elaissari, Abdelhamid

2015-12-01

Fluorescent materials have recently attracted considerable attention due to their unique properties and high performance as imaging agent in biomedical fields. Different imaging agents have been encapsulated in order to restrict its delivery to a specific area. In this study, a fluorescent contrast agent was encapsulated for in vitro application by polycaprolactone (PCL) polymer. The encapsulation was performed using modified double emulsion solvent evaporation technique with sonication. Fluorescent nanoparticles (20 nm) were incorporated in the inner aqueous phase of double emulsion. A number of samples were fabricated using different concentrations of fluorescent contrast agent. The contrast agent-containing submicron particle was characterized by a zetasizer for average particle size, SEM and TEM for morphology observations and fluorescence spectrophotometer for encapsulation efficiency. Moreover, contrast agent distribution in the PCL matrix was determined by confocal microscopy. The incorporation of contrast agent in different concentrations did not affect the physicochemical properties of PCL particles and the average size of encapsulated particles was found to be in the submicron range. Copyright © 2015 Elsevier B.V. All rights reserved.

Starch Applications for Delivery Systems

NASA Astrophysics Data System (ADS)

Li, Jason

2013-03-01

Starch is one of the most abundant and economical renewable biopolymers in nature. Starch molecules are high molecular weight polymers of D-glucose linked by α-(1,4) and α-(1,6) glycosidic bonds, forming linear (amylose) and branched (amylopectin) structures. Octenyl succinic anhydride modified starches (OSA-starch) are designed by carefully choosing a proper starch source, path and degree of modification. This enables emulsion and micro-encapsulation delivery systems for oil based flavors, micronutrients, fragrance, and pharmaceutical actives. A large percentage of flavors are encapsulated by spray drying in today's industry due to its high throughput. However, spray drying encapsulation faces constant challenges with retention of volatile compounds, oxidation of sensitive compound, and manufacturing yield. Specialty OSA-starches were developed suitable for the complex dynamics in spray drying and to provide high encapsulation efficiency and high microcapsule quality. The OSA starch surface activity, low viscosity and film forming capability contribute to high volatile retention and low active oxidation. OSA starches exhibit superior performance, especially in high solids and high oil load encapsulations compared with other hydrocolloids. The submission is based on research and development of Ingredion

Co-delivery of Dual Toll-Like Receptor Agonists and Antigen in Poly(Lactic-Co-Glycolic) Acid/Polyethylenimine Cationic Hybrid Nanoparticles Promote Efficient In Vivo Immune Responses.

PubMed

Ebrahimian, Mahboubeh; Hashemi, Maryam; Maleki, Mohsen; Hashemitabar, Gholamreza; Abnous, Khalil; Ramezani, Mohammad; Haghparast, Alireza

2017-01-01

Strategies to design delivery vehicles are critical in modern vaccine-adjuvant development. Nanoparticles (NPs) encapsulating antigen(s) and adjuvant(s) are promising vehicles to deliver antigen(s) and adjuvant(s) to antigen-presenting cells (APCs), allowing optimal immune responses against a specific pathogen. In this study, we developed a novel adjuvant delivery approach for induction of efficient in vivo immune responses. Polyethylenimine (PEI) was physically conjugated to poly(lactic-co-glycolic) acid (PLGA) to form PLGA/PEI NPs. This complex was encapsulated with resiquimod (R848) as toll-like receptor (TLR) 7/8 agonist, or monophosphoryl lipid A (MPLA) as TLR4 agonist and co-assembled with cytosine-phosphorothioate-guanine oligodeoxynucleotide (CpG ODN) as TLR9 agonist to form a tripartite formulation [two TLR agonists (inside and outside NPs) and PLGA/PEI NPs as delivery system]. The physicochemical characteristics, cytotoxicity and cellular uptake of these synthesized delivery vehicles were investigated. Cellular viability test revealed no pronounced cytotoxicity as well as increased cellular uptake compared to control groups in murine macrophage cells (J774 cell line). In the next step, PLGA (MPLA or R848)/PEI (CpG ODN) were co-delivered with ovalbumin (OVA) encapsulated into PLGA NPs to enhance the induction of immune responses. The immunogenicity properties of these co-delivery formulations were examined in vivo by evaluating the cytokine (IFN-γ, IL-4, and IL-1β) secretion and antibody (IgG1, IgG2a) production. Robust and efficient immune responses were achieved after in vivo administration of PLGA (MPLA or R848)/PEI (CpG ODN) co-delivered with OVA encapsulated in PLGA NPs in BALB/c mice. Our results demonstrate a rational design of using dual TLR agonists in a context-dependent manner for efficient nanoparticulate adjuvant-vaccine development.

Release mechanism of insulin encapsulated in trehalose ester derivative microparticles delivered via inhalation.

PubMed

Davidson, Iain G; Langner, Eric J; Plowman, Steven V; Blair, Julian A

2003-03-26

The aim of this study was to evaluate properties of amorphous oligosaccharide ester derivative (OED) microparticles in order to determine drug release mechanisms in the lung. Trehalose OEDs with a wide range of properties were synthesised using conventional methods. The interaction of spray dried amorphous microparticles (2-3 microm) with water was investigated using attenuated total reflectance Fourier transform infra-red spectroscopy (ATR-FTIR) and dynamic vapour sorption (DVS). The in vivo performance of insulin/OED microparticles was assessed using a modified Higuchi kinetic model. A modified Hansen solvent parameter approach was used to analyse the interactions with water and in vivo trends. In water or high humidity, OED powders absorb water, lose relaxation energy and crystallise. The delay of the onset of crystallisation depends on the OED and the amount of water present. Crystallisation follows first order Arrhenius kinetics and release of insulin from OED microparticles closely matches the degree of crystallisation. The induction period depends on dispersive interactions between the OED and water while crystallisation is governed by polarity and hydrogen bonding. Drug release from OED microparticles is, therefore, controlled by crystallisation of the matrix on contact with water. The pulmonary environment was found to resemble one of high humidity rather than a liquid medium. Copyright 2003 Elsevier Science B.V.

[Preparation and in vitro release characteristics of vincristine sulphate loaded poly (butylcyanoacrylate) nanoparticles].

PubMed

Tan, Rong; Liu, Ying; Feng, Nianping; Zhao, Jihui

2011-06-01

To prepare vincristine sulphate loaded poly (butylcyanoacrylate) nanoparticles (VCR-PBCA-NPs) and to investigate the in vitro release charactersitics. VCR-PBCA-NPs were prepared by emulsion polymerization method, and characterized for morphology, particle size, drug encapsulation efficiency and loading efficiency. The formulation was optimized using central composite design and response surface methodology. In vitro release study of VCR-PBCA-NPs was performed by dialysis technique. Model fitting was used to determine the kinetics and to discuss the mechanism. The nanoparticles were spherical and uniform with a mean diameter of (98.9 +/- 3.05) nm. The drug encapsulation efficiency and loading efficiency were (55.23 +/- 0.96)% and (7.87 +/- 0.11)%, respectively. In vitro release results showed that 63.66% of VCR was released from VCR-PBCA-NPs in 4 h, and the Weibull model fitted VCR release pattern best. The VCR-PBCA-NPs prepared in this study showed sustained release compared with VCR solution.

Encapsulated Pseudomonas putida for phenol biodegradation: Use of a structural membrane for construction of a well-organized confined particle.

PubMed

Kurzbaum, Eyal; Raizner, Yasmin; Cohen, Oded; Suckeveriene, Ran Y; Kulikov, Anatoly; Hakimi, Ben; Iasur Kruh, Lilach; Armon, Robert; Farber, Yair; Menashe, Ofir

2017-09-15

Phenols are toxic byproducts from a wide range of industry sectors. If not treated, they form effluents that are very hazardous to the environment. This study presents the use of a Pseudomonas putida F1 culture encapsulated within a confined environment particle as an efficient technique for phenol biodegradation. The innovative encapsulation technique method, named the "Small Bioreactor Platform" (SBP) technology, enables the use of a microfiltration membrane constructed as a physical barrier for creating a confined environment for the encapsulated culture. The phenol biodegradation rate of the encapsulated culture was compared to its suspended state in order to evaluate the effectiveness of the encapsulation technique for phenol biodegradation. A maximal phenol biodegradation rate (q) of 2.12/d was exhibited by encapsulated P. putida at an initial phenol concentration of 100 mg/L. The biodegradation rate decreased significantly at lower and higher initial phenol concentrations of 50 and up to 3000 mg/L, reaching a rate of 0.1018/d. The results also indicate similar and up to double the degradation rate between the two bacterial states (encapsulated vs. suspended). High resolution scanning electron microscopy images of the SBP capsule's membrane morphology demonstrated a highly porous microfiltration membrane. These results, together with the long-term activity of the SBP capsules and verification that the culture remains pure after 60 days using 16S rRNA gene phylogenetic affiliation tests, provide evidence for a successful application of this new encapsulation technique for bioaugmentation of selected microbial cultures in water treatment processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fat encapsulation enhances dietary nutrients utilization and growth performance of nursery pigs.

PubMed

Yang, F; Zhang, S H; Kim, S W; Ren, C X; Tian, M; Cheng, L; Song, J J; Chen, J; Chen, F; Guan, W T

2018-05-31

Encapsulation of fat may facilitate digestion and absorption of fat in nursery pigs. Two experiments were conducted to evaluate (1) effects of encapsulation of palm oil and coconut oil on growth performance, feed intake, feed efficiency, and blood parameters, and (2) effects of encapsulation of palm oil and coconut oil on apparent total tract digestibility (ATTD) of nutrients, and the activity of digestive enzymes in nursery pigs. In Exp. 1, 540 pigs (28 d of age, 8.23 ± 0.22 kg BW) were allotted to 5 treatments based on a randomized complete block design (as-fed basis). Pigs were fed basal diets with 5 different fat sources: 6.0% soybean oil (SBO), 6.0% palm oil (PO), 6.0% palm oil from encapsulated fat (EPO), 6.0% coconut oil (CO), and 6.0% coconut oil from encapsulated fat (ECO) respectively, with 6 pens per treatment and 18 pigs per pen for a 4-wk feeding trial. Dried casein and whey powder used for encapsulation were included at identical levels in all diets. Pigs fed EPO had increased (PPPad libitum for 4 weeks to measure ATTD of diets weekly and digestive enzyme activity at wk 4. Pigs fed EPO, CO, and ECO had increased (PPPEE) compared to other treatments. Pigs fed PO had greater (PP = 0.073) pancreatic lipase activity compared to other treatments whereas dietary treatments had no effect on pancreatic amylase activity. In conclusion, this study indicates that encapsulation of palm oil improved growth performance and ATTD of diets in nursery pigs, whereas the limited effects of encapsulated coconut oil were likely due to the high digestibility of the medium chain triglycerides (MCT) abundant in coconut oil.

Selective Co-Encapsulation Inside an M6 L4 Cage.

PubMed

Leenders, Stefan H A M; Becker, René; Kumpulainen, Tatu; de Bruin, Bas; Sawada, Tomohisa; Kato, Taito; Fujita, Makoto; Reek, Joost N H

2016-10-17

There is broad interest in molecular encapsulation as such systems can be utilized to stabilize guests, facilitate reactions inside a cavity, or give rise to energy-transfer processes in a confined space. Detailed understanding of encapsulation events is required to facilitate functional molecular encapsulation. In this contribution, it is demonstrated that Ir and Rh-Cp-type metal complexes can be encapsulated inside a self-assembled M 6 L 4 metallocage only in the presence of an aromatic compound as a second guest. The individual guests are not encapsulated, suggesting that only the pair of guests can fill the void of the cage. Hence, selective co-encapsulation is observed. This principle is demonstrated by co-encapsulation of a variety of combinations of metal complexes and aromatic guests, leading to several ternary complexes. These experiments demonstrate that the efficiency of formation of the ternary complexes depends on the individual components. Moreover, selective exchange of the components is possible, leading to formation of the most favorable complex. Besides the obvious size effect, a charge-transfer interaction may also contribute to this effect. Charge-transfer bands are clearly observed by UV/Vis spectrophotometry. A change in the oxidation potential of the encapsulated electron donor also leads to a shift in the charge-transfer energy bands. As expected, metal complexes with a higher oxidation potential give rise to a higher charge-transfer energy and a larger hypsochromic shift in the UV/Vis spectrum. These subtle energy differences may potentially be used to control the binding and reactivity of the complexes bound in a confined space. © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Insulin chains as efficient fusion tags for prokaryotic expression of short peptides.

PubMed

Deng, Ligang; Xue, Xiaoying; Shen, Cangjie; Song, Xiaohan; Wang, Chunyang; Wang, Nan

2017-10-01

Insulin chains are usually expressed in Escherichia coli as fusion proteins with different tags, including various low molecular weight peptide tags. The objective of this study was to determine if insulin chains could facilitate the recombinant expression of other target proteins, with an emphasis on low molecular weight peptides. A series of short peptides were fused to mini-proinsulin, chain B or chain A, and induced for expression in Escherichia coli. All the tested peptides including glucagon-like peptide 1 (GLP-1), a C-terminal extended GLP-1, oxyntomodulin, enfuvirtide, linaclotide, and an unstructured artificial peptide were expressed with reasonable yields, identified by Tricine-SDS-PAGE and immunoblotting. All recombinant products were expressed in inclusion bodies. The effective accumulation of products was largely attributed to the insoluble expression induced by fusion with insulin chains, and was confirmed by the fusion expression of transthyretin. Insulin chains thus show promise as efficient fusion tags for mass production of heterologous peptides in prokaryotes. Copyright © 2017 Elsevier Inc. All rights reserved.

Reprogramming of Pancreatic Exocrine Cells AR42J Into Insulin-producing Cells Using mRNAs for Pdx1, Ngn3, and MafA Transcription Factors.

PubMed

Koblas, Tomas; Leontovyc, Ivan; Loukotova, Sarka; Kosinova, Lucie; Saudek, Frantisek

2016-05-17

Direct reprogramming of pancreatic nonendocrine cells into insulin-producing β-cells represents a promising approach for the treatment of insulin-dependent diabetes. However, its clinical application is limited by the potential for insertional mutagenesis associated with the viral vectors currently used for cell reprogramming. With the aim of developing a nonintegrative reprogramming strategy for derivation of insulin-producing cells, here, we evaluated a new approach utilizing synthetic messenger RNAs encoding reprogramming transcription factors. Administration of synthetic mRNAs encoding three key transcription regulators of β-cell differentiation-Pdx1, Neurogenin3, and MafA-efficiently reprogrammed the pancreatic exocrine cells into insulin-producing cells. In addition to the insulin genes expression, the synthetic mRNAs also induced the expressions of genes important for proper pancreatic β-cell function, including Sur1, Kir6.2, Pcsk1, and Pcsk2. Pretreating cells with the chromatin-modifying agent 5-Aza-2'-deoxycytidine further enhanced reprogramming efficiency, increasing the proportion of insulin-producing cells from 3.5 ± 0.9 to 14.3 ± 1.9% (n = 4). Moreover, 5-Aza-2'-deoxycytidine pretreatment enabled the reprogrammed cells to respond to glucose challenge with increased insulin secretion. In conclusion, our results support that the reprogramming of pancreatic exocrine cells into insulin-producing cells, induced by synthetic mRNAs encoding pancreatic transcription factors, represents a promising approach for cell-based diabetes therapy.

Liposomes containing glycocholate as potential oral insulin delivery systems: preparation, in vitro characterization, and improved protection against enzymatic degradation

PubMed Central

Niu, Mengmeng; Lu, Yi; Hovgaard, Lars; Wu, Wei

2011-01-01

Background: Oral delivery of insulin is challenging and must overcome the barriers of gastric and enzymatic degradation as well as low permeation across the intestinal epithelium. The present study aimed to develop a liposomal delivery system containing glycocholate as an enzyme inhibitor and permeation enhancer for oral insulin delivery. Methods: Liposomes containing sodium glycocholate were prepared by a reversed-phase evaporation method followed by homogenization. The particle size and entrapment efficiency of recombinant human insulin (rhINS)-loaded sodium glycocholate liposomes can be easily adjusted by tuning the homogenization parameters, phospholipid:sodium glycocholate ratio, insulin:phospholipid ratio, water:ether volume ratio, interior water phase pH, and the hydration buffer pH. Results: The optimal formulation showed an insulin entrapment efficiency of 30% ± 2% and a particle size of 154 ± 18 nm. A conformational study by circular dichroism spectroscopy and a bioactivity study confirmed the preserved integrity of rhINS against preparative stress. Transmission electron micrographs revealed a nearly spherical and deformed structure with discernable lamella for sodium glycocholate liposomes. Sodium glycocholate liposomes showed better protection of insulin against enzymatic degradation by pepsin, trypsin, and α-chymotrypsin than liposomes containing the bile salt counterparts of sodium taurocholate and sodium deoxycholate. Conclusion: Sodium glycocholate liposomes showed promising in vitro characteristics and have the potential to be able to deliver insulin orally. PMID:21822379

Efficient, Glucose Responsive, and Islet-Specific Transgene Expression by a Modified Rat Insulin Promoter

PubMed Central

Chai, Renjie; Chen, Shuyuan; Ding, Jiahuan; Grayburn, Paul A

2009-01-01

This study was done to improve efficiency and islet specificity of the rat insulin promoter (RIP). Various rat insulin promoter lengths were prepared and tested in vitro to drive luciferase reporter gene expression in INS1-cells, alpha-cells, acinar cells, ductal cells, and fibroblasts. The CMV promoter was used as a positive control. In addition, the DsRed reporter gene was administered in vivo to rat pancreas by ultrasound-targeted microbubble destruction (UTMD). Confocal microscopy was used to detect the presence and distribution of DsRed within the pancreas after UTMD. A modified RIP3.1 promoter, which includes portions of the insulin gene after its transcription start site is 5-fold more active in INS-1 cells than the full length RIP promoter or the CMV promoter. RIP3.1 is regulated by glucose level and various islet transcription factors in vitro, and exhibits activity in alpha-cells, but not exocrine cells. In vivo delivery of RIP3.1-DsRed resulted in expression of DsRed protein in beta-cells, and to a lesser extent alpha cells under normal glucose conditions. No DsRed signal was present in exocrine pancreas under RIP3.1. A modified rat insulin promoter, RIP3.1, efficiently and specifically directs gene expression to endocrine pancreas. PMID:19727136

Biodegradable Chitosan Magnetic Nanoparticle Carriers for Sub-Cellular Targeting Delivery of Artesunate for Efficient Treatment of Breast Cancer

NASA Astrophysics Data System (ADS)

Subramanian, Natesan; Abimanyu, Sugumaran; Vinoth, Jeevanesan; Sekar, Ponnusamy Chandra

2010-12-01

Artesunate is a semi-synthetic derivative of artemisinin, the active principle extracted from Artemisia annua. It possesses good anti-proliferative activity and anti-angiogenic activity with very low toxicity to normal healthy cells. The drawback of most cancer drugs is their inability to accumulate selectively in the cancerous cells. So, large quantities of doses have to be administered to get the required therapeutic concentration in the target site and it resulted in many serious side effects due to the exposure of healthy cells to higher concentrations of cytotoxic drugs. The problem may be solved by selectively and quantitatively accumulating the drug at target site using magnetic nanoparticles guided by an externally applied magnetic field. A modest attempt has been made in this present study, the artesunate magnetic nanoparticle was successfully formulated using two forms of chitosan and evaluated for its in-vitro characteristics like surface morphology, particle size and distribution, zeta potential, magnetic susceptibility, encapsulation efficiency, loading capacity and in-vitro drug release. The synthesized magnetite size was 73 nm and the size of developed magnetic nanoparticles of artesunate was in the range of 90 to 575 nm. Acetic acid soluble chitosan at low concentration exhibit highest encapsulation efficiency and drug loading whereas increase in water soluble chitosan concentration increases the encapsulation efficiency and drug loading in formulations. The developed chitosan magnetic nanoparticles of artesunate shows better release characteristics and may be screened for its in-vivo breast cancer activity.

Simple and efficient liposomal encapsulation of topotecan by ammonium sulfate gradient: stability, pharmacokinetic and therapeutic evaluation.

PubMed

Liu, Jun-Jen; Hong, Ruey-Long; Cheng, Wen-Fang; Hong, Keelung; Chang, Fu-Hsiung; Tseng, Yun-Long

2002-08-01

Topotecan (TPT), a topoisomerase I inhibitor, is presently undergoing clinical evaluation worldwide. Previous studies have shown that entrapping TPT within multi-lamellar vesicle liposome can stabilize the lactone moiety, which is structurally important for biological activity. However, low drug:lipid ratios due to the amphipathic character and small entrapment volume in the unilamellar vesicle limits the development of pharmaceutically acceptable liposomal formulation. With an aim to improve on this drawback, we herein describe a method that utilizes the ammonium sulfate gradient to entrap TPT into liposomes. By this method, the encapsulation efficiency was over 90% and a drug:lipid molar ratio as high as 1:5.4 was reached. In comparison with free drug, liposome-encapsulated TPT is more stable in physiological conditions and shows higher in vitro cytotoxicity. Because of increased blood circulation time, the initial plasma concentration and area under the plasma concentration of liposomal drugs were 14 and 40 times, respectively, of those of free drug. Furthermore, liposome encapsulation enhanced the antitumor activity of TPT in syngeneic murine C-26 and human HTB-9 xenograft models in vivo. At a dose of 5 mg/kg, the tumor growth delay of liposomal formulation was significantly than that of free TPT. Based on these results, we believe that this liposomal TPT formulation is worthy of further clinical study. Copyright 2002 Lippincott Williams & Wilkins.

Biocompatible nanotubes as potential carrier for curcumin as a model bioactive compound

NASA Astrophysics Data System (ADS)

Sadeghi, R.; Kalbasi, A.; Emam-jomeh, Z.; Razavi, S. H.; Kokini, J.; Moosavi-Movahedi, A. A.

2013-11-01

We show the ability of poly- d-lysine (PDL) and BSA to form bionanotubes (BNTs) through layer by layer deposition. The process is driven through electrostatic interactions in the interior of a polycarbonate template's nanopores with a diameter of 400 nm. The BNTs are optimally formed at pH 7.4, where the difference in the magnitude of opposite charge is largest. The results show that three bilayers are necessary to form a stable BNT. SEM data shows that well-formed, uniform, and strong BNTs are formed when three bilayers are used and progressively malformed nanotubes are observed with two and one bilayer. Our studies on the evaluation of curcumin encapsulation into the BNTs with two different interior layers show that encapsulation is favored when the interior layer is predominantly made of BSA. BNTs with a BSA interior have the most efficient encapsulation with an efficiency reaching a maximum of 45 %. We achieved loading capacities in the range of 0.20-0.27 g/g of BNT. We also report the entrapment/encapsulation of curcumin by BNTs made by mixing first BSA with curcumin in a water ethanol solution and then using the curcumin bound BSA solution with PDL to construct BNTs. The SEM images show that the (PDL/BSA-Cur)2 BNTs had relatively large hydrophobic cavities demonstrated by the fact that an aqueous solution couldn't pass through them.

Incorporation of liposomes containing squid tunic ACE-inhibitory peptides into fish gelatin.

PubMed

Mosquera, Mauricio; Giménez, Begoña; Montero, Pilar; Gómez-Guillén, Maria Carmen

2016-02-01

Hydrolysates from collagen of jumbo squid (Dosidicus gigas) tunics have shown excellent angiotensin I-converting enzyme (ACE)-inhibitory activity. However, peptides directly included in food systems may suffer a decrease in activity, which could be minimized by loading them into nanoliposomes. A fraction of peptides with molecular weights <1 kDa obtained from hydrolyzed squid tunics, with reasonably high ACE-inhibitory activity (half-maximal inhibitory concentration IC50 = 0.096 g L(-1)), was encapsulated in phosphatidylcholine nanoliposomes. The peptide concentration affected the encapsulation efficiency and the stability of the resulting liposomes, which remained with a high zeta potential value (-54.3 mV) for at least 1 week at the most suitable peptide concentration. The optimal peptide concentration was established as 1.75 g L(-1). Liposomes obtained with this peptide concentration showed an encapsulation efficiency of 53%, a zeta potential of -59 mV, an average diameter of 70.3 nm and proved to be stable in the pH range 3-7 at 4 °C. Liposomes containing ACE-inhibitory peptides were incorporated in fish gelatin without detriment to the rheological properties and thermal stability of the resulting cold-induced gel. The ACE-inhibitory activity of the peptide fraction, which was not affected by the encapsulation process, conferred the bioactive potential to the nanoliposome-containing gelatin gel. © 2015 Society of Chemical Industry.

Thermosensitive gemcitabine-magnetoliposomes for combined hyperthermia and chemotherapy

NASA Astrophysics Data System (ADS)

Ferreira, Roberta V.; da Mata Martins, Thaís Maria; Goes, Alfredo Miranda; Fabris, José D.; Cavalcante, Luis Carlos D.; Eugenio Fernandez Outon, Luis; Domingues, Rosana Z.

2016-02-01

The combination of magnetic hyperthermia therapy with the controlled release of chemotherapeutic agents in tumors may be an efficient therapeutic with few side effects because the bioavailability, tolerance and amount of the drug can be optimized. Here, we prepared magnetoliposomes consisting of magnetite nanoparticle cores and the anticancer drug gemcitabine encapsulated by a phospholipid bilayer. The potential of these magnetoliposomes for controlled drug release and cancer treatment via hyperthermic behavior was investigated. The magnetic nanoparticle encapsulation efficiency was dependent on the initial amount of magnetite nanoparticles present at the encapsulation stage; the best formulation was 66%. We chose this formulation to characterize the physicochemical properties of the magnetoliposomes and to encapsulate gemcitabine. The mean particle size and distribution were determined by dynamic light scattering (DLS), and the zeta potential was measured. The magnetoliposome formulations all had acceptable characteristics for systemic administration, with a mean size of approximately 150 nm and a polydispersity index <0.2. The magnetoliposomes were stable in aqueous suspension for at least one week, as determined by DLS. Temperature increases due to the dissipation energy of magnetoliposome suspensions subjected to an applied alternating magnetic field (AMF) were measured at different magnetic field intensities, and the values were appropriated for cancer treatments. The drug release profile at 37 °C showed that 17% of the gemcitabine was released after 72 h. Drug release from magnetoliposomes exposed to an AMF for 5 min reached 70%.

Thai Silk Fibroin/Gelatin Sponges for the Dual Controlled Release of Curcumin and Docosahexaenoic Acid for Anticancer Treatment.

PubMed

Lerdchai, Kantarat; Kitsongsermthon, Jutarat; Ratanavaraporn, Juthamas; Kanokpanont, Sorada; Damrongsakkul, Siriporn

2016-01-01

In this study, curcumin and/or docosahexaenoic acid (DHA) were encapsulated in Thai silk fibroin/gelatin (SF/G) sponges, prepared at different blending ratios, aimed to be applied as a controlled release system for localized cancer therapy. The SF/G sponges were fabricated by freeze-drying and glutaraldehyde cross-linking techniques. Physicochemical properties of the SF/G sponges were characterized. Then, curcumin and/or DHA were loaded in the sponges by physical adsorption. The encapsulation efficiency and the in vitro release of curcumin and/or DHA from the sponges were evaluated. SF/G sponges could encapsulate curcumin and/or DHA at high encapsulation efficiency. The highly cross-linked and slowly degrading SF/G (50/50) sponge released curcumin and/or DHA at the slowest rate. The in vitro cytotoxicity of the sponges against noncancer cells (L929 mouse fibroblast) and anticancer of curcumin and/or DHA released from the sponges against cervical cancer cells (CaSki) were tested. All sponges were not toxic to L929 mouse fibroblast. The mixed curcumin–DHA at the ratio of 1:4 had the highest inhibiting effect on the growth of CaSki, comparing with the release of curcumin or DHA alone. SF/G sponges could be a potential carrier for dual release of curcumin and DHA for anticancer effect.

