Improved drug loading and antibacterial activity of minocycline-loaded PLGA nanoparticles prepared by solid/oil/water ion pairing method.

PubMed

Kashi, Tahereh Sadat Jafarzadeh; Eskandarion, Solmaz; Esfandyari-Manesh, Mehdi; Marashi, Seyyed Mahmoud Amin; Samadi, Nasrin; Fatemi, Seyyed Mostafa; Atyabi, Fatemeh; Eshraghi, Saeed; Dinarvand, Rassoul

2012-01-01

Low drug entrapment efficiency of hydrophilic drugs into poly(lactic-co-glycolic acid) (PLGA) nanoparticles is a major drawback. The objective of this work was to investigate different methods of producing PLGA nanoparticles containing minocycline, a drug suitable for periodontal infections. Different methods, such as single and double solvent evaporation emulsion, ion pairing, and nanoprecipitation were used to prepare both PLGA and PEGylated PLGA nanoparticles. The resulting nanoparticles were analyzed for their morphology, particle size and size distribution, drug loading and entrapment efficiency, thermal properties, and antibacterial activity. The nanoparticles prepared in this study were spherical, with an average particle size of 85-424 nm. The entrapment efficiency of the nanoparticles prepared using different methods was as follows: solid/oil/water ion pairing (29.9%) > oil/oil (5.5%) > water/oil/water (4.7%) > modified oil/water (4.1%) > nano precipitation (0.8%). Addition of dextran sulfate as an ion pairing agent, acting as an ionic spacer between PEGylated PLGA and minocycline, decreased the water solubility of minocycline, hence increasing the drug entrapment efficiency. Entrapment efficiency was also increased when low molecular weight PLGA and high molecular weight dextran sulfate was used. Drug release studies performed in phosphate buffer at pH 7.4 indicated slow release of minocycline from 3 days to several weeks. On antibacterial analysis, the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles was at least two times lower than that of the free drug. Novel minocycline-PEGylated PLGA nanoparticles prepared by the ion pairing method had the best drug loading and entrapment efficiency compared with other prepared nanoparticles. They also showed higher in vitro antibacterial activity than the free drug.

Improved drug loading and antibacterial activity of minocycline-loaded PLGA nanoparticles prepared by solid/oil/water ion pairing method

PubMed Central

Kashi, Tahereh Sadat Jafarzadeh; Eskandarion, Solmaz; Esfandyari-Manesh, Mehdi; Marashi, Seyyed Mahmoud Amin; Samadi, Nasrin; Fatemi, Seyyed Mostafa; Atyabi, Fatemeh; Eshraghi, Saeed; Dinarvand, Rassoul

2012-01-01

Background Low drug entrapment efficiency of hydrophilic drugs into poly(lactic-co-glycolic acid) (PLGA) nanoparticles is a major drawback. The objective of this work was to investigate different methods of producing PLGA nanoparticles containing minocycline, a drug suitable for periodontal infections. Methods Different methods, such as single and double solvent evaporation emulsion, ion pairing, and nanoprecipitation were used to prepare both PLGA and PEGylated PLGA nanoparticles. The resulting nanoparticles were analyzed for their morphology, particle size and size distribution, drug loading and entrapment efficiency, thermal properties, and antibacterial activity. Results The nanoparticles prepared in this study were spherical, with an average particle size of 85–424 nm. The entrapment efficiency of the nanoparticles prepared using different methods was as follows: solid/oil/water ion pairing (29.9%) > oil/oil (5.5%) > water/oil/water (4.7%) > modified oil/water (4.1%) > nano precipitation (0.8%). Addition of dextran sulfate as an ion pairing agent, acting as an ionic spacer between PEGylated PLGA and minocycline, decreased the water solubility of minocycline, hence increasing the drug entrapment efficiency. Entrapment efficiency was also increased when low molecular weight PLGA and high molecular weight dextran sulfate was used. Drug release studies performed in phosphate buffer at pH 7.4 indicated slow release of minocycline from 3 days to several weeks. On antibacterial analysis, the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles was at least two times lower than that of the free drug. Conclusion Novel minocycline-PEGylated PLGA nanoparticles prepared by the ion pairing method had the best drug loading and entrapment efficiency compared with other prepared nanoparticles. They also showed higher in vitro antibacterial activity than the free drug. PMID:22275837

Solidification of liposomes by freeze-drying: the importance of incorporating gelatin as interior support on enhanced physical stability.

PubMed

Guan, Peipei; Lu, Yi; Qi, Jianping; Niu, Mengmeng; Lian, Ruyue; Wu, Wei

2015-01-30

The main purpose of this study was to investigate the effect of gelatin as interior support on the physical stability of freeze-dried liposomes. Anticancer agent paclitaxel (PTX) was selected as a model drug. Freeze-dried liposomes containing interior gelatin support (GLs) were prepared by thin-film dispersion/freeze-drying method. Several properties of the GLs, including entrapment efficiency, particle size and gelation temperature, were extensively characterized. Encapsulation efficiency of conventional liposomes (CLs) and liposomes containing lyoprotectants as interior support dropped to lower than 20% after reconstitution, while GLs still maintained an entrapment efficiency of over 84%. Scanning electron microscopy revealed well preserved liposomal structure of GLs after reconstitution. Meanwhile, the particle size and entrapment efficiency of GLs were also well preserved after reconstitution. In contrary, deformation of CLs and recrystallization of PTX were observed, as well as significant changes in particle size and entrapment efficiency. Taken together, interior gelatin support obviously enhanced the physical stability of liposomes against the lyophilization stress. Copyright © 2014 Elsevier B.V. All rights reserved.

Development and evaluation of N-naphthyl-N,O-succinyl chitosan micelles containing clotrimazole for oral candidiasis treatment.

PubMed

Tonglairoum, Prasopchai; Woraphatphadung, Thisirak; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Akkaramongkolporn, Prasert; Sajomsang, Warayuth; Opanasopit, Praneet

2017-03-01

Clotrimazole (CZ)-loaded N-naphthyl-N,O-succinyl chitosan (NSCS) micelles have been developed as an alternative for oral candidiasis treatment. NSCS was synthesized by reductive N-amination and N,O-succinylation. CZ was incorporated into the micelles using various methods, including the dropping method, the dialysis method, and the O/W emulsion method. The size and morphology of the CZ-loaded micelles were characterized using dynamic light scattering measurements (DLS) and a transmission electron microscope (TEM), respectively. The drug entrapment efficiency, loading capacity, release characteristics, and antifungal activity against Candida albicans were also evaluated. The CZ-loaded micelles prepared using different methods differed in the size of micelles. The micelles ranged in size from 120 nm to 173 nm. The micelles prepared via the O/W emulsion method offered the highest percentage entrapment efficiency and loading capacity. The CZ released from the CZ-loaded micelles at much faster rate compared to CZ powder. The CZ-loaded NSCS micelles can significantly hinder the growth of Candida cells after contact. These CZ-loaded NSCS micelles offer great antifungal activity and might be further developed to be a promising candidate for oral candidiasis treatment.

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.

Structure and properties of hybrid biopolymer particles fabricated by co-precipitation cross-linking dissolution procedure.

PubMed

Xiong, Yu; Georgieva, Radostina; Steffen, Axel; Smuda, Kathrin; Bäumler, Hans

2018-03-15

The Co-precipitation Crosslinking Dissolution technique (CCD-technique) allows a few-steps fabrication of particles composed of different biopolymers and bioactive agents under mild conditions. Morphology and properties of the fabricated biopolymer particles depend on the fabrication conditions, the nature of the biopolymers and additives, but also on the choice of the inorganic templates for co-precipitation. Here, we investigate the influence of an acidic biopolymer, hyaluronic acid (HA), on the formation of particles from bovine hemoglobin and bovine serum albumin applying co-precipitation with CaCO 3 and MnCO 3 . CaCO 3 templated biopolymer particles are almost spherical with particle size from 2 to 20 µm and protein entrapment efficiency from 13 to 77%. Presence of HA causes significant structural changes of the particles and decreasing protein entrapment efficiency. In contrast, MnCO 3 templated particles exhibit uniform peanut shape and submicron size with remarkably high protein entrapment efficiency of nearly 100%. Addition of HA has no influence on the protein entrapment efficiency or on morphology and size of the particles. These effects can be attributed to the strong interaction of Mn 2+ with proteins and much weaker interaction with HA. Therefore, entrapment efficiency, size and structure of biopolymer particles can be optimized by varying the mineral templates and additives. Copyright © 2017 Elsevier Inc. All rights reserved.

Poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped trans-cinnamaldehyde and eugenol for antimicrobial delivery applications.

PubMed

Gomes, Carmen; Moreira, Rosana G; Castell-Perez, Elena

2011-03-01

Eugenol and trans-cinnamaldehyde are natural compounds known to be highly effective antimicrobials; however, both are hydrophobic molecules, a limitation to their use within the food industry. The goal of this study was to synthesize spherical poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped eugenol and trans-cinnamaldehyde for future antimicrobial delivery applications. The emulsion evaporation method was used to form the nanoparticles in the presence of poly (vinyl alcohol) (PVA) as a surfactant. The inclusion of antimicrobial compounds into the PLGA nanoparticles was accomplished in the organic phase. Synthesis was followed by ultrafiltration (performed to eliminate the excess of PVA and antimicrobial compound) and freeze-drying. The nanoparticles were characterized by their shape, size, entrapment efficiency, and antimicrobial efficiency. The entrapment efficiency for eugenol and trans-cinnamaldehyde was approximately 98% and 92%, respectively. Controlled release experiments conducted in vitro at 37 °C and 100 rpm for 72 h showed an initial burst followed by a slower rate of release of the antimicrobial entrapped inside the PLGA matrix. All loaded nanoparticles formulations proved to be efficient in inhibiting growth of Salmonella spp. (Gram-negative bacterium) and Listeria spp. (Gram-positive bacterium) with concentrations ranging from 20 to 10 mg/mL. Results suggest that the application of these antimicrobial nanoparticles in food systems may be effective at inhibiting specific pathogens. Nanoencapsulation of lipophilic antimicrobial compounds has great potential for improving the effectiveness and efficiency of delivery in food systems. This study consisted of synthesizing PLGA nanoparticles with entrapped eugenol and trans-cinnamaldehyde. By characterizing these new delivery systems, one can understand the controlled-release mechanism and antimicrobial efficiency that provides a foundation that will enable food manufacturers to design smart food systems for future delivery applications, including packaging and processing, capable of ensuring food safety to consumers.

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.

Improved catalytic properties of Penicillium notatum lipase immobilized in nanoscale silicone polymeric films.

PubMed

Rehman, Saima; Wang, Ping; Bhatti, Haq Nawaz; Bilal, Muhammad; Asgher, Muhammad

2017-04-01

Lipases are one of the most proficient biocatalysts having enormous biotechnological prospective. Immobilization offers a potential solution to improve the stability and recycling characteristics of lipases. An extracellular lipase from Penicillium notatum (PNL) was immobilized in silicon polymers (SiP) through entrapment, and subsequently coated this matrix on the network of fibers in the sponges. The silicone polymers-immobilized lipase (SiP-lipase) displayed highest apparent activity and entrapment efficiency of 1.19Ug -1 polymers and 92.3%, respectively. It also exhibited greater catalytic activity in broad-working pHs and higher temperature than equivalent free-state of enzyme. Immobilization caused an improvement in thermo-stability of the lipase with an increase in energy of activation. The recycling potential of SiP-lipase was investigated. After reusing the sponge pieces for ten reaction cycles, the SiP preserved its structure without leakage of enzyme, and retained around 90% of its original activity. The SiP surface analysis was envisaged by scanning electron microscopy that further confirmed the recycling efficiency of SiP-lipase. Overall, SiP-lipase displayed a number of useful properties that make it a promising candidate for future applications in different chemical processes. Copyright © 2017 Elsevier B.V. All rights reserved.

Dorzolamide Loaded Niosomal Vesicles: Comparison of Passive and Remote Loading Methods

PubMed Central

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. PMID:28979296

Application of rotatable central composite design in the preparation and optimization of poly(lactic-co-glycolic acid) nanoparticles for controlled delivery of paclitaxel.

PubMed

Kollipara, Sivacharan; Bende, Girish; Movva, Snehalatha; Saha, Ranendra

2010-11-01

Polymeric carrier systems of paclitaxel (PCT) offer advantages over only available formulation Taxol® in terms of enhancing therapeutic efficacy and eliminating adverse effects. The objective of the present study was to prepare poly (lactic-co-glycolic acid) nanoparticles containing PCT using emulsion solvent evaporation technique. Critical factors involved in the processing method were identified and optimized by scientific, efficient rotatable central composite design aiming at low mean particle size and high entrapment efficiency. Twenty different experiments were designed and each formulation was evaluated for mean particle size and entrapment efficiency. The optimized formulation was evaluated for in vitro drug release, and absorption characteristics were studied using in situ rat intestinal permeability study. Amount of polymer and duration of ultrasonication were found to have significant effect on mean particle size and entrapment efficiency. First-order interactions of amount of miglyol with amount of polymer were significant in case of mean particle size, whereas second-order interactions of polymer were significant in mean particle size and entrapment efficiency. The developed quadratic model showed high correlation (R(2) > 0.85) between predicted response and studied factors. The optimized formulation had low mean particle size (231.68 nm) and high entrapment efficiency (95.18%) with 4.88% drug content. The optimized formulation showed controlled release of PCT for more than 72 hours. In situ absorption study showed faster and enhanced extent of absorption of PCT from nanoparticles compared to pure drug. The poly (lactic-co-glycolic acid) nanoparticles containing PCT may be of clinical importance in enhancing its oral bioavailability.

Nanoethosomes mediated transdermal delivery of vinpocetine for management of Alzheimer's disease.

PubMed

Moghaddam, Atefeh Afshar; Aqil, Mohd; Ahmad, Farhan J; Ali, Mushir M; Sultana, Yasmin; Ali, Asgar

2015-12-01

To develop and statistically optimize nanoethosomal formulation for transdermal delivery of vinpocetine as an anti-Alzheimer's drug. Box-Behnken experimental design was applied for optimization of nanoethosomes. The independent variables were phospholipid (X 1 ), Tween 80 (X 2 ) and Ethanol (X 3 ) while entrapment efficiency (Y 1 ), particle sizes (Y 2 ), elasticity (Y 3 ) and flux (Y 4 ) were the dependent variables. Optimized nanoethosomal vinpocetine formulation with mean particle size 50.57 ± 26.11 nm showed 97.51 ± 0.86% entrapment efficiency, achieved mean transdermal flux 925.60 ± 39.80 µg/cm 2 /h and elasticity of 86.61 ± 2.88. Ex-vivo study of nanoethosomal formulation showed a significant increase flux and entrapment efficiency compared with control vinpocetine solution. Our results suggest that nanoethosome is an efficient carrier for transdermal delivery of vinpocetine as compared to its oral form.

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.

[Orthogonal experiments for optimizing the formulation and preparation conditions of temozolomide solid lipid nanoparticles].

PubMed

Dou, Mingjin; Huang, Guihua; Xi, Yanwei; Zhang, Na

2008-10-01

TMZ-SLN were prepared by emulsification-low temperature solidification method with stearic acid. The formulation and the preparation conditions were optimized by orthogonal experiments using entrapment efficiency as the evaluation index. The morphology was detected by transmission electron microscope. The Zeta potentials and the particle size distribution were evaluated by Laser Doppler Anemometry. The entrapment efficiencies and the drug release characteristics in vitro were assessed. The result showed that TMZ-SLN were concinnous and spherical in shape. The mean diameter (d(av) ) was 65.0 +/- 6.2 nm and the Zeta potential was -37.2 mV. The average entrapment efficiency was 58.9% +/- 1.21 %. The drug release behavior in vitro conformed to Higuchi Equation. The formation of a new material phase was testified by analysis of differential scanning calorimetry.

Entrapping of fullerenes, nanotubes, and inorganic nanoparticles by a DNA-chitosan complex: a method for nanomaterials removal.

PubMed

Zinchenko, Anatoly A; Maeda, Noriko; Pu, Shengyan; Murata, Shizuaki

2013-05-07

We report a protocol for entrapping of various water-dispersed nanomaterials: fullerenes, multiwall carbon nanotubes, quantum dots (semiconductor nanoparticles), and gold nanorods, into a DNA-chitosan complex. In contrast to small-size nanomaterial particles, the bulky DNA-chitosan interpolyelectrolyte complex incorporating the dispersed nanomaterials can be easily separated from aqueous media by centrifugation, filtration, or decantation. While the removal of nanoparticles by centrifugation is equally efficient for every type of nanoparticles and reaches 100%, the higher efficiency of the nanomaterials removal by other two methods is favored by larger size of nanoparticles. The application of this entrapping protocol for removal of nanomaterials from water is discussed.

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.

Effect of Formulation Variables on Preparation of Celecoxib Loaded Polylactide-Co-Glycolide Nanoparticles

PubMed Central

Cooper, Dustin L.; Harirforoosh, Sam

2014-01-01

Polymer based nanoparticle formulations have been shown to increase drug bioavailability and/or reduce drug adverse effects. Nonsteroidal anti-inflammatory drugs (e.g. celecoxib) reduce prostaglandin synthesis and cause side effects such as gastrointestinal and renal complications. The aim of this study was to formulate celecoxib entrapped poly lactide-co-glycolide based nanoparticles through a solvent evaporation process using didodecyldimethylammonium bromide or poly vinyl alcohol as stabilizer. Nanoparticles were characterized for zeta potential, particle size, entrapment efficiency, and morphology. Effects of stabilizer concentration (0.1, 0.25, 0.5, and 1% w/v), drug amount (5, 10, 15, and 20 mg), and emulsifier (lecithin) on nanoparticle characterization were examined for formula optimization. The use of 0.1, 0.25, and 0.5% w/v didodecyldimethylammonium bromide resulted in a more than 5-fold increase in zeta potential and a more than 1.5-fold increase in entrapment efficiency with a reduction in particle size over 35%, when compared to stabilizer free formulation. Nanoparticle formulations were also highly influenced by emulsifier and drug amount. Using 0.25% w/v didodecyldimethylammonium bromide NP formulations, peak zeta potential was achieved using 15 mg celecoxib with emulsifier (17.15±0.36 mV) and 20 mg celecoxib without emulsifier (25.00±0.18 mV). Peak NP size reduction and entrapment efficiency was achieved using 5 mg celecoxib formulations with (70.87±1.24 nm and 95.55±0.66%, respectively) and without (92.97±0.51 nm and 95.93±0.27%, respectively) emulsifier. In conclusion, formulations using 5 mg celecoxib with 0.25% w/v didodecyldimethylammonium bromide concentrations produced nanoparticles exhibiting enhanced size reduction and entrapment efficiency. Furthermore, emulsifier free formulations demonstrated improved zeta potential when compared to formulations containing emulsifier (p<0.01). Therefore, our results suggest the use of emulsifier free 5 mg celecoxib drug formulations containing 0.25% w/v didodecyldimethylammonium bromide for production of polymeric NPs that demonstrate enhanced zeta potential, small particle size, and high entrapment efficiency. PMID:25502102

[Determination of content and entrapment efficiency of 20 (S)-protopanaxadiol in pharmacosomes by RP-HPLC method].

PubMed

Han, Meihua; Chen, Jing; Chen, Shilin; Wang, Xiangtao

2009-05-01

To establish a RP-HPLC method for content and entrapment efficiency of 20 (S)-protopanaxadiol in pharmacosomes. The separation was performed with a COSMOSIL 5 C18-MS-II column (4.6 mm x 250 mm, 5 mmicrom) using methanol-water (95:5) as the mobile phase and detected at 203 nm. The flow rate was 1.0 mL x min(-1) and 50 microL sample solution was injected for each time. The calibration curve was linear within the range 0.1-0.5 mg x mL(-1) (r = 0. 9999) , the intra-day RSD and inter-day RSD were less than 2% and the average recovery was between 101.44%-103.11% (n = 3). The method is simple, accurate, sensitive and applicable for determination of content and entrapment efficiency of 20 (S)-protopanaxadiol pharmacosomes.

Synchronous microencapsulation of multiple components in silymarin into PLGA nanoparticles by an emulsification/solvent evaporation method.

PubMed

Xie, Yunchang; Yi, Yueneng; Hu, Xiongwei; Shangguan, Mingzhu; Wang, Lijuan; Lu, Yi; Qi, Jianping; Wu, Wei

2016-09-01

The development of polymeric carriers loaded with extracts suffers from the drawback not to be able to incorporate simultaneously various pharmacological compounds into the formulation. The aim of this study was therefore to achieve synchronous microencapsulation of multiple components of silymarin into poly (lactic-co-glycolic acid) nanoparticle, the most commonly used polymeric carrier with biodegradability and safety. The main strategy taken was to improve the overall entrapment efficiency and to reduce the escaping ratio of the components of different physicochemical properties. The optimized nanoparticles were spherical in morphology with a mean particle size of 150 ± 5 nm. Under common preparative conditions, silybin and isosilybin were entrapped in high efficiency, whereas taxifolin, silychristin and silydianin, especially taxifolin, showed less entrapment because they were more hydrophilic. By changing the pH of the outer aqueous phase and saturating it with silymarin, the entrapment efficiency of taxifolin, silychristin and silydianin could be significantly improved to over 90%, the level similar to silybin and isosilybin, thereby achieving synchronous encapsulation. It could be concluded that synchronous encapsulation of multiple components of silymarin was achieved by optimizing the preparative variables.

Preparation and Characterization of Minoxidil Loaded Nanostructured Lipid Carriers.

PubMed

Wang, Wenxi; Chen, Lina; Huang, Xinyan; Shao, Anna

2017-02-01

Nanostructured lipid carriers (NLCs) are interesting delivery systems for enhancing the penetration of an active substance through the skin after topical administration. The present paper described the development of a novel NLCs for minoxidil (MXD) topical delivery. Stearic acid and oleic acid that showed the highest solubility for MXD were selected as solid lipid and liquid lipid, respectively, and the NLCs were prepared by hot high pressure homogenization method. The minoxidil loaded NLCs prepared accordingly to the optimal formulation exhibited spherical shape with a mean diameter of 281.4 ± 7.4 nm, polydispersity of 0.207 ± 0.009, zeta potential of -32.90 ± 1.23 mV, drug entrapment efficiency of 92.48 ± 0.31%, and drug loading of 13.85 ± 0.47%. Storage stability studies demonstrated that the particle size and entrapment efficiency of the MXD-NLCs were not changed during 3 months both at 4°C and room temperature. Moreover, the release of MXD from the NLCs was faster than drug release from SLNs. In vitro skin permeability test demonstrated that MXD-NLCs had a more pronounced permeation and retention profile than MXD-SLNs. Furthermore, no erythema was observed after administration of MXD-NLCs. All these results indicated that the developed MXD-NLCs could be a promising and effective nanocarrier for topical delivery of MXD.