Microencapsulation of Islets of Langerhans via selective withdrawal to achieve immunoisolation

NASA Astrophysics Data System (ADS)

Wyman, Jason; Dillmore, Shannon; Murphy, William; Garfinkel, Marc; Mrksich, Milan; Nagel, Sidney

2004-03-01

Cohen phet al. [1] described how the selective-withdrawal geometry may be used to microencapsulate particles in thin coats whose thickness is independent of the size of the encapsulated particle. We have applied a modified version of this geometry to the microencapsulation of Islets of Langerhans for the purpose of immunoisolation. The Islets are initially placed in a polymer-containing aqueous solution which is then drawn up into a selective-withdrawal spout. As that spout breaks up, it leaves the Islets coated with the polymer solution. These coats are then photo-crosslinked leaving the Islets encapsulated in a hydrogel coating. This coating provides a semi-permeable membrane which allows for the diffusion of small molecules such as nutrients, glucose, and insulin, but which excludes larger proteins such as antibodies. If one can successfully microencapsulate 10^6 islets in uniform coats such as these, then one may transplant Islets without immuno-suppression as a treatment for Type-I Diabetes. We will discuss preliminary phin vitro results. [1] I. Cohen, H. Li, J. L. Hougland, M. Mrksich, and S. R. Nagel Science 292, 265-267 (2001).

Hybrid Encapsulated Ionic Liquids for Post-Combustion Carbon Dioxide (CO 2) Capture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brennecke, Joan; Degnan, Thomas; McCready, Mark

Ionic liquids (ILs) and Phase Change Ionic Liquids (PCILs) are excellent materials for selective removal of carbon dioxide from dilute post-combustion streams. However, they are typically characterized as having high viscosities, which impairs their effectiveness due to mass transfer limitations, caused by the high viscosities. In this project, we are examining the benefits of encapsulating ILs and PCILs in thin polymeric shells to produce particles of approximately 100 to 600 μm in diameter that can be used in a fluidized bed absorber. The particles are produced by microencapsulation of the ILs and PCILs in CO 2-permeable polymer shells. Here wemore » report on the synthesis of the IL and PCIL materials, measurements of thermophysical properties including CO 2 capacity and reprotonation equilibrium and kinetics, encapsulation of the ILs and PCILs, mechanical and thermodynamic testing of the encapsulated materials, development of a rate based model of the absorber, and the design of a laboratory scale unit to test the encapsulated particles for CO 2 capture ability and efficiency. We show that the IL/PCIL materials can be successfully encapsulated, that they retain CO 2 uptake capacity, and that the uptake rates are increased relative to a stagnant sample of IL liquid or PCIL powder.« less

Cellular trafficking and anticancer activity of Garcinia mangostana extract-encapsulated polymeric nanoparticles

PubMed Central

Pan-In, Porntip; Wanichwecharungruang, Supason; Hanes, Justin; Kim, Anthony J

2014-01-01

Garcinia mangostana Linn extract (GME) is a natural product that has received considerable attention in cancer therapy, and has the potential to reduce side effects of chemotherapeutics and improve efficacy. We formulated GME-encapsulated ethyl cellulose (GME-EC) and a polymer blend of ethyl cellulose and methyl cellulose (GME-EC/MC) nanoparticles. We achieved high drug-loading and encapsulation efficiency using a solvent-displacement method with particle sizes around 250 nm. Cellular uptake and accumulation of GME was higher for GME-encapsulated nanoparticles compared to free GME. In vitro cytotoxicity analysis showed effective anticancer activity of GME-EC and GME-EC/MC nanoparticles in HeLa cells in a dose-dependent manner. GME-EC/MC nanoparticles showed approximately twofold-higher anticancer activity compared to GME-EC nanoparticles, likely due to their enhanced bioavailability. GME-encapsulated nanoparticles primarily entered HeLa cells by clathrin-mediated endocytosis and trafficked through the endolysosomal pathway. As far as we know, this is the first report on the cellular uptake and intracellular trafficking mechanism of drug-loaded cellulose-based nanoparticles. In summary, encapsulation of GME using cellulose-derivative nanoparticles – GME-EC and GME-EC/MC nanoparticles – successfully improved the bioavailability of GME in aqueous solution, enhanced cellular uptake, and displayed effective anticancer activity. PMID:25125977

Synthesis and characterization of a stable humic-urease complex: application to barley seed encapsulation for improving N uptake.

PubMed

Mvila, Beaufray G; Pilar-Izquierdo, María C; Busto, María D; Perez-Mateos, Manuel; Ortega, Natividad

2016-07-01

Most N fertilizers added to soil are not efficiently used by plants and are lost to the atmosphere or leached from the soil, causing environmental pollution and increasing cost. Barley seed encapsulation in calcium alginate gels containing free or immobilized urease to enhance plant utilization of soil N was investigated. Urease was immobilized with soil humic acids (HA). A central composite face-centered design was applied to optimize the immobilization process, reaching an immobilization yield of 127%. Soil stability of urease was enhanced after the immobilization. Seed encapsulation with free urease (FU) and humic-urease complex (HUC) resulted in a urease activity retention in the coating layer of 46% and 24%, and in germination rates of 87% and 92%, respectively. Under pot culture conditions, the pots planted with seeds encapsulated with FU and HUC showed higher ammonium N (NH4 (+) -N) (26% and 64%, respectively) than the control soil at 28 days after planting (DAP). Moreover, the seed encapsulation with FU and HUC increased the N uptake 83% and 97%, respectively, at 35 DAP. Seed encapsulation with urease could substantially contribute to enhancing plant N nutrition in the early stages of seedling establishment. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Influence of lecithin-lipid composition on physico-chemical properties of nanoliposomes loaded with a hydrophobic molecule.

PubMed

Bouarab, Lynda; Maherani, Behnoush; Kheirolomoom, Azadeh; Hasan, Mahmoud; Aliakbarian, Bahar; Linder, Michel; Arab-Tehrany, Elmira

2014-03-01

In this work, we studied the effect of nanoliposome composition based on phospholipids of docosahexaenoic acid (PL-DHA), salmon and soya lecithin, on physico-chemical characterization of vector. Cinnamic acid was encapsulated as a hydrophobic molecule in nanoliposomes made of three different lipid sources. The aim was to evaluate the influence of membrane lipid structure and composition on entrapment efficiency and membrane permeability of cinnamic acid. These properties are important for active molecule delivery. In addition, size, electrophoretic mobility, phase transition temperature, elasticity and membrane fluidity were measured before and after encapsulation. The results showed a correlation between the size of the nanoliposome and the entrapment. The entrapment efficiency of cinnamic acid was found to be the highest in liposomes prepared from salmon lecithin. The nanoliposomes composed of salmon lecithin presented higher capabilities as a carrier for cinnamic acid encapsulation. These vesicles also showed a high stability which in turn increases the membrane rigidity of nanoliposome as evaluated by their elastic properties, membrane fluidity and phase transition temperature. Copyright © 2013 Elsevier B.V. All rights reserved.

Förster resonance energy transfer between pyrene and bovine serum albumin: effect of the hydrophobic pockets of cyclodextrins.

PubMed

Maity, Arnab; Mukherjee, Puspal; Das, Tarasankar; Ghosh, Prasun; Purkayastha, Pradipta

2012-06-15

The phenomenon of Förster resonance energy transfer (FRET) between pyrene and bovine serum albumin (BSA) protein in presence of cyclodextrins (CDs) is explored in the present work. CDs provide hydrophobic environment and thus the aromatic molecules get encapsulated in them depending on the relative size and space. In this work we revealed that along with pyrene monomer, the side chains of amino acids in BSA can get trapped partly in the hydrophobic cavities of CDs if space permits. While being encapsulated by β-CD as pyrene monomer, it can interact with the BSA tryptophan moiety exposed toward the aqueous environment to form a dimer through π-π interaction. This, in turn, affects the energy transfer process by reducing the efficiency. On the other hand, pyrene excimer gets encapsulated in a γ-CD molecule due to availability of enough space. The excimer shows a new band at a higher wavelength. This further reduces FRET efficiency due to scarcity of acceptor for the tryptophan moieties in BSA. Copyright © 2012 Elsevier B.V. All rights reserved.

Preparation and investigation of Ulex europaeus agglutinin I-conjugated liposomes as potential oral vaccine carriers.

PubMed

Li, KeXin; Chen, DaWei; Zhao, XiuLi; Hu, HaiYang; Yang, ChunRong; Pang, DaHai

2011-11-01

We prepared and optimized Ulex europaeus agglutinin I (UEAI)-modified Bovine serum albumin (BSA)-encapsulating liposomes (UEAI-LIP) as oral vaccine carriers and examined the feasibility of inducing systemic and mucosal immune responses by oral administration of UEAILIP. The prepared systems were characterized in vitro for their average size, zeta potential, encapsulation efficiency (EE%) and conjugation efficiency (CE%). In vitro release studies indicated that the presence of UEAI around the optimized liposomes was able to prevent a burst release of loaded BSA and provide sustained release of the encapsulated protein. In vivo immune-stimulating results in KM mice showed that BSA given intramuscularly generated systemic response only but both systemic and mucosal immune responses could be induced simultaneously in the groups in which BSA-loaded liposomes (LIP) and UEAI-LIP were administered intragastrically. Furthermore, the modification of UEAI on the surface of liposomes could further enhance the IgA and IgG levels obviously. In conclusion, this study demonstrated the high potential of lectin-modified liposomes containing the antigen as carriers for oral vaccine.

Micro-emulsification/encapsulation of krill oil by complex coacervation with krill protein isolated using isoelectric solubilization/precipitation.

PubMed

Shi, Liu; Beamer, Sarah K; Yang, Hong; Jaczynski, Jacek

2018-04-01

This study determined feasibility of krill protein isolated with isoelectric solubilization/precipitation (ISP) as wall material to microencapsulate krill oil by freeze-drying. Effects of krill oil/krill protein ratio on properties of microcapsules were investigated. With increased ratio, crude protein of microcapsules decreased, while total lipid increased. Although microcapsule oil loading capacity increased, loading and encapsulation efficiencies decreased. Thin layer chromatography (TLC) confirmed abundance of phospholipids, which are amphiphilic; and thus, resulted in stable emulsion (emulsion stability index). Microcapsules contained ω-3 polyunsaturated fatty acids (PUFAs) at 43-60, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at 28-41 and 9-11 g/100g of total FAs, respectively. SDS-PAGE electrophoresis revealed proteolysis of ISP krill protein, probably causing reduced loading and encapsulation efficiencies. SEM showed that krill oil/krill protein ratio affected surface microstructure. ISP krill protein showed potential as a wall material to microencapsulate krill oil; and thus, expand application of krill oil/protein for human consumption. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nanovesicle encapsulation of antimicrobial peptide P34: physicochemical characterization and mode of action on Listeria monocytogenes

NASA Astrophysics Data System (ADS)

da Silva Malheiros, Patrícia; Sant'Anna, Voltaire; Micheletto, Yasmine Miguel Serafini; da Silveira, Nadya Pesce; Brandelli, Adriano

2011-08-01

Antimicrobial peptide P34, a substance showing antibacterial activity against pathogenic and food spoilage bacteria, was encapsulated in liposomes prepared from partially purified soybean phosphatidylcholine, and their physicochemical characteristics were evaluated. The antimicrobial activity was estimated by agar diffusion assay using Listeria monocytogenes ATCC 7644 as indicator strain. A concentration of 3,200 AU/mL of P34 was encapsulated in nanovesicles and stocked at 4 °C. No significant difference ( p > 0.05) in the biological activity of free and encapsulated P34 was observed through 24 days. Size and PDI of liposomes, investigated by light scattering analysis, were on average 150 nm and 0.22 respectively. Zeta potential was -27.42 mV. There was no significant change ( p > 0.05) in the physicochemical properties of liposomes during the time of evaluation. The liposomes presented closed spherical morphology as visualized by transmission electron microscopy (TEM). The mode of action of liposome-encapsulated P34 under L. monocytogenes cells was investigated by TEM. Liposomes appeared to adhere but not fuse with the bacterial cell wall, suggesting that the antimicrobial is released from nanovesicles to act against the microorganism. The effect of free and encapsulated P34 was tested against L. monocytogenes, showing that free bacteriocin inhibited the pathogen more quickly than the encapsulated P34. Liposomes prepared with low-cost lipid showed high encapsulation efficiency for a new antimicrobial peptide and were stable during storage. The mode of action against the pathogen L. monocytogenes was characterized.

Radioprotective activity of curcumin-encapsulated liposomes against genotoxicity caused by Gamma Cobalt-60 irradiation in human blood cells.

PubMed

Nguyen, Minh-Hiep; Pham, Ngoc-Duy; Dong, Bingxue; Nguyen, Thi-Huynh-Nga; Bui, Chi-Bao; Hadinoto, Kunn

2017-11-01

While the radioprotective activity of curcumin against genotoxicity has been well established, its poor oral bioavailability has limited its successful clinical applications. Nanoscale formulations, including liposomes, have been demonstrated to improve curcumin bioavailability. The objective of the present work was (1) to prepare and characterize curcumin-encapsulated liposomes (i.e. size, colloidal stability, encapsulation efficiency, and payload), and (2) subsequently to evaluate their radioprotective activity against genotoxicity in human blood cells caused by Gamma Cobalt-60 irradiation. The curcumin-encapsulated liposomes were prepared by lipid-film hydration method using commercial phosphatidylcholine (i.e. Phospholipon ® 90G). The blood cells were obtained from healthy male donors (n = 3) under an approved ethics protocol. The cell uptake and the radioprotective activity of the curcumin-encapsulated liposomes were characterized by fluorescence microscopy and micronucleus assay, respectively. Nanoscale curcumin-encapsulated liposomes exhibiting good physical characteristics and successful uptake by the human blood cells were successfully prepared. The radioprotective activity of the curcumin-encapsulated liposomes was found to be dependent on the curcumin concentration, where an optimal concentration existed (i.e. 30 μg/mL) independent of the irradiation dose, above which the radioprotective activity had become stagnant (i.e. no more reduction in the micronuclei frequency). The present results established for the first time the radioprotective activity of curcumin-encapsulated liposomes in human blood cells, which coupled by its well-established bioavailability, boded well for its potential application as a nanoscale delivery system of other radioprotective phytochemicals.

Concanavalin A conjugated biodegradable nanoparticles for oral insulin delivery

NASA Astrophysics Data System (ADS)

Hurkat, Pooja; Jain, Aviral; Jain, Ashish; Shilpi, Satish; Gulbake, Arvind; Jain, Sanjay K.

2012-11-01

Major research issues in oral protein delivery include the stabilization of protein in delivery devices which could increase its oral bioavailability. The study deals with development of oral insulin delivery system utilizing biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles and modifying its surface with Concanavalin A to increase lymphatic uptake. Surface-modified PLGA nanoparticles were characterized for conjugation efficiency of ligand, shape and surface morphology, particle size, zeta potential, polydispersity index, entrapment efficiency, and in vitro drug release. Stability of insulin in the developed formulation was confirmed by SDS-PAGE, and integrity of entrapped insulin was assessed using circular dichroism spectrum. Ex vivo study was performed on Wistar rats, which exhibited the higher intestinal uptake of Con A conjugated nanoparticles. In vivo study performed on streptozotocin-induced diabetic rats which indicate that a surface-modified nanoparticle reduces blood glucose level effectively within 4 h of its oral administration. In conclusion, the present work resulted in successful production of Con A NPs bearing insulin with sustained release profile, and better absorption and stability. The Con A NPs showed high insulin uptake, due to its relative high affinity for non-reducing carbohydrate residues i.e., fucose present on M cells and have the potential for oral insulin delivery in effective management of Type 1 diabetes condition.

Scope and Limitations of Fmoc Chemistry SPPS-Based Approaches to the Total Synthesis of Insulin Lispro via Ester Insulin.

PubMed

Dhayalan, Balamurugan; Mandal, Kalyaneswar; Rege, Nischay; Weiss, Michael A; Eitel, Simon H; Meier, Thomas; Schoenleber, Ralph O; Kent, Stephen B H

2017-01-31

We have systematically explored three approaches based on 9-fluorenylmethoxycarbonyl (Fmoc) chemistry solid phase peptide synthesis (SPPS) for the total chemical synthesis of the key depsipeptide intermediate for the efficient total chemical synthesis of insulin. The approaches used were: stepwise Fmoc chemistry SPPS; the "hybrid method", in which maximally protected peptide segments made by Fmoc chemistry SPPS are condensed in solution; and, native chemical ligation using peptide-thioester segments generated by Fmoc chemistry SPPS. A key building block in all three approaches was a Glu[O-β-(Thr)] ester-linked dipeptide equipped with a set of orthogonal protecting groups compatible with Fmoc chemistry SPPS. The most effective method for the preparation of the 51 residue ester-linked polypeptide chain of ester insulin was the use of unprotected peptide-thioester segments, prepared from peptide-hydrazides synthesized by Fmoc chemistry SPPS, and condensed by native chemical ligation. High-resolution X-ray crystallography confirmed the disulfide pairings and three-dimensional structure of synthetic insulin lispro prepared from ester insulin lispro by this route. Further optimization of these pilot studies could yield an efficient total chemical synthesis of insulin lispro (Humalog) based on peptide synthesis by Fmoc chemistry SPPS. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Functional Design of Dielectric-Metal-Dielectric-Based Thin-Film Encapsulation with Heat Transfer and Flexibility for Flexible Displays.

PubMed

Kwon, Jeong Hyun; Choi, Seungyeop; Jeon, Yongmin; Kim, Hyuncheol; Chang, Ki Soo; Choi, Kyung Cheol

2017-08-16

In this study, a new and efficient dielectric-metal-dielectric-based thin-film encapsulation (DMD-TFE) with an inserted Ag thin film is proposed to guarantee the reliability of flexible displays by improving the barrier properties, mechanical flexibility, and heat dissipation, which are considered to be essential requirements for organic light-emitting diode (OLED) encapsulation. The DMD-TFE, which is composed of Al 2 O 3 , Ag, and a silica nanoparticle-embedded sol-gel hybrid nanocomposite, shows a water vapor transmission rate of 8.70 × 10 -6 g/m 2 /day and good mechanical reliability at a bending radius of 30 mm, corresponding to 0.41% strain for 1000 bending cycles. The electrical performance of a thin-film encapsulated phosphorescent organic light-emitting diode (PHOLED) was identical to that of a glass-lid encapsulated PHOLED. The operational lifetimes of the thin-film encapsulated and glass-lid encapsulated PHOLEDs are 832 and 754 h, respectively. After 80 days, the thin-film encapsulated PHOLED did not show performance degradation or dark spots on the cell image in a shelf-lifetime test. Finally, the difference in lifetime of the OLED devices in relation to the presence and thickness of a Ag film was analyzed by applying various TFE structures to fluorescent organic light-emitting diodes (FOLEDs) that could generate high amounts of heat. To demonstrate the difference in heat dissipation effect among the TFE structures, the saturated temperatures of the encapsulated FOLEDs were measured from the back side surface of the glass substrate, and were found to be 67.78, 65.12, 60.44, and 39.67 °C after all encapsulated FOLEDs were operated at an initial luminance of 10 000 cd/m 2 for sufficient heat generation. Furthermore, the operational lifetime tests of the encapsulated FOLED devices showed results that were consistent with the measurements of real-time temperature profiles taken with an infrared camera. A multifunctional hybrid thin-film encapsulation based on a dielectric-metal-dielectric structure was thus effectively designed considering the transmittance, gas-permeation barrier properties, flexibility, and heat dissipation effect by exploiting the advantages of each separate layer.

[Historical review of insulin and its preparations in pharmacopoeia (3). Fish insulins].

PubMed

Suehiro, M

1992-01-01

Existence of encapsulated glands situated in the mesentery of certain teleosti was reported by Brockmann (1846) and Stannius (1848), respectively. Thus the gland was named stannius corpuscle or Brockmann body. Later, as results of histological study, cells of stannius corpuscle tissues were constituted with Langerhans islet cells observed in mammalian pancreas by Diammare (1899) and Laguesse (1906). Thus, before the days of discovery of insulin by Banting and Best in 1921, stannius corpuscle has been interesting from the aspects of comparative anatomy and physiology. Rennie (1906) examined a large number of specimens in various species of teleosti and gave the term "principal islet" to easily recognizable stannius corpuscle. Osawa studied comparative anatomy in Freiburg and returned to Tokyo. He continued the study of comparative anatomy of Langerhans islet aand published a report on observation of "principal islet" of flatfish, limanda yokohamae Gth. in 1912 in Japanese. His report seemed to be a milestone of studies of fish insulin in Japan. Macleod attempted to demonstrate direct evidence on secretion of insulin from Langerhans islet cells. Experiments were made on extraction of "principal islet" of teleosti, angler Lophius) and sculpin (Myoxocephalus) to obtain insulin and demonstrated activity. No insulin activity was obtained from pancreatic tissues constituted with acinar cells of these fishes. In the case of elasmobranch, Langerhans islets are not separated, but potent insulin could be extracted from the pancreas. His report published in 1922 was the first report on fish insulin. Succeeding to Macleod's report, several reports on fish insulin were contnributed from Canada, England and U.S.A. until 1929. Dr. Kkumagai, Professor of Internal Medicine, Tohoku Imperial University (Sendai) also conducted the studies on extraction of active principle of pancreas since 1920, independently. But, a Toronto group reached the goal on discovery of insulin earlier than the Sendai group. The Sendai group also described extraction of active principle from the "principal islet" of teleosti. Especially, Ukai (1926) described morphological study on pancreas and stannius corpuscle for more than twenty species of fish. His report played an important role as the next milestone on the road of fish insulin development studies in Japan. In 1926, Dr. Sakaguchi who was a leading clinical diabetologist in Japan published a monograph entitled "Insulin" written in Japanese. He referred the report on fish insulins of McCormick and Noble and Dr. Kumagai's report, however, he commented that production of insulin from fish seemed to be less worthy due to requirements of laborious work to collect small stannius corpuscle from fish. Professor A. Ogata described a textbook entitled "Zoki-Yakuhin-Kagaku (chemistry of organotherapeutics): in 1931. In the first edition, papers of Macleod, McCormick, Dudley and Osawa were referred. In the revised fifth edition (1940) contained description of unpublished data of insulin content of various kinds of fish caught in Japan and supplied from his student Nagasawa. Under the circumstance of expanding tendency of the China Incident to World War II, shortage of importation and production of insulin preparations manufactured from domestic animals was anticipated. Development on manufacture of fish insulin became urgent. [Truncated

Preparation and characterization of protein-loaded poly(epsilon-caprolactone) microparticles for oral vaccine delivery.

PubMed

Benoit, M A; Baras, B; Gillard, J

1999-07-05

This paper describes the conditions of preparation of poly(epsilon-caprolactone) (PCL) microparticles with a mean size between 5 and 10 microm, obtained by a double emulsion-solvent evaporation technique, suitable for oral vaccine delivery. Bovine serum albumin (BSA) was used as water-soluble model antigen for encapsulation. Different parameters influencing the microparticle size, the BSA loading and entrapment efficiency were investigated. Spherical, smooth and homogeneously distributed microparticles were produced with a BSA loading and entrapment efficiency reaching, respectively, 5% (w/w) and 30%. Polyacrylamide gel electrophoresis (PAGE) and isoelectric focusing (IEF) analyses of BSA released from these particles confirmed that the entrapped protein seemed to remain unaltered by the protein encapsulation process. Copyright.

Phthalocyanine-sulfonamide conjugates: Synthesis and photodynamic inactivation of Gram-negative and Gram-positive bacteria.

PubMed

da Silva, Raquel Nunes; Cunha, Ângela; Tomé, Augusto C

2018-06-25

Phthalocyanines bearing four or eight sulfonamide units were synthesized and their efficiency in the photodynamic inactivation of Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) bacteria was evaluated. Conjugates with simpler sulfonamide units (N,N-diethylbenzenesulfonamide, N-isopropylbenzenesulfonamide and N-(4-methoxyphenyl)benzenesulfonamide) caused stronger inactivation than those with heterocyclic groups (N-(thiazol-2-yl)benzenesulfonamide) or long alkyl chains (N-dodecylbenzenesulfonamide) in both bacteria. Furthermore, the encapsulation of the phthalocyanine-sulfonamide conjugates within polyvinylpyrrolidone micelles, used as drug delivery vehicles, in general showed to enhance the inactivation efficiency. The results show that encapsulated phthalocyanine-sulfonamide conjugates are a promising class of photosensitizers to be used in photodynamic antimicrobial therapy. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Delivery of multiple siRNAs using lipid-coated PLGA nanoparticles for treatment of prostate cancer.

PubMed

Hasan, Warefta; Chu, Kevin; Gullapalli, Anuradha; Dunn, Stuart S; Enlow, Elizabeth M; Luft, J Christopher; Tian, Shaomin; Napier, Mary E; Pohlhaus, Patrick D; Rolland, Jason P; DeSimone, Joseph M

2012-01-11

Nanotechnology can provide a critical advantage in developing strategies for cancer management and treatment by helping to improve the safety and efficacy of novel therapeutic delivery vehicles. This paper reports the fabrication of poly(lactic acid-co-glycolic acid)/siRNA nanoparticles coated with lipids for use as prostate cancer therapeutics made via a unique soft lithography particle molding process called Particle Replication In Nonwetting Templates (PRINT). The PRINT process enables high encapsulation efficiency of siRNA into neutral and monodisperse PLGA particles (32-46% encapsulation efficiency). Lipid-coated PLGA/siRNA PRINT particles were used to deliver therapeutic siRNA in vitro to knockdown genes relevant to prostate cancer. © 2011 American Chemical Society

Anti-botulism single-shot vaccine using chitosan for protein encapsulation by simple coacervation.

PubMed

Sari, Roger S; de Almeida, Anna Christina; Cangussu, Alex S R; Jorge, Edson V; Mozzer, Otto D; Santos, Hércules Otacílio; Quintilio, Wagner; Brandi, Igor Viana; Andrade, Viviane Aguiar; Miguel, Angelo Samir M; Sobrinho Santos, Eliane M

2016-12-01

The aim of the present study was to compare the potency and safety of vaccines against Clostridium botulinum (C. botulinum) type C and D formulated with chitosan as controlled release matrix and vaccines formulated in conventional manner using aluminum hydroxide. Parameters were established for the development of chitosan microspheres, using simple coacervation to standardize the use of this polymer in protein encapsulation for vaccine formulation. To formulate a single shot vaccine inactivated antigens of C. botulinum type C and D were used with original toxin titles equal to 5.2 and 6.2 log LD50/ml, respectively. For each antigen a chitosan based solution of 50 mL was prepared. Control vaccines were formulated by mixing toxoid type C and D with aluminum hydroxide [25% Al(OH) 3 , pH 6.3]. The toxoid sterility, innocuity and potency of vaccines were evaluated as stipulated by MAPA-BRASIL according to ministerial directive no. 23. Encapsulation efficiency of BSA in chitosan was 32.5-40.37%, while that the encapsulation efficiency to toxoid type C was 41,03% (1.94 mg/mL) and of the toxoid type D was 32.30% (1.82 mg/mL). The single shot vaccine formulated using chitosan for protein encapsulation through simple coacervation showed potency and safety similar to conventional vaccine currently used in Brazilian livestock (10 and 2 IU/mL against C. botulinum type C and D, respectively). The present work suggests that our single shot vaccine would be a good option as a cattle vaccine against these C. botulinum type C and D. Copyright © 2016 Elsevier Ltd. All rights reserved.

Glass for low-cost photovoltaic solar arrays

NASA Technical Reports Server (NTRS)

Bouquet, F. L.

1980-01-01

Various aspects of glass encapsulation that are important for the designer of photovoltaic systems are discussed. Candidate glasses and available information defining the state of the art of glass encapsulation materials and processes for automated, high volume production of terrestrial photovoltaic devices and related applications are presented. The criteria for consideration of the glass encapsulation systems were based on the low-cost solar array project goals for arrays: (1) a low degradation rate, (2) high reliability, (3) an efficiency greater than 10 percent, (4) a total array price less than $500/kW, and (5) a production capacity of 500,000 kW/yr. The glass design areas discussed include the types of glass, sources and costs, physical properties, and glass modifications, such as antireflection coatings.

Investigation of Test Methods, Material Properties and Processes for Solar Cell Encapsulants

NASA Technical Reports Server (NTRS)

Willis, P.; Baum, B.

1982-01-01

The evaluation of potentially useful low cost encapsulation materials is discussed. The goal is to identify, evaluate, test and recommend encapsulant materials and processes for the production of cost effective, long life solar cell modules. Technical investigations concerned the development of advanced cure chemistries for lamination type pottants; the continued evaluation of soil resistant surface treatment, and the results of an accelerated aging test program for the comparison of material stabilities. New compounds were evaluated for efficiency in curing both ethylene/vinyl acetate and ethylene/methyl acrylate pottants intended for vacuum bag lamination of solar cells. Two component aliphatic urethane casting syrups were evaluated for suitability as solar module pottants on the basis of optical, physical and fabrication characteristics.