Optimization of long circulating mixed polymeric micelles containing vinpocetine using simple lattice mixture design, in vitro and in vivo characterization.

PubMed

El-Dahmy, Rania Moataz; Elsayed, Ibrahim; Elshafeey, Ahmed Hassen; Gawad, Nabaweya Abdelaziz Abd El; El-Gazayerly, Omaima Naim

2014-12-30

The aim of this study was to increase the in vivo mean residence time of vinpocetine after IV injection utilizing long circulating mixed micellar systems. Mixed micelles were prepared using Pluronics L121, P123 and F127. The systems were characterized by testing their entrapment efficiency, particle size, polydispersity index, zeta potential, transmission electron microscopy and in vitro drug release. Simple lattice mixture design was planned for the optimization using Design-Expert(®) software. The optimized formula was lyophilized, sterilized and imaged by scanning electron microscope. Moreover, the in vivo behavior of the optimized formula was evaluated after IV injection in rabbits. The optimized formula, containing 68% w/w Pluronic L121 and 32% w/w Pluronic F127, had the highest desirability value (0.621). Entrapment efficiency, particle size, polydispersity index and zeta potential of the optimized formula were 50.74 ± 3.26%, 161.50 ± 7.39 nm, 0.21 ± 0.03 and -22.42 ± 1.72 mV, respectively. Lyophilization and sterilization did not affect the characteristics of the optimized formula. Upon in vivo investigation in rabbits, the optimized formula showed a significantly higher elimination half-life and mean residence time than the market product. Finally, mixed micelles could be considered as a promising long circulating nanocarrier for lipophilic drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

Alendronate Sodium as Enteric Coated Solid Lipid Nanoparticles; Preparation, Optimization, and In Vivo Evaluation to Enhance Its Oral Bioavailability.

PubMed

Hosny, Khaled Mohamed

2016-01-01

Treatment of osteoporosis with alendronate sodium has several challenges. The first challenge is the low bioavailability. The second main challenge is side effects, which include oesophageal ulceration. The aim of this research was to reformulate alendronate sodium as enteric coated solid lipid nanoparticles in order to enhance its bioavailability, and preventing the free alendronate sodium from coming into direct contact with the gastrointestinal mucosa, and thereby reducing the possibility of side effects. Enteric coated solid lipid nanoparticles were prepared according to the Box-Behnken design employing Design expert® software, and characterized for size, morphology, and entrapment efficiency. The optimized formula was coated with an Eudragit S100 and evaluated for drug release in acidic and basic media, stability studies and pharmacokinetic evaluations on rabbits. The results indicated that, using Derringer's desirability functional tool for optimization, the highest entrapment efficiency value of 74.3% and the smallest size value of 98 nm were predicted under optimum conditions with a desirability value of 0.917. The optimized nanoparticles released alendronate sodium only at an alkaline pH. The pharmacokinetic evaluation revealed that alendronate sodium bioavailability was enhanced by more than 7.4-fold in rabbits. In conclusion, enteric coated solid lipid nanoparticles is a promising formula for the delivery of alendronate sodium, eliminating its oesophageal side effects and enhancing its bioavailability.

Alendronate Sodium as Enteric Coated Solid Lipid Nanoparticles; Preparation, Optimization, and In Vivo Evaluation to Enhance Its Oral Bioavailability

PubMed Central

Hosny, Khaled Mohamed

2016-01-01

Treatment of osteoporosis with alendronate sodium has several challenges. The first challenge is the low bioavailability. The second main challenge is side effects, which include oesophageal ulceration. The aim of this research was to reformulate alendronate sodium as enteric coated solid lipid nanoparticles in order to enhance its bioavailability, and preventing the free alendronate sodium from coming into direct contact with the gastrointestinal mucosa, and thereby reducing the possibility of side effects. Enteric coated solid lipid nanoparticles were prepared according to the Box-Behnken design employing Design expert® software, and characterized for size, morphology, and entrapment efficiency. The optimized formula was coated with an Eudragit S100 and evaluated for drug release in acidic and basic media, stability studies and pharmacokinetic evaluations on rabbits. The results indicated that, using Derringer's desirability functional tool for optimization, the highest entrapment efficiency value of 74.3% and the smallest size value of 98 nm were predicted under optimum conditions with a desirability value of 0.917. The optimized nanoparticles released alendronate sodium only at an alkaline pH. The pharmacokinetic evaluation revealed that alendronate sodium bioavailability was enhanced by more than 7.4-fold in rabbits. In conclusion, enteric coated solid lipid nanoparticles is a promising formula for the delivery of alendronate sodium, eliminating its oesophageal side effects and enhancing its bioavailability. PMID:27148747

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.

Encapsulation of porphyrins and chlorins in biodegradable nanoparticles: the effect of dye lipophilicity on the extravasation and the photothrombic activity. A comparative study.

PubMed

Pegaz, Bernadette; Debefve, Elodie; Borle, Francois; Ballini, Jean-Pierre; van den Bergh, Hubert; Kouakou-Konan, Yvette Niamien

2005-07-01

In the present work, we performed a preclinical inter-comparison study using several photosensitizers with the goal of optimizing photodynamic therapy (PDT) for the treatment of choroidal neovascularization (CNV) associated with age-related macular degeneration. The tested molecules were the porphyrins meso-tetraphenylporphyrin (TPP) and meso-tetra-(4-carboxyphenyl)-porphyrin (TCPP), and the chlorins pheophorbide-a (Pheo-a) and chlorin e(6) (Ce(6)). Each of these molecules was entrapped in biodegradable nanoparticles (NP) based on poly(d,l-lactic acid). The influence of the degree of lipophilicity on the incorporation efficiency of the drug in the NPs, and on the dye leakage from blood vessels as well as on the photothrombic efficiency was investigated using the chick chorioallantoic membrane (CAM) as in vivo model. NP characterization showed that the dye was more effectively entrapped in the polymeric matrix when its degree of lipophilicity increased. While less lipophilic compounds (TCPP, Ce(6)) extravasate rather easily, the more lipophilic dyes (TPP, Pheo-a) tend to remain inside the blood vessels. After injection of a drug dose of 1 mg/kg body weight and a drug-light application interval of 1 min, irradiation with light doses ranging from 5 to 20 J/cm(2) led to the highest photothrombic efficiency when using the NPs loaded with the most lipophilic molecule (TPP). The latter induced vascular damage, which was significantly higher than that observed with the other molecules tested. Thus, in addition to minimal leakage from blood vessels, the TPP in NP formulation exhibited photothrombic efficiency similar to Visudyne which was also tested in the CAM model.

Formulation and development of bicontinuous nanostructured liquid crystalline particles of efavirenz.

PubMed

Avachat, Amelia M; Parpani, Shreekrishna S

2015-02-01

Efavirenz is a lipophilic non-nucleoside reverse transcriptase inhibitor used in the first-line pediatric therapeutic cocktail. Due to its high lipophilicity (logP = 5.4) and poor aqueous solubility (intrinsic water solubility = 8.3 μg/mL) efavirenz has low bioavailability. A 30 mg/mL solution in a medium-chain triglyceride vehicle is the only pediatric formulation available with an oral bioavailability 20% lower than the solid form. The current work was aimed at formulating and characterizing liquid crystal nanoparticles for oral delivery of efavirenz to improve oral bioavailability, provide sustained release, minimize side effects and drug resistance. Formulation of cubosomes was done by two methods; sonication and spray drying. Sonication gave highest entrapment efficiency and least particle size. Further, monoolein was substituted with phytantriol as monoolein gets degraded in the presence of lipase when administered orally with consequent loss of liquid crystalline structure. It was confirmed that there was no difference in particle size, entrapment efficiency and nature of product formed by using monoolein or phytantriol. The best formulation was found to be F9, having particle size 104.19 ± 0.21 nm and entrapment efficiency 91.40 ± 0.10%. In vitro release at the end of 12h was found to be 56.45% and zeta potential to be -23.14 mV which stabilized the cubic phase dispersions. It was further characterized for TEM, small angle X-ray scattering (SAXS), DSC and stability studies. SAXS revealed Pn3m space group, indicating a diamond cubic phase which was further confirmed by TEM. Pharmacokinetics of EFV was studied in male Wistar rats. EFV-loaded cubosome dispersions exhibited 1.93 and 1.62-fold increase in peak plasma concentration (Cmax) and 1.48 and 1.42-fold increase in AUC in comparison to that of a suspension prepared with the contents of EFV capsules suspended in 1.5% carboxymethylcellulose PBS solution (pH 5.0), and an EFV solution in medium-chain triglyceride respectively. Thus, stable cubosomes of efavirenz with increased bioavailability providing sustained release effect could be prepared successfully using phytantriol and poloxamer 407. Copyright © 2014 Elsevier B.V. All rights reserved.

Cell growth and protein expression of Shewanella oneidensis in biofilms and hydrogel-entrapped cultures.

PubMed

Zhang, Yingdan; Ng, Chun Kiat; Cohen, Yehuda; Cao, Bin

2014-05-01

The performance of biofilm-based bioprocesses is difficult to predict and control because of the intrinsic heterogeneous and dynamic properties of microbial biofilms. Biofilm mimics, such as microbial cells entrapped in polymeric scaffolds that are permeable for nutrients, have been proposed to replace real biofilms to achieve long-term robust performance in engineering applications. However, the physiological differences between cells that are physically entrapped in a synthetic polymeric matrix and biofilm cells that are encased in a self-produced polymeric matrix remain unknown. In this study, using Shewanella oneidensis as a model organism and alginate hydrogel as a model synthetic matrix, we compared the cell growth and protein expression in entrapped cultures and biofilms. The hydrogel-entrapped cultures were found to exhibit a growth rate comparable with biofilms. There was no substantial difference in cell viability, surface charge, as well as hydrophobicity between the cells grown in alginate hydrogel and those grown in biofilms. However, the gel-entrapped cultures were found to be physiologically different from biofilms. The gel-entrapped cultures had a higher demand for metabolic energy. The siderophore-mediated iron uptake was repressed in the gel-entrapped cells. The presence of the hydrogel matrix decreased the expression of proteins involved in biofilm formation, while inducing the production of extracellular DNA (eDNA) in the gel-entrapped cultures. These results advance the fundamental understanding of the physiology of hydrogel-entrapped cells, which can lead to more efficient biofilm mimic-based applications.

A logical approach to optimize the nanostructured lipid carrier system of irinotecan: efficient hybrid design methodology

NASA Astrophysics Data System (ADS)

Mohan Negi, Lalit; Jaggi, Manu; Talegaonkar, Sushama

2013-01-01

Development of an effective formulation involves careful optimization of a number of excipient and process variables. Sometimes the number of variables is so large that even the most efficient optimization designs require a very large number of trials which put stress on costs as well as time. A creative combination of a number of design methods leads to a smaller number of trials. This study was aimed at the development of nanostructured lipid carriers (NLCs) by using a combination of different optimization methods. A total of 11 variables were first screened using the Plackett-Burman design for their effects on formulation characteristics like size and entrapment efficiency. Four out of 11 variables were found to have insignificant effects on the formulation parameters and hence were screened out. Out of the remaining seven variables, four (concentration of tween-80, lecithin, sodium taurocholate, and total lipid) were found to have significant effects on the size of the particles while the other three (phase ratio, drug to lipid ratio, and sonication time) had a higher influence on the entrapment efficiency. The first four variables were optimized for their effect on size using the Taguchi L9 orthogonal array. The optimized values of the surfactants and lipids were kept constant for the next stage, where the sonication time, phase ratio, and drug:lipid ratio were varied using the Box-Behnken design response surface method to optimize the entrapment efficiency. Finally, by performing only 38 trials, we have optimized 11 variables for the development of NLCs with a size of 143.52 ± 1.2 nm, zeta potential of -32.6 ± 0.54 mV, and 98.22 ± 2.06% entrapment efficiency.