Physico-chemical state influences in vitro release profile of curcumin from pectin beads.

PubMed

Nguyen, An Thi-Binh; Winckler, Pascale; Loison, Pauline; Wache, Yves; Chambin, Odile

2014-09-01

Curcumin is a polyphenolic compound with diverse effects interesting to develop health benefit products but its formulation in functional foods or in food supplement is hampered by its poor water solubility and susceptibility to alkaline conditions, light, oxidation and heat. Encapsulation of curcumin could be a mean to overcome these difficulties. In this paper, curcumin was encapsulated by ionotropic gelation method in low methoxyl pectin beads associated with different surfactants: Solutol(®), Transcutol(®) and sodium caseinate. After encapsulation, physico-chemical properties of encapsulated curcumin such as its solubility, physical state, tautomeric forms and encapsulation efficiency as well as encapsulation yield were characterized. In vitro dissolution of curcumin from beads displayed different kinetic profiles according to bead composition due to different matrix network. As Solutol(®) was a good solvent for curcumin, the drug was present into amorphous form in these beads inducing a rapid release of curcumin in the simulated digestive fluids. In contrast, drug release was slower from sodium caseinate beads since curcumin was not totally dissolved during the manufacturing process. Moreover, the FLIM studies showed that a part of curcumin was encapsulated in caseinate micelles and that 34% of this drug was in keto form which may delay the curcumin release. The Transcutol beads showed also a slow drug release because of the low curcumin solubility and the high density of the matrix. Copyright © 2014 Elsevier B.V. All rights reserved.

A hydrophobic dye-encapsulated nano-hybrid as an efficient fluorescent probe for living cell imaging.

PubMed

Chang, Shu; Wu, Xumeng; Li, Yongsheng; Niu, Dechao; Ma, Zhi; Zhao, Wenru; Gu, Jinlou; Dong, Wenjie; Ding, Feng; Zhu, Weihong; Shi, Jianlin

2012-07-01

Water-soluble hydrophobic-dye@nano-hybrids (DPN@NHs) with extraordinarily enhanced fluorescent performance were fabricated by encapsulating the hydrophobic dye molecules into the core of the hybrid nanospheres based on the self-assembly of amphiphilic block copolymers followed by shell cross-linking using 3-mercaptopropyltrimethoxy-silane. The DPN@NHs are 50 nm in size, are monodispersed in aqueous solution and have a quantum yield enhanced by 30 times. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Treatment of diabetic rats with encapsulated islets.

PubMed

Sweet, Ian R; Yanay, Ofer; Waldron, Lanaya; Gilbert, Merle; Fuller, Jessica M; Tupling, Terry; Lernmark, Ake; Osborne, William R A

2008-12-01

Immunoprotection of islets using bioisolator systems permits introduction of allogeneic cells to diabetic patients without the need for immunosuppression. Using TheraCyte immunoisolation devices, we investigated two rat models of type 1 diabetes mellitus (T1DM), BB rats and rats made diabetic by streptozotocin (STZ) treatment. We chose to implant islets after the onset of diabetes to mimic the probable treatment of children with T1DM as they are usually diagnosed after disease onset. We encapsulated 1000 rat islets and implanted them subcutaneously (SQ) into diabetic biobreeding (BB) rats and STZ-induced diabetic rats, defined as two or more consecutive days of blood glucose>350 mg/dl. Rats were monitored for weight and blood glucose. Untreated BB rats rapidly lost weight and were euthanized at >20% weight loss that occurred between 4 and 10 days from implantation. For period of 30-40 days following islet implantation weights of treated rats remained steady or increased. Rapid weight loss occurred after surgical removal of devices that contained insulin positive islets. STZ-treated rats that received encapsulated islets showed steady weight gain for up to 130 days, whereas untreated control rats showed steady weight loss that achieved >20% at around 55 days. Although islet implants did not normalize blood glucose, treated rats were apparently healthy and groomed normally. Autologous or allogeneic islets were equally effective in providing treatment. TheraCyte devices can sustain islets, protect allogeneic cells from immune attack and provide treatment for diabetic-mediated weight loss in both BB rats and STZ-induced diabetic rats.

New Method to Prepare Mitomycin C Loaded PLA-Nanoparticles with High Drug Entrapment Efficiency

NASA Astrophysics Data System (ADS)

Hou, Zhenqing; Wei, Heng; Wang, Qian; Sun, Qian; Zhou, Chunxiao; Zhan, Chuanming; Tang, Xiaolong; Zhang, Qiqing

2009-07-01

The classical utilized double emulsion solvent diffusion technique for encapsulating water soluble Mitomycin C (MMC) in PLA nanoparticles suffers from low encapsulation efficiency because of the drug rapid partitioning to the external aqueous phase. In this paper, MMC loaded PLA nanoparticles were prepared by a new single emulsion solvent evaporation method, in which soybean phosphatidylcholine (SPC) was employed to improve the liposolubility of MMC by formation of MMC-SPC complex. Four main influential factors based on the results of a single-factor test, namely, PLA molecular weight, ratio of PLA to SPC (wt/wt) and MMC to SPC (wt/wt), volume ratio of oil phase to water phase, were evaluated using an orthogonal design with respect to drug entrapment efficiency. The drug release study was performed in pH 7.2 PBS at 37 °C with drug analysis using UV/vis spectrometer at 365 nm. MMC-PLA particles prepared by classical method were used as comparison. The formulated MMC-SPC-PLA nanoparticles under optimized condition are found to be relatively uniform in size (594 nm) with up to 94.8% of drug entrapment efficiency compared to 6.44 μm of PLA-MMC microparticles with 34.5% of drug entrapment efficiency. The release of MMC shows biphasic with an initial burst effect, followed by a cumulated drug release over 30 days is 50.17% for PLA-MMC-SPC nanoparticles, and 74.1% for PLA-MMC particles. The IR analysis of MMC-SPC complex shows that their high liposolubility may be attributed to some weak physical interaction between MMC and SPC during the formation of the complex. It is concluded that the new method is advantageous in terms of smaller size, lower size distribution, higher encapsulation yield, and longer sustained drug release in comparison to classical method.

Functionalization of Lipid-Based Nutrient Supplement with β-Cyclodextrin Inclusions of Oregano Essential Oil.

PubMed

Gaur, Shashank; Lopez, Emely C; Ojha, Ankur; Andrade, Juan E

2018-06-01

Intestinal parasitic infection is one of the main causes of acute undernutrition in children. Oral consumption of oregano essential oil (OEO) can reduce intestinal parasitic infections, however, its addition to therapeutic and supplementary foods is hampered by its undesirable flavor. The objective of this study was to develop a functional lipid-based nutrient supplement (LNS) containing OEO, which is stable, acceptable and provides targeted intestinal delivery of bioactive. β-cyclodextrin (β-CyD) inclusion complexes of OEO (β-CyD-OEO), and carvacrol (β-CyD-CV) (1:1 molar) were prepared using slurry complexation (-20 °C) method and characterized based on encapsulation efficiency, moisture content, morphology, and 2-phase in vitro digestion stability. Carvacrol (CV) content was measured using reverse phase HPLC-UV. LNS containing β-CyD-OEO (27.2 mg encapsulate/20 g LNS) was formulated using Indian staples and ingredients. Discriminatory sensory tests (triangle) were performed with college students (n = 58) and low-income women (n = 25), with young children at home (1 to 6 years), living in Mehsana, India to evaluate differences between LNS with and without bioactive ingredient (β-CyD-OEO only). Moisture of dried complexes ranged 9.1% to 9.7% d.b., whereas water activity 0.35 to 0.412. The complex size and encapsulation efficiency of β-CyD-OEO and β-CyD-CV were 1.5 to 7 μm and 4 to 20 μm, and 86.04 ± 4.48% and 81.39 ± 3.34%, respectively. The bioactive complexes were stable through the gastric and intestinal phases. Bioaccessibility of encapsulated CV ranged 6.0% to 7.7%. Sensory tests revealed no differences (P > 0.05) in color, aroma, and taste between LNS with and without β-CyD-OEO complexes. Functionalization of LNS with β-CyD-OEO is feasible based on in vitro stability and sensory studies. Despite its antiparasitic activities, the addition of oregano essential oil into foods is limited due to its strong flavor and volatility. In this study, we evaluated the encapsulation of oregano essential oil with β-cyclodextrin and its addition into lipid-based nutrition supplements. The results revealed that complex encapsulation efficiency was above 80%. Also, the bioactive complexes were stable under in vitro gastrointestinal conditions. Sensory evaluation of LNS with and without encapsulated essential oil showed no difference in terms of color, aroma, and taste. The functional LNS can both address nutrient insufficiency as well as parasitic infection among malnourished populations in low-resource settings. © 2018 Institute of Food Technologists®.

Encapsulation of ascorbyl palmitate in chitosan nanoparticles by oil-in-water emulsion and ionic gelation processes.

PubMed

Yoksan, Rangrong; Jirawutthiwongchai, Jatesuda; Arpo, Kridsada

2010-03-01

The encapsulation of ascorbyl palmitate (AP) in chitosan particles was carried out by droplet formation via an oil-in-water emulsion, followed by droplet solidification via ionic gelation using sodium triphosphate pentabasic (TPP) as a cross-linking agent. The success of AP encapsulation was confirmed by FT-IR, UV-vis spectrophotometry, TGA, and XRD techniques. The obtained AP-loaded chitosan particles were spherical in shape with an average diameter of 30-100nm as observed by SEM and TEM. Loading capacity (LC) and encapsulation efficiency (EE) of AP in the nanoparticles were about 8-20% and 39-77%, respectively, when the initial AP concentration was in the range of 25-150% (w/w) of chitosan. Augmentation of the initial AP concentration led to an increase of LC and a reduction of EE. The amount of AP released from the nanoparticles in ethanol and tris buffer (pH approximately 8.0) increased with increasing LC and decreasing TPP concentration.

Encapsulation of ultrafine metal-oxide nanoparticles within mesopores for biomass-derived catalytic applications† †Electronic supplementary information (ESI) available: Experimental section, additional characterization and reaction results. See DOI: 10.1039/c7sc04724j

PubMed Central

Fang, Ruiqi; Tian, Panliang; Yang, Xianfeng

2018-01-01

The development of efficient encapsulation strategies has attracted intense interest for preparing highly active and stable heterogeneous metal catalysts. However, issues related to low loadings, costly precursors and complex synthesis processes restrict their potential applications. Herein, we report a novel and general strategy to encapsulate various ultrafine metal-oxides nanoparticles (NPs) into the mesoporous KIT-6. The synthesis is facile, which only involves self-assembly of a metal–organic framework (MOF) precursor in the silica mesopores and a subsequent calcination process to transform the MOF into metal-oxide NPs. After the controlled calcination, the metal-oxide NPs produced from MOF decomposition are exclusively confined and uniformly distributed in the mesopores of KIT-6 with high metal loadings. Benefitting from the encapsulation effects, as-synthesized Co@KIT-6 materials exhibit superior catalytic activity and recycling stability in biomass-derived HMF oxidation under mild reaction conditions. PMID:29675231

Degradation of Silicone Encapsulants in CPV Optics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai, Can; Miller, David C.; Tappan, Ian A.

High efficiency multijunction solar cells in terrestrial concentrator photovoltaic (CPV) modules are becoming an increasingly cost effective and viable option in utility scale power generation. As with other utility scale photovoltaics, CPV modules need to guarantee operational lifetimes of at least 25 years. The reliability of optical elements in CPV modules poses a unique materials challenge due to the increased UV irradiance and enhanced temperature cycling associated with concentrated solar flux. The polymeric and thin film materials used in the optical elements are especially susceptible to UV damage, diurnal temperature cycling and active chemical species from the environment. We usedmore » fracture mechanics approaches to study the degradation modes including: the adhesion between the encapsulant and the cell or secondary optical element; and the cohesion of the encapsulant itself. Understanding the underlying mechanisms of materials degradation under elevated stress conditions is critical for commercialization of CPV technology and can offer unique insights into degradation modes in similar encapsulants used in other photovoltaic modules.« less

Degradation of Silicone Encapsulants in CPV Optics: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, David C.; Tappan, Ian A.; Cai, Can

High efficiency multijunction solar cells in terrestrial concentrator photovoltaic (CPV) modules are becoming an increasingly cost effective and viable option in utility scale power generation. As with other utility scale photovoltaics, CPV modules need to guarantee operational lifetimes of at least 25 years. The reliability of optical elements in CPV modules poses a unique materials challenge due to the increased UV irradiance and enhanced temperature cycling associated with concentrated solar flux. The polymeric and thin film materials used in the optical elements are especially susceptible to UV damage, diurnal temperature cycling and active chemical species from the environment. We usedmore » fracture mechanics approaches to study the degradation modes including: the adhesion between the encapsulant and the cell or secondary optical element; and the cohesion of the encapsulant itself. Understanding the underlying mechanisms of materials degradation under elevated stress conditions is critical for commercialization of CPV technology and can offer unique insights into degradation modes in similar encapsulants used in other photovoltaic modules.« less

Laser Glass Frit Sealing for Encapsulation of Vacuum Insulation Glasses

NASA Astrophysics Data System (ADS)

Kind, H.; Gehlen, E.; Aden, M.; Olowinsky, A.; Gillner, A.

Laser glass frit sealing is a joining method predestined in electronics for the sealing of engineered materials housings in dimensions of some 1 mm2 to several 10 mm2. The application field ranges from encapsulation of display panels to sensor housings. Laser glass frit sealing enables a hermetical closure excluding humidity and gas penetration. But the seam quality is also interesting for other applications requiring a hermetical sealing. One application is the encapsulation of vacuum insulation glass. The gap between two panes must be evacuated for reducing the thermal conductivity. Only an efficient encapsulating technique ensures durable tight joints of two panes for years. Laser glass frit sealing is an alternative joining method even though the material properties of soda lime glass like sensitivity to thermal stresses are much higher as known from engineered materials. An adapted thermal management of the process is necessary to prevent the thermal stresses within the pane to achieve crack free and tight glass frit seams.

Fluorescence Characterization of Gold Modified Liposomes with Antisense N-myc DNA Bound to the Magnetisable Particles with Encapsulated Anticancer Drugs (Doxorubicin, Ellipticine and Etoposide).

PubMed

Skalickova, Sylvie; Nejdl, Lukas; Kudr, Jiri; Ruttkay-Nedecky, Branislav; Jimenez, Ana Maria Jimenez; Kopel, Pavel; Kremplova, Monika; Masarik, Michal; Stiborova, Marie; Eckschlager, Tomas; Adam, Vojtech; Kizek, Rene

2016-02-25

Liposome-based drug delivery systems hold great potential for cancer therapy. The aim of this study was to design a nanodevice for targeted anchoring of liposomes (with and without cholesterol) with encapsulated anticancer drugs and antisense N-myc gene oligonucleotide attached to its surface. To meet this main aim, liposomes with encapsulated doxorubicin, ellipticine and etoposide were prepared. They were further characterized by measuring their fluorescence intensity, whereas the encapsulation efficiency was estimated to be 16%. The hybridization process of individual oligonucleotides forming the nanoconstruct was investigated spectrophotometrically and electrochemically. The concentrations of ellipticine, doxorubicin and etoposide attached to the nanoconstruct in gold nanoparticle-modified liposomes were found to be 14, 5 and 2 µg·mL(-1), respectively. The study succeeded in demonstrating that liposomes are suitable for the transport of anticancer drugs and the antisense oligonucleotide, which can block the expression of the N-myc gene.

Hypoxia-Responsive Polymersomes for Drug Delivery to Hypoxic Pancreatic Cancer Cells.

PubMed

Kulkarni, Prajakta; Haldar, Manas K; You, Seungyong; Choi, Yongki; Mallik, Sanku

2016-08-08

Hypoxia in tumors contributes to overall tumor progression by assisting in epithelial-to-mesenchymal transition, angiogenesis, and metastasis of cancer. In this study, we have synthesized a hypoxia-responsive, diblock copolymer poly(lactic acid)-azobenzene-poly(ethylene glycol), which self-assembles to form polymersomes in an aqueous medium. The polymersomes did not release any encapsulated contents for 50 min under normoxic conditions. However, under hypoxia, 90% of the encapsulated dye was released in 50 min. The polymersomes encapsulated the combination of anticancer drugs gemcitabine and erlotinib with entrapment efficiency of 40% and 28%, respectively. We used three-dimensional spheroid cultures of pancreatic cancer cells BxPC-3 to demonstrate hypoxia-mediated release of the drugs from the polymersomes. The vesicles were nontoxic. However, a significant decrease in cell viability was observed in hypoxic spheroidal cultures of BxPC-3 cells in the presence of drug encapsulated polymersomes. These polymersomes have potential for future applications in imaging and treatment of hypoxic tumors.

Nootkatone encapsulation by cyclodextrins: Effect on water solubility and photostability.

PubMed

Kfoury, Miriana; Landy, David; Ruellan, Steven; Auezova, Lizette; Greige-Gerges, Hélène; Fourmentin, Sophie

2017-12-01

Nootkatone (NO) is a sesquiterpenoid volatile flavor, used in foods, cosmetics and pharmaceuticals, possessing also insect repellent activity. Its application is limited because of its low aqueous solubility and stability; this could be resolved by encapsulation in cyclodextrins (CDs). This study evaluated the encapsulation of NO by CDs using phase solubility studies, Isothermal Titration Calorimetry, Nuclear Magnetic Resonance spectroscopy and molecular modeling. Solid CD/NO inclusion complex was prepared and characterized for encapsulation efficiency and loading capacity using UV-Visible. Thermal properties were investigated by thermogravimetric-differential thermal analysis and release studies were performed using multiple headspace extraction. Formation constants (K f ) proved the formation of stable inclusion complexes. NO aqueous solubility, photo- and thermal stability were enhanced and the release could be insured from solid complex in aqueous solution. This suggests that CDs are promising carrier to improve NO properties and, consequently, to enlarge its use in foods, cosmetics, pharmaceuticals and agrochemicals preparations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Encapsulation of sulfur with thin-layered nickel-based hydroxides for long-cyclic lithium–sulfur cells

PubMed Central

Jiang, Jian; Zhu, Jianhui; Ai, Wei; Wang, Xiuli; Wang, Yanlong; Zou, Chenji; Huang, Wei; Yu, Ting

2015-01-01

Elemental sulfur cathodes for lithium/sulfur cells are still in the stage of intensive research due to their unsatisfactory capacity retention and cyclability. The undesired capacity degradation upon cycling originates from gradual diffusion of lithium polysulfides out of the cathode region. To prevent losses of certain intermediate soluble species and extend lifespan of cells, the effective encapsulation of sulfur plays a critical role. Here we report an applicable way, by using thin-layered nickel-based hydroxide as a feasible and effective encapsulation material. In addition to being a durable physical barrier, such hydroxide thin films can irreversibly react with lithium to generate protective layers that combine good ionic permeability and abundant functional polar/hydrophilic groups, leading to drastic improvements in cell behaviours (almost 100% coulombic efficiency and negligible capacity decay within total 500 cycles). Our present encapsulation strategy and understanding of hydroxide working mechanisms may advance progress on the development of lithium/sulfur cells for practical use. PMID:26470847

Solvothermal method as a green chemistry solution for micro-encapsulation of phase change materials for high temperature thermal energy storage

NASA Astrophysics Data System (ADS)

Tudor, Albert Ioan; Motoc, Adrian Mihail; Ciobota, Cristina Florentina; Ciobota, Dan. Nastase; Piticescu, Radu Robert; Romero-Sanchez, Maria Dolores

2018-05-01

Thermal energy storage systems using phase change materials (PCMs) as latent heat storage are one of the main challenges at European level in improving the performances and efficiency of concentrated solar power energy generation due to their high energy density. PCM with high working temperatures in the temperature range 300-500 °C are required for these purposes. However their use is still limited due to the problems raised by the corrosion of the majority of high temperature PCMs and lower thermal transfer properties. Micro-encapsulation was proposed as one method to overcome these problems. Different micro-encapsulation methods proposed in the literature are presented and discussed. An original process for the micro-encapsulation of potassium nitrate as PCM in inorganic zinc oxide shells based on a solvothermal method followed by spray drying to produce microcapsules with controlled phase composition and distribution is proposed and their transformation temperatures and enthalpies measured by differential scanning calorimetry are presented.

Novel pH responsive polymethacrylic acid-chitosan-polyethylene glycol nanoparticles for oral peptide delivery.

PubMed

Sajeesh, S; Sharma, Chandra P

2006-02-01

In present study, novel pH sensitive polymethacrylic acid-chitosan-polyethylene glycol (PCP) nanoparticles were prepared under mild aqueous conditions via polyelectrolyte complexation. Free radical polymerization of methacrylic acid (MAA) was carried out in presence of chitosan (CS) and polyethylene glycol (PEG) using a water-soluble initiator and particles were obtained spontaneously during polymerization without using organic solvents or surfactants/steric stabilizers. Dried particles were analyzed by scanning electron microscopy (SEM) and particles dispersed in phosphate buffer (pH 7.0) were visualized under transmission electron microscope (TEM). SEM studies indicated that PCP particles have an aggregated and irregular morphology, however, TEM revealed that these aggregated particles were composed of smaller fragments with size less than 1 micron. Insulin and bovine serum albumin (BSA) as model proteins were incorporated into the nanoparticles by diffusion filling method and their in vitro release characteristics were evaluated at pH 1.2 and 7.4. PCP nanoparticles exhibited good protein encapsulation efficiency and pH responsive release profile was observed under in vitro conditions. Trypsin inhibitory effect of these PCP nanoparticles was studied using casein substrate and these particles displayed lesser inhibitory effect than reference polymer carbopol. Preliminary investigation suggests that these particles can serve as good candidate for oral peptide delivery. Copyright 2005 Wiley Periodicals, Inc.

Cryopreservation of Cyrtopodium hatschbachii Pabst (Orchidaceae) immature seeds by encapsulation-dehydration.

PubMed

Surenciski, Mauro Rodrigo; Flachsland, Eduardo Alberto; Terada, Graciela; Mroginski, Luis Amado; Rey, Hebe Yolanda

2012-04-01

The aim of the present study was to investigate the efficiency of the encapsulation-dehydration technique for cryopreservation of Cyrtopodium hastchbachii Pabst seeds. Immature seeds of this species were cryopreserved by an encapsulation-dehydration technique. Seeds of five immature pods, 120 days after pollination, were encapsulated in 3% calcium alginate matrix and pretreated in liquid medium supplemented with 0.08 M sucrose (24 h), 0.15 M sucrose (24 h), 0.25 M sucrose (48 h), 0.5 M sucrose (24 h) and 0.75 M sucrose (24 h) in shaker at 60 rpm. Alginate beads were dehydrated 5 h in silicagel and immersed in liquid nitrogen for 12 h. Cryopreserved beads were thawed at 30 degrees C for 1 min, rehydrated using the same liquid mediums [0.75 M sucrose (24 h), 0.5 M sucrose (24 h), 0.25 M sucrose (48 h) and 0.15 M sucrose (24 h)] and cultivated in half strength Murashige & Skoog medium (1962) with the addition of 2 g/L activated charcoal. Sixty four percent of seeds survived and developed into acclimatized plants after being cryopreserved. In this work, the encapsulation-dehydration technique was employed for first time in Cyrtopodium hatschbachii.

Niosomal encapsulation of ethambutol hydrochloride for increasing its efficacy and safety.

PubMed

El-Ridy, Mohammed Shafik; Yehia, Soad Aly; Kassem, Mahfouz Abd-El-Megeid; Mostafa, Dina Mahmoud; Nasr, Essam Amin; Asfour, Marwa Hasanin

2015-01-01

Tuberculosis (TB) is a worldwide health concern. In 2011, about 8.7 million new cases developed TB and 1.4 million people died from it. Enhancement of ethambutol hydrochloride activity and safety in treatment of TB through niosomal encapsulation. Niosomes were prepared by the thin-film hydration method. They were characterized, investigated for in vitro release, lung disposition and in vivo biological evaluation. Entrapment efficiency of ethambutol hydrochloride ranged from 12.20% to 25.81%. Zeta potential values inferred stability of neutral and negatively charged formulations. In vitro release was biphasic. Lung targeting was increased by niosomal encapsulation. Biological evaluation revealed superiority of niosomal ethambutol hydrochloride over the free drug. Neutral and negatively charged niosomal vesicles are dispersed homogenously unlike positively charged vesicles. Niosomal encapsulation results in controlled drug release. Niosomal formulations targeted more drugs to mice lungs for a prolonged period of time resulting in: decreased root-specific lung weight, bacterial counts in lung homogenates and optimizing pathological effect on guinea pigs lungs, livers and spleens. Encapsulation of ethambutol hydrochloride in niosomal formulations for the treatment of TB provides higher efficacy and safety compared with the free drug.

Highly Stable Near-Unity Photoluminescence Yield in Monolayer MoS2 by Fluoropolymer Encapsulation and Superacid Treatment.

PubMed

Kim, Hyungjin; Lien, Der-Hsien; Amani, Matin; Ager, Joel W; Javey, Ali

2017-05-23

Recently, there has been considerable research interest in two-dimensional (2D) transition-metal dichalcogenides (TMDCs) for future optoelectronic applications. It has been shown that surface passivation with the organic nonoxidizing superacid bis(trifluoromethane)sulfonamide (TFSI) produces MoS 2 and WS 2 monolayers whose recombination is at the radiative limit, with a photoluminescence (PL) quantum yield (QY) of ∼100%. While the surface passivation persists under ambient conditions, exposure to conditions such as water, solvents, and low pressure found in typical semiconductor processing degrades the PL QY. Here, an encapsulation/passivation approach is demonstrated that yields near-unity PL QY in MoS 2 and WS 2 monolayers which are highly stable against postprocessing. The approach consists of two simple steps: encapsulation of the monolayers with an amorphous fluoropolymer and a subsequent TFSI treatment. The TFSI molecules are able to diffuse through the encapsulation layer and passivate the defect states of the monolayers. Additionally, we demonstrate that the encapsulation layer can be patterned by lithography and is compatible with subsequent fabrication processes. Therefore, our work presents a feasible route for future fabrication of highly efficient optoelectronic devices based on TMDCs.

Viability preserved capture of microorganism by plasma functionalized carbon-encapsulated iron nanoparticles

NASA Astrophysics Data System (ADS)

Viswan, Anchu; Sugiura, Kuniaki; Nagatsu, Masaaki

2015-09-01

Carbon-encapsulated iron nanoparticles (Fe@C NPs) were synthesized by DC arc discharge method. Carbon encapsulation makes the particles hydrophobic, however for most of the biomedical applications they need to be hydrophilic. To attain this, the particles were amino functionalized by RF plasma. Effect of gas mixture ratio (Ar/NH3), pretreatment, post-treatment times and RF power were optimized. By varying the RF plasma conditions, the amino group population on the surface of Fe@C NPs were increased. With conventional chemical method the amino group population on particles, synthesized in different conditions was found to be ranging from 3-7 × 104 per particle. Bioconjugation efficiency of the nanoparticles was examined by biotin-avidin system, which can be simulated for antigen-antibody reactions. Results from the UV absorption and fluorescence spectroscopy shows increment in bioconjugation efficiency, with the increase of amino group population on the nanoparticles. After confirming the bioconjugation efficiency, the amino functionalized Fe@C NPs were modified with antibodies for targeting specific microorganisms. Our aim is to capture the microbes in viable and concentrated form even from less populated samples, with lesser time compared to the presently available methods. This work has been supported in part by Grant-in-Aid for Scientific Research (Nos. 21110010 and 25246029) from the Japan Society for the Promotion of Science (JSPS).

Novel method of niosome generation using supercritical carbon dioxide part I: process mechanics.

PubMed

Wagner, Michael E; Rizvi, Syed S H

2015-01-01

A novel method for the production of non-ionic surfactant vesicles (niosomes) using an rapid expansion of supercritical solution (RESS)-based process coupled with a gas ejector is presented along with an investigation of parameters affecting niosome morphology, size and encapsulation efficiency of a 0.2 M D-glucose solution in Tris buffer at physiological pH. The solubility of the non-ionic surfactant polyoxyethylene(4) sorbitan monostearate in SC-CO2 was determined at three pressures (10, 15 and 20 MPa) and three temperatures (40, 50 and 60 °C). Mole fraction of Tween61 in the vapor phase increased with pressure at 40 °C, but did not change with pressure at 50 or 60 °C. Solubility data were correlated using the Peng-Robinson equation of state (PREOS) with the Panagiotopoulos and Reid mixing rule. Vesicles were either multilamellar or unilamellar, depending on the degree of precipitation of the lipid formulation at the point of aqueous cargo introduction. Vesicle particle size distributions were bimodal, with the 80-99% of the liposomal volume contributed niosomes ranging in size from 3 to 7 μm and the remaining niosomes ranging from 239 to 969 nm, depending on the system configuration. Encapsulation efficiency as high as 28% using the gas ejector to introduce the glucose cargo solution was achieved. Vesicle particle size and encapsulation efficiency were shown to be dependent on cargo droplet formation.