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.

Formulation and statistical optimization of gastric floating alginate/oil/chitosan capsules loading procyanidins: in vitro and in vivo evaluations.

PubMed

Chen, Rencai; Guo, Xiaomin; Liu, Xuecong; Cui, Haiming; Wang, Rui; Han, Jing

2018-03-01

The aim of the present work was to develop gastric floating capsules containing oil-entrapped beads loading procyanidins. The floating beads were prepared by ionotropic gelation method using sodium alginate, CaCl 2 and chitosan. The effect of three independent parameters (concentration of sodium alginate, CaCl 2 and chitosan) on entrapment efficiency were analyzed by Box-Behnken design. The floating beads were evaluated for surface morphology, particle size, density, entrapment efficiency, buoyancy, release behavior in vitro and floating ability in vivo. The prepared beads were grossly spherical in shape and the mean size was approximately 1.54±0.17mm. The density was 0.97g/cm 3 . And the optimal conditions were as follows: concentration of sodium alginate, CaCl 2 and chitosan were 33.75mg/mL, 9.84mg/mL and 9.05mg/mL, respectively. The optimized formulation showed entrapment efficiency of 88.84±1.04% within small error-value (0.65). The release mechanism of floating capsules followed Korsmeyer-Peppas model (r 2 =0.9902) with non-Fickian release. The gastric floating capsules exhibited 100% floating percentage in vitro and they could float on the top of gastric juice for 5h in vivo. Therefore, the floating capsules are able to prolong the gastroretentive delivery of procyanidins. Copyright © 2017 Elsevier B.V. All rights reserved.

Optimization and evaluation of gastroretentive ranitidine HCl microspheres by using design expert software.

PubMed

Hooda, Aashima; Nanda, Arun; Jain, Manish; Kumar, Vikash; Rathee, Permender

2012-12-01

The current study involves the development and optimization of their drug entrapment and ex vivo bioadhesion of multiunit chitosan based floating system containing Ranitidine HCl by ionotropic gelation method for gastroretentive delivery. Chitosan being cationic, non-toxic, biocompatible, biodegradable and bioadhesive is frequently used as a material for drug delivery systems and used to transport a drug to an acidic environment where it enhances the transport of polar drugs across epithelial surfaces. The effect of various process variables like drug polymer ratio, concentration of sodium tripolyphosphate and stirring speed on various physiochemical properties like drug entrapment efficiency, particle size and bioadhesion was optimized using central composite design and analyzed using response surface methodology. The observed responses were coincided well with the predicted values given by the optimization technique. The optimized microspheres showed drug entrapment efficiency of 74.73%, particle size 707.26 μm and bioadhesion 71.68% in simulated gastric fluid (pH 1.2) after 8 h with floating lag time 40s. The average size of all the dried microspheres ranged from 608.24 to 720.80 μm. The drug entrapment efficiency of microspheres ranged from 41.67% to 87.58% and bioadhesion ranged from 62% to 86%. Accelerated stability study was performed on optimized formulation as per ICH guidelines and no significant change was found in drug content on storage. Copyright © 2012 Elsevier B.V. All rights reserved.

Indirect calculation of monoclonal antibodies in nanoparticles using the radiolabeling process with technetium 99 metastable as primary factor: Alternative methodology for the entrapment efficiency.

PubMed

Helal-Neto, Edward; Cabezas, Santiago Sánchez; Sancenón, Félix; Martínez-Máñez, Ramón; Santos-Oliveira, Ralph

2018-05-10

The use of monoclonal antibodies (Mab) in the current medicine is increasing. Antibody-drug conjugates (ADCs) represents an increasingly and important modality for treating several types of cancer. In this area, the use of Mab associated with nanoparticles is a valuable strategy. However, the methodology used to calculate the Mab entrapment, efficiency and content is extremely expensive. In this study we developed and tested a novel very simple one-step methodology to calculate monoclonal antibody entrapment in mesoporous silica (with magnetic core) nanoparticles using the radiolabeling process as primary methodology. The magnetic core mesoporous silica were successfully developed and characterised. The PXRD analysis at high angles confirmed the presence of magnetic cores in the structures and transmission electron microscopy allowed to determine structures size (58.9 ± 8.1 nm). From the isotherm curve, a specific surface area of 872 m 2 /g was estimated along with a pore volume of 0.85 cm 3 /g and an average pore diameter of 3.15 nm. The radiolabeling process to proceed the indirect determination were well-done. Trastuzumab were successfully labeled (>97%) with Tc-99m generating a clear suspension. Besides, almost all the Tc-99m used (labeling the trastuzumab) remained trapped in the surface of the mesoporous silica for a period as long as 8 h. The indirect methodology demonstrated a high entrapment in magnetic core mesoporous silica surface of Tc-99m-traztuzumab. The results confirmed the potential use from the indirect entrapment efficiency methodology using the radiolabeling process, as a one-step, easy and cheap methodology. Copyright © 2018 Elsevier B.V. All rights reserved.

Tailoring magnetic PLGA nanoparticles suitable for doxorubicin delivery

NASA Astrophysics Data System (ADS)

Tansık, Gülistan; Yakar, Arzu; Gündüz, Ufuk

2014-01-01

One of the main problems of current cancer chemotherapy is the lack of selectivity of anti-cancer drugs to tumor cells, which leads to systemic toxicity and adverse side effects. In order to overcome these limitations, researches on controlled drug delivery systems have gained much attention. Nanoscale-based drug delivery systems provide tumor targeting. Among many types of nanocarriers, superparamagnetic nanoparticles with their biocompatible polymer coatings can be targeted to an intented site by an external magnetic field. Thus, the drug can be carried to the targeted site safely. The aim of this study is to prepare poly( dl-lactic- co-glycolic acid) (PLGA)-coated magnetic nanoparticles and load anti-cancer drug, doxorubicin to them. For this purpose, magnetite (Fe3O4) iron oxide nanoparticles were synthesized as a magnetic core material (MNP) and then coated with oleic acid. Oleic acid-coated MNP (OA-MNP) was encapsulated into PLGA. Effects of different OA-MNP/PLGA ratios on magnetite entrapment efficiency were investigated. Doxorubicin-loaded magnetic polymeric nanoparticles (DOX-PLGA-MNP) were prepared. After the characterization of prepared nanoparticles, their cytotoxic effects on MCF-7 cell line were studied. PLGA-coated magnetic nanoparticles (PLGA-MNP) had a proper size and superparamagnetic character. The highest magnetite entrapment efficiency of PLGA-MNP was estimated as 63 % at 1:8 ratio. Cytotoxicity studies of PLGA-MNP did not indicate any notable cell death between the concentration ranges of 2 and 125 μg/ml. Drug loading efficiency was estimated as 32 %, and it was observed that DOX-PLGA-MNP showed significant cytotoxicity on MCF-7 cells compared to PLGA-MNP. The results showed that prepared nanoparticles have desired size and superparamagnetic characteristics without serious toxic effects on cells. These nanoparticles may be suitable for targeted drug delivery applications.

Wood mimetic hydrogel beads for enzyme immobilization.

PubMed

Park, Saerom; Kim, Sung Hee; Won, Keehoon; Choi, Joon Weon; Kim, Yong Hwan; Kim, Hyung Joo; Yang, Yung-Hun; Lee, Sang Hyun

2015-01-22

Wood component-based composite hydrogels have potential applications in biomedical fields owing to their low cost, biodegradability, and biocompatibility. The controllable properties of wood mimetic composites containing three major wood components are useful for enzyme immobilization. Here, lipase from Candida rugosa was entrapped in wood mimetic beads containing cellulose, xylan, and lignin by dissolving wood components with lipase in [Emim][Ac], followed by reconstitution. Lipase entrapped in cellulose/xylan/lignin beads in a 5:3:2 ratio showed the highest activity; this ratio is very similar to that in natural wood. The lipase entrapped in various wood mimetic beads showed increased thermal and pH stability. The half-life times of lipase entrapped in cellulose/alkali lignin hydrogel were 31- and 82-times higher than those of free lipase during incubation under denaturing conditions of high temperature and low pH, respectively. Owing to their biocompatibility, biodegradability, and controllable properties, wood mimetic hydrogel beads can be used to immobilize various enzymes for applications in the biomedical, bioelectronic, and biocatalytic fields. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Optimization of riboflavin sodium phosphate loading to calcium alginate floating microspheres by response surface methodology].

PubMed

Zhang, An-yang; Fan, Tian-yuan

2009-12-18

To investigate the preparation, optimization and in vitro properties of riboflavin sodium phosphate floating microspheres. The floating microspheres composed of riboflavin sodium phosphate and calcium alginate were prepared using ion gelatin-oven drying method. The properties of the microspheres were investigated, including the buoyancy, release, appearance and entrapment efficiency. The formulation was optimized by response surface methodology (RSM). The optimized microspheres were round. The entrapment efficiency was 57.49%. All the microspheres could float on the artificial gastric juice over 8 hours. The release of the drug from the microspheres complied with Fick's diffusion.

Stimulation of mucosal immune response following oral administration of enterotoxigenic Escherichia coli fimbriae (CFA/I) entrapped in liposomes in conjunction with inactivated whole-cell Vibrio cholerae vaccine.

PubMed

Dima, V F; Ionescu, M D; Palade, R; Balotescu, C; Becheanu, G; Dima, S V

2001-01-01

In this study, we have searched for an effective mucosal vaccine. An oral enterotoxigenic E. coli vaccine containing colonization factor antigen (CFA/I) associated with inactivated whole-cell V. cholerae vaccine (WCV) has been tested for safety and immunogenicity in animals. Five groups of animals were used. The results showed the following: (a) vaccine containing CFA/I antigen entrapped in liposomes and associated with WCV (batch C) had increased titers of specific antibodies to CFA/I antigen in 15 to 18 (83.3%) animals; (b) specific Peyer's patches (PP), lymph nodes (LN) and spleen (SPL) lymphocytes proliferation was detected following in vitro restimulation with CFA/I antigen or WCV. This response gradually increased to the highest value by the 35th postimmunization day. Moreover, lower PP, LN and spleen (SPL) proliferation was observed in rabbits receiving soluble CFA/I antigen (S-CFA/I) or free liposomes (F-L) alone; (c) adhesion of E. coli H10407 strain labelled with 3H-leucine in immunized and control animals revealed the following local effects: (i) protection of rabbit intestinal mucosa against virulent E. coli cells; (ii) inhibition of adhesion of ETEC bacteria to intestinal mucosa and (iii) significantly faster release of E. coli H 10407 strain labelled with 3H-leucine from the intestinal tract of immunized animals. The histopathological and electron microscope findings confirmed the above results. The experimental results point out an efficient protection against infection with E. coli strains (ETEC), after mucosal vaccination with CFA/I antigen entrapped in liposomes associated with inactivated whole-cell Vibrio cholerae as immunological adjuvant.

Nano-proniosomes enhancing the transdermal delivery of mefenamic acid.