Effect drug loading process on dissolution mechanism of encapsulated amoxicillin trihydrate in hydrogel semi-IPN chitosan methyl cellulose with pore forming agent KHCO3 as a floating drug delivery system

NASA Astrophysics Data System (ADS)

Fithawati, Garnis; Budianto, Emil

2018-04-01

Common treatment for Helicobacter pylori by repeated oral consumption of amoxicillin trihydrate is not effective. Amoxicillin trihydrate has a very short residence time in stomach which leads into its ineffectiveness. Residence time of amoxicillin trihydrate can be improved by encapsulating amoxicillin trihydrate into a floating drug delivery system. In this study, amoxicillin trihydrate is encapsulated into hydrogel semi-IPN chitosan methyl cellulose matrix as a floating drug delivery system and then treated with 20% KHCO3 as pore forming agent. Drug loading process used are in-situ loading and post loading. In-situ loading process has higher efficiency percentage and dissolution percentage than post loading process. In-situ loading process resulted 100% efficiency with 92,70% dissolution percentage. Post loading process resulted 98,7% efficiency with 90,42% dissolution percentage. Mechanism of drug dissolution study by kinetics approach showed both in-situ loading process and post loading process are diffusion and degradation process (n=0,4913) and (n=0,4602) respectively. These results are supported by characterization data from optical microscope and scanning electron microscopy (SEM). Data from optical microscope showed both loading process resulted in coarser hydrogel surface. Characterization using SEM showed elongated pores in both loading process after dissolution test.

A human beta cell line with drug inducible excision of immortalizing transgenes

PubMed Central

Benazra, Marion; Lecomte, Marie-José; Colace, Claire; Müller, Andreas; Machado, Cécile; Pechberty, Severine; Bricout-Neveu, Emilie; Grenier-Godard, Maud; Solimena, Michele; Scharfmann, Raphaël; Czernichow, Paul; Ravassard, Philippe

2015-01-01

Objectives Access to immortalized human pancreatic beta cell lines that are phenotypically close to genuine adult beta cells, represent a major tool to better understand human beta cell physiology and develop new therapeutics for Diabetes. Here we derived a new conditionally immortalized human beta cell line, EndoC-βH3 in which immortalizing transgene can be efficiently removed by simple addition of tamoxifen. Methods We used lentiviral mediated gene transfer to stably integrate a tamoxifen inducible form of CRE (CRE-ERT2) into the recently developed conditionally immortalized EndoC βH2 line. The resulting EndoC-βH3 line was characterized before and after tamoxifen treatment for cell proliferation, insulin content and insulin secretion. Results We showed that EndoC-βH3 expressing CRE-ERT2 can be massively amplified in culture. We established an optimized tamoxifen treatment to efficiently excise the immortalizing transgenes resulting in proliferation arrest. In addition, insulin expression raised by 12 fold and insulin content increased by 23 fold reaching 2 μg of insulin per million cells. Such massive increase was accompanied by enhanced insulin secretion upon glucose stimulation. We further observed that tamoxifen treated cells maintained a stable function for 5 weeks in culture. Conclusions EndoC βH3 cell line represents a powerful tool that allows, using a simple and efficient procedure, the massive production of functional non-proliferative human beta cells. Such cells are close to genuine human beta cells and maintain a stable phenotype for 5 weeks in culture. PMID:26909308

Formulation, characterization, and expression of a recombinant MOMP Chlamydia trachomatis DNA vaccine encapsulated in chitosan nanoparticles

PubMed Central

Cambridge, Chino D; Singh, Shree R; Waffo, Alain B; Fairley, Stacie J; Dennis, Vida A

2013-01-01

Chlamydia trachomatis is a bacterial sexually transmitted infection affecting millions of people worldwide. Previous vaccination attempts have employed the recombinant major outer membrane protein (MOMP) of C. trachomatis nonetheless, with limited success, perhaps, due to stability, degradation, and delivery issues. In this study we cloned C. trachomatis recombinant MOMP DNA (DMOMP) and encapsulated it in chitosan nanoparticles (DMCNP) using the complex coacervation technique. Physiochemical characterizations of DMCNP included transmission and scanning electron microcopy, Fourier transform infrared and ultraviolet-visible spectroscopy, and zeta potential. Encapsulated DMOMP was 167–250 nm, with a uniform spherical shape and homogenous morphology, and an encapsulation efficiency > 90%. A slow release pattern of encapsulated DMOMP, especially in acidic solution, was observed over 7 days. The zeta potential of DMCNP was ~8.80 mV, which indicated that it was highly stable. Toxicity studies of DMCNP (25–400 μg/mL) to Cos-7 cells using the MTT assay revealed minimal toxicity over 24–72 hours with >90% viable cells. Ultra-violet visible (UV-vis) spectra indicated encapsulated DMOMP protection by chitosan, whereas agarose gel electrophoresis verified its protection from enzymatic degradation. Expression of MOMP protein in DMCNP-transfected Cos-7 cells was demonstrated via Western blotting and immunofluorescence microscopy. Significantly, intramuscular injection of BALB/c mice with DMCNP confirmed the delivery of encapsulated DMOMP, and expression of the MOMP gene transcript in thigh muscles and spleens. Our data show that encapsulation of DMOMP in biodegradable chitosan nanoparticles imparts stability and protection from enzymatic digestion, and enhances delivery and expression of DMOMP in vitro and in mice. Further investigations of the nanoencapsulated DMCNP vaccine formulation against C. trachomatis in mice are warranted. PMID:23690681

Evolution of availability of curcumin inside poly-lactic-co-glycolic acid nanoparticles: impact on antioxidant and antinitrosant properties

PubMed Central

Betbeder, Didier; Lipka, Emmanuelle; Howsam, Mike; Carpentier, Rodolphe

2015-01-01

Purpose Curcumin exhibits antioxidant properties potentially beneficial for human health; however, its use in clinical applications is limited by its poor solubility and relative instability. Nanoparticles exhibit interesting features for the efficient distribution and delivery of curcumin into cells, and could also increase curcumin stability in biological systems. There is a paucity of information regarding the evolution of the antioxidant properties of nanoparticle-encapsulated curcumin. Method We described a simple method of curcumin encapsulation in poly-lactic-co-glycolic acid (PLGA) nanoparticles without the use of detergent. We assessed, in epithelial cells and in an acellular model, the evolution of direct antioxidant and antinitrosant properties of free versus PLGA-encapsulated curcumin after storage under different conditions (light vs darkness, 4°C vs 25°C vs 37°C). Results In epithelial cells, endocytosis and efflux pump inhibitors showed that the increased antioxidant activity of PLGA-encapsulated curcumin relied on bypassing the efflux pump system. Acellular assays showed that the antioxidant effect of curcumin was greater when loaded in PLGA nanoparticles. Furthermore, we observed that light decreased, though heat restored, antioxidant activity of PLGA-encapsulated curcumin, probably by modulating the accessibility of curcumin to reactive oxygen species, an observation supported by results from quenching experiments. Moreover, we demonstrated a direct antinitrosant activity of curcumin, enhanced by PLGA encapsulation, which was increased by light exposure. Conclusion These results suggest that the antioxidant and antinitrosant activities of encapsulated curcumin are light sensitive and that nanoparticle modifications over time and with temperature may facilitate curcumin contact with reactive oxygen species. These results highlight the importance of understanding effects of nanoparticle maturation on an encapsulated drug’s activity. PMID:26345627

Synthesis of Polyamidoamine Dendrimer for Encapsulating Tetramethylscutellarein for Potential Bioactivity Enhancement.

PubMed

Shadrack, Daniel M; Mubofu, Egid B; Nyandoro, Stephen S

2015-11-04

The biomedical potential of flavonoids is normally restricted by their low water solubility. However, little has been reported on their encapsulation into polyamidoamine (PAMAM) dendrimers to improve their biomedical applications. Generation four (G4) PAMAM dendrimer containing ethylenediaminetetraacetic acid core with acrylic acid and ethylenediamine as repeating units was synthesized by divergent approach and used to encapsulate a flavonoid tetramethylscutellarein (TMScu, 1) to study its solubility and in vitro release for potential bioactivity enhancement. The as-synthesized dendrimer and the dendrimer-TMScu complex were characterized by spectroscopic and spectrometric techniques. The encapsulation of 1 into dendrimer was achieved by a co-precipitation method with the encapsulation efficiency of 77.8% ± 0.69% and a loading capacity of 6.2% ± 0.06%. A phase solubility diagram indicated an increased water solubility of 1 as a function of dendrimer concentration at pH 4.0 and 7.2. In vitro release of 1 from its dendrimer complex indicated high percentage release at pH 4.0. The stability study of the TMScu-dendrimer at 0, 27 and 40 °C showed the formulations to be stable when stored in cool and dark conditions compared to those stored in light and warmer temperatures. Overall, PAMAM dendrimer-G4 is capable of encapsulating 1, increasing its solubility and thus could enhance its bioactivity.

Thermoacoustic sound projector: exceeding the fundamental efficiency of carbon nanotubes.

PubMed

Aliev, Ali E; Codoluto, Daniel; Baughman, Ray H; Ovalle-Robles, Raquel; Inoue, Kanzan; Romanov, Stepan A; Nasibulin, Albert G; Kumar, Prashant; Priya, Shashank; Mayo, Nathanael K; Blottman, John B

2018-08-10

The combination of smooth, continuous sound spectra produced by a sound source having no vibrating parts, a nanoscale thickness of a flexible active layer and the feasibility of creating large, conformal projectors provoke interest in thermoacoustic phenomena. However, at low frequencies, the sound pressure level (SPL) and the sound generation efficiency of an open carbon nanotube sheet (CNTS) is low. In addition, the nanoscale thickness of fragile heating elements, their high sensitivity to the environment and the high surface temperatures practical for thermoacoustic sound generation necessitate protective encapsulation of a freestanding CNTS in inert gases. Encapsulation provides the desired increase of sound pressure towards low frequencies. However, the protective enclosure restricts heat dissipation from the resistively heated CNTS and the interior of the encapsulated device. Here, the heat dissipation issue is addressed by short pulse excitations of the CNTS. An overall increase of energy conversion efficiency by more than four orders (from 10 -5 to 0.1) and the SPL of 120 dB re 20 μPa @ 1 m in air and 170 dB re 1 μPa @ 1 m in water were demonstrated. The short pulse excitation provides a stable linear increase of output sound pressure with substantially increased input power density (>2.5 W cm -2 ). We provide an extensive experimental study of pulse excitations in different thermodynamic regimes for freestanding CNTSs with varying thermal inertias (single-walled and multiwalled with varying diameters and numbers of superimposed sheet layers) in vacuum and in air. The acoustical and geometrical parameters providing further enhancement of energy conversion efficiency are discussed.

Zirconium phosphatidylcholine-based nanocapsules as an in vivo degradable drug delivery system of MAP30, a momordica anti-HIV protein.

PubMed

Caizhen, Guo; Yan, Gao; Ronron, Chang; Lirong, Yang; Panpan, Chu; Xuemei, Hu; Yuanbiao, Qiao; Qingshan, Li

2015-04-10

An essential in vivo drug delivery system of a momordica anti-HIV protein, MAP30, was developed through encapsulating in chemically synthesized matrices of zirconium egg- and soy-phosphatidylcholines, abbreviated to Zr/EPC and Zr/SPC, respectively. Matrices were characterized by transmission electron microscopy and powder X-ray diffractometry studies. Zr/EPC granule at an approximate diameter of 69.43±7.78 nm was a less efficient encapsulator than the granule of Zr/SPC. Interlayer spacing of the matrices encapsulating MAP30 increased from 8.8 and 9.7 Å to 7.4 and 7.9 nm, respectively. In vivo kinetics on degradation and protein release was performed by analyzing the serum sampling of intravenously injected SPF chickens. The first order and biphasic variations were obtained for in vivo kinetics using equilibrium dialysis. Antimicrobial and anti-HIV assays yielded greatly decreased MIC50 and EC50 values of nanoformulated MAP30. An acute toxicity of MAP30 encapsulated in Zr/EPC occurred at a single intravenous dose above 14.24 mg/kg bw in NIH/KM/ICR mice. The folding of MAP30 from Zr/EPC sustained in vivo chickens for more than 8 days in high performance liquid chromatography assays. These matrices could protect MAP30 efficiently with strong structure retention, lowered toxicity and prolonged in vivo life. Copyright © 2015 Elsevier B.V. All rights reserved.

Characterization and oxidative stability of purslane seed oil microencapsulated in yeast cells biocapsules.

PubMed

Kavosi, Maryam; Mohammadi, Abdorreza; Shojaee-Aliabadi, Saeedeh; Khaksar, Ramin; Hosseini, Seyede Marzieh

2018-05-01

Purslane seed oil, as a potential nutritious source of omega-3 fatty acid, is susceptible to oxidation. Encapsulation in yeast cells is a possible approach for overcoming this problem. In the present study, purslane seed oil was encapsulated in non-plasmolysed, plasmolysed and plasmolysed carboxy methyl cellulose (CMC)-coated Saccharomyces cerevisiae cells and measurements of oil loading capacity (LC), encapsulation efficiency (EE), oxidative stability and the fatty acid composition of oil-loaded microcapsules were made. Furthermore, investigations of morphology and thermal behavior, as well as a Fourier transform-infrared (FTIR) analyses of microcapsules, were performed. The values of EE, LC were approximately 53-65% and 187-231 g kg -1 , respectively. Studies found that the plasmolysis treatment increased EE and LC and decreased the mean peroxide value (PV) of microencapsulated oil. The presence of purslane seed oil in yeast microcapsules was confirmed by FTIR spectroscopy and differential scanning calorimetry analyses. The lowest rate of oxidation belonged to the oil-loaded plasmolysed CMC-coated microcapsules (16.73 meqvO 2 kg -1 ), whereas the highest amount of oxidation regardless of native oil referred to the oil-loaded in non-plasmolysed cells (28.15 meqvO 2 kg -1 ). The encapsulation of purslane seed oil in the yeast cells of S. cerevisiae can be considered as an efficient approach for extending the oxidative stability of this nutritious oil and facilitating its application in food products. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Design and evaluation of liposomal formulation of pilocarpine nitrate.

PubMed

Rathod, S; Deshpande, S G

2010-03-01

Prolonged release drug delivery system of pilocarpine nitrate was made by optimizing thin layer film hydration method. Egg phosphatidylcholine and cholesterol were used to make multilamellar vesicles. Effects of charges over the vesicles were studied by incorporating dicetylphosphate and stearylamine. Various factors, which may affect the size, shape, encapsulation efficiency and release rate, were studied. Liposomes in the size range 0.2 to 1 µm were obtained by optimizing the process. Encapsulation efficiency of neutral, positive and negatively charged liposomes were found to be 32.5, 35.4 and 34.2 percent, respectively. In vitro drug release rate was studied on specially designed model. Biological response in terms of reduction in intraocular pressure was observed on rabbit eyes. Pilocarpine nitrate liposomes were lyophilized and stability studies were conducted.

Treatment of Francisella infections via PLGA- and lipid-based nanoparticle delivery of antibiotics in a zebrafish model.

PubMed

Ulanova, Lilia S; Pinheiro, Marina; Vibe, Carina; Nunes, Claudia; Misaghian, Dorna; Wilson, Steven; Zhu, Kaizheng; Fenaroli, Federico; Winther-Larsen, Hanne C; Reis, Salette; Griffiths, Gareth

2017-06-19

We tested the efficiency of 2 different antibiotics, rifampicin and oxolinic acid, against an established infection caused by fish pathogen Francisella noatunensis ssp. orientalis (F.n.o.) in zebrafish. The drugs were tested in the free form as well as encapsulated into biodegradable nanoparticles, either polylactic-co-glycolic acid (PLGA) nanoparticles or nanostructured lipid carriers. The most promising therapies were PLGA-rifampicin nanoparticles and free oxolinic acid; the PLGA nanoparticles significantly delayed embryo mortality while free oxolinic acid prevented it. Encapsulation of rifampicin in both PLGA and nanostructured lipid carriers enhanced its efficiency against F.n.o. infection relative to the free drug. We propose that the zebrafish model is a robust, rapid system for initial testing of different treatments of bacterial diseases important for aquaculture.

Insulin Infusion Set: The Achilles Heel of Continuous Subcutaneous Insulin Infusion

PubMed Central

Heinemann, Lutz; Krinelke, Lars

2012-01-01

Continuous subcutaneous insulin infusion from an insulin pump depends on reliable transfer of the pumped insulin to the subcutaneous insulin depot by means of an insulin infusion set (IIS). Despite their widespread use, the published knowledge about IISs and related issues regarding the impact of placement and wear time on insulin absorption/insulin action is relatively small. We also have to acknowledge that our knowledge is limited with regard to how often patients encounter issues with IISs. Reading pump wearer blogs, for instance, suggests that these are a frequent source of trouble. There are no prospective clinical studies available on current IIS and insulin formulations that provide representative data on the type and frequency of issues with infusion sets. The introduction of new IISs and patch pumps may foster a reassessment of available products and of patient problems related to their use. The aim of this review is to summarize the current knowledge and recommendations about IISs and to highlight potential directions of IIS development in order to make insulin absorption safer and more efficient. PMID:22920824

Encapsulation of new active ingredients.

PubMed

Onwulata, C I

2012-01-01

The organic construct consumed as food comes packaged in units that carry the active components and protect the entrapped active materials until delivered to targeted human organs. The packaging and delivery role is mimicked in the microencapsulation tools used to deliver active ingredients in processed foods. Microencapsulation efficiency is balanced against the need to access the entrapped nutrients in bioavailable forms. Encapsulated ingredients boosted with bioactive nutrients are intended for improved health and well-being and to prevent future health problems. Presently, active ingredients are delivered using new techniques, such as hydrogels, nanoemulsions, and nanoparticles. In the future, nutraceuticals and functional foods may be tailored to individual metabolic needs and tied to each person's genetic makeup. Bioactive ingredients provide health-enhancing nutrients and are protected through encapsulation processes that shield the active ingredients from deleterious environments.

Measure Guideline: Buried and/or Encapsulated Ducts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shapiro, C.; Zoeller, W.; Mantha, P.

2013-08-01

Buried and/or encapsulated ducts (BEDs) are a class of advanced, energy-efficiency strategies intended to address the significant ductwork thermal losses associated with ducts installed in unconditioned attics. BEDs are ducts installed in unconditioned attics that are covered in loose-fill insulation and/or encapsulated in closed cell polyurethane spray foam insulation. This Measure Guideline covers the technical aspects of BEDs as well as the advantages, disadvantages, and risks of BEDs compared to other alternative strategies. This guideline also provides detailed guidance on installation of BEDs strategies in new and existing homes through step-by-step installation procedures. Some of the procedures presented here, however,more » require specialized equipment or expertise. In addition, some alterations to duct systems may require a specialized license.« less

Encapsulation of ZnO particles by metal fluorides: Towards an application as transparent insulating coatings for windows

NASA Astrophysics Data System (ADS)

Trenque, Isabelle; Mornet, Stéphane; Duguet, Etienne; Majimel, Jérôme; Brüll, Annelise; Teinz, Katharina; Kemnitz, Erhard; Gaudon, Manuel

2013-01-01

Because ZnO is a promising candidate for getting efficient films or varnishes with thermal insulating abilities for windows applications, the effect of the encapsulation of ZnO particles in shells of low refractive index material on the improvement of the visible light transmission was investigated. ZnO-MgF2 core-shell particles were synthesized by deposition of fluoride sols on ZnO particles through a vacuum slip casting process like. The transmission behaviours were first indirectly studied by diffuse reflexion measurements on powder beds. Then, particle films were elaborated by a screen printing process which ensured direct transmission measurements. The encapsulation of ZnO particles with a coating shell of 1.3 wt.% of MgF2 improves the visible light transmission of 32%.

Insulin-secreting non-islet cells are resistant to autoimmune destruction.

PubMed Central

Lipes, M A; Cooper, E M; Skelly, R; Rhodes, C J; Boschetti, E; Weir, G C; Davalli, A M

1996-01-01

Transgenic nonobese diabetic mice were created in which insulin expression was targeted to proopiomelanocortin-expressing pituitary cells. Proopiomelanocortin-expressing intermediate lobe pituitary cells efficiently secrete fully processed, mature insulin via a regulated secretory pathway, similar to islet beta cells. However, in contrast to the insulin-producing islet beta cells, the insulin-producing intermediate lobe pituitaries are not targeted or destroyed by cells of the immune system. Transplantation of the transgenic intermediate lobe tissues into diabetic nonobese diabetic mice resulted in the restoration of near-normoglycemia and the reversal of diabetic symptoms. The absence of autoimmunity in intermediate lobe pituitary cells engineered to secrete bona fide insulin raises the potential of these cell types for beta-cell replacement therapy for the treatment of insulin-dependent diabetes mellitus. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8710916

In Vitro Co-Delivery Evaluation of Novel Pegylated Nano-Liposomal Herbal Drugs of Silibinin and Glycyrrhizic Acid (Nano-Phytosome) to Hepatocellular Carcinoma Cells

PubMed Central

Ochi, Mohammad Mahdi; Amoabediny, Ghasem; Rezayat, Seyed Mahdi; Akbarzadeh, Azim; Ebrahimi, Bahman

2016-01-01

Objective This study aimed to evaluate a co-encapsulated pegylated nano-liposome system based on two herbal anti-tumor drugs, silibinin and glycyrrhizic acid, for delivery to a hepatocellular carcinoma (HCC) cell line (HepG2). Materials and Methods In this experimental study, co-encapsulated nano-liposomes by the thin layer film hydration method with HEPES buffer and sonication at 60% amplitude. Liposomes that co-encapsulated silibinin and glycyrrhizic acid were prepared with a specified molar ratio of dipalmitoylphosphatidylcholine (DPPC), cholesterol (CHOL), and methoxy-polyethylene glycol 2000 (PEG2000)–derived distearoyl phosphatidylethanolamine (mPEG2000-DSPE). We used the MTT technique to assess cytotoxicity for various concentrations of co-encapsulated nano-liposomes, free silibinin (25% w/v) and glycyrrhizic acid (75% w/v) on HepG2 and fibroblast cell lines over a 48-hour period. Results Formulation of pegylated nano-liposomes showed a narrow size distribution with an average diameter of 46.3 nm. The encapsulation efficiency (EE) for silibinin was 24.37%, whereas for glycyrrhizic acid it was 68.78%. Results of in vitro cytotoxicity showed significantly greater co-encapsulated nano-liposomes on the HepG2 cell line compared to the fibroblast cell line. The half maximal inhibitory concentration (IC50) for co-encapsulated pegylated nanoliposomal herbal drugs was 48.68 µg/ml and free silibinin with glycyrrhizic acid was 485.45 µg/ml on the HepG2 cell line. Conclusion This in vitro study showed that nano-liposome encapsulation of silibinin with glycyrrhizic acid increased the biological activity of free drugs, increased the stability of silibinin, and synergized the therapeutic effect of silibinin with glycyrrhizic acid. The IC50 of the co-encapsulated nano-liposomes was lower than the combination of free silibinin and glycyrrhizic acid on the HepG2 cell line. PMID:27540518

Efficiency improvement of GaN-on-silicon thin-film light-emitting diodes with optimized via-like n-electrodes

NASA Astrophysics Data System (ADS)

Feng, Bo; Deng, Biao; Fu, Yi; Liu, Le Gong; Li, Zeng Cheng; Feng, Mei Xin; Zhao, Han Min; Sun, Qian

2017-07-01

This work reports a significant improvement in efficiency by optimizing the via-like n-electrode architecture design of a GaN-based thin-film LED grown on a 6-inch silicon substrate. The external quantum efficiency of the as-fabricated 1.1 mm × 1.1 mm via-thin-film LED chip at 350 mA was increased by 11.3% compared to that of a vertical thin-film LED chip with a conventional finger-like n-electrode. Detailed analysis of encapsulation gain and false color emission patterns illustrated that the significantly improved LED performance was due to enhanced light extraction efficiency and more uniform current spreading, both of which can be attributed to the optimized via-thin-film chip structure. Minimizing the light loss at the periphery of the Ag mirror was demonstrated to be a critical factor for improving light extraction, rather than simply replacing the finger-like n-electrodes with via-like ones. After encapsulation, the median blue lamp power and the wall-plug efficiency of the via-thin-film LED at 350 mA reached 659 mW and 63.7%, respectively.

C-Peptide Is a Sensitive Indicator for the Diagnosis of Metabolic Syndrome in Subjects from Central Mexico.

PubMed

Gonzalez-Mejia, M Elba; Porchia, Leonardo M; Torres-Rasgado, Enrique; Ruiz-Vivanco, Guadalupe; Pulido-Pérez, Patricia; Báez-Duarte, Blanca G; Pérez-Fuentes, Ricardo

2016-05-01

Metabolic Syndrome (MetS) is associated with elevated risk for developing diabetes and cardiovascular disease. A key component of MetS is the development of insulin resistance (IR). The homeostatic model assessment (HOMA) model can determine IR by using insulin or C-peptide concentrations; however, the efficiency of insulin and C-peptide to determine MetS has not been compared. The aim of the study was to compare the efficiency of C-peptide and insulin to determine MetS in Mexicans. Anthropometrics, glucose, insulin, C-peptide, triglycerides, and high-density lipoproteins were determined in 156 nonpregnant females and 114 males. Subjects were separated into normal or positive for MetS. IR was determined by the HOMA2 calculator using insulin or C-peptide. Correlations were calculated using the Spearman correlation coefficient (ρ). Differences between correlations were determined by calculating Steiger's Z. The sensitivity was determined by the area under receiver operating characteristics curve (AUC) analysis. Independent of the MetS definition [Adult Treatment Panel III (ATP III), International Diabetes Federation (IDF), or World Health Organization (WHO)], C-peptide and insulin were significantly higher in MetS subjects (P < 0.05). C-peptide and insulin correlated with all components of MetS; however, for waist circumference, waist-to-hip ratio, and fasting plasma glucose, C-peptide correlated better than insulin (P < 0.05). Moreover, C-peptide (AUC = 0.72-0.78) was a better marker than insulin (AUC = 0.62-0.72) for MetS (P < 0.05). Finally, HOMA2-IR calculated with C-peptide (AUC = 0.80-0.84) was more accurate than HOMA2-IR calculated with insulin (AUC = 0.68-0.75, P < 0.05) at determining MetS. C-peptide is a strong indicator of MetS. Since C-peptide has recently emerged as a biomolecule with significant importance for inflammatory diseases, monitoring C-peptide levels will aid clinicians in preventing MetS.

Encapsulation of grape seed extract in polylactide microcapsules for sustained bioactivity and time-dependent release in dental material applications.

PubMed

Yourdkhani, Mostafa; Leme-Kraus, Ariene Arcas; Aydin, Berdan; Bedran-Russo, Ana Karina; White, Scott R

2017-06-01

To sustain the bioactivity of proanthocyanidins-rich plant-derived extracts via encapsulation within biodegradable polymer microcapsules. Polylactide microcapsules containing grape seed extract (GSE) were manufactured using a combination of double emulsion and solvent evaporation techniques. Microcapsule morphology, size distribution, and cross-section were examined via scanning electron microscopy. UV-vis measurements were carried out to evaluate the core loading and encapsulation efficiency of microcapsules. The bioactivity of extracts was evaluated after extraction from capsules via solvent partitioning one week or one year post-encapsulation process. Fifteen human molars were cut into 7mm×1.7mm×0.5mm thick mid-coronal dentin beams, demineralized, and treated with either encapsulated GSE, pristine GSE, or left untreated. The elastic modulus of dentin specimens was measured based on three-point bending experiments as an indirect assessment of the bioactivity of grape seed extracts. The effects of the encapsulation process and storage time on the bioactivity of extracts were analyzed. Polynuclear microcapsules with average diameter of 1.38μm and core loading of up to 38wt% were successfully manufactured. There were no statistically significant differences in the mean fold increase of elastic modulus values among the samples treated with encapsulated or pristine GSE (p=0.333), or the storage time (one week versus one year storage at room temperature, p=0.967). Polynuclear microcapsules containing proanthocyanidins-rich plant-derived extracts were prepared. The bioactivity of extracts was preserved after microencapsulation. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Calcium phosphate cement chamber as an immunoisolative device for bioartificial pancreas: in vitro and preliminary in vivo study.