PubMed

Wen, Ming Ming; Farid, Ragwa M; Kassem, Abeer A

2014-12-01

Mefenamic acid (MA) is a BCS II class NSAID drug. It is available only in the form of tablets, capsules, and pediatric suspensions. Oral administration of MA is associated with severe gastrointestinal side effects. The aim of this study was to develop a convenient and low-cost transdermal drug delivery system for MA using proniosome as a novel carrier without the addition of penetration enhancers. The formulation factors, such as the presence of cholesterol, types of lecithin, and surfactants were investigated for their influence on the entrapment efficiency, rate of hydration, vesicle size, and zeta potential, in vitro drug release and skin permeation in order to optimize the proniosomal formulations with the minimum dose of the drug. Furthermore, the in vivo anti-inflammatory effect was evaluated on a formalin-induced rat paw edema model. The results showed that the type of surfactants had higher impact on the entrapment efficiency than the type of lecithins, with the highest in Span 80 (82.84%). The release of MA from Span 80 proniosomal gel was significantly affected by the type of lecithin used. The addition of cholesterol significantly increased both the drug release and the skin permeation flux of MA. Zeta potential showed a stable A4 noisomal suspension. DSC revealed the molecular dispersion of MA into the loaded proniosomes. In vivo study of the treatment group with MA proniosome gel showed a significant inhibition of rat paw edema compared with the same gel without the drug (control). The results of this study suggest that proniosomes are promising nano vesicular carriers and safe alternatives to enhance the transdermal delivery of MA.

Transferrin-tailored solid lipid nanoparticles as vectors for site-specific delivery of temozolomide to brain

NASA Astrophysics Data System (ADS)

Jain, Aviral; Singhai, Priyanka; Gurnany, Ekta; Updhayay, Satish; Mody, Nishi

2013-03-01

Blood-brain barrier restricts the uptake of many important hydrophilic drugs and limits their efficacy in the treatment of brain diseases because of the presence of tight junctions, high metabolic capacity, low pinocytic vesicular traffic, and efficient efflux mechanisms. In the present project, transferrin (Tf)-conjugated solid lipid nanoparticles (Tf-SLNs) were investigated for their ability to deliver temozolomide (TMZ) to the brain. SLNs were prepared by an ethanol injection method using hydrogenated soya phosphatidylcholine, triolein, cholesterol and distearoylphosphatidylethanolamine. Conjugation of SLNs with Tf was achieved by incubation of Tf with TMZ-loaded SLNs in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride in phosphate buffered saline (pH 7.4) as a cross linker. SLNs preparation were characterized for particle size, polydispersity index, zeta potential, surface morphology, percent drug entrapment efficiency, in vitro drug release, and hemolytic toxicity studies. In vitro cytotoxicity studies were performed on human cancer cell lines. The average size was found to be 221 ± 3.22 nm with entrapment efficiency of 69.83 ± 2.52 and 249 ± 2.61 nm with entrapment efficiency decreased to 64.21 ± 2.27 % for unconjugated SLNs and Tf-SLNs, respectively. Fluorescence studies revealed the enhanced uptake of Tf-SLNs in brain tissue compared with unconjugated SLNs.

Albumin microspheres as an ocular delivery system for pilocarpine nitrate.

PubMed

Rathod, Sudha; Deshpande, S G

2008-01-01

Pilocarpine nitrate loaded egg albumin microspheres were prepared by thermal denaturation process in the size range of 1-12 mum. A series of batches were prepared to study factors, which may affect the size and entrapment efficiency of drug in microspheres and optimized the process. Drug loaded microspheres so obtained were evaluated for their size, entrapment efficiency, release rate and biological response. Electron photomicrographs were taken (8000X) to study the morphological characteristics of microspheres. The entrapment and encapsulation of pilocarpine after process optimization was found to be 82.63% and 62.5% respectively. In vitro dissolution rate studies revealed that the release of drug from the microspheres followed spherical matrix mechanism. Biological response of microspheric suspension was measured by reduction in intraocular pressure in albino rabbit eyes and compared with marketed eye drops. Various pharmacokinetic parameters viz. onset of action, duration of action, Tmax and AUC were studied. A measurable difference was found in the mean miotic response, duration and AUC of pilocarpine nitrate microspheric suspension.

Role of edge activators and surface charge in developing ultradeformable vesicles with enhanced skin delivery.

PubMed

El Zaafarany, Ghada M; Awad, Gehanne A S; Holayel, Samar M; Mortada, Nahed D

2010-09-15

Transfersomes are highly efficient edge activator (EA)-based ultraflexible vesicles capable of, non-invasively, trespassing skin by virtue of their high, self-optimizing deformability. This investigation presents different approaches for the optimization of Transfersomes for enhanced transepidermal delivery of Diclofenac sodium (DS). Different methods of preparation, drug and lipid concentrations and vesicle compositions were employed, resulting in ultraflexible vesicles with diverse membrane characteristics. Evaluation of Transfersomes was implemented in terms of their shapes, sizes, entrapment efficiencies (EE%), relative deformabilities and in vitro skin permeation. Transfersomes prepared with 95:5% (w/w) (PC:EA) ratio showed highest EE% (Span 85>Span 80>Na cholate>Na deoxycholate>Tween 80). Whereas, those prepared using 85:15% (w/w) ratio showed highest deformability (Tween 80 was superior to bile salts and spans). Transfersomes were proved significantly superior in terms of, the amount of drug deposited in the skin and the amount permeated, with an enhancement ratio of 2.45, when compared to a marketed product. The study proved that the type and concentration of EA, as well as, the method of preparation had great influences on the properties of Transfersomes. Hence, optimized Transfersomes can significantly increase transepidermal flux and prolong the release of DS, when applied non-occlusively. Copyright 2010 Elsevier B.V. All rights reserved.

Terbinafine hydrochloride nanovesicular gel: In vitro characterization, ex vivo permeation and clinical investigation.

PubMed

AbdelSamie, Sara M; Kamel, Amany O; Sammour, Omaima A; Ibrahim, Shady M

2016-06-10

In this work, nanovesicular chitosan gels were prepared for dermal delivery of terbinafine hydrochloride (TBN HCl). Ethosomes and vesicles containing different types of penetration enhancers (PEs) viz. Terpenes (cineole and limonene), labrasol and transcutol were developed. The prepared vesicles were evaluated for physical characteristics as well as skin interaction. The selected vesicles were incorporated into chitosan gel. An in vivo animal study was done on rat induced superficial Candida infection model. Moreover, randomized double blind clinical study was done on patients to compare the effect of the selected nanovesicular gel against the market product. Results showed the formation of nearly spherical, mostly deformable vesicular systems with size range of 95.5-530nm, zeta potential range of -0.1 to 15mV and entrapment efficiency range of 20-96.7%. Penetration enhancer vesicles (PEVs) prepared with 4% limonene (ELI4) showed the highest percent of drug deposition in the skin (53%) and the highest local accumulation efficiency value (35.3). In vivo animal study showed that the lowest fungal burden produced with ELI4 chitosan gel. Clinical studies showed cure rate of 86% within 7days treatment in case of limonene nanovesicular gel compared to 20% for market product (Lamisil® cream). Copyright © 2016 Elsevier B.V. All rights reserved.

Whole cell entrapment techniques.

PubMed

Trelles, Jorge A; Rivero, Cintia W

2013-01-01

Microbial whole cells are efficient, ecological, and low-cost catalysts that have been successfully applied in the pharmaceutical, environmental, and alimentary industries, among others. Microorganism immobilization is a good way to carry out the bioprocess under preparative conditions. The main advantages of this methodology lie in their high operational stability, easy upstream separation and bioprocess scale-up feasibility. Cell entrapment is the most widely used technique for whole cell immobilization. This technique-in which the cells are included within a rigid network-is porous enough to allow the diffusion of substrates and products, protects the selected microorganism from the reaction medium, and has high immobilization efficiency (100 % in most cases).

Liposomes as potential masking agents in sport doping. Part 2: Detection of liposome-entrapped haemoglobin by flow cytofluorimetry.

PubMed

Esposito, Simone; Colicchia, Sonia; de la Torre, Xavier; Donati, Francesco; Mazzarino, Monica; Botrè, Francesco

2017-02-01

This work presents an analytical procedure for the identification and characterization of liposome-entrapped haemoglobins, based on flow cytofluorimetry. Flow cytofluorimetric detection is carried out following labelling by two distinct fluorescent reagents, an anti-haemoglobin antibody, fluorescein isothiocyanate conjugated, and an anti-poly(ethylene glycol) antibody, streptavidin-phycoerythrin conjugated. This experimental strategy allows the detection of liposome-entrapped haemoglobins in aqueous media, including plasma; the efficacy of the proposed approach has been verified on whole blood samples added with the liposomal formulation (ex-vivo). Additionally, the proposed technique allows the characterization of several key parameters in the study of liposomal haemoglobins, including, for instance (1) the determination of the degree of haemoglobin entrapment by liposomes; (2) the poly(ethylene glycol) insertion efficiency; and (3) the evaluation of liposome-entrapped haemoglobins stability following storage at 4 °C, allowing to follow both the process of haemoglobin loss from liposomes and the liposome degradation. The procedure is proposed for the detection and characterization of liposome-entrapped haemoglobin formulations to control their misuse in sport, but is also suggested for further applications in biological and clinical laboratory investigations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Proximity of arthroscopic ankle stabilization procedures to surrounding structures: an anatomic study.

PubMed

Drakos, Mark; Behrens, Steve B; Mulcahey, Mary K; Paller, David; Hoffman, Eve; DiGiovanni, Christopher W

2013-06-01

To examine the anatomy of the lateral ankle after arthroscopic repair of the lateral ligament complex (anterior talofibular ligament [ATFL] and calcaneofibular ligament [CFL]) with regard to structures at risk. Ten lower extremity cadaveric specimens were obtained and were screened for gross anatomic defects and pre-existing ankle laxity. The ATFL and CFL were sectioned from the fibula by an open technique. Standard anterolateral and anteromedial arthroscopy portals were made. An additional portal was created 2 cm distal to the anterolateral portal. The articular surface of the fibula was identified, and the ATFL and CFL were freed from the superficial and deeper tissues. Suture anchors were placed in the fibula at the ATFL and CFL origins and were used to repair the origin of the lateral collateral structures. The distance from the suture knot to several local anatomic structures was measured. Measurements were taken by 2 separate observers, and the results were averaged. Several anatomic structures lie in close proximity to the ATFL and CFL sutures. The ATFL sutures entrapped 9 of 55 structures, and no anatomic structures were inadvertently entrapped by the CFL sutures. The proximity of the peroneus tertius and the extensor tendons to the ATFL makes them at highest risk of entrapment, but the proximity of the intermediate branch of the superficial peroneal nerve (when present) is a risk with significant morbidity. Our results indicate that the peroneus tertius and extensor tendons have the highest risk for entrapment and show the smallest mean distances from the anchor knot to the identified structure. Careful attention to these structures, as well as the superficial peroneal nerve, is mandatory to prevent entrapment of tendons and nerves when one is attempting arthroscopic lateral ankle ligament reconstruction. Defining the anatomic location and proximity of the intervening structures adjacent to the lateral ligament complex of the ankle may help clarify the anatomic safe zone through which arthroscopic repair of the lateral ligament complex can be safely performed. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Optimization of nanostructured lipid carriers for topical delivery of nimesulide using Box-Behnken design approach.