PubMed

Yang, Kai-Chiang; Wu, Chang-Chin; Sumi, Shoichiro; Tseng, Ching-Li; Wu, Yueh-Hsiu Steven; Kuo, Tzong-Fu; Lin, Feng-Huei

2010-05-01

This study examined a calcium phosphate cement (CPC) chamber as an immunoisolative device to facilitate the use of xenogeneic cell sources without immunosuppression for the bioartificial pancreas (BAP). Mouse insulinoma cells were encapsulated in agarose gel and then enclosed in a CPC chamber to create a BAP. Bioartificial pancreas were evaluated by cell viability, live-dead cell ratio, and cytokine-mediated cytotoxicity assay and implanted into the peritoneal cavity of diabetic rats. Nonfasting blood glucose and serum insulin levels were analyzed perioperatively; BAPs were also retrieved for histological examination. Insulinoma cells enclosed in the CPC chamber had normal viability, cell survival, and insulin secretion that was even cultured in media with cytokines. The nonfasting blood glucose level of rats was decreased from 460 +/- 50 to 132 +/- 43 mg/dL and maintained euglycemia for 22 days; serum insulin level was increased from 0.34 +/- 0.11 to 1.43 +/- 0.30 microg/dL after operation. Histological examination revealed the fibrous tissue envelopment, and immune-related cells that competed for oxygen resulting in hypoxia could be attributed to the dysfunction of BAPs. This study proved the feasibility for using a CPC chamber as an immunoisolative device for the BAP. An alternative implanted site should be considered to extend the functional longevity of BAPs in further study.

Paclitaxel loaded folic acid targeted nanoparticles of mixed lipid-shell and polymer-core: in vitro and in vivo evaluation.

PubMed

Zhao, Peiqi; Wang, Hanjie; Yu, Man; Liao, Zhenyu; Wang, Xianhuo; Zhang, Fei; Ji, Wei; Wu, Bing; Han, Jinghua; Zhang, Haichang; Wang, Huaqing; Chang, Jin; Niu, Ruifang

2012-06-01

A functional drug carrier comprised of folic acid modified lipid-shell and polymer-core nanoparticles (FLPNPs) including poly(D,L-lactide-co-glycolide) (PLGA) core, PEGylated octadecyl-quaternized lysine modified chitosan (PEG-OQLCS) as lipid-shell, folic acid as targeting ligand and cholesterol was prepared and evaluated for targeted delivery of paclitaxel (PTX). Confocal microscopy analysis confirmed the coating of the lipid-shell on the polymer-core. Physicochemical characterizations of FLPNPs, such as particle size, zeta potential, morphology, encapsulation efficiency, and in vitro PTX release, were also evaluated. The internalization efficiency and targeting ability of FLPNPs were demonstrated by flow cytometry and confocal microscopy. PTX loaded FLPNPs showed a significantly higher cytotoxicity than the commercial PTX formulation (Taxol®). The intravenous administration of PTX encapsulated FLPNPs led to tumor regression and improvement of animal survival in a murine model, compared with that observed with Taxol® and biodistribution study showed that PTX concentration in tumor for PTX encapsulated FLPNPs was higher than other PTX formulations. Our data indicate that PTX loaded FLPNPs are a promising nano-sized drug formulation for cancer therapy. Copyright © 2012 Elsevier B.V. All rights reserved.

Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids.

PubMed

Karandish, Fataneh; Haldar, Manas K; You, Seungyong; Brooks, Amanda E; Brooks, Benjamin D; Guo, Bin; Choi, Yongki; Mallik, Sanku

2016-11-30

Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-independent prostate cancer, and mocetinostat is a potent inhibitor of class I histone deacetylases. In this study, we prepared reduction-sensitive polymersomes presenting folic acid on the surface and encapsulating either docetaxel or mocetinostat. The presence of folic acid allowed efficient targeting of the PSMA receptor and subsequent internalization of the polymeric vesicles in cultured LNCaP prostate cancer cell spheroids. The intracellular reducing agents efficiently released docetaxel and mocetinostat from the polymersomes. The combination of the two drug-encapsulated polymersome formulations significantly ( p < 0.05) decreased the viability of the LNCaP cells (compared to free drugs or control) in three-dimensional spheroid cultures. The calculated combination index value indicated a synergistic effect for the combination of mocetinostat and docetaxel. Thus, our PSMA-targeted drug-encapsulated polymersomes has the potential to lead to a new direction in prostate cancer therapy that decreases the toxicity and increases the efficacy of the drug delivery systems.

Prostate-Specific Membrane Antigen Targeted Polymersomes for Delivering Mocetinostat and Docetaxel to Prostate Cancer Cell Spheroids

PubMed Central

2016-01-01

Prostate cancer cells overexpress the prostate-specific membrane antigen (PSMA) receptors on the surface. Targeting the PSMA receptor creates a unique opportunity for drug delivery. Docetaxel is a Food and Drug Administration-approved drug for treating metastatic and androgen-independent prostate cancer, and mocetinostat is a potent inhibitor of class I histone deacetylases. In this study, we prepared reduction-sensitive polymersomes presenting folic acid on the surface and encapsulating either docetaxel or mocetinostat. The presence of folic acid allowed efficient targeting of the PSMA receptor and subsequent internalization of the polymeric vesicles in cultured LNCaP prostate cancer cell spheroids. The intracellular reducing agents efficiently released docetaxel and mocetinostat from the polymersomes. The combination of the two drug-encapsulated polymersome formulations significantly (p < 0.05) decreased the viability of the LNCaP cells (compared to free drugs or control) in three-dimensional spheroid cultures. The calculated combination index value indicated a synergistic effect for the combination of mocetinostat and docetaxel. Thus, our PSMA-targeted drug-encapsulated polymersomes has the potential to lead to a new direction in prostate cancer therapy that decreases the toxicity and increases the efficacy of the drug delivery systems. PMID:27917408

Dorzolamide Loaded Niosomal Vesicles: Comparison of Passive and Remote Loading Methods.

PubMed

Hashemi Dehaghi, Mohadeseh; Haeri, Azadeh; Keshvari, Hamid; Abbasian, Zahra; Dadashzadeh, Simin

2017-01-01

Glaucoma is a common progressive eye disorder and the treatment strategies will benefit from nanoparticulate delivery systems with high drug loading and sustained delivery of intraocular pressure lowering agents. Niosomes have been reported as a novel approach to improve drug low corneal penetration and bioavailability characteristics. Along with this, poor entrapment efficiency of hydrophilic drug in niosomal formulation remains as a major formulation challenge. Taking this perspective into consideration, dorzolamide niosomes were prepared employing two different loading methodologies (passive and remote loading methods) and the effects of various formulation variables (lipid to drug ratio, cholesterol percentage, drug concentration, freeze/thaw cycles, TPGS content, and external and internal buffer molarity and pH) on encapsulation efficiency were assessed. Encapsulation of dorzolamide within niosomes increased remarkably by the incorporation of higher cholesterol percentage as well as increasing the total lipid concentration. Remote loading method showed higher efficacy for drug entrapment compared to passive loading technique. Incorporation of TPGS in bilayer led to decrease in EE; however, retarded drug release rate. Scanning electron microscopy (SEM) studies confirmed homogeneous particle distribution, and spherical shape with smooth surface. In conclusion, the highest encapsulation can be obtained using phosphate gradient method and 50% cholesterol in Span 60 niosomal formulation.

Electrosprayed nanoparticle delivery system for controlled release.

PubMed

Eltayeb, Megdi; Stride, Eleanor; Edirisinghe, Mohan; Harker, Anthony

2016-09-01

This study utilises an electrohydrodynamic technique to prepare core-shell lipid nanoparticles with a tunable size and high active ingredient loading capacity, encapsulation efficiency and controlled release. Using stearic acid and ethylvanillin as model shell and active ingredients respectively, we identify the processing conditions and ratios of lipid:ethylvanillin required to form nanoparticles. Nanoparticles with a mean size ranging from 60 to 70nm at the rate of 1.37×10(9) nanoparticles per minute were prepared with different lipid:ethylvanillin ratios. The polydispersity index was ≈21% and the encapsulation efficiency ≈70%. It was found that the rate of ethylvanillin release was a function of the nanoparticle size, and lipid:ethylvanillin ratio. The internal structure of the lipid nanoparticles was studied by transmission electron microscopy which confirmed that the ethylvanillin was encapsulated within a stearic acid shell. Fourier transform infrared spectroscopy analysis indicated that the ethylvanillin had not been affected. Extensive analysis of the release of ethylvanillin was performed using several existing models and a new diffusive release model incorporating a tanh function. The results were consistent with a core-shell structure. Copyright © 2016 Elsevier B.V. All rights reserved.

Optimising the synthesis, polymer membrane encapsulation and photoreduction performance of Ru(II)- and Ir(III)-bis(terpyridine) cytochrome c bioconjugates.

PubMed

Hvasanov, David; Mason, Alexander F; Goldstein, Daniel C; Bhadbhade, Mohan; Thordarson, Pall

2013-07-28

Ruthenium(II) and iridium(III) bis(terpyridine) complexes were prepared with maleimide functionalities in order to site-specifically modify yeast iso-1 cytochrome c possessing a single cysteine residue available for modification (CYS102). Single X-ray crystal structures were solved for aniline and maleimide Ru(II) 3 and Ru(II) 4, respectively, providing detailed structural detail of the complexes. Light-activated bioconjugates prepared from Ru(II) 4 in the presence of tris(2-carboxyethyl)-phosphine (TCEP) significantly improved yields from 6% to 27%. Photoinduced electron transfer studies of Ru(II)-cyt c in bulk solution and polymer membrane encapsulated specimens were performed using EDTA as a sacrificial electron donor. It was found that membrane encapsulation of Ru(II)-cyt c in PS140-b-PAA48 resulted in a quantum efficiency of 1.1 ± 0.3 × 10(-3), which was a two-fold increase relative to the bulk. Moreover, Ir(III)-cyt c bioconjugates showed a quantum efficiency of 3.8 ± 1.9 × 10(-1), equivalent to a ∼640-fold increase relative to bulk Ru(II)-cyt c.

Common elements in interleukin 4 and insulin signaling pathways in factor-dependent hematopoietic cells.

PubMed

Wang, L M; Keegan, A D; Li, W; Lienhard, G E; Pacini, S; Gutkind, J S; Myers, M G; Sun, X J; White, M F; Aaronson, S A

1993-05-01

Interleukin 4 (IL-4), insulin, and insulin-like growth factor I (IGF-I) efficiently induced DNA synthesis in the IL-3-dependent murine myeloid cell lines FDC-P1 and FDC-P2. Although these factors could not individually sustain long-term growth of these lines, a combination of IL-4 with either insulin or IGF-I did support continuous growth. The principal tyrosine-phosphorylated substrate observed in FDC cells stimulated with IL-4, previously designated 4PS, was of the same size (170 kDa) as the major substrate phosphorylated in response to insulin or IGF-I. These substrates had phosphopeptides of the same size when analyzed by digestion with Staphylococcus aureus V8 protease, and each tightly associated with the 85-kDa component of phosphatidylinositol 3-kinase after factor stimulation. IRS-1, the principal substrate phosphorylated in response to insulin or IGF-I stimulation in nonhematopoietic cells, is similar in size to 4PS. However, anti-IRS-1 antibodies failed to efficiently precipitate 4PS, and some phosphopeptides generated by V8 protease digestion of IRS-1 were distinct in size from the phosphopeptides of 4PS. Nevertheless, IL-4, insulin, and IGF-I were capable of stimulating tyrosine phosphorylation of IRS-1 in FDC cells that expressed this substrate as a result of transfection. These findings indicate that (i) IL-4, insulin, and IGF-I use signal transduction pathways in FDC lines that have at least one major feature in common, the rapid tyrosine phosphorylation of 4PS, and (ii) insulin and IGF-I stimulation of hematopoietic cell lines leads to the phosphorylation of a substrate that may be related to but is not identical to IRS-1.

Common elements in interleukin 4 and insulin signaling pathways in factor-dependent hematopoietic cells.

PubMed Central

Wang, L M; Keegan, A D; Li, W; Lienhard, G E; Pacini, S; Gutkind, J S; Myers, M G; Sun, X J; White, M F; Aaronson, S A

1993-01-01

Interleukin 4 (IL-4), insulin, and insulin-like growth factor I (IGF-I) efficiently induced DNA synthesis in the IL-3-dependent murine myeloid cell lines FDC-P1 and FDC-P2. Although these factors could not individually sustain long-term growth of these lines, a combination of IL-4 with either insulin or IGF-I did support continuous growth. The principal tyrosine-phosphorylated substrate observed in FDC cells stimulated with IL-4, previously designated 4PS, was of the same size (170 kDa) as the major substrate phosphorylated in response to insulin or IGF-I. These substrates had phosphopeptides of the same size when analyzed by digestion with Staphylococcus aureus V8 protease, and each tightly associated with the 85-kDa component of phosphatidylinositol 3-kinase after factor stimulation. IRS-1, the principal substrate phosphorylated in response to insulin or IGF-I stimulation in nonhematopoietic cells, is similar in size to 4PS. However, anti-IRS-1 antibodies failed to efficiently precipitate 4PS, and some phosphopeptides generated by V8 protease digestion of IRS-1 were distinct in size from the phosphopeptides of 4PS. Nevertheless, IL-4, insulin, and IGF-I were capable of stimulating tyrosine phosphorylation of IRS-1 in FDC cells that expressed this substrate as a result of transfection. These findings indicate that (i) IL-4, insulin, and IGF-I use signal transduction pathways in FDC lines that have at least one major feature in common, the rapid tyrosine phosphorylation of 4PS, and (ii) insulin and IGF-I stimulation of hematopoietic cell lines leads to the phosphorylation of a substrate that may be related to but is not identical to IRS-1. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7683417

Block versus Random Amphiphilic Glycopolymer Nanopaticles as Glucose-Responsive Vehicles.

PubMed

Guo, Qianqian; Zhang, Tianqi; An, Jinxia; Wu, Zhongming; Zhao, Yu; Dai, Xiaomei; Zhang, Xinge; Li, Chaoxing

2015-10-12

To explore the effect of polymer structure on their self-assembled aggregates and their unique characteristics, this study was devoted to developing a series of amphiphilic block and random phenylboronic acid-based glycopolymers by RAFT polymerization. The amphiphilic glycopolymers were successfully self-assembled into spherically shaped nanoparticles with narrow size distribution in aqueous solution. For block and random copolymers with similar monomer compositions, block copolymer nanoparticles exhibited a more regular transmittance change with the increasing glucose level, while a more evident variation of size and quicker decreasing tendency in I/I0 behavior in different glucose media were observed for random copolymer nanoparticles. Cell viability of all the polymer nanoparticles investigated by MTT assay was higher than 80%, indicating that both block and random copolymers had good cytocompatibility. Insulin could be encapsulated into both nanoparticles, and insulin release rate for random glycopolymer was slightly quicker than that for the block ones. We speculate that different chain conformations between block and random glycopolymers play an important role in self-assembled nanoaggregates and underlying glucose-sensitive behavior.

Preparation of non-porous microspheres with high entrapment efficiency of proteins by a (water-in-oil)-in-oil emulsion technique.

PubMed

Viswanathan, N B; Thomas, P A; Pandit, J K; Kulkarni, M G; Mashelkar, R A

1999-03-08

Emulsification-solvent removal methods have been widely used for encapsulating bioactive macromolecules like proteins and polypeptides in biodegradable polymers. We report, a (water-in-oil)-in-oil emulsion technique wherein proteins and polypeptides differing in molecular weight and shape were encapsulated in polymers of current biomedical interest. When an oil was used as the processing medium in combination with a carefully selected mixed solvent system such that a stable (w/o1/o2 emulsion is formed and solvents are removed by a combination of extraction and evaporation, the entrapment efficiency was high and the product nonporous. The entrapment efficiency of globular proteins exceeded 90% while that of fibrous proteins was around 70%. Fracture studies revealed that the polymer matrix was dense. The mechanism of entrapment involved solvent-induced precipitation of the protein as the microspheres were being formed. The principle of the method will find use in preparation of non-porous polymer microparticles with reduced burst effect.

Preparation of astaxanthin-loaded DNA/chitosan nanoparticles for improved cellular uptake and antioxidation capability.

PubMed

Wang, Qian; Zhao, Yingyuan; Guan, Lei; Zhang, Yaping; Dang, Qifeng; Dong, Ping; Li, Jing; Liang, Xingguo

2017-07-15

DNA/chitosan co-assemblies were initially used as nanocarriers for efficient astaxanthin encapsulation and delivery. The obtained astaxanthin-loaded DNA/chitosan (ADC) colloidal system was transparent and homogenous, with astaxanthin content up to 65μg/ml. Compared to free astaxanthin, ADC nanoparticles with an astaxanthin concentration as low as 3.35nM still showed a more powerful cytoprotective effect on H 2 O 2 -induced oxidative cell damage, and improved cell viability from 49.9% to 61.9%. The ROS scavenging efficiency of ADC nanoparticles was as high as 54.3%, which was 2-fold higher than that of free astaxanthin. Besides this, ADC nanoparticles were easily engulfed by Caco-2 cells in a short time, indicating that the encapsulated astaxanthin could be absorbed through endocytosis by intestinal epithelial cells. The improved antioxidation capability and facilitated cellular uptake enabled the ADC nanoparticles to be good candidates for efficient delivery and absorption of astaxanthin. Copyright © 2017 Elsevier Ltd. All rights reserved.

PLA-PEG-PLA copolymer-based polymersomes as nanocarriers for delivery of hydrophilic and hydrophobic drugs: preparation and evaluation with atorvastatin and lisinopril.

PubMed

Danafar, H; Rostamizadeh, K; Davaran, S; Hamidi, M

2014-10-01

Tri-block poly(lactide)-poly(ethylene glycol)-poly(lactide) (PLA-PEG-PLA) copolymers were synthesized and used to prepare polymersomes loaded separately by the hydrophobic and hydrophilic model drugs, atorvastatin and lisinopril, respectively. The resulting nanostructures were characterized by various techniques such as FTIR, DSC, PCS and AFM. The polymersomes exhibited high encapsulation efficiencies of almost 78% and 70.8% for atorvastatin and lisinopril, respectively. Investigation on FTIR and DSC results revealed that such a high encapsulation efficiency is due to strong interaction between atorvastatin and the copolymer. The impact of drug/copolymer ratio and copolymer composition on drug-loading efficiency and drug release behavior were also studied. The results showed that in case of lisinopril, polymersomes exhibited a triphasic drug release, while for atorvastatin a biphasic release profile was obtained. Overall, the results indicated that PLA-PEG-PLA polymersomes can be considered as a promising carrier for both hydrophilic and hydrophobic drugs.

Iron complexation to histone deacetylase inhibitors SAHA and LAQ824 in PEGylated liposomes can considerably improve pharmacokinetics in rats.

PubMed

Wang, Yan; Tu, Sheng; Steffen, Dana; Xiong, May

2014-01-01

The formulation of histone deacetylase inhibitors (HDACi) is challenging due to poor water solubility and rapid elimination of drugs in vivo. This study investigated the effects of complexing iron (Fe3+) to the HDACi suberoylanilide hydroxamic acid (SAHA) and LAQ824 (LAQ) prior to their encapsulation into PEGylated liposomes, and investigated whether this technique could improve drug solubility, in vitro release and in vivo pharmacokinetic (PK) properties. METHODS. The reaction stoichiometry, binding constants and solubility were measured for Fe complexes of SAHA and LAQ. The complexes were passively encapsulated into PEGylated liposomes and characterized by size distribution, zeta-potential, encapsulation efficiency (EE), and in vitro drug release studies. PC-3 cells were used to verify the in vitro anticancer activity of the formulations. In vivo pharmacokinetic properties of liposomal LAQ-Fe (L-LAQ-Fe) was evaluated in rats. RESULTS. SAHA and LAQ form complexes with Fe at 1:1 stoichiometric ratio, with a binding constant on the order of 104 M-1. Fe complexation improved the aqueous solubility and the liposomal encapsulation efficiency of SAHA and LAQ (29-35% EE, final drug concentration > 1 mM). Liposomal encapsulated complexes (L-HDACi-Fe) exhibited sustained in vitro release properties compared to L-HDACi but cytotoxicity on PC-3 cells was comparable to free drugs. The PK of L-LAQ-Fe revealed 15-fold improvement in the plasma t1/2 (12.11 h)and 211-fold improvement in the AUC∞ (105.7 µg·h/ml) compared to free LAQ (0.79 h, 0.5 µg·h/ml). Similarly, the plasma t1/2 of Fe was determined to be 11.83 h in a separate experiment using radioactive Fe-59. The majority of Fe-59 activity was found in liver and spleen of rats and correlates with liposomal uptake by the mononuclear phagocyte system. CONCLUSIONS. We have demonstrated that encapsulation of Fe complexes of HDACi into PEGylated liposomes can improve overall drug aqueous solubility, in vitro release and in vivo pharmacokinetic properties.

Iron Complexation to Histone Deacetylase Inhibitors SAHA and LAQ824 in PEGylated Liposomes Can Considerably Improve Pharmacokinetics in Rats

PubMed Central

Wang, Yan; Tu, Sheng; Steffen, Dana; Xiong, May P.

2015-01-01

PURPOSE The formulation of histone deacetylase inhibitors (HDACi) is challenging due to poor water solubility and rapid elimination of drugs in vivo. This study investigated the effects of complexing iron (Fe3+) to the HDACi suberoylanilide hydroxamic acid (SAHA) and LAQ824 (LAQ) prior to their encapsulation into PEGylated liposomes, and investigated whether this technique could improve drug solubility, in vitro release and in vivo pharmacokinetic (PK) properties. METHODS The reaction stoichiometry, binding constants and solubility were measured for Fe complexes of SAHA and LAQ. The complexes were passively encapsulated into PEGylated liposomes and characterized by size distribution, zeta-potential, encapsulation efficiency (EE), and in vitro drug release studies. PC-3 cells were used to verify the in vitro anticancer activity of the formulations. In vivo pharmacokinetic properties of liposomal LAQ-Fe (L-LAQ-Fe) was evaluated in rats. RESULTS SAHA and LAQ form complexes with Fe at 1:1 stoichiometric ratio, with a binding constant on the order of 104 M−1. Fe complexation improved the aqueous solubility and the liposomal encapsulation efficiency of SAHA and LAQ (29–35% EE, final drug concentration > 1 mM). Liposomal encapsulated complexes (L-HDACi-Fe) exhibited sustained in vitro release properties compared to L-HDACi but cytotoxicity on PC-3 cells was comparable to free drugs. The PK of L-LAQ-Fe revealed 15-fold improvement in the plasma t1/2 (12.11 h) and 211-fold improvement in the AUC∞ (105.7 μg·h/ml) compared to free LAQ (0.79 h, 0.5 μg·h/ml). Similarly, the plasma t1/2 of Fe was determined to be 11.83 h in a separate experiment using radioactive Fe-59. The majority of Fe-59 activity was found in liver and spleen of rats and correlates with liposomal uptake by the mononuclear phagocyte system. CONCLUSIONS We have demonstrated that encapsulation of Fe complexes of HDACi into PEGylated liposomes can improve overall drug aqueous solubility, in vitro release and in vivo pharmacokinetic properties. PMID:25579435

Deficiency of a beta-arrestin-2 signal complex contributes to insulin resistance.

PubMed

Luan, Bing; Zhao, Jian; Wu, Haiya; Duan, Baoyu; Shu, Guangwen; Wang, Xiaoying; Li, Dangsheng; Jia, Weiping; Kang, Jiuhong; Pei, Gang

2009-02-26

Insulin resistance, a hallmark of type 2 diabetes, is a defect of insulin in stimulating insulin receptor signalling, which has become one of the most serious public health threats. Upon stimulation by insulin, insulin receptor recruits and phosphorylates insulin receptor substrate proteins, leading to activation of the phosphatidylinositol-3-OH kinase (PI(3)K)-Akt pathway. Activated Akt phosphorylates downstream kinases and transcription factors, thus mediating most of the metabolic actions of insulin. Beta-arrestins mediate biological functions of G-protein-coupled receptors by linking activated receptors with distinct sets of accessory and effecter proteins, thereby determining the specificity, efficiency and capacity of signals. Here we show that in diabetic mouse models, beta-arrestin-2 is severely downregulated. Knockdown of beta-arrestin-2 exacerbates insulin resistance, whereas administration of beta-arrestin-2 restores insulin sensitivity in mice. Further investigation reveals that insulin stimulates the formation of a new beta-arrestin-2 signal complex, in which beta-arrestin-2 scaffolds Akt and Src to insulin receptor. Loss or dysfunction of beta-arrestin-2 results in deficiency of this signal complex and disturbance of insulin signalling in vivo, thereby contributing to the development of insulin resistance and progression of type 2 diabetes. Our findings provide new insight into the molecular pathogenesis of insulin resistance, and implicate new preventive and therapeutic strategies against insulin resistance and type 2 diabetes.

Assessment of myocardial metabolic flexibility and work efficiency in human type 2 diabetes using 16-[18F]fluoro-4-thiapalmitate, a novel PET fatty acid tracer

PubMed Central

Hutchins, G. D.; Perry, K.; Territo, W.; Chisholm, R.; Acton, A.; Glick-Wilson, B.; Considine, R. V.; Moberly, S.; DeGrado, T. R.

2015-01-01

Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human type 2 diabetes mellitus (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation {16-[18F]fluoro-4-thia-palmitate (FTP)} and myocardial perfusion and total oxidation ([11C]acetate). Participants underwent paired studies under fasting conditions, comparing 3-h insulin + glucose euglycemic clamp conditions (120 mU·m−2·min−1) to 3-h saline infusion. Lean controls (n = 10) were compared with glycemically controlled volunteers with T2DM (n = 8). Insulin augmented heart rate, blood pressure, and stroke index in both groups (all P < 0.01) and significantly increased myocardial oxygen consumption (P = 0.04) and perfusion (P = 0.01) in both groups. Insulin suppressed available nonesterified fatty acids (P < 0.0001), but fatty acid concentrations were higher in T2DM under both conditions (P < 0.001). Insulin-induced suppression of fatty acid oxidation was seen in both groups (P < 0.0001). However, fatty acid oxidation rates were higher under both conditions in T2DM (P = 0.003). Myocardial work efficiency was lower in T2DM (P = 0.006) and decreased in both groups with the insulin-induced increase in work and shift in fuel utilization (P = 0.01). Augmented fatty acid oxidation is present under baseline and insulin-treated conditions in T2DM, with impaired insulin-induced shifts away from fatty acid oxidation. This is accompanied by reduced work efficiency, possibly due to greater oxygen consumption with fatty acid metabolism. These observations suggest that improved fatty acid suppression, or reductions in myocardial fatty acid uptake and retention, could be therapeutic targets to improve myocardial ischemia tolerance in T2DM. PMID:26732686

Assessment of myocardial metabolic flexibility and work efficiency in human type 2 diabetes using 16-[18F]fluoro-4-thiapalmitate, a novel PET fatty acid tracer.

PubMed

Mather, K J; Hutchins, G D; Perry, K; Territo, W; Chisholm, R; Acton, A; Glick-Wilson, B; Considine, R V; Moberly, S; DeGrado, T R

2016-03-15

Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human type 2 diabetes mellitus (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation {16-[(18)F]fluoro-4-thia-palmitate (FTP)} and myocardial perfusion and total oxidation ([(11)C]acetate). Participants underwent paired studies under fasting conditions, comparing 3-h insulin + glucose euglycemic clamp conditions (120 mU·m(-2)·min(-1)) to 3-h saline infusion. Lean controls (n = 10) were compared with glycemically controlled volunteers with T2DM (n = 8). Insulin augmented heart rate, blood pressure, and stroke index in both groups (all P < 0.01) and significantly increased myocardial oxygen consumption (P = 0.04) and perfusion (P = 0.01) in both groups. Insulin suppressed available nonesterified fatty acids (P < 0.0001), but fatty acid concentrations were higher in T2DM under both conditions (P < 0.001). Insulin-induced suppression of fatty acid oxidation was seen in both groups (P < 0.0001). However, fatty acid oxidation rates were higher under both conditions in T2DM (P = 0.003). Myocardial work efficiency was lower in T2DM (P = 0.006) and decreased in both groups with the insulin-induced increase in work and shift in fuel utilization (P = 0.01). Augmented fatty acid oxidation is present under baseline and insulin-treated conditions in T2DM, with impaired insulin-induced shifts away from fatty acid oxidation. This is accompanied by reduced work efficiency, possibly due to greater oxygen consumption with fatty acid metabolism. These observations suggest that improved fatty acid suppression, or reductions in myocardial fatty acid uptake and retention, could be therapeutic targets to improve myocardial ischemia tolerance in T2DM. Copyright © 2016 the American Physiological Society.

[Cyanidin-3-glucoside attenuates body weight gain, serum lipid concentrations and insulin resistance in high-fat diet-induced obese rats].

PubMed

Yu, Ren-Qiang; Wu, Xiao-You; Zhou, Xiang; Zhu, Jing; Ma, Lu-Yi

2014-05-01

Cyanidin-3-glucoside (C3G) is the main active ingredient of anthocyanidin. This study aimed to evaluate the effects of C3G on body weight gain, visceral adiposity, lipid profiles and insulin resistance in high-fat diet-induced obese rats. Thirty male Sprague-Dawley rats were randomly divided into a control group (n=8) and a high fat diet group (n=22), and were fed with standard diet or high fat diet. Five weeks later, 17 high-fat diet-induced obese rats were randomly given C3G [100 mg/(kg·d)] or normal saline via intragastric administration for 5 weeks. Five weeks later, body weight, visceral adiposity and food intake were measured. Blood samples were collected for detecting fasting glucose, serum insulin, lipid profiles and adiponectin. Insulin resistance index, atherosclerosis index and average feed efficiency ratio were calculated. C3G supplementation markedly decreased body weight, visceral adiposity, average feed efficiency ratio, triglyceride, total cholesterol, low density lipoprotein cholesterol, fasting glucose, serum insulin, insulin resistance index and atherosclerosis index in high-fat diet-induced obese rats. C3G supplementation normalized serum adiponectin and high density lipoprotein cholesterol levels in high-fat diet-induced obese rats. Cyanidin-3-glucoside can reduce body weight gain, and attenuate obesity-associated dyslipidemia and insulin resistance in high-fat diet-fed rats via up-regulating serum adiponectin level.

Cell microencapsulation with synthetic polymers

PubMed Central

Olabisi, Ronke M

2015-01-01

The encapsulation of cells into polymeric microspheres or microcapsules has permitted the transplantation of cells into human and animal subjects without the need for immunosuppressants. Cell-based therapies use donor cells to provide sustained release of a therapeutic product, such as insulin, and have shown promise in treating a variety of diseases. Immunoisolation of these cells via microencapsulation is a hotly investigated field, and the preferred material of choice has been alginate, a natural polymer derived from seaweed due to its gelling conditions. Although many natural polymers tend to gel in conditions favorable to mammalian cell encapsulation, there remain challenges such as batch to batch variability and residual components from the original source that can lead to an immune response when implanted into a recipient. Synthetic materials have the potential to avoid these issues; however, historically they have required harsh polymerization conditions that are not favorable to mammalian cells. As research into microencapsulation grows, more investigators are exploring methods to microencapsulate cells into synthetic polymers. This review describes a variety of synthetic polymers used to microencapsulate cells. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 846–859, 2015. PMID:24771675

PLGA-encapsulated tea polyphenols enhance the chemotherapeutic efficacy of cisplatin against human cancer cells and mice bearing Ehrlich ascites carcinoma

PubMed Central

Singh, Madhulika; Bhatnagar, Priyanka; Mishra, Sanjay; Kumar, Pradeep; Shukla, Yogeshwer; Gupta, Kailash Chand

2015-01-01

The clinical success of the applicability of tea polyphenols awaits efficient systemic delivery and bioavailability. Herein, following the concept of nanochemoprevention, which uses nanotechnology for enhancing the efficacy of chemotherapeutic drugs, we employed tea polyphenols, namely theaflavin (TF) and epigallocatechin-3-gallate (EGCG) encapsulated in a biodegradable nanoparticulate formulation based on poly(lactide-co-glycolide) (PLGA) with approximately 26% and 18% encapsulation efficiency, respectively. It was observed that TF/EGCG encapsulated PLGA nanoparticles (NPs) offered an up to ~7-fold dose advantage when compared with bulk TF/EGCG in terms of exerting its antiproliferative effects and also enhanced the anticancer potential of cisplatin (CDDP) in A549 (lung carcinoma), HeLa (cervical carcinoma), and THP-1 (acute monocytic leukemia) cells. Cell cycle analysis revealed that TF/EGCG-NPs were more efficient than bulk TF/EGCG in sensitizing A549 cells to CDDP-induced apoptosis, with a dose advantage of up to 20-fold. Further, TF/EGCG-NPs, alone or in combination with CDDP, were more effective in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase-9, and vascular endothelial growth factor, involved in cell proliferation, metastasis, and angiogenesis, respectively. EGCG and TF-NPs were also found to be more effective than bulk TF/EGCG in inducing the cleavage of caspase-3 and caspase-9 and Bax/Bcl2 ratio in favor of apoptosis. Further, in vivo evaluation of these NPs in combination with CDDP showed an increase in life span (P<0.05) in mice bearing Ehrlich’s ascites carcinoma cells, with apparent regression of tumor volume in comparison with mice treated with bulk doses with CDDP. These results indicate that EGCG and TF-NPs have superior cancer chemosensitization activity when compared with bulk TF/EGCG. PMID:26586942

Nano spray drying for encapsulation of pharmaceuticals.

PubMed

Arpagaus, Cordin; Collenberg, Andreas; Rütti, David; Assadpour, Elham; Jafari, Seid Mahdi

2018-05-17

Many pharmaceuticals such as pills, capsules, or tablets are prepared in a dried and powdered form. In this field, spray drying plays a critical role to convert liquid pharmaceutical formulations into powders. In addition, in many cases it is necessary to encapsulate bioactive drugs into wall materials to protect them against harsh process and environmental conditions, as well as to deliver the drug to the right place and at the correct time within the body. Thus, spray drying is a common process used for encapsulation of pharmaceuticals. In view of the rapid progress of nanoencapsulation techniques in pharmaceutics, nano spray drying is used to improve drug formulation and delivery. The nano spray dryer developed in the recent years provides ultrafine powders at nanoscale and high product yields. In this paper, after explaining the concept of nano spray drying and understanding the key elements of the equipment, the influence of the process parameters on the final powders properties, like particle size, morphology, encapsulation efficiency, drug loading and release, will be discussed. Then, numerous application examples are reviewed for nano spray drying and encapsulation of various drugs in the early stages of product development along with a brief overview of the obtained results and characterization techniques. Copyright © 2018 Elsevier B.V. All rights reserved.

Health Benefits of Anthocyanins and Their Encapsulation for Potential Use in Food Systems: A Review.

PubMed

Yousuf, Basharat; Gul, Khalid; Wani, Ali Abas; Singh, Preeti

2016-10-02

Anthocyanins are one of the six subgroups of large and widespread group of plant constituents known as flavonoids. These are responsible for the bright and attractive orange, red, purple, and blue colors of most fruits, vegetables, flowers and some cereal grains. More than 600 structurally distinct anthocyanins have been identified in nature. Earlier, anthocyanins were only known for their coloring properties but now interest in anthocyanin pigments has intensified because of their possible health benefits as dietary antioxidants, which help to prevent neuronal diseases, cardiovascular illnesses, cancer, diabetes, inflammation, and many such others diseases. Ability of anthocyanins to counter oxidants makes them atherosclerosis fighters. Therefore, anthocyanin-rich foods may help to boost overall health by offering an array of nutrients. However, the incorporation of anthocyanins into food and medical products is a challenging task due to their low stability toward environmental conditions during processing and storage. Encapsulation seems to be an efficient way to introduce such compounds into these products. Encapsulating agents act as a protector coat against ambient adverse conditions such as light, humidity, and oxygen. Encapsulated bioactive compounds are easier to handle and offer improved stability. The main objective of this review is to explore health benefits of anthocyanins and their extraction, characterization, encapsulation, and delivery.

Characterization of Encapsulated Corrosion Inhibitors for Environmentally Friendly Smart Coatings

NASA Technical Reports Server (NTRS)

Pearman, Benjamin Pieter; Li, Wenyan; Buhrow, Jerry; Zhang, Xuejun; Surma, Jan; Fitzpatrick, Lilly; Montgomery, Eliza; Calle, Luz Marina

2014-01-01

Research efforts are under way to replace current corrosion inhibitors with more environmentally friendly alternatives. However, problems with corrosion inhibition efficiency, coating compatibility and solubility have hindered the use of many of these materials as simple pigment additives.This paper will present technical details on how the Corrosion Technology Lab at NASAs Kennedy Space Center (KSC) has addressed these issues by encapsulating environmentally friendly inhibitors into organic and inorganic microparticles and microcapsules. The synthetic process for polymer particles was characterized and post-synthesis analysis was performed to determine the interactions between the inhibitors and the encapsulation material. The pH-controlled release of inhibitors from various particle formulations in aqueous base was monitored and compared to both electrochemical and salt immersion accelerated corrosion experiment. Furthermore, synergistic corrosion inhibition effects observed during the corrosion testing of several inhibitor combinations will be presented.

Camphor-mediated synthesis of carbon nanoparticles, graphitic shell encapsulated carbon nanocubes and carbon dots for bioimaging

PubMed Central

Oza, Goldie; Ravichandran, M.; Merupo, Victor-Ishrayelu; Shinde, Sachin; Mewada, Ashmi; Ramirez, Jose Tapia; Velumani, S.; Sharon, Madhuri; Sharon, Maheshwar

2016-01-01

A green method for an efficient synthesis of water-soluble carbon nanoparticles (CNPs), graphitic shell encapsulated carbon nanocubes (CNCs), Carbon dots (CDs) using Camphor (Cinnamomum camphora) is demonstrated. Here, we describe a competent molecular fusion and fission route for step-wise synthesis of CDs. Camphor on acidification and carbonization forms CNPs, which on alkaline hydrolysis form CNCs that are encapsulated by thick graphitic layers and on further reduction by sodium borohydride yielded CDs. Though excitation wavelength dependent photoluminescence is observed in all the three carbon nanostructures, CDs possess enhanced photoluminescent properties due to more defective carbonaceous structures. The surface hydroxyl and carboxyl functional groups make them water soluble in nature. They possess excellent photostability, higher quantum yield, increased absorption, decreased cytotoxicity and hence can be utilized as a proficient bio imaging agent. PMID:26905737

Marine polysaccharides in microencapsulation and application to aquaculture: "from sea to sea".

PubMed

Borgogna, Massimiliano; Bellich, Barbara; Cesàro, Attilio

2011-12-01

This review's main objective is to discuss some physico-chemical features of polysaccharides as intrinsic determinants for the supramolecular structures that can efficiently provide encapsulation of drugs and other biological entities. Thus, the general characteristics of some basic polysaccharides are outlined in terms of their conformational, dynamic and thermodynamic properties. The analysis of some polysaccharide gelling properties is also provided, including the peculiarity of the charged polysaccharides. Then, the way the basic physical chemistry of polymer self-assembly is made in practice through the laboratory methods is highlighted. A description of the several literature procedures used to influence molecular interactions into the macroscopic goal of the encapsulation is given with an attempt at classification. Finally, a practical case study of specific interest, the use of marine polysaccharide matrices for encapsulation of vaccines in aquaculture, is reported.

Biofriendly bonding processes for nanoporous implantable SU-8 microcapsules for encapsulated cell therapy.

PubMed

Nemani, Krishnamurthy; Kwon, Joonbum; Trivedi, Krutarth; Hu, Walter; Lee, Jeong-Bong; Gimi, Barjor

2011-01-01

Mechanically robust, cell encapsulating microdevices fabricated using photolithographic methods can lead to more efficient immunoisolation in comparison to cell encapsulating hydrogels. There is a need to develop adhesive bonding methods which can seal such microdevices under physiologically friendly conditions. We report the bonding of SU-8 based substrates through (i) magnetic self assembly, (ii) using medical grade photocured adhesive and (iii) moisture and photochemical cured polymerization. Magnetic self-assembly, carried out in biofriendly aqueous buffers, provides weak bonding not suitable for long term applications. Moisture cured bonding of covalently modified SU-8 substrates, based on silanol condensation, resulted in weak and inconsistent bonding. Photocured bonding using a medical grade adhesive and of acrylate modified substrates provided stable bonding. Of the methods evaluated, photocured adhesion provided the strongest and most stable adhesion.

Camphor-mediated synthesis of carbon nanoparticles, graphitic shell encapsulated carbon nanocubes and carbon dots for bioimaging

NASA Astrophysics Data System (ADS)

Oza, Goldie; Ravichandran, M.; Merupo, Victor-Ishrayelu; Shinde, Sachin; Mewada, Ashmi; Ramirez, Jose Tapia; Velumani, S.; Sharon, Madhuri; Sharon, Maheshwar

2016-02-01

A green method for an efficient synthesis of water-soluble carbon nanoparticles (CNPs), graphitic shell encapsulated carbon nanocubes (CNCs), Carbon dots (CDs) using Camphor (Cinnamomum camphora) is demonstrated. Here, we describe a competent molecular fusion and fission route for step-wise synthesis of CDs. Camphor on acidification and carbonization forms CNPs, which on alkaline hydrolysis form CNCs that are encapsulated by thick graphitic layers and on further reduction by sodium borohydride yielded CDs. Though excitation wavelength dependent photoluminescence is observed in all the three carbon nanostructures, CDs possess enhanced photoluminescent properties due to more defective carbonaceous structures. The surface hydroxyl and carboxyl functional groups make them water soluble in nature. They possess excellent photostability, higher quantum yield, increased absorption, decreased cytotoxicity and hence can be utilized as a proficient bio imaging agent.

Impact of zeolite-Y framework on the geometry and reactivity of Ru (III) benzimidazole complexes - A DFT study

NASA Astrophysics Data System (ADS)

Selvaraj, Tamilmani; Rajalingam, Renganathan; Balasubramanian, Viswanathan

2018-03-01

A detailed comparative Density Functional Theory (DFT) study is made to understand the structural changes of the guest complex due to steric and electronic interactions with the host framework. In this study, Ru(III) benzimidazole and 2- ethyl Ru(III) benzimidazole complexes encapsulated in a supercage of zeolite Y. The zeolitic framework integrity is not disturbed by the intrusion of the large guest complex. A blue shift in the d-d transition observed in the UV-Visible spectroscopic studies of the zeolite encapsulated complexes and they shows a higher catalytic efficiency. Encapsulation of zeolite matrix makes the metal center more viable to nucleophilic attack and favors the phenol oxidation reaction. Based on the theoretical calculations, transition states and structures of reaction intermediates involved in the catalytic cycles are derived.

Encapsulating urban traffic rhythms into road networks.

PubMed

Wang, Junjie; Wei, Dong; He, Kun; Gong, Hang; Wang, Pu

2014-02-20

Using road GIS (geographical information systems) data and travel demand data for two U.S. urban areas, the dynamical driver sources of each road segment were located. A method to target road clusters closely related to urban traffic congestion was then developed to improve road network efficiency. The targeted road clusters show different spatial distributions at different times of a day, indicating that our method can encapsulate dynamical travel demand information into the road networks. As a proof of concept, when we lowered the speed limit or increased the capacity of road segments in the targeted road clusters, we found that both the number of congested roads and extra travel time were effectively reduced. In addition, the proposed modeling framework provided new insights on the optimization of transport efficiency in any infrastructure network with a specific supply and demand distribution.

Encapsulating Urban Traffic Rhythms into Road Networks

PubMed Central

Wang, Junjie; Wei, Dong; He, Kun; Gong, Hang; Wang, Pu

2014-01-01

Using road GIS (geographical information systems) data and travel demand data for two U.S. urban areas, the dynamical driver sources of each road segment were located. A method to target road clusters closely related to urban traffic congestion was then developed to improve road network efficiency. The targeted road clusters show different spatial distributions at different times of a day, indicating that our method can encapsulate dynamical travel demand information into the road networks. As a proof of concept, when we lowered the speed limit or increased the capacity of road segments in the targeted road clusters, we found that both the number of congested roads and extra travel time were effectively reduced. In addition, the proposed modeling framework provided new insights on the optimization of transport efficiency in any infrastructure network with a specific supply and demand distribution. PMID:24553203

Efficient Human Breast Cancer Xenograft Regression after a Single Treatment with a Novel Liposomal Formulation of Epirubicin Prepared Using the EDTA Ion Gradient Method

PubMed Central

Gubernator, Jerzy; Lipka, Dominik; Korycińska, Mariola; Kempińska, Katarzyna; Milczarek, Magdalena; Wietrzyk, Joanna; Hrynyk, Rafał; Barnert, Sabine; Süss, Regine; Kozubek, Arkadiusz

2014-01-01

Liposomes act as efficient drug carriers. Recently, epirubicin (EPI) formulation was developed using a novel EDTA ion gradient method for drug encapsulation. This formulation displayed very good stability and drug retention in vitro in a two-year long-term stability experiment. The cryo-TEM images show drug precipitate structures different than ones formed with ammonium sulfate method, which is usually used to encapsulate anthracyclines. Its pharmacokinetic properties and its efficacy in the human breast MDA-MB-231 cancer xenograft model were also determined. The liposomal EPI formulation is eliminated slowly with an AUC of 7.6487, while the free drug has an AUC of only 0.0097. The formulation also had a much higher overall antitumor efficacy than the free drug. PMID:24621591

Encapsulating Silica/Antimony into Porous Electrospun Carbon Nanofibers with Robust Structure Stability for High-Efficiency Lithium Storage.

PubMed

Wang, Hongkang; Yang, Xuming; Wu, Qizhen; Zhang, Qiaobao; Chen, Huixin; Jing, Hongmei; Wang, Jinkai; Mi, Shao-Bo; Rogach, Andrey L; Niu, Chunming

2018-04-24

To address the volume-change-induced pulverization problems of electrode materials, we propose a "silica reinforcement" concept, following which silica-reinforced carbon nanofibers with encapsulated Sb nanoparticles (denoted as SiO 2 /Sb@CNFs) are fabricated via an electrospinning method. In this composite structure, insulating silica fillers not only reinforce the overall structure but also contribute to additional lithium storage capacity; encapsulation of Sb nanoparticles into the carbon-silica matrices efficiently buffers the volume changes during Li-Sb alloying-dealloying processes upon cycling and alleviates the mechanical stress; the porous carbon nanofiber framework allows for fast charge transfer and electrolyte diffusion. These advantageous characteristics synergistically contribute to the superior lithium storage performance of SiO 2 /Sb@CNF electrodes, which demonstrate excellent cycling stability and rate capability, delivering reversible discharge capacities of 700 mA h/g at 200 mA/g, 572 mA h/g at 500 mA/g, and 468 mA h/g at 1000 mA/g each after 400 cycles. Ex situ as well as in situ TEM measurements confirm that the structural integrity of silica-reinforced Sb@CNF electrodes can efficiently withstand the mechanical stress induced by the volume changes. Notably, the SiO 2 /Sb@CNF//LiCoO 2 full cell delivers high reversible capacities of ∼400 mA h/g after 800 cycles at 500 mA/g and ∼336 mA h/g after 500 cycles at 1000 mA/g.

Simple nanoliposomes encapsulating Lycium barbarum polysaccharides as adjuvants improve humoral and cellular immunity in mice.

PubMed

Bo, Ruonan; Sun, Yaqin; Zhou, Shuzhen; Ou, Ning; Gu, Pengfei; Liu, Zhenguang; Hu, Yuanliang; Liu, Jiaguo; Wang, Deyun

2017-01-01

The success of subunit vaccines has been hampered by the problems of weak or short-term immunity and the lack of availability of nontoxic, potent adjuvants. It would be desirable to develop safe and efficient adjuvants with the aim of improving the cellular immune response against the target antigen. In this study, the targeting and sustained release of simple nanoliposomes containing Lycium barbarum polysaccharides (LBP) as an efficacious immune adjuvant to improve immune responses were explored. LBP liposome (LBPL) with high entrapment efficiency (86%) were obtained using a reverse-phase evaporation method and then used to encapsulate the model antigen, ovalbumin (OVA). We demonstrated that the as-synthesized liposome loaded with OVA and LBP (LBPL-OVA) was stable for 45 days and determined the encapsulation stability of OVA at 4°C and 37°C and the release profile of OVA from LBPL-OVA was investigated in pH 7.4 and pH 5.0. Further in vivo investigation showed that the antigen-specific humoral response was correlated with antigen delivery to the draining lymph nodes. The LBPL-OVA were also associated with high levels of uptake by key dendritic cells in the draining lymph nodes and they efficiently stimulated CD4 + and CD8 + T cell proliferation in vivo, further promoting antibody production. These features together elicited a significant humoral and celluar immune response, which was superior to that produced by free antigen alone.

Development of curcumin-loaded poly(hydroxybutyrate- co-hydroxyvalerate) nanoparticles as anti-inflammatory carriers to human-activated endothelial cells

NASA Astrophysics Data System (ADS)

Simion, Viorel; Stan, Daniela; Gan, Ana-Maria; Pirvulescu, Monica Madalina; Butoi, Elena; Manduteanu, Ileana; Deleanu, Mariana; Andrei, Eugen; Durdureanu-Angheluta, Anamaria; Bota, Marian; Enachescu, Marius; Calin, Manuela; Simionescu, Maya

2013-12-01

Curcumin (Cm)-loaded poly(hydroxybutyrate- co-hydroxyvalerate) (PHBV) nanoparticles (CmPN) were obtained and characterized and their effect on human endothelial cells (HEC) was assessed. Different CmPN formulations have been prepared using the emulsion solvent evaporation technique, and characterized for size, structure, Zeta potential, Cm entrapment efficiency, and in vitro Cm release. CmPN cytotoxicity and cellular uptake have been followed using HEC. Also, the effect of CmPN treatment on the p38MAPK signaling pathway in endothelial cells was investigated. The results obtained by electron and atomic force microscopy revealed the spherical shape of the CmPN formulation. Based on size and encapsulation efficiency, the CmPN formulation with the average diameter of 186 nm and with the highest encapsulation efficiency (83 %) has been used in the further studies. The release of Cm from CmPN was 18 % after 8 h of incubation at 37 °C, followed by a slow release until 144 h, when it reached 44 %, indicating a controlled release. CmPN are taken up by HEC and exhibited low cytotoxicity at concentrations up to 10 μM. The pre-treatment of HEC with CmPN before exposure to tumor necrosis factor-alpha (TNF-α) determined a decrease of p38MAPK phosphorylation. In conclusion, Cm encapsulated into PHBV nanoparticles, at concentration up to 10 μM, has low cytotoxicity and display anti-inflammatory activity on TNF-α-activated HEC by suppressing the phosphorylation of p38MAPK.

PEG-PLA-PEG block copolymeric nanoparticles for oral immunization against hepatitis B.

PubMed

Jain, Arvind K; Goyal, Amit K; Mishra, Neeraj; Vaidya, Bhuvaneshwar; Mangal, Sharad; Vyas, Suresh P

2010-03-15

PLA/PLGA nanoparticles are well known as efficient vaccine delivery systems, but they have got limitation in oral vaccine delivery because of their sensitivity to harsh gastric environment. The aim of present study was to improve the stability of PLA nanoparticles in such environment by copolymerizing PLA with PEG. Nanoparticles were formulated using different block copolymers AB, ABA and BAB (where 'A' is PLA and 'B' is PEG) encapsulating hepatitis B surface antigen (HBsAg) to evaluate their efficacy as oral vaccine delivery system. The results of in vitro studies engrave the efficiency of copolymeric nanoparticles to retain encapsulated antigen and average particle size even after 2 h incubation in simulated gastric fluid and simulated intestinal fluid. Fluorescence microscopic studies indicated efficient uptake of copolymeric nanoparticles by gut mucosa of immunized mice model as compared to control. Finally copolymeric and PLA nanoparticles, encapsulating HBsAg, were evaluated for their adjuvancity in generating immune response after oral administration. PLA nanoparticles could not generate an effective immune response due to stability issues. On the other hand, oral administration of copolymeric nanoparticles exhibited effective levels of humoral immunity along with the mucosal (sIgA) and cellular immune response (T(H)1). The results of in vitro and in vivo studies demonstrate that BAB nanoparticles depict enhanced mucosal uptake leading to effective immune response as compared to other copolymeric nanoparticles. Present study indicates the efficacy of BAB nanoparticles as a promising carrier for oral immunization. 2009 Elsevier B.V. All rights reserved.

In line monitoring of the preparation of water-in-oil-in-water (W/O/W) type multiple emulsions via dielectric spectroscopy.

PubMed

Beer, Sebastian; Dobler, Dorota; Gross, Alexander; Ost, Martin; Elseberg, Christiane; Maeder, Ulf; Schmidts, Thomas Michael; Keusgen, Michael; Fiebich, Martin; Runkel, Frank

2013-01-30

Multiple emulsions offer various applications in a wide range of fields such as pharmaceutical, cosmetics and food technology. Two features are known to yield a great influence on multiple emulsion quality and utility as encapsulation efficiency and prolonged stability. To achieve a prolonged stability, the production of the emulsions has to be observed and controlled, preferably in line. In line measurements provide available parameters in a short time frame without the need for the sample to be removed from the process stream, thereby enabling continuous process control. In this study, information about the physical state of multiple emulsions obtained from dielectric spectroscopy (DS) is evaluated for this purpose. Results from dielectric measurements performed in line during the production cycle are compared to theoretically expected results and to well established off line measurements. Thus, a first step to include the production of multiple emulsions into the process analytical technology (PAT) guidelines of the Food and Drug Administration (FDA) is achieved. DS proved to be beneficial in determining the crucial stopping criterion, which is essential in the production of multiple emulsions. The stopping of the process at a less-than-ideal point can severely lower the encapsulation efficiency and the stability, thereby lowering the quality of the emulsion. DS is also expected to provide further information about the multiple emulsion like encapsulation efficiency. Copyright © 2012 Elsevier B.V. All rights reserved.

Development of biodegradable drug delivery system to treat addiction.

PubMed

Mandal, T K

1999-06-01

Opiate addiction is a serious problem that has now spread worldwide to all levels of society. Buprenorphine has been used for several years for the treatment of opiate addiction. The objective of this project was to develop sustained-release biodegradable microcapsules for the parenteral delivery of buprenorphine. Biodegradable microcapsules of buprenorphine/poly(lactide-co-glycolide) were prepared using two main procedures based on an in-water drying process in a complex emulsion system. These procedures differ in the way the organic solvent was eliminated: evaporation or extraction. The effect of drug loading and the effect of partial saturation of the aqueous phase with the core material during the in-water solvent evaporation were also studied. The efficiency of encapsulation increased from 11% to 34% when the drug loading was decreased from 20% to 5%. There was no significant change in the efficiency of encapsulation when the aqueous phase was partially saturated with buprenorphine. In changing the solvent removal process from evaporation to extraction, no significant change in the efficiency of encapsulation was observed. The microcapsules prepared by the solvent evaporation were smooth and spherical. However, the microcapsules prepared by the extraction of the organic solvent lost their surface smoothness and became slightly irregular and porous compared with the other batches. The average particle size of the microcapsules was between 14 and 49 microns. The cumulative drug release was between 2% and 4% within the first 24 hr. A sustained drug release continued over 45 days.

In situ forming biodegradable poly(ε-caprolactone) microsphere systems: a challenge for transarterial embolization therapy. In vitro and preliminary ex vivo studies.