PubMed

Moghddam, Seyedeh Marziyeh Mahdavi; Ahad, Abdul; Aqil, Mohd; Imam, Syed Sarim; Sultana, Yasmin

2017-05-01

The aim of the present study was to develop and optimize topically applied nimesulide-loaded nanostructured lipid carriers. Box-Behnken experimental design was applied for optimization of nanostructured lipid carriers. The independent variables were ratio of stearic acid: oleic acid (X 1 ), poloxamer 188 concentration (X 2 ) and lecithin concentration (X 3 ) while particle size (Y 1 ) and entrapment efficiency (Y 2 ) were the chosen responses. Further, skin penetration study, in vitro release, confocal laser scanning microscopy and stability study were also performed. The optimized nanostructured lipid carriers of nimesulide provide reasonable particle size, flux, and entrapment efficiency. Optimized formulation (F9) with mean particle size of 214.4 ± 11 nm showed 89.4 ± 3.40% entrapment efficiency and achieved mean flux 2.66 ± 0.09 μg/cm 2 /h. In vitro release study showed prolonged drug release from the optimized formulation following Higuchi release kinetics with R 2 value of 0.984. Confocal laser scanning microscopy revealed an enhanced penetration of Rhodamine B-loaded nanostructured lipid carriers to the deeper layers of the skin. The stability study confirmed that the optimized formulation was considerably stable at refrigerator temperature as compared to room temperature. Our results concluded that nanostructured lipid carriers are an efficient carrier for topical delivery of nimesulide.

Synthesis and characterization of thiolated carboxymethyl chitosan-graft-cyclodextrin nanoparticles as a drug delivery vehicle for albendazole.

PubMed

Alamdarnejad, Ghazaleh; Sharif, Alireza; Taranejoo, Shahrouz; Janmaleki, Mohsen; Kalaee, Mohammad Reza; Dadgar, Mohsen; Khakpour, Mazyar

2013-08-01

A new strategy for the synthesis of thiolated carboxymethyl chitosan-g-cyclodextrin nanoparticles by an ionic-gelation method is presented. The synthetic approach was based on the utilization of 1,6-hexamethylene diisocyanate during cyclodextrin grafting onto carboxymethyl chitosan. The use of the 1,6-hexamethylene diisocyanate resulted in reactions between cyclodextrin and active sites at the C6-position of chitosan, and preserved amino groups of chitosan for subsequent reactions with thioglycolic acid, as the thiolating agent, and tripolyphosphate, as the gelling counterion. Various methods such as scanning electron microscopy, rheology and in vitro release studies were employed to exhibit significant features of the nanoparticles for mucosal albendazole delivery applications. It was found that the thiolated carboxymethyl chitosan-g-cyclodextrin nanoparticles prepared using an aqueous solution containing 1 wt% of tripolyphosphate and having 115.65 (μmol/g polymer) of grafted thiol groups show both the highest mucoadhesive properties and the highest albendazole entrapment efficiency. The latter was confirmed theoretically by calculating the enthalpy of mixing of albendazole in the above thiolated chitosan polymer.

More Efficient Media Design for Enhanced Biofouling Control in a Membrane Bioreactor: Quorum Quenching Bacteria Entrapping Hollow Cylinder.

PubMed

Lee, Sang H; Lee, Seonki; Lee, Kibaek; Nahm, Chang H; Kwon, Hyeokpil; Oh, Hyun-Suk; Won, Young-June; Choo, Kwang-Ho; Lee, Chung-Hak; Park, Pyung-Kyu

2016-08-16

Recently, membrane bioreactors (MBRs) with quorum quenching (QQ) bacteria entrapping beads have been reported as a new paradigm in biofouling control because, unlike conventional post-biofilm control methods, bacterial QQ can inhibit biofilm formation through its combined effects of physical scouring of the membrane and inhibition of quorum sensing (QS). In this study, using a special reporter strain (Escherichia coli JB525), the interaction between QS signal molecules and quorum quenching bacteria entrapping beads (QQ-beads) was elucidated through visualization of the QS signal molecules within a QQ-bead using a fluorescence microscope. As a result, under the conditions considered in this study, the surface area of QQ-media was likely to be a dominant parameter in enhancing QQ activity over total mass of entrapped QQ bacteria because QQ bacteria located near the core of a QQ-bead were unable to display their QQ activities. On the basis of this information, a more efficient QQ-medium, a QQ hollow cylinder (QQ-HC), was designed and prepared. In batch experiments, QQ-HCs showed greater QQ activity than QQ-beads as a result of their higher surface area and enhanced physical washing effect because of their larger impact area against the membrane surface. Furthermore, it was shown that such advantages of QQ-HCs resulted in more effective mitigation of membrane fouling than from QQ-beads in lab-scale continuous MBRs.

Effects of pore forming agents on chitosan-graft-poly(N-vinylpyrrolidone) hydrogel properties for use as a matrix for floating drug delivery

NASA Astrophysics Data System (ADS)

Budianto, E.; Al-Shidqi, M. F.; Cahyana, A. H.

2017-07-01

Eradicating H. pylori-based infection by using conventional oral dosage form of amoxicillin trihydrate finds difficulties to overcome rapid gastric retention time. Encapsulating amoxicillin trihydrate in floating drug delivery system may solve the problem. In this research, the floating drug delivery system of amoxicillin trihydrate encapsulated in floating chitosan-graft-poly(N-vinyl pyrrolidone) hydrogels containing CaCO3 and NaHCO3 as pore forming agents has been successfully prepared. Pore forming agents used was varied with the ratio of 10 to 25% pore forming agents to total mass of the used materials. The hydrogel were characterizedusing FTIR spectrophotometer and stereo microscope. As pore forming agents compositions increased, the porosity (%) and floating properties increased but followed by decrease in drug entrapment efficiency. Most of the floating hydrogels possessed floating ability longer than 180 min and the highest porosity was found in hydrogel containing 25% NaHCO3. Hydrogel containing CaCO3 showed sustained drug release profile than hydrogel containing NaHCO3. However, the optimum formulation was achieved at composition of 10% NaHCO3 with 57% of drug entrapped within the hydrogel and 43% drug released. The results of these studies show that NaHCO3 is an effective pore forming agents for chitosan-graft-poly(N-vinyl pyrrolidone) hydrogel preparation as compare to CaCO3.

Dermatopharmacokinetic and pharmacodynamic evaluation of ethosomes of griseofulvin designed for dermal delivery

NASA Astrophysics Data System (ADS)

Aggarwal, Nidhi; Goindi, Shishu

2013-10-01

The present study is aimed at evaluation of the dermal delivery potential of griseofulvin-loaded ethosomes. Griseofulvin-loaded ethosomes were prepared using "Cold technique" (Indian Patent Application 208/DEL/2009). The optimized formulation was characterized for vesicular shape and size, drug entrapment efficiency, drug content, pH, stability, and spreadability. Ex vivo skin permeation, dermatopharmacokinetics, and skin sensitivity studies were carried out using male Laca mice. In vivo antifungal activity was assessed against Microsporum canis using guinea pig model for dermatophytosis. The optimized formulation E7 possessing 2 % phospholipid (PL) and 30 % ethanol exhibited the highest drug entrapment (72.94 ± 0.80 %) and optimum vesicle size (148.5 ± 0.48 nm). E7 illustrated remarkably higher drug permeation and skin retention when compared with liposomes. Pharmacodynamic studies in guinea pigs induced with M. canis revealed that the dermal fungal infection was completely cured in 8 days upon twice daily topical application of griseofulvin-loaded ethosomes whereas liposomes led to complete cure in 14 days. The formulation was observed to be non-sensitizing, histopathologically safe, and stable at 5 ± 3, 25 ± 2, and 40 ± 2 °C for a period of 1 year. Results indicated that dermal delivery of griseofulvin employing ethosomes could be a commendable alternative to reduce the bio-burden associated with conventional oral formulations.

Delivery of phytochemical thymoquinone using molecular micelle modified poly(D, L lactide-co-glycolide) (PLGA) nanoparticles

NASA Astrophysics Data System (ADS)

Ganea, Gabriela M.; Fakayode, Sayo O.; Losso, Jack N.; van Nostrum, Cornelus F.; Sabliov, Cristina M.; Warner, Isiah M.

2010-07-01

Continuous efforts have been made in the development of potent benzoquinone-based anticancer drugs aiming for improved water solubility and reduced adverse reactions. Thymoquinone is a liposoluble benzoquinone-based phytochemical that has been shown to have remarkable antioxidant and anticancer activities. In the study reported here, thymoquinone-loaded PLGA nanoparticles were synthesized and evaluated for physico-chemical, antioxidant and anticancer properties. The nanoparticles were synthesized by an emulsion solvent evaporation method using anionic molecular micelles as emulsifiers. The system was optimized for maximum entrapment efficiency using a Box-Behnken experimental design. Optimum conditions were found for 100 mg PLGA, 15 mg TQ and 0.5% w/v poly(sodium N-undecylenyl-glycinate) (poly-SUG). In addition, other structurally related molecular micelles such as poly(sodium N-heptenyl-glycinate) (poly-SHG), poly(sodium N-undecylenyl-leucinate) (poly-SUL), and poly(sodium N-undecylenyl-valinate) (poly-SUV) were also examined as emulsifiers. All investigated molecular micelles provided excellent emulsifier properties, leading to maximum optimized TQ entrapment efficiency, and monodispersed particle sizes below 200 nm. The release of TQ from molecular micelle modified nanoparticles was investigated by dialysis and reached lower levels than the free drug. The antioxidant activity of TQ-loaded nanoparticles, indicated by IC50 (mg ml - 1 TQ for 50% 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity), was highest for poly-SUV emulsified nanoparticles (0.030 ± 0.002 mg ml - 1) as compared to free TQ. In addition, it was observed that TQ-loaded nanoparticles emulsified with poly-SUV were more effective than free TQ against MDA-MB-231 cancer cell growth inhibition, presenting a cell viability of 16.0 ± 5.6% after 96 h.

Encapsulation of Naproxen in Lipid-Based Matrix Microspheres: Characterization and Release Kinetics

PubMed Central

Bhoyar, PK; Morani, DO; Biyani, DM; Umekar, MJ; Mahure, JG; Amgaonkar, YM

2011-01-01

The objective of this study was to microencapsulate the anti-inflammatory drug (naproxen) to provide controlled release and minimizing or eliminating local side effect by avoiding the drug release in the upper gastrointestinal track. Naproxen was microencapsulated with lipid-like carnauba wax, hydrogenated castor oil using modified melt dispersion (modified congealable disperse phase encapsulation) technique. Effect of various formulation and process variables such as drug-lipid ratio, concentration of modifier, concentration of dispersant, stirring speed, stirring time, temperature of external phase, on evaluatory parameters such as size, entrapment efficiency, and in vitro release of naproxen were studied. The microspheres were characterized for particle size, scanning electron microscopy (SEM), FT-IR spectroscopy, drug entrapment efficiency, in vitro release studies, for in vitro release kinetics. The shape of microspheres was found to be spherical by SEM. The drug entrapment efficiency of various batches of microspheres was found to be ranging from 60 to 90 %w/w. In vitro drug release studies were carried out up to 24 h in pH 7.4 phosphate buffer showing 50-65% drug release. In vitro drug release from all the batches showed better fitting with the Korsmeyer-Peppas model, indicating the possible mechanism of drug release to be by diffusion and erosion of the lipid matrix. PMID:21731354

Encapsulation of naproxen in lipid-based matrix microspheres: characterization and release kinetics.