PubMed

Salis, Andrea; Porcu, Elena P; Gavini, Elisabetta; Fois, Giulia R; Icaro Cornaglia, Antonia; Rassu, Giovanna; Diana, Marco; Maestri, Marcello; Giunchedi, Paolo; Nikolakakis, Ioannis

2017-04-01

In situ forming biodegradable poly(ε-caprolactone) (PCL) microspheres (PCL-ISM) system was developed as a novel embolic agent for transarterial embolization (TAE) therapy of hepatocellular carcinoma (HCC). Ibuprofen sodium (Ibu-Na) was loaded on this platform to evaluate its potential for the treatment of post embolization syndrome. The influence of formulation parameters on the size/shape, encapsulation efficiency and drug release was investigated using mixture experimental design. Regression models were derived and used to optimize the formulation for particle size, encapsulation efficiency and drug release profile for TAE therapy. An ex vivo model using isolated rat livers was established to assess the in situ formation of microspheres. All PCL-ISM components affected the studied properties and fitting indices of the regression models were high (Radj 2  = 0.810 for size, 0.964 encapsulation efficiency, and 0.993 or 0.971 for drug release at 30 min or 48 h). The optimized composition was: PCL = 4%, NMP = 43.1%, oil = 48.9%, surfactant = 2% and drug = 2%. Ex vivo studies revealed that PCL-ISM was able to form microspheres in the hepatic arterial bed. PCL-ISM system provides a novel tool for the treatment of HCC and post-embolization syndrome. It is capable of forming microspheres with desirable size and Ibu-Na release profile after injection into blood vessels.

Diet-genotype interactions in the development of the obese, insulin-resistant phenotype of C57BL/6J mice lacking melanocortin-3 or -4 receptors.

PubMed

Sutton, Gregory M; Trevaskis, James L; Hulver, Matthew W; McMillan, Ryan P; Markward, Nathan J; Babin, M Josephine; Meyer, Emily A; Butler, Andrew A

2006-05-01

Loss of brain melanocortin receptors (Mc3rKO and Mc4rKO) causes increased adiposity and exacerbates diet-induced obesity (DIO). Little is known about how Mc3r or Mc4r genotype, diet, and obesity affect insulin sensitivity. Insulin resistance, assessed by insulin and glucose tolerance tests, Ser(307) phosphorylation of insulin receptor substrate 1, and activation of protein kinase B, was examined in control and DIO wild-type (WT), Mc3rKO and Mc4rKO C57BL/6J mice. Mc4rKO mice were hyperphagic and had increased metabolic efficiency (weight gain per kilojoule consumed) relative to WT; both parameters increased further on high-fat diet. Obesity of Mc3rKO was more dependent on fat intake, involving increased metabolic efficiency. Fat mass of DIO Mc3rKO and Mc4rKO was similar, although Mc4rKO gained weight more rapidly. Mc4rKO develop hepatic insulin resistance and severe hepatic steatosis with obesity, independent of diet. DIO caused further deterioration of insulin action in Mc4rKO of either sex and, in male Mc3rKO, compared with controls, associated with increased fasting insulin, severe glucose intolerance, and reduced insulin signaling in muscle and adipose tissue. DIO female Mc3rKO exhibited very modest perturbations in glucose metabolism and insulin sensitivity. Consistent with previous data suggesting impaired fat oxidation, both Mc3rKO and Mc4rKO had reduced muscle oxidative metabolism, a risk factor for weight gain and insulin resistance. Energy expenditure was, however, increased in Mc4rKO compared with Mc3rKO and controls, perhaps due to hyperphagia and metabolic costs associated with rapid growth. In summary, DIO affects insulin sensitivity more severely in Mc4rKO compared with Mc3rKO, perhaps due to a more positive energy balance.

A simple dilute and shoot methodology for the identification and quantification of illegal insulin.

PubMed

Vanhee, Celine; Janvier, Steven; Moens, Goedele; Deconinck, Eric; Courselle, Patricia

2016-10-01

The occurrence of illegal medicines is a well-established global problem and concerns mostly small molecules. However, due to the advances in genomics and recombinant expression technologies there is an increased development of polypeptide therapeutics. Insulin is one of the best known polypeptide drug, and illegal versions of this medicine led to lethal incidents in the past. Therefore, it is crucial for the public health sector to develop reliable, efficient, cheap, unbiased and easily applicable active pharmaceutical ingredient (API) identification and quantification strategies for routine analysis of suspected illegal insulins. Here we demonstrate that our combined label-free full scan approach is not only able to distinguish between all those different versions of insulin and the insulins originating from different species, but also able to chromatographically separate human insulin and insulin lispro in conditions that are compatible with mass spectrometry (MS). Additionally, we were also able to selectively quantify the different insulins, including human insulin and insulin lispro according to the validation criteria, put forward by the United Nations (UN), for the analysis of seized illicit drugs. The proposed identification and quantification method is currently being used in our official medicines control laboratory to analyze insulins retrieved from the illegal market.

Development of test models to quantify encapsulated bioburden in spacecraft polymer materials by cultivation-dependent and molecular methods

NASA Astrophysics Data System (ADS)

Bauermeister, Anja; Moissl-Eichinger, Christine; Mahnert, Alexander; Probst, Alexander; Flier, Niwin; Auerbach, Anna; Weber, Christina; Haberer, Klaus; Boeker, Alexander

Bioburden encapsulated in spacecraft polymers (such as adhesives and coatings) poses a potential risk to scientific exploration of other celestial bodies, but it is not easily detectable. In this study, we developed novel testing strategies to estimate the quantity of intrinsic encapsulated bioburden in polymers used frequently on spaceflight hardware. In particular Scotch-Weld (TM) 2216 B/A (Epoxy adhesive); MAP SG121FD (Silicone coating), Solithane (®) 113 (Urethane resin); ESP 495 (Silicone adhesive); and Dow Corning (®) 93-500 (Silicone encapsulant) were investigated. As extraction of bioburden from polymerized (solid) materials did not prove feasible, a method was devised to extract contaminants from uncured polymer precursors by dilution in organic solvents. Cultivation-dependent analyses showed less than 0.1-2.5 colony forming units (cfu) per cm³ polymer, whereas quantitative PCR with extracted DNA indicated considerably higher values, despite low DNA extraction efficiency. Results obtained by this method reflected the most conservative proxy for encapsulated bioburden. To observe the effect of physical and chemical stress occurring during polymerization on the viability of encapsulated contaminants, Bacillus safensis spores were embedded close to the surface in cured polymer, which facilitated access for different analytical techniques. Staining by AlexaFluor succinimidyl ester 488 (AF488), propidium monoazide (PMA), CTC (5-cyano-2,3-diotolyl tetrazolium chloride) and subsequent confocal laser scanning microscopy (CLSM) demonstrated that embedded spores retained integrity, germination and cultivation ability even after polymerization of the adhesive Scotch-Weld™ 2216 B/A.

Gold nanorods in an oil-base formulation for transdermal treatment of type 1 diabetes in mice

NASA Astrophysics Data System (ADS)

Nose, Keisuke; Pissuwan, Dakrong; Goto, Masahiro; Katayama, Yoshiki; Niidome, Takuro

2012-05-01

Efficient transdermal insulin delivery to the systemic circulation would bring major benefit to diabetic patients. We investigated the possibility of using gold nanorods (GNRs) that formed a complex with an edible surfactant and insulin (INS) in an oil phase to form a solid-in-oil (SO) formulation (SO-INS-GNR) for transdermal treatment of diabetes. Diabetic mice comprised the model for our study. In vitro, there was high penetration of insulin through the stratum corneum (SC) and the dermis in mouse skin treated with an SO-INS-GNR complex plus near-infrared (NIR) light irradiation. Blood glucose levels in the diabetic mice were significantly decreased after treatment with SO-INS-GNR plus irradiation. To our knowledge, this is the first study to use gold nanorods for systemic insulin delivery through the skin. The use of an SO-INS-GNR complex combined with NIR irradiation may provide the possibility of transdermal insulin delivery to diabetic patients.Efficient transdermal insulin delivery to the systemic circulation would bring major benefit to diabetic patients. We investigated the possibility of using gold nanorods (GNRs) that formed a complex with an edible surfactant and insulin (INS) in an oil phase to form a solid-in-oil (SO) formulation (SO-INS-GNR) for transdermal treatment of diabetes. Diabetic mice comprised the model for our study. In vitro, there was high penetration of insulin through the stratum corneum (SC) and the dermis in mouse skin treated with an SO-INS-GNR complex plus near-infrared (NIR) light irradiation. Blood glucose levels in the diabetic mice were significantly decreased after treatment with SO-INS-GNR plus irradiation. To our knowledge, this is the first study to use gold nanorods for systemic insulin delivery through the skin. The use of an SO-INS-GNR complex combined with NIR irradiation may provide the possibility of transdermal insulin delivery to diabetic patients. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr30651d

Solid lipid nanoparticles for hydrophilic biotech drugs: optimization and cell viability studies (Caco-2 & HEPG-2 cell lines).

PubMed

Severino, Patrícia; Andreani, Tatiana; Jäger, Alessandro; Chaud, Marco V; Santana, Maria Helena A; Silva, Amélia M; Souto, Eliana B

2014-06-23

Insulin was used as model protein to developed innovative Solid Lipid Nanoparticles (SLNs) for the delivery of hydrophilic biotech drugs, with potential use in medicinal chemistry. SLNs were prepared by double emulsion with the purpose of promoting stability and enhancing the protein bioavailability. Softisan(®)100 was selected as solid lipid matrix. The surfactants (Tween(®)80, Span(®)80 and Lipoid(®)S75) and insulin were chosen applying a 2(2) factorial design with triplicate of central point, evaluating the influence of dependents variables as polydispersity index (PI), mean particle size (z-AVE), zeta potential (ZP) and encapsulation efficiency (EE) by factorial design using the ANOVA test. Therefore, thermodynamic stability, polymorphism and matrix crystallinity were checked by Differential Scanning Calorimetry (DSC) and Wide Angle X-ray Diffraction (WAXD), whereas the effect of toxicity of SLNs was check in HepG2 and Caco-2 cells. Results showed a mean particle size (z-AVE) width between 294.6 nm and 627.0 nm, a PI in the range of 0.425-0.750, ZP about -3 mV, and the EE between 38.39% and 81.20%. After tempering the bulk lipid (mimicking the end process of production), the lipid showed amorphous characteristics, with a melting point of ca. 30 °C. The toxicity of SLNs was evaluated in two distinct cell lines (HEPG-2 and Caco-2), showing to be dependent on the concentration of particles in HEPG-2 cells, while no toxicity in was reported in Caco-2 cells. SLNs were stable for 24 h in in vitro human serum albumin (HSA) solution. The resulting SLNs fabricated by double emulsion may provide a promising approach for administration of protein therapeutics and antigens. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Encapsulation of biological active phenolic compounds extracted from wine wastes in alginate-chitosan microbeads.

PubMed

Moschona, Alexandra; Liakopoulou-Kyriakides, Maria

2018-04-23

Grapes (Vitis vinifera) are produced in large amounts worldwide and mostly are used for winemaking. Their untreated wastes are rich in valuable secondary metabolites, such as phenolics. Thus, in this study, white and red wine wastes (Malagouzia and Syrah variety) were investigated for their added value phenolics, which were analysed by high performance liquid chromatography (HPLC) and electrospray ionisation-mass spectrometry (ESI/MS) and subsequently encapsulated in several polymers. Extracts from all wastes gave high amounts of total phenolics (13 ± 2.72-22 ± 2.69 mg g -1 ) and possessed high antioxidant activity (67-97%). In addition to their significant antibacterial activity against gram-negative and gram-positive bacteria, interesting results were also obtained from their anti-inflammatory and antiplatelet activity, in vitro. Encapsulation of the extracts was selective, leaving out most of sugars and other organic compounds when alginate-chitosan was used. Encapsulation efficiency recorded for all extracts ranged from 55% to 79%. Release studies were also performed in several solutions aiming in their commercial use in food and pharmaceutical industries.

Development and characterization of phosphatidylcholine nanovesicles, containing garlic extract, with antilisterial activity in milk.

PubMed

Pinilla, Cristian Mauricio Barreto; Noreña, Caciano Pelayo Zapata; Brandelli, Adriano

2017-04-01

Phospholipid nanovesicles were developed to improve the stability of garlic (Allium sativum L.) extract. Electron microscopy of liposomes revealed nanometric and spherical-shaped vesicles with a mean particle size of 174.6±17.3nm and polydispersity index of 0.26±0.02. The entrapment efficiency was 47.5±7.3% and the nanoliposomes had a zeta potential of -16.2±5.5mV. The antimicrobial activity of free and encapsulated garlic extract was evaluated against different strains of Listeria spp. in milk at 37°C for 24h. For free and encapsulated garlic extracts at 5% concentration, a decrease of 4log cycles in viable cell counts was observed at 10h, against four of the five strains of Listeria spp. tested. The results indicate that liposomes constitute a suitable system for encapsulation of unstable garlic active compounds and the encapsulation of garlic extract proves to be a promising technology for multiple applications, including antimicrobial agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development and characterization of a novel drug nanocarrier for oral delivery, based on self-assembled β-casein micelles.

PubMed

Bachar, Michal; Mandelbaum, Amitai; Portnaya, Irina; Perlstein, Hadas; Even-Chen, Simcha; Barenholz, Yechezkel; Danino, Dganit

2012-06-10

β-casein is an amphiphilic protein that self-organizes into well-defined core-shell micelles. We developed these micelles as efficient nanocarriers for oral drug delivery. Our model drug is celecoxib, an anti-inflammatory hydrophobic drug utilized for treatment of rheumatoid arthritis and osteoarthritis, now also evaluated as a potent anticancer drug. This system is unique as it enables encapsulation loads >100-fold higher than other β-casein/drug formulations, and does not require additives as do other formulations that have high loadings. This is combined with the ability to lyophilize the formulation without a cryoprotectant, long-term physical and chemical stability of the resulting powder, and fully reversible reconstitution of the structures by rehydration. The dry dosage form, in which >95% of the drug is encapsulated, meets the daily dose. Cryo-TEM and DLS prove that drug encapsulation results in micelle swelling, and X-ray diffraction shows that the encapsulated drug is amorphous. Altogether, our novel dosage form is highly advantageous for oral administration. Copyright © 2012 Elsevier B.V. All rights reserved.

Improvement of curcuminoid bioaccessibility from turmeric by a nanostructured lipid carrier system.

PubMed

Park, Sung Jin; Garcia, Coralia V; Shin, Gye Hwa; Kim, Jun Tae

2018-06-15

Turmeric contains curcumin and its analogues, which show anticancer and antiinflammatory effects; however, curcuminoids are lipophilic and are poorly absorbed by the human body. Nanostructured lipid carriers for encapsulating whole turmeric powder were successfully produced by ultrasonication, and their physicochemical properties and stability in simulated gastric and intestinal media were evaluated. The turmeric nanostructured lipid carriers (TNLCs) exhibited a round shape, small diameter (282 ± 7.19 nm), adequate zeta potential (-22.75 ± 1.20 mV), and high encapsulation efficiency (93.3 ± 0.01%). The TNLCs were able to protect the encapsulated curcuminoids under acidic gastric conditions, and effectively released 95 ± 2.51% of the curcuminoids in the simulated intestinal medium, demonstrating their suitability for controlled release. The in vitro bioaccessibility of the encapsulated curcuminoids was 75 ± 1.24%, representing more than a fourfold increase compared to that of free turmeric. Therefore, the proposed TNLCs are a promising delivery system for increasing the bioaccessibility of curcuminoids from turmeric. Copyright © 2018 Elsevier Ltd. All rights reserved.

Silica-Protection-Assisted Encapsulation of Cu2 O Nanocubes into a Metal-Organic Framework (ZIF-8) To Provide a Composite Catalyst.

PubMed

Li, Bo; Ma, Jian-Gong; Cheng, Peng

2018-06-04

The integration of metal/metal oxide nanoparticles (NPs) into metal-organic frameworks (MOFs) to form composite materials has attracted great interest due to the broad range of applications. However, to date, it has not been possible to encapsulate metastable NPs with high catalytic activity into MOFs, due to their instability during the preparation process. For the first time, we have successfully developed a template protection-sacrifice (TPS) method to encapsulate metastable NPs such as Cu 2 O into MOFs. SiO 2 was used as both a protective shell for Cu 2 O nanocubes and a sacrificial template for forming a yolk-shell structure. The obtained Cu 2 O@ZIF-8 composite exhibits excellent cycle stability in the catalytic hydrogenation of 4-nitrophenol with high activity. This is the first report of a Cu 2 O@MOF-type composite material. The TPS method provides an efficient strategy for encapsulating unstable active metal/metal oxide NPs into MOFs or maybe other porous materials. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Treatment of diabetic rats with encapsulated islets

PubMed Central

Sweet, Ian R; Yanay, Ofer; Waldron, Lanaya; Gilbert, Merle; Fuller, Jessica M; Tupling, Terry; Lernmark, Ake; Osborne, William R A

2008-01-01

Immunoprotection of islets using bioisolator systems permits introduction of allogeneic cells to diabetic patients without the need for immunosuppression. Using TheraCyte™ immunoisolation devices, we investigated two rat models of type 1 diabetes mellitus (T1DM), BB rats and rats made diabetic by streptozotocin (STZ) treatment. We chose to implant islets after the onset of diabetes to mimic the probable treatment of children with T1DM as they are usually diagnosed after disease onset. We encapsulated 1000 rat islets and implanted them subcutaneously (SQ) into diabetic biobreeding (BB) rats and STZ-induced diabetic rats, defined as two or more consecutive days of blood glucose >350 mg/dl. Rats were monitored for weight and blood glucose. Untreated BB rats rapidly lost weight and were euthanized at >20% weight loss that occurred between 4 and 10 days from implantation. For period of 30–40 days following islet implantation weights of treated rats remained steady or increased. Rapid weight loss occurred after surgical removal of devices that contained insulin positive islets. STZ-treated rats that received encapsulated islets showed steady weight gain for up to 130 days, whereas untreated control rats showed steady weight loss that achieved >20% at around 55 days. Although islet implants did not normalize blood glucose, treated rats were apparently healthy and groomed normally. Autologous or allogeneic islets were equally effective in providing treatment. TheraCyte™ devices can sustain islets, protect allogeneic cells from immune attack and provide treatment for diabetic-mediated weight loss in both BB rats and STZ-induced diabetic rats. PMID:18373735

An Encapsulated Yersinia pseudotuberculosis Is a Highly Efficient Vaccine against Pneumonic Plague

PubMed Central

Derbise, Anne; Cerdà Marín, Alba; Ave, Patrick; Blisnick, Thierry; Huerre, Michel; Carniel, Elisabeth; Demeure, Christian E.

2012-01-01

Background Plague is still a public health problem in the world and is re-emerging, but no efficient vaccine is available. We previously reported that oral inoculation of a live attenuated Yersinia pseudotuberculosis, the recent ancestor of Yersinia pestis, provided protection against bubonic plague. However, the strain poorly protected against pneumonic plague, the most deadly and contagious form of the disease, and was not genetically defined. Methodology and Principal Findings The sequenced Y. pseudotuberculosis IP32953 has been irreversibly attenuated by deletion of genes encoding three essential virulence factors. An encapsulated Y. pseudotuberculosis was generated by cloning the Y. pestis F1-encoding caf operon and expressing it in the attenuated strain. The new V674pF1 strain produced the F1 capsule in vitro and in vivo. Oral inoculation of V674pF1 allowed the colonization of the gut without lesions to Peyer's patches and the spleen. Vaccination induced both humoral and cellular components of immunity, at the systemic (IgG and Th1 cells) and the mucosal levels (IgA and Th17 cells). A single oral dose conferred 100% protection against a lethal pneumonic plague challenge (33×LD50 of the fully virulent Y. pestis CO92 strain) and 94% against a high challenge dose (3,300×LD50). Both F1 and other Yersinia antigens were recognized and V674pF1 efficiently protected against a F1-negative Y. pestis. Conclusions and Significance The encapsulated Y. pseudotuberculosis V674pF1 is an efficient live oral vaccine against pneumonic plague, and could be developed for mass vaccination in tropical endemic areas to control pneumonic plague transmission and mortality. PMID:22348169

An encapsulated Yersinia pseudotuberculosis is a highly efficient vaccine against pneumonic plague.

PubMed

Derbise, Anne; Cerdà Marín, Alba; Ave, Patrick; Blisnick, Thierry; Huerre, Michel; Carniel, Elisabeth; Demeure, Christian E

2012-01-01

Plague is still a public health problem in the world and is re-emerging, but no efficient vaccine is available. We previously reported that oral inoculation of a live attenuated Yersinia pseudotuberculosis, the recent ancestor of Yersinia pestis, provided protection against bubonic plague. However, the strain poorly protected against pneumonic plague, the most deadly and contagious form of the disease, and was not genetically defined. The sequenced Y. pseudotuberculosis IP32953 has been irreversibly attenuated by deletion of genes encoding three essential virulence factors. An encapsulated Y. pseudotuberculosis was generated by cloning the Y. pestis F1-encoding caf operon and expressing it in the attenuated strain. The new V674pF1 strain produced the F1 capsule in vitro and in vivo. Oral inoculation of V674pF1 allowed the colonization of the gut without lesions to Peyer's patches and the spleen. Vaccination induced both humoral and cellular components of immunity, at the systemic (IgG and Th1 cells) and the mucosal levels (IgA and Th17 cells). A single oral dose conferred 100% protection against a lethal pneumonic plague challenge (33×LD(50) of the fully virulent Y. pestis CO92 strain) and 94% against a high challenge dose (3,300×LD(50)). Both F1 and other Yersinia antigens were recognized and V674pF1 efficiently protected against a F1-negative Y. pestis. The encapsulated Y. pseudotuberculosis V674pF1 is an efficient live oral vaccine against pneumonic plague, and could be developed for mass vaccination in tropical endemic areas to control pneumonic plague transmission and mortality.

Hybrid Encapsulated Ionic Liquids for Post-Combustion Carbon Dioxide (CO 2) Capture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brennecke, Joan F; Degnan, Jr, Thomas Francis; McCready, Mark J.

Ionic liquids (ILs) and Phase Change Ionic Liquids (PCILs) are excellent materials for selective removal of carbon dioxide from dilute post-combustion streams. However, they are typically characterized as having high viscosities, which impairs their effectiveness due to mass transfer limitations, caused by the high viscosities. In this project, we are examining the benefits of encapsulating ILs and PCILs in thin polymeric shells to produce particles of approximately 100 to 600 µm in diameter that can be used in a fluidized bed absorber. The particles are produced by microencapsulation of the ILs and PCILs in CO 2-permeable polymer shells. Here wemore » report on the encapsulation of the IL and PCIL materials, thermodynamic testing of the encapsulated materials, mass transfer measurements in both a fluidized bed and a packed bed, determination of the effect of impurities (SO 2, NO x and water) on the free and encapsulated IL and PCIL, recyclability of the CO 2 uptake, selection and synthesis of kg quantities of the IL and PCIL, identification of scale-up methods for encapsulation and production of a kg quantity of the PCIL, construction and shakedown of the laboratory scale unit to test the encapsulated particles for CO 2 capture ability and efficiency, use of our mass transfer model to predict mass transfer and identify optimal properties of the encapsulated particles, and initial testing of the encapsulated particles in the laboratory scale unit. We also show our attempts at developing shell materials that are resistant to water permeation. Overall, we have shown that the selected IL and PCIL can be successfully encapsulated in polymer shells and the methods scaled up to production levels. The IL/PCIL and encapsulated IL/PCIL react irreversibly with SO 2 and NO x so the CO 2 capture unit would need to be placed after the flue gas desulfurization and NO x reduction units. However, the reaction with CO 2 in the presence of water is completely reversible. Therefore, it is not necessary to exclude water from the capsules. Mass transfer in the fluidized and packed beds confirm that the fluidized bed arrangement is preferred and that the mass transfer can be predicted accurately by the rate based model that we have developed. Absorption and desorption experiments in the laboratory scale unit show good uptake and recyclability.« less

Improved sugar co-utilisation by encapsulation of a recombinant Saccharomyces cerevisiae strain in alginate-chitosan capsules

PubMed Central

2014-01-01

Background Two major hurdles for successful production of second-generation bioethanol are the presence of inhibitory compounds in lignocellulosic media, and the fact that Saccharomyces cerevisiae cannot naturally utilise pentoses. There are recombinant yeast strains that address both of these issues, but co-utilisation of glucose and xylose is still an issue that needs to be resolved. A non-recombinant way to increase yeast tolerance to hydrolysates is by encapsulation of the yeast. This can be explained by concentration gradients occuring in the cell pellet inside the capsule. In the current study, we hypothesised that encapsulation might also lead to improved simultaneous utilisation of hexoses and pentoses because of such sugar concentration gradients. Results In silico simulations of encapsulated yeast showed that the presence of concentration gradients of inhibitors can explain the improved inhibitor tolerance of encapsulated yeast. Simulations also showed pronounced concentration gradients of sugars, which resulted in simultaneous xylose and glucose consumption and a steady state xylose consumption rate up to 220-fold higher than that found in suspension culture. To validate the results experimentally, a xylose-utilising S. cerevisiae strain, CEN.PK XXX, was constructed and encapsulated in semi-permeable alginate-chitosan liquid core gel capsules. In defined media, encapsulation not only increased the tolerance of the yeast to inhibitors, but also promoted simultaneous utilisation of glucose and xylose. Encapsulation of the yeast resulted in consumption of at least 50% more xylose compared with suspended cells over 96-hour fermentations in medium containing both sugars. The higher consumption of xylose led to final ethanol titres that were approximately 15% higher. In an inhibitory dilute acid spruce hydrolysate, freely suspended yeast cells consumed the sugars in a sequential manner after a long lag phase, whereas no lag phase was observed for the encapsulated yeast, and glucose, mannose, galactose and xylose were utilised in parallel from the beginning of the cultivation. Conclusions Encapsulation of xylose-fermenting S. cerevisiae leads to improved simultaneous and efficient utilisation of several sugars, which are utilised sequentially by suspended cells. The greatest improvement is obtained in inhibitory media. These findings show that encapsulation is a promising option for production of second-generation bioethanol. PMID:25050138

Microencapsulation of pancreatic islets with canine ear cartilage for immunoisolation.

PubMed

Lee, J I; Kim, H W; Kim, J Y; Bae, S J; Joo, D J; Huh, K H; Fang, Y H; Jeong, J H; Kim, M S; Kim, Y S

2012-05-01

Improving human islet transplantation is often limited by the shortage of donors and the side effects of immunosuppressive agents. If immunoisolation is properly used, it can overcome these obstacles. Because artificial materials are adopted in this technique, however, there are still multiple issues with biocompatibility and foreign body reactions. We developed a chondrocyte microencapsulated immunoisolated islet (CMI-islet) that allows living cells to act as the immunoisolating material. To manufacture CMI-islets for xenotransplantation, isolated rat pancreatic islets were placed on low cell-binding culture dishes. Subsequently, expanded canine auricular cartiage primary cells were seeded on these dishes at a high density and maintained in a suspended state via a shaking culture system. Morphological evaluations showed good islet viability and a clear progression of the islet- encapsulation events. When the cells were challenged with glucose, they were able to secrete sufficient insulin according to glucose concentrations. The CMI-islets responded better to the glucose challenge than did nude pancreatic islets and created better glucose-insulin feedback regulation. Moreover, insulin secretion into the culture medium was confirmed over a period of 100 days, showing the survival and secretory capacity of the CMI-islet cells. By microencapsulating pancreatic islets with recipient ear cartilage cells, long-term insulin secretion can be maintained and the response to glucose challenges improved. This new immunodelusion technology differs from other immunoisolation techniques in that the donor tissue is enclosed with the recipient's tissue, thus allowing the transplanted cells to be recognized as recipient cells. This microencapsulation method may lead to developing viable xenotransplantation techniques that do not use immunosuppressive drugs. Copyright © 2012 Elsevier Inc. All rights reserved.

Ramizol® encapsulation into extended release PLGA micro- and nanoparticle systems for subcutaneous and intramuscular administration: in vitro and in vivo evaluation.