PubMed

Bhoyar, P K; Morani, D O; Biyani, D M; Umekar, M J; Mahure, J G; Amgaonkar, Y M

2011-04-01

The objective of this study was to microencapsulate the anti-inflammatory drug (naproxen) to provide controlled release and minimizing or eliminating local side effect by avoiding the drug release in the upper gastrointestinal track. Naproxen was microencapsulated with lipid-like carnauba wax, hydrogenated castor oil using modified melt dispersion (modified congealable disperse phase encapsulation) technique. Effect of various formulation and process variables such as drug-lipid ratio, concentration of modifier, concentration of dispersant, stirring speed, stirring time, temperature of external phase, on evaluatory parameters such as size, entrapment efficiency, and in vitro release of naproxen were studied. The microspheres were characterized for particle size, scanning electron microscopy (SEM), FT-IR spectroscopy, drug entrapment efficiency, in vitro release studies, for in vitro release kinetics. The shape of microspheres was found to be spherical by SEM. The drug entrapment efficiency of various batches of microspheres was found to be ranging from 60 to 90 %w/w. In vitro drug release studies were carried out up to 24 h in pH 7.4 phosphate buffer showing 50-65% drug release. In vitro drug release from all the batches showed better fitting with the Korsmeyer-Peppas model, indicating the possible mechanism of drug release to be by diffusion and erosion of the lipid matrix.

Application of Box-Behnken design to prepare gentamicin-loaded calcium carbonate nanoparticles.

PubMed

Maleki Dizaj, Solmaz; Lotfipour, Farzaneh; Barzegar-Jalali, Mohammad; Zarrintan, Mohammad-Hossein; Adibkia, Khosro

2016-09-01

The aim of this research was to prepare and optimize calcium carbonate (CaCO3) nanoparticles as carriers for gentamicin sulfate. A chemical precipitation method was used to prepare the gentamicin sulfate-loaded CaCO3 nanoparticles. A 3-factor, 3-level Box-Behnken design was used for the optimization procedure, with the molar ratio of CaCl2: Na2CO3 (X1), the concentration of drug (X2), and the speed of homogenization (X3) as the independent variables. The particle size and entrapment efficiency were considered as response variables. Mathematical equations and response surface plots were used, along with the counter plots, to relate the dependent and independent variables. The results indicated that the speed of homogenization was the main variable contributing to particle size and entrapment efficiency. The combined effect of all three independent variables was also evaluated. Using the response optimization design, the optimized Xl-X3 levels were predicted. An optimized formulation was then prepared according to these levels, resulting in a particle size of 80.23 nm and an entrapment efficiency of 30.80%. It was concluded that the chemical precipitation technique, together with the Box-Behnken experimental design methodology, could be successfully used to optimize the formulation of drug-incorporated calcium carbonate nanoparticles.

Efficient entrapment of large and small compounds during vesiculation of intestinal microvilli.

PubMed Central

van Dommelen, F S; Hamer, C M; De Jonge, H R

1986-01-01

An efficient method is described permitting the encapsulation of membrane-impermeable compounds at the interior of intestinal microvilli during vesicle formation. Rat intestinal epithelial cells were isolated by high-frequency vibration and exposed transiently to iso-osmotic medium containing 5 mM-EDTA. Vesiculation of microvilli was effected by freeze-thawing instead of mechanical fragmentation or hypo-osmotic lysis. Solutes to be entrapped were mixed with the extracellular medium before freezing in liquid N2. Microvillous vesicles were isolated from thawed cell suspensions by Ca2+- or Mg2+-aggregation of contaminants and differential centrifugation. The yield, purity, orientation and transport properties of the vesicles were similar, or superior, to preparations described in the literature. A high loading efficiency was demonstrated for small impermeants (cyclic GMP, ATP, Arsenazo III) as well as proteins (albumin); in contrast, loading of isolated vesicles by hypo-osmotic shock was only partially effective (cyclic GMP, ATP) or ineffective (albumin). Entrapment of an ATP-regenerating system could partially block a Mg2+-dependent conversion of intravesicular ATP into ADP. No evidence was obtained for the contribution of a proton pump to the intrinsic Mg2+-ATPase of the vesicle. Potential applications of the vesicle-loading technique in studies of brush-border transport regulation by intramicrovillar factors are discussed. Images Fig. 1. Fig. 2. PMID:3024625

Short sleep duration and poor sleep quality predict next-day suicidal ideation: an ecological momentary assessment study.

PubMed

Littlewood, Donna L; Kyle, Simon D; Carter, Lesley-Anne; Peters, Sarah; Pratt, Daniel; Gooding, Patricia

2018-04-26

Sleep problems are a modifiable risk factor for suicidal thoughts and behaviors. Yet, sparse research has examined temporal relationships between sleep disturbance, suicidal ideation, and psychological factors implicated in suicide, such as entrapment. This is the first in-the-moment investigation of relationships between suicidal ideation, objective and subjective sleep parameters, and perceptions of entrapment. Fifty-one participants with current suicidal ideation completed week-long ecological momentary assessments. An actigraph watch was worn for the duration of the study, which monitored total sleep time, sleep efficiency, and sleep latency. Daily sleep diaries captured subjective ratings of the same sleep parameters, with the addition of sleep quality. Suicidal ideation and entrapment were measured at six quasi-random time points each day. Multi-level random intercept models and moderation analyses were conducted to examine the links between sleep, entrapment, and suicidal ideation, adjusting for anxiety and depression severity. Analyses revealed a unidirectional relationship whereby short sleep duration (both objective and subjective measures), and poor sleep quality, predicted the higher severity of next-day suicidal ideation. However, there was no significant association between daytime suicidal ideation and sleep the following night. Sleep quality moderated the relationship between pre-sleep entrapment and awakening levels of suicidal ideation. This is the first study to report night-to-day relationships between sleep disturbance, suicidal ideation, and entrapment. Findings suggest that sleep quality may alter the strength of the relationship between pre-sleep entrapment and awakening suicidal ideation. Clinically, results underscore the importance of assessing and treating sleep disturbance when working with those experiencing suicidal ideation.

Effective immobilization of alcohol dehydrogenase on carbon nanoscaffolds for ethanol biofuel cell.

PubMed

Umasankar, Yogeswaran; Adhikari, Bal-Ram; Chen, Aicheng

2017-12-01

An efficient approach for immobilizing alcohol dehydrogenase (ADH) while enhancing its electron transfer ability has been developed using poly(2-(trimethylamino)ethyl methacrylate) (MADQUAT) cationic polymer and carbon nanoscaffolds. The carbon nanoscaffolds were comprised of single-walled carbon nanotubes (SWCNTs) wrapped with reduced graphene oxide (rGO). The ADH entrapped within the MADQUAT that was present on the carbon nanoscaffolds exhibited a high electron exchange capability with the electrode through its cofactor β-nicotinamide adenine dinucleotide hydrate and β-nicotinamide adenine dinucleotide reduced disodium salt hydrate (NAD + /NADH) redox reaction. The advantages of the carbon nanoscaffolds used as the support matrix and the MADQUAT employed for the entrapment of ADH versus physisorption were demonstrated via cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Our experimental results showed a higher electron transfer, electrocatalytic activity, and rate constant for MADQUAT entrapped ADH on the carbon nanoscaffolds. The immobilization of ADH using both MADQUAT and carbon nanoscaffolds exhibited strong potential for the development of an efficient bio-anode for ethanol powered biofuel cells. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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

Co-precipitation of asiatic acid and poly( l-lactide) using rapid expansion of subcritical solutions into liquid solvents

NASA Astrophysics Data System (ADS)

Sane, Amporn; Limtrakul, Jumras

2011-09-01

Poly( l-lactide) (PLLA) nanoparticles loaded with asiatic acid (AA) were successfully produced by rapid expansion of a subcritical solution into an aqueous receiving solution containing a dispersing agent. A mixture of carbon dioxide (CO2) and ethanol (EtOH) with a weight ratio of 1:1 was used as the solvent for AA and PLLA. Two surfactants, Pluronic F127 and sodium dodecyl sulfate were employed. The former was found to be more effective for stabilizing AA-loaded PLLA nanoparticles, as a rapid expansion into a 0.1 wt% Pluronic F127 solution produced a stable nanosuspension consisting mainly of well-dispersed, individual nanoparticles. The effects of rapid expansion-processing conditions—AA to PLLA weight ratio and pre-expansion temperature (Tpre)—on the size and morphology of composite nanoparticles, and the loading capacity and entrapment efficiency of AA in PLLA nanoparticles, were systematically investigated. It was found that AA-loaded PLLA nanoparticles with a size range of 30-100 nm were consistently fabricated by rapid expansion at Tpre of 70-100 °C and AA to PLLA weight ratios of 1:2 and 1:4, and with a constant pre-expansion pressure of 330 bar. The Tpre and AA to PLLA weight ratio had no significant effects on the size of the nanoparticles. The AA to PLLA weight ratio is a controlling parameter for both the loading capacity and the entrapment efficiency of AA in PLLA nanoparticles. The loading capacity and entrapment efficiency increased from 8-11 to 16-21 wt%, and 38-57 to 50-62 wt%, respectively, when the AA to PLLA weight ratio changed from 1:4 to 1:2. However, increasing the Tpre from 70 to 100 °C decreased both the loading capacity and entrapment efficiency of AA in PLLA nanoparticles by 20-30%.

Preformulation Studies of a Liposomal Formulation Containing Sirolimus for the Treatment of Dry Eye Disease

PubMed Central

Linares-Alba, Mónica Anayántzin; Gómez-Guajardo, Magda Berenice; Fonzar, Joice Furtado; Brooks, Dennis E.; García-Sánchez, Gustavo Adolfo

2016-01-01

Abstract Purpose: The aim of this study was to develop and characterize a liposomal product containing sirolimus to be administered subconjunctivally for the treatment of nonresponsive keratoconjunctivitis sicca (KCS) or dry eye. Methods: Formulations were prepared using an ethanol injection method and an adaptation of the heating method in pursuance of the most suitable methodology for future industrial production. Liposomes were loaded with either a high dose of 1 mg/mL of sirolimus or a less toxic dose of 0.4 mg/mL. The effects of critical process and formulation parameters were investigated. Liposomes were characterized in terms of size, zeta potential, polydispersity, differential scanning calorimetry, morphology, entrapment efficiency, phospholipid content, thermal stability, and sterility. The formulation was evaluated clinically in dogs with spontaneous KCS. Results: Sterile liposomal dispersions with sizes ranging from 140 to 211 nm, were successfully obtained. High entrapment efficiency of 93%–98% was achieved. The heating method allowed an easier production of liposomes with high entrapment efficiency, to significantly shorten production time and the elimination of the use of alcohol. The poor stability of the obtained liposomes in aqueous dispersion made the inclusion of a lyophilization step necessary to the manufacturing process. In vivo testing of the liposomal sirolimus formulations in the spontaneous KCS dog model have produced promising results, particularly with a sirolimus dose of 1 mg/mL, indicating the need for further development and study of proposed formulations in the treatment of canine KCS. Clinical improvement in tear production in dogs with spontaneous KCS treated with the 1 mg/mL dose product was observed. Conclusions: The heating method allowed easier production of high entrapment efficiency liposomes to significantly shorten production time and the elimination of the use of alcohol. Tear production was increased in dogs administered with the formulation. PMID:26469946

Manipulating the membrane penetration mechanism of helical polypeptides via aromatic modification for efficient gene delivery.