PubMed

Wright, Leah; Rao, Shasha; Thomas, Nicky; Boulos, Ramiz A; Prestidge, Clive A

2018-04-11

Novel antibiotic Ramizol ® is advancing to clinical trials for the treatment of gastrointestinal Clostridium difficile associated disease. Despite this, previous studies have shown a rapid plasma clearance upon intravenous administration and low oral bioavailability indicating pure drug is unsuitable for systemic infection treatment following oral dosing. The current study aims to investigate the development of poly-lactic-(co-glycolic) acid (PLGA) particles to overcome this limitation and increase the systemic half-life following subcutaneous and intramuscular dosing. The development of new antibiotic treatments will help in combatting the rising incidence of antimicrobial resistance. Ramizol ® was encapsulated into PLGA nano and microparticles using nanoprecipitation and emulsification solvent evaporation techniques. Formulations were analyzed for particle size, loading level and encapsulation efficiency as well as in vitro drug release profiles. Final formulation was advanced to in vivo pharmacokinetic studies in Sprague-Dawley rats. Formulation technique showed major influence on particle size and loading levels with optimal loading of 9.4% and encapsulation efficiency of 92.06%, observed using emulsification solvent evaporation. Differences in formulation technique were also linked with subsequent differences in release profiles. Pharmacokinetic studies in Sprague-Dawley rats confirmed extended absorption and enhanced bioavailability following subcutaneous and intramuscular dosing with up to an 8-fold increase in T max and T 1/2 when compared to the oral and IV routes. Subcutaneous and intramuscular dosing of PLGA particles successfully increased systemic half-life and bioavailability of Ramizol ® . This formulation will allow further development of Ramizol ® for systemic infection eradication.

Encapsulation of lutein in liposomes using supercritical carbon dioxide.

PubMed

Zhao, Lisha; Temelli, Feral; Curtis, Jonathan M; Chen, Lingyun

2017-10-01

Liposomes loaded with lutein were prepared utilizing supercritical carbon dioxide (SC-CO 2 ). The effects of pressure, depressurization rate, temperature and lutein-to-lipid ratio on particle size distribution, zeta potential, encapsulation efficiency (EE), bioactive loading, morphology, phase transition and crystallinity were investigated. Liposomes prepared by the SC-CO 2 method had a particle size of 147.6±1.9nm-195.4±2.3nm, an encapsulation efficiency of 56.7±0.7%-97.0±0.8% and a zeta potential of -54.5±1.2mV to -61.7±0.6mV. A higher pressure (200-300bar) and depressurization rate (90-200bar/min) promoted a higher encapsulation of lutein whereas the lutein-to-lipid ratio had the dominant effect on the morphology of vesicles along with size distribution and EE. X-ray diffraction data implied a substantial drop in the crystallinity of lutein upon its redistribution in the liposome membranes. Differential scanning calorimetry indicated a broadened phase transition upon the simultaneous rearrangement of lutein and phospholipid molecules into liposomal vesicles. The SC-CO 2 method resulted in particle characteristics highly associated with the ability of CO 2 to disperse phospholipids and lutein molecules. It offers a promising approach to use dense phase CO 2 to homogenize hydrophobic or amphiphilic aggregates suspended in an aqueous medium and regulate the vesicular characteristics via pressure and depressurization rate. The SC-CO 2 method has potential for scalable production of liposomal nanovesicles with desirable characteristics and free of organic solvents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fast and efficient proteolysis by reusable pepsin-encapsulated magnetic sol-gel material for mass spectrometry-based proteomics applications.

PubMed

Kayili, H Mehmet; Salih, Bekir

2016-08-01

Hydrophobic silicon-based material having magnetic properties was fairly synthesized by a classical sol-gel approach. Pepsin enzyme was encapsulated in the sol-gel material and the enzyme activity was evaluated in consequence of the digestion of some common proteins such as α- and β-casein, cytochrome c, myoglobin, and bovine serum albumin (BSA) both in a single protein batch and in the protein mixture. The optimum digestion time of the studied proteins using pepsin-encapsulated magnetic sol-gel material was found to be 20min. To produce the magnetic sol-gel material for convenient and easy proteomics applications, Fe3O4 was doped inside sol-gel material during the gelation step. It was observed that the activity of encapsulated pepsin was not affected by the amount of Fe3O4. Poly(ethylene glycol) was also inserted in sol-gel bulk to obtain suitable roughness and increase the hydrophilicity of the material surface to let protein molecules reach to the sol-gel material easily. The digestion of the protein mixture and non-fat bovine milk was performed with the pepsin-encapsulated magnetic sol-gel material and the digested solutions were analyzed using SDS-PAGE, MALDI-TOF-MS and LC-MS/MS for the protein identification. Reusability of the pepsin-encapsulated sol-gel material was examined and it was determined that they could be used at least 20 times. Finally, IgG digestions with a fast incubation time period were carried out using pepsin-encapsulated sol-gel material for generation of (Fab)2 product to evaluate the kinetic performance of the material. Copyright © 2016 Elsevier B.V. All rights reserved.

Formulation and in vitro characterization of protein-loaded liposomes

NASA Astrophysics Data System (ADS)

Kuzimski, Lauren

Background/Objective: Protein-based drugs are increasingly used to treat a variety of conditions including cancer and cardio-vascular disease. Due to the immune system's innate ability to degrade the foreign particles quickly, protein-based treatments are generally short-lived. To address this limitation, the objective of the study was to: 1) develop protein-loaded liposomes; 2) characterize size, stability, encapsulation efficiency and rate of protein release; and 3) determine intracellular uptake and distribution; and 4) protein structural changes. Method: Liposomes were loaded with a fluorescent-albumin using freeze-thaw (F/T) methodology. Albumin encapsulation and release were quantified by fluorescence spectroscopic techniques. Flow cytometry was used to determine liposome uptake by macrophages. Epifluorescence microscopy was used to determine cellular distribution of liposomes. Stability was determined using dynamic light scattering by measuring liposome size over one month period. Protein structure was determined using circular dichroism (CD). Result: Encapsulation of albumin in liposome was ˜90% and was dependent on F/T rates, with fifteen cycles yielding the highest encapsulation efficacy (p < 0.05). Albumin-loaded liposomes demonstrated consistent size (<300nm). Release of encapsulated albumin in physiological buffer at 25°C was ˜60% in 72 h. Fluorescence imaging suggested an endosomal route of cellular entry for the FITC-albumin liposome with maximum uptake rates in immune cells (30% at 2hour incubation). CD suggested protein structure is minimally impacted by freeze-thaw methodology. Conclusion: Using F/T as a loading method, we were able to successfully achieve a protein-loaded liposome that was under 300nm, had encapsulation of ˜90%. Synthesized liposomes demonstrated a burst release of encapsulate protein (60%) at 72 hours. Cellular trafficking confirmed endosomal uptake, and minimal protein damage was noticed in CD.

Dual-modality, fluorescent, PLGA encapsulated bismuth nanoparticles for molecular and cellular fluorescence imaging and computed tomography

NASA Astrophysics Data System (ADS)

Swy, Eric R.; Schwartz-Duval, Aaron S.; Shuboni, Dorela D.; Latourette, Matthew T.; Mallet, Christiane L.; Parys, Maciej; Cormode, David P.; Shapiro, Erik M.

2014-10-01

Reports of molecular and cellular imaging using computed tomography (CT) are rapidly increasing. Many of these reports use gold nanoparticles. Bismuth has similar CT contrast properties to gold while being approximately 1000-fold less expensive. Herein we report the design, fabrication, characterization, and CT and fluorescence imaging properties of a novel, dual modality, fluorescent, polymer encapsulated bismuth nanoparticle construct for computed tomography and fluorescence imaging. We also report on cellular internalization and preliminary in vitro and in vivo toxicity effects of these constructs. 40 nm bismuth(0) nanocrystals were synthesized and encapsulated within 120 nm Poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles by oil-in-water emulsion methodologies. Coumarin-6 was co-encapsulated to impart fluorescence. High encapsulation efficiency was achieved ~70% bismuth w/w. Particles were shown to internalize within cells following incubation in culture. Bismuth nanocrystals and PLGA encapsulated bismuth nanoparticles exhibited >90% and >70% degradation, respectively, within 24 hours in acidic, lysosomal environment mimicking media and both remained nearly 100% stable in cytosolic/extracellular fluid mimicking media. μCT and clinical CT imaging was performed at multiple X-ray tube voltages to measure concentration dependent attenuation rates as well as to establish the ability to detect the nanoparticles in an ex vivo biological sample. Dual fluorescence and CT imaging is demonstrated as well. In vivo toxicity studies in rats revealed neither clinically apparent side effects nor major alterations in serum chemistry and hematology parameters. Calculations on minimal detection requirements for in vivo targeted imaging using these nanoparticles are presented. Indeed, our results indicate that these nanoparticles may serve as a platform for sensitive and specific targeted molecular CT and fluorescence imaging.Reports of molecular and cellular imaging using computed tomography (CT) are rapidly increasing. Many of these reports use gold nanoparticles. Bismuth has similar CT contrast properties to gold while being approximately 1000-fold less expensive. Herein we report the design, fabrication, characterization, and CT and fluorescence imaging properties of a novel, dual modality, fluorescent, polymer encapsulated bismuth nanoparticle construct for computed tomography and fluorescence imaging. We also report on cellular internalization and preliminary in vitro and in vivo toxicity effects of these constructs. 40 nm bismuth(0) nanocrystals were synthesized and encapsulated within 120 nm Poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles by oil-in-water emulsion methodologies. Coumarin-6 was co-encapsulated to impart fluorescence. High encapsulation efficiency was achieved ~70% bismuth w/w. Particles were shown to internalize within cells following incubation in culture. Bismuth nanocrystals and PLGA encapsulated bismuth nanoparticles exhibited >90% and >70% degradation, respectively, within 24 hours in acidic, lysosomal environment mimicking media and both remained nearly 100% stable in cytosolic/extracellular fluid mimicking media. μCT and clinical CT imaging was performed at multiple X-ray tube voltages to measure concentration dependent attenuation rates as well as to establish the ability to detect the nanoparticles in an ex vivo biological sample. Dual fluorescence and CT imaging is demonstrated as well. In vivo toxicity studies in rats revealed neither clinically apparent side effects nor major alterations in serum chemistry and hematology parameters. Calculations on minimal detection requirements for in vivo targeted imaging using these nanoparticles are presented. Indeed, our results indicate that these nanoparticles may serve as a platform for sensitive and specific targeted molecular CT and fluorescence imaging. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr01405g

Facile thiol-ene thermal crosslinking reaction facilitated hole-transporting layer for highly efficient and stable perovskite solar cells

DOE PAGES

Li, Zhong'an; Zhu, Zonglong; Chueh, Chu -Chen; ...

2016-08-08

A crosslinked organic hole-transporting layer (HTL) is developed to realize highly efficient and stable perovskite solar cells via a facile thiol-ene thermal reaction. This crosslinked HTL not only facilitates hole extraction from perovskites, but also functions as an effective protective barrier. Lastly, a high-performance (power conversion efficiency: 18.3%) device is demonstrated to show respectable photo and thermal stability without encapsulation.

Subcutaneous insulin therapy - end of the road after 80 years?

PubMed

Leifke, E; Strack, T R

2014-02-01

Subcutaneous (SC) insulin therapy has been a mainstay of pharmacological diabetes management from the moment insulin was successfully developed as treatment. Insulin formulations have become more refined and less allergenic over time, and ancillary technologies such as injection devices and glucose measurement tools have evolved to the extent of permitting closed-loop therapy. However, investigations have continued exploring alternative routes of administration with the ultimate goal of implantable islet replacements, whether cell- or "silicon"-based. Progress on these lines of research, however, has been slow to present patients with viable options: alternative delivery routes have failed to deliver insulin reliably and with commercially viable efficiency, while beta cell transplantation continues to struggle with tissue availability and in vivo viability. In the meantime, SC insulin formulations have advanced for rapid- and long-acting formulations, to better meet typical insulin requirements across the day. Thus, SC insulin will likely remain a key technology for the foreseeable future in order to address the needs of an ever larger number of insulin-dependent patients with diabetes. Copyright 2014 Prous Science, S.A.U. or its licensors. All rights reserved.

Insulin-loaded pH-sensitive hyaluronic acid nanoparticles enhance transcellular delivery.

PubMed

Han, Lina; Zhao, Yuefang; Yin, Lifang; Li, Ruiming; Liang, Yang; Huang, Huan; Pan, Shirong; Wu, Chuanbin; Feng, Min

2012-09-01

In the present study, we developed novel insulin-loaded hyaluronic acid (HA) nanoparticles for insulin delivery. The insulin-loaded HA nanoparticles were prepared by reverse-emulsion-freeze-drying method. This method led to a homogenous population of small HA nanoparticles with average size of 182.2 nm and achieved high insulin entrapment efficiencies (approximately 95%). The pH-sensitive HA nanoparticles as an oral delivery carrier showed advantages in protecting insulin against the strongly acidic environment of the stomach, and not destroying the junction integrity of epithelial cells which promise long-term safety for chronic insulin treatment. The results of transport experiments suggested that insulin-loaded HA nanoparticles were transported across Caco-2 cell monolayers mainly via transcellular pathway and their apparent permeability coefficient from apical to basolateral had more than twofold increase compared with insulin solution. The efflux ratio of P (app) (B to A) to P (app) (A to B) less than 1 demonstrated that HA nanoparticle-mediated transport of insulin across Caco-2 cell monolayers underwent active transport. The results of permeability through the rat small intestine confirmed that HA nanoparticles significantly enhanced insulin transport through the duodenum and ileum. Diabetic rats treated with oral insulin-loaded HA nanoparticles also showed stronger hypoglycemic effects than insulin solution. Therefore, these HA nanoparticles could be a promising candidate for oral insulin delivery.

Encapsulation of sex sorted boar semen: sperm membrane status and oocyte penetration parameters.

PubMed

Spinaci, Marcella; Chlapanidas, Theodora; Bucci, Diego; Vallorani, Claudia; Perteghella, Sara; Lucconi, Giulia; Communod, Ricardo; Vigo, Daniele; Galeati, Giovanna; Faustini, Massimo; Torre, Maria Luisa

2013-03-01

Although sorted semen is experimentally used for artificial, intrauterine, and intratubal insemination and in vitro fertilization, its commercial application in swine species is still far from a reality. This is because of the low sort rate and the large number of sperm required for routine artificial insemination in the pig, compared with other production animals, and the greater susceptibility of porcine spermatozoa to stress induced by the different sex sorting steps and the postsorting handling protocols. The encapsulation technology could overcome this limitation in vivo, protecting and allowing the slow release of low-dose sorted semen. The aim of this work was to evaluate the impact of the encapsulation process on viability, acrosome integrity, and on the in vitro fertilizing potential of sorted boar semen. Our results indicate that the encapsulation technique does not damage boar sorted semen; in fact, during a 72-hour storage, no differences were observed between liquid-stored sorted semen and encapsulated sorted semen in terms of plasma membrane (39.98 ± 14.38% vs. 44.32 ± 11.72%, respectively) and acrosome integrity (74.32 ± 12.17% vs. 66.07 ± 10.83%, respectively). Encapsulated sorted spermatozoa presented a lower penetration potential than nonencapsulated ones (47.02% vs. 24.57%, respectively, P < 0.0001), and a significant reduction of polyspermic fertilization (60.76% vs. 36.43%, respectively, polyspermic ova/total ova; P < 0.0001). However, no difference (P > 0.05) was observed in terms of total efficiency of fertilization expressed as normospermic oocytes/total oocytes (18.45% vs. 15.43% for sorted diluted and sorted encapsulated semen, respectively). The encapsulation could be an alternative method of storing of pig sex sorted spermatozoa and is potentially a promising technique in order to optimize the use of low dose of sexed spermatozoa in vivo. Copyright © 2013 Elsevier Inc. All rights reserved.

Rapid Characterization of Insulin Modifications and Sequence Variations by Proteinase K Digestion and UHPLC-ESI-MS

NASA Astrophysics Data System (ADS)

Yang, Rong-Sheng; Tang, Weijuan; Sheng, Huaming; Meng, Fanyu

2018-01-01

Discovery of novel insulin analogs as therapeutics has remained an active area of research. Compared with native human insulin, insulin analog molecules normally incorporate either covalent modifications or amino acid sequence variations. From the drug discovery and development perspective, methods for efficient and detailed characterization of these primary structural changes are very important. In this report, we demonstrate that proteinase K digestion coupled with UPLC-ESI-MS analysis provides a simple and rapid approach to characterize the modifications and sequence variations of insulin molecules. A commercially available proteinase K digestion kit was used to process recombinant human insulin (RHI), insulin glargine, and fluorescein isothiocynate-labeled recombinant human insulin (FITC-RHI) samples. The LC-MS data clearly showed that RHI and insulin glargine samples can be differentiated, and the FITC modifications in all three amine sites of the RHI molecule are well characterized. The end-to-end experiment and data interpretation was achieved within 60 min. This approach is fast and simple, and can be easily implemented in early drug discovery laboratories to facilitate research on more advanced insulin therapeutics. [Figure not available: see fulltext.

Rapid Characterization of Insulin Modifications and Sequence Variations by Proteinase K Digestion and UHPLC-ESI-MS

NASA Astrophysics Data System (ADS)

Yang, Rong-Sheng; Tang, Weijuan; Sheng, Huaming; Meng, Fanyu

2018-05-01

Discovery of novel insulin analogs as therapeutics has remained an active area of research. Compared with native human insulin, insulin analog molecules normally incorporate either covalent modifications or amino acid sequence variations. From the drug discovery and development perspective, methods for efficient and detailed characterization of these primary structural changes are very important. In this report, we demonstrate that proteinase K digestion coupled with UPLC-ESI-MS analysis provides a simple and rapid approach to characterize the modifications and sequence variations of insulin molecules. A commercially available proteinase K digestion kit was used to process recombinant human insulin (RHI), insulin glargine, and fluorescein isothiocynate-labeled recombinant human insulin (FITC-RHI) samples. The LC-MS data clearly showed that RHI and insulin glargine samples can be differentiated, and the FITC modifications in all three amine sites of the RHI molecule are well characterized. The end-to-end experiment and data interpretation was achieved within 60 min. This approach is fast and simple, and can be easily implemented in early drug discovery laboratories to facilitate research on more advanced insulin therapeutics. [Figure not available: see fulltext.

Treating acute cystitis with biodegradable micelle-encapsulated quercetin

PubMed Central

Wang, Bi Lan; Gao, Xiang; Men, Ke; Qiu, Jinfeng; Yang, Bowen; Gou, Ma Ling; Huang, Mei Juan; Huang, Ning; Qian, Zhi Yong; Zhao, Xia; Wei, Yu Quan

2012-01-01

Intravesical application of an anti-inflammatory drug is an efficient strategy for acute cystitis therapy. Quercetin (QU) is a potent anti-inflammatory agent; however, its poor water solubility restricts its clinical application. In an attempt to improve water solubility of QU, biodegradable monomethoxy poly(ethylene glycol)-poly(ɛ-caprolactone) (MPEG-PCL) micelles were used to encapsulate QU by self-assembly methods, creating QU/MPEG-PCL micelles. These QU/MPEG-PCL micelles with DL of 7% had a mean particle size of <34 nm, and could release QU for an extended period in vitro. The in vivo study indicated that intravesical application of MPEG-PCL micelles did not induce any toxicity to the bladder, and could efficiently deliver cargo to the bladder. Moreover, the therapeutic efficiency of intravesical administration of QU/MPEG-PCL micelles on acute cystitis was evaluated in vivo. Results indicated that QU/MPEG-PCL micelle treatment efficiently reduced the edema and inflammatory cell infiltration of the bladder in an Escherichia coli-induced acute cystitis model. These data suggested that MPEG-PCL micelle was a candidate intravesical drug carrier, and QU/MPEG-PCL micelles may have potential application in acute cystitis therapy. PMID:22661886

Microfluidic Encapsulation of Prickly Zinc-Doped Copper Oxide Nanoparticles with VD1142 Modified Spermine Acetalated Dextran for Efficient Cancer Therapy.

PubMed

Zhang, Hongbo; Liu, Dongfei; Wang, Liang; Liu, Zehua; Wu, Runrun; Janoniene, Agne; Ma, Ming; Pan, Guoqing; Baranauskiene, Lina; Zhang, Linlin; Cui, Wenguo; Petrikaite, Vilma; Matulis, Daumantas; Zhao, Hongxia; Pan, Jianming; Santos, Hélder A

2017-06-01

Structural features of nanoparticles have recently been explored for different types of applications. To explore specific particles as nanomedicine and physically destroy cancer is interesting, which might avoid many obstacles in cancer treatment, for example, drug resistance. However, one key element and technical challenge of those systems is to selectively target them to cancer cells. As a proof-of-concept, Prickly zinc-doped copper oxide (Zn-CuO) nanoparticles (Prickly NPs) have been synthesized, and subsequently encapsulated in a pH-responsive polymer; and the surface has been modified with a novel synthesized ligand, 3-(cyclooctylamino)-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl] benzenesulfonamide (VD1142). The Prickly NPs exhibit very effective cancer cell antiproliferative capability. Moreover, the polymer encapsulation shields the Prickly NPs from unspecific nanopiercing and, most importantly, VD1142 endows the engineered NPs to specifically target to the carbonic anhydrase IX, a transmembrane protein overexpressed in a wide variety of cancer tumors. Intracellularly, the Prickly NPs disintegrate into small pieces that upon endosomal escape cause severe damage to the endoplasmic reticulum and mitochondria of the cells. The engineered Prickly NP is promising in efficient and targeted cancer treatment and it opens new avenue in nanomedication. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Curcumin-encapsulated polymeric micelles suppress the development of colon cancer in vitro and in vivo.

PubMed

Yang, Xi; Li, Zhaojun; Wang, Ning; Li, Ling; Song, Linjiang; He, Tao; Sun, Lu; Wang, Zhihan; Wu, Qinjie; Luo, Na; Yi, Cheng; Gong, Changyang

2015-05-18

To develop injectable formulation and improve the stability of curcumin (Cur), Cur was encapsulated into monomethyl poly (ethylene glycol)-poly (ε-caprolactone)-poly (trimethylene carbonate) (MPEG-P(CL-co-TMC)) micelles through a single-step solid dispersion method. The obtained Cur micelles had a small particle size of 27.6 ± 0.7 nm with polydisperse index (PDI) of 0.11 ± 0.05, drug loading of 14.07 ± 0.94%, and encapsulation efficiency of 96.08 ± 3.23%. Both free Cur and Cur micelles efficiently suppressed growth of CT26 colon carcinoma cells in vitro. The results of in vitro anticancer studies confirmed that apoptosis induction and cellular uptake on CT26 cells had completely increased in Cur micelles compared with free Cur. Besides, Cur micelles were more effective in suppressing the tumor growth of subcutaneous CT26 colon in vivo, and the mechanisms included the inhibition of tumor proliferation and angiogenesis and increased apoptosis of tumor cells. Furthermore, few side effects were found in Cur micelles. Overall, our findings suggested that Cur micelles could be a stabilized aqueous formulation for intravenous application with improved antitumor activity, which may be a potential treatment strategy for colon cancer in the future.

Zinc phthalocyanine-loaded PLGA biodegradable nanoparticles for photodynamic therapy in tumor-bearing mice.

PubMed

Fadel, Maha; Kassab, Kawser; Fadeel, Doa Abdel

2010-03-01

Nanoparticles formulated from the biodegradable copolymer poly(lactic-coglycolic acid) (PLGA) were investigated as a drug delivery system to enhance tissue uptake, permeation, and targeting of zinc(II) phthalocyanine (ZnPc) for photodynamic therapy. Three ZnPc nanoparticle formulations were prepared using a solvent emulsion evaporation method and the influence of sonication time on nanoparticle shape, encapsulation and size distribution, in vitro release, and in vivo photodynamic efficiency in tumor-bearing mice were studied. Sonication time did not affect the process yield or encapsulation efficiency, but did affect significantly the particle size. Sonication for 20 min reduced the mean particle size to 374.3 nm and the in vitro release studies demonstrated a controlled release profile of ZnPc. Tumor-bearing mice injected with ZnPc nanoparticles exhibited significantly smaller mean tumor volume, increased tumor growth delay and longer survival compared with the control group and the group injected with free ZnPc during the time course of the experiment. Histopathological examination of tumor from animals treated with PLGA ZnPc showed regression of tumor cells, in contrast to those obtained from animals treated with free ZnPc. The results indicate that ZnPc encapsulated in PLGA nanoparticles is a successful delivery system for improving photodynamic activity in the target tissue.

Optimization of Microencapsulation Composition of Menthol, Vanillin, and Benzyl Acetate inside Polyvinyl Alcohol with Coacervation Method for Application in Perfumery

NASA Astrophysics Data System (ADS)

Sahlan, Muhamad; Raihani Rahman, Mohammad

2017-07-01

One of many applications of essential oils is as fragrance in perfumery. Menthol, benzyl acetate, and vanillin, each represents olfactive characteristic of peppermint leaves, jasmine flowers, and vanilla beans, are commonly used in perfumery. These components are highly volatile, hence the fragrance components will quickly evaporate resulting in short-lasting scent and low shelf life. In this research, said components have been successfully encapsulated simultaneously inside Polyvinyl Alcohol (PVA) using simple coacervation method to increase its shelf life. Optimization has been done using Central Composite Diagram with 4 independent variables, i.e. composition of menthol, benzyl acetate, vanillin, and tergitol 15-S-9 (as emulsifier). Encapsulation efficiency, loading capacity, and microcapsule size have been measured. In optimized composition of menthol (13.98 %w/w), benzyl acetate (14.75 %w/w), vanillin (17.84 %w/w), and tergitol 15-S-9 (13.4 %w/w) encapsulation efficiency of 97,34% and loading capacity of 46,46% have been achieved. Mean diameter of microcapsule is 20,24 μm and within range of 2,011-36,24 μm. Final product was achieved in the form of cross linked polyvinyl alcohol with hydrogel consistency and orange to yellow in color.

Development and characterization of electrosprayed Alyssum homolocarpum seed gum nanoparticles for encapsulation of d-limonene.

PubMed

Khoshakhlagh, Khadije; Koocheki, Arash; Mohebbi, Mohebbat; Allafchian, Alireza

2017-03-15

In this study, the feasibility of developing Alyssum homolocarpum seed gum (AHSG) nanocapsules containing d-limonene by electrospraying has been investigated. d-limonene emulsions with constant AHSG (0.5% w/w) and various flavor concentrations (10-30% based on gum weight) with 0.1% Tween 20 were electrosprayed at 20kV and 0.1ml/h of flow rate. The effects of key parameters of emulsions (rheological properties, droplet size, surface tension and electrical conductivity) on the morphology of structures have been studied. The morphology of nanocapsules had strong dependency on solution properties. The aggregated irregular shaped nanoparticles were obtained from electrospraying of AHSG solution. After incorporation of 10 and 20% d-limonene, spherical nanocapsules were yielded. However, morphology of nanocapsules changed to nanofibers by increasing the flavor content to 30%. The encapsulation efficiency for 10 and 20% d-limonene loaded nanocapsules was around 87-93%. Attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) were also employed to study the physicochemical characteristics of nanocapsules. These experiments provided evidences that electrosprayed AHSG nanoparticles introduce a novel and efficient carrier for encapsulation of bioactive ingredients. Copyright © 2016 Elsevier Inc. All rights reserved.

Preparation of a Nanoscaled Poly(vinyl alcohol)/Hydroxyapatite/DNA Complex Using High Hydrostatic Pressure Technology for In Vitro and In Vivo Gene Delivery.

PubMed

Kimura, Tsuyoshi; Nibe, Yoichi; Funamoto, Seiichi; Okada, Masahiro; Furuzono, Tsutomu; Ono, Tsutomu; Yoshizawa, Hidekazu; Fujisato, Toshiya; Nam, Kwangwoo; Kishida, Akio

2011-01-01

Our previous research showed that poly(vinyl alcohol) (PVA) nanoparticles incorporating DNA with hydrogen bonds obtained by high hydrostatic pressurization are able to deliver DNA without any significant cytotoxicity. To enhance transfection efficiency of PVA/DNA nanoparticles, we describe a novel method to prepare PVA/DNA nanoparticles encapsulating nanoscaled hydroxyapatites (HAps) prepared by high hydrostatic pressurization (980 MPa), which is designed to facilitate endosomal escape induced by dissolving HAps in an endosome. Scanning electron microscopic observation and dynamic light scattering measurement revealed that HAps were significantly encapsulated in PVA/HAp/DNA nanoparticles. The cytotoxicity, cellular uptake, and transgene expression of PVA/HAp/DNA nanoparticles were investigated using COS-7 cells. It was found that, in contrast to PVA/DNA nanoparticles, their internalization and transgene expression increased without cytotoxicity occurring. Furthermore, a similar level of transgene expression between plasmid DNA and PVA/HAp/DNA nanoparticles was achieved using in vivo hydrodynamic injection. Our results show a novel method of preparing PVA/DNA nanoparticles encapsulating HAp nano-crystals by using high hydrostatic pressure technology and the potential use of HAps as an enhancer of the transfection efficiency of PVA/DNA nanoparticles without significant cytotoxicity.