PubMed

Zheng, Nan; Song, Ziyuan; Yang, Jiandong; Liu, Yang; Li, Fangfang; Cheng, Jianjun; Yin, Lichen

2017-08-01

The delivery performance of non-viral gene vectors is greatly related to their intracellular kinetics. Cationic helical polypeptides with potent membrane penetration properties and gene transfection efficiencies have been recently developed by us. However, they suffer from severe drawbacks in terms of their membrane penetration mechanisms that mainly include endocytosis and pore formation. The endocytosis mechanism leads to endosomal entrapment of gene cargos, while the charge- and helicity-induced pore formation causes appreciable cytotoxicity at high concentrations. With the attempt to overcome such critical challenges, we incorporated aromatic motifs into the design of helical polypeptides to enhance their membrane activities and more importantly, to manipulate their membrane penetration mechanisms. The aromatically modified polypeptides exhibited higher cellular internalization level than the unmodified analogue by up to 2.5 folds. Such improvement is possibly because aromatic domains promoted the polypeptides to penetrate cell membranes via direct transduction, a non-endocytosis and non-pore formation mechanism. As such, gene cargos were more efficiently delivered into cells by bypassing endocytosis and subsequently avoiding endosomal entrapment, and the material toxicity associated with excessive pore formation was also reduced. The top-performing aromatic polypeptide containing naphthyl side chains at the incorporated content of 20mol% revealed notably higher transfection efficiencies than commercial reagents in melanoma cells in vitro (by 11.7 folds) and in vivo (by 9.1 folds), and thus found potential utilities toward topical gene delivery for cancer therapy. Cationic helical polypeptides, as efficient gene delivery materials, suffer from severe drawbacks in terms of their membrane penetration mechanisms. The main cell penetration mechanisms involved are endocytosis and pore formation. However, the endocytosis mechanism has the limitation of endosomal entrapment of gene cargos, while the charge- and helicity-induced pore formation causes cytotoxicity at high concentrations. To address such critical issues toward the maximization of gene delivery efficiency, we incorporated aromatic domains into helical polypeptides to promote the cell membrane penetrations via direct transduction, which is a non-endocytosis and non-pore formation mechanism. The manipulation of their membrane penetration mechanisms allows gene cargos to be more efficiently delivered by bypassing endocytosis and subsequently avoiding endosomal entrapment. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Increased skin permeation efficiency of imperatorin via charged ultradeformable lipid vesicles for transdermal delivery

PubMed Central

Lin, Hongwei; Xie, Qingchun; Huang, Xin; Ban, Junfeng; Wang, Bo; Wei, Xing

2018-01-01

Aim The aim of this work was to develop a novel vesicular carrier, ultradeformable liposomes (UDLs), to expand the applications of the Chinese herbal medicine, imperatorin (IMP), and increase its transdermal delivery. Methods In this study, we prepared IMP-loaded UDLs using the thin-film hydration method and evaluated their encapsulation efficiency, vesicle deformability, skin permeation, and the amounts accumulated in different depths of the skin in vitro. The influence of different charged surfactants on the properties of the UDLs was also investigated. Results The results showed that the UDLs containing cationic surfactants had high entrapment efficiency (60.32%±2.82%), an acceptable particle size (82.4±0.65 nm), high elasticity, and prolonged drug release. The penetration rate of IMP in cationic-UDLs was 3.45-fold greater than that of IMP suspension, which was the highest value among the vesicular carriers. UDLs modified with cationic surfactant also showed higher fluorescence intensity in deeper regions of the epidermis. Conclusion The results of our study suggest that cationic surfactant-modified UDLs could increase the transdermal flux, prolong the release of the drug, and serve as an effective dermal delivery system for IMP. PMID:29467573

Increased skin permeation efficiency of imperatorin via charged ultradeformable lipid vesicles for transdermal delivery.

PubMed

Lin, Hongwei; Xie, Qingchun; Huang, Xin; Ban, Junfeng; Wang, Bo; Wei, Xing; Chen, Yanzhong; Lu, Zhufen

2018-01-01

The aim of this work was to develop a novel vesicular carrier, ultradeformable liposomes (UDLs), to expand the applications of the Chinese herbal medicine, imperatorin (IMP), and increase its transdermal delivery. In this study, we prepared IMP-loaded UDLs using the thin-film hydration method and evaluated their encapsulation efficiency, vesicle deformability, skin permeation, and the amounts accumulated in different depths of the skin in vitro. The influence of different charged surfactants on the properties of the UDLs was also investigated. The results showed that the UDLs containing cationic surfactants had high entrapment efficiency (60.32%±2.82%), an acceptable particle size (82.4±0.65 nm), high elasticity, and prolonged drug release. The penetration rate of IMP in cationic-UDLs was 3.45-fold greater than that of IMP suspension, which was the highest value among the vesicular carriers. UDLs modified with cationic surfactant also showed higher fluorescence intensity in deeper regions of the epidermis. The results of our study suggest that cationic surfactant-modified UDLs could increase the transdermal flux, prolong the release of the drug, and serve as an effective dermal delivery system for IMP.

Development and optimization of enteric coated mucoadhesive microspheres of duloxetine hydrochloride using 3(2) full factorial design.

PubMed

Setia, Anupama; Kansal, Sahil; Goyal, Naveen

2013-07-01

Microspheres constitute an important part of oral drug delivery system by virtue of their small size and efficient carrier capacity. However, the success of these microspheres is limited due to their short residence time at the site of absorption. The objective of the present study was to formulate and systematically evaluate in vitro performance of enteric coated mucoadhesive microspheres of duloxetine hydrochloride (DLX), an acid labile drug. DLX microspheres were prepared by simple emulsification phase separation technique using chitosan as carrier and glutaraldehyde as a cross-linking agent. Microspheres prepared were coated with eudragit L-100 using an oil-in-oil solvent evaporation method. Eudragit L-100was used as enteric coating polymer with the aim to release the drug in small intestine The microspheres prepared were characterized by particle size, entrapment efficiency, swelling index (SI), mucoadhesion time, in vitro drug release and surface morphology. A 3(2) full factorial design was employed to study the effect of independent variables polymer-to-drug ratio (X1) and stirring speed (X2) on dependent variables, particle size, entrapment efficiency, SI, in vitro mucoadhesion and drug release up to 24 h (t24). Microspheres formed were discrete, spherical and free flowing. The microspheres exhibited good mucoadhesive property and also showed high percentage entrapment efficiency. The microspheres were able to sustain the drug release up to 24 h. Thus, the prepared enteric coated mucoadhesive microspheres may prove to be a potential controlled release formulation of DLX for oral administration.

Design of a nanostructured lipid carrier intended to improve the treatment of tuberculosis

PubMed Central

Pinheiro, Marina; Ribeiro, Ricardo; Vieira, Alexandre; Andrade, Fernanda; Reis, Salette

2016-01-01

This work aimed to design, develop, and characterize a lipid nanocarrier system for the selective delivery of rifabutin (RFB) to alveolar macrophages. Lipid nanoparticles, specifically nanostructured lipid carriers (NLC), were synthetized by the high-shear homogenization and ultrasonication techniques. These nanoparticles were designed to exhibit both passive and active targeting strategies to be efficiently internalized by the alveolar macrophages, traffic to the acidified phagosomes and phagolysosomes, and release bactericidal concentrations of the antituberculosis drug intracellularly. NLC that could entrap RFB were prepared, characterized, and further functionalized with mannose. Particles’ diameter, zeta potential, morphology, drug% entrapping efficiency, and drug release kinetics were evaluated. The mannose coating process was confirmed by Fourier transform infrared. Further, the cytotoxicity of the formulations was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay in A549, Calu-3, and Raw 264.7 cells. The diameter of NLC formulations was found to be in the range of 175–213 nm, and drug entrapping efficiency was found to be above 80%. In addition, high storage stability for the formulations was expected since they maintained the initial characteristics for 6 months. Moreover, the drug release was pH-sensitive, with a faster drug release at acidic pH than at neutral pH. These results pose a strong argument that the developed nanocarrier can be explored as a promising carrier for safer and more efficient management of tuberculosis by exploiting the pulmonary route of administration. PMID:27536067

Characterization and decolorization applicability of xerogel matrix immobilized manganese peroxidase produced from Trametes versicolor IBL-04.

PubMed

Iqbal, Hafiz Muhammad Nasir; Asgher, Muhammad

2013-05-01

A novel manganese peroxidase (MnP) isolated from solid state culture of Trametes versicolor IBL-04 was immobilized using xerogel matrix composed of trimethoxysilane (TMOS) and propyltetramethoxysilane (PTMS). FTIR spectroscopy confirmed the successful entrapment of MnP into the xerogel matrix. An immobilization efficiency of 92.2% was achieved with a purified active fraction containing 2 mg/mL MnP. After 24 h incubation at varying pH and temperatures, the immobilized MnP retained 82 and 75% activity at pH 4 and 80°C, respectively. Xerogel matrix immobilization enhanced the catalytic efficiency of entrapped MnP. Metal ions including Cu2+, Mn2+ and Fe2+ stimulated enzyme activity while cysteine, EDTA and Ag+ inhibited the activity. MnP preserved 82% of its initial activity during oxidation of MnSO4 in 10 consecutive cycles, demonstrating the reusability of xerogel entrapped MnP. The immobilized MnP could be stored for up to 75 days at 4°C without significant activity loss. To explore the industrial applicability of MnP, the immobilized MnP was tested for decolorization of textile industry effluent in a Packed Bed Reactor System (PBRS). After five consecutive cycles, 98.8% decolorization of effluent was achieved within 5 h. The kinetic properties, storage stability and reusability of entrapped MnP from T. versicolor IBL-04 reflect its prospects as biocatalyst for bioremediation and other industrial applications.

Melittin liposomes surface modified with poloxamer 188: in vitro characterization and in vivo evaluation.

PubMed

Tian, J L; Ke, X; Chen, Z; Wang, C J; Zhang, Y; Zhong, T C

2011-05-01

Melittin liposomes surface modified with poloxamer 188 were developed, and the effect of poloxamer 188 was investigated with regard to anti-cancer effect and vascular stimulation. Melittin liposomes surface modified with poloxamer 188 at different concentrations (0%, 2%, and 5%) were prepared using the adsorption method, followed by in vitro characterization, including entrapment efficiency, zeta potential, particle size, and morphology. Subsequently, the influence of repeated freeze-thawing on the liposomes was investigated, and the effect of poloxamer 188 on the repeated freeze-thawing process was explored. Vascular stimulation effects of MLT, and MLT liposome that surface coated with or without poloxamer were all studied. Pharmacokinetics of the different MLT preparations were determined and the anticancer activity of the MLT formulations was investigated. The particle size of the liposomes gradually increased with increasing poloxamer 188 content, while the entrapment efficiency did not change significantly. After the first freeze-thaw cycle, size and PDI were both markedly reduced, entrapment efficiency rose, and there was no significant change of zeta potential. The vascular irritation caused by MLT could be reduced to an extent by encapsulation in liposome, but not completely eliminated, while liposomes coated with poloxamer 188 can effectively abolish the phenomenon. Melittin liposomes with surface modified by poloxamer exhibit enhanced bioavailability, effective anticancer activity, and reduced side effects compared with melittin solution. Poloxamer plays an important role in melittin liposomes.

Nifedipine-loaded polymeric nanocapsules: validation of a stability-indicating HPLC method to evaluate the drug entrapment efficiency and in vitro release profiles.

PubMed

Granada, Andréa; Tagliari, Monika Piazzon; Soldi, Valdir; Silva, Marcos António Segatto; Zanetti-Ramos, Betina Ghiel; Fernandes, Daniel; Stulzer, Hellen Karine

2013-01-01

A simple stability-indicating analytical method was developed and validated to quantify nifedipine in polymeric nanocapsule suspensions; an in vitro drug release study was then carried out. The analysis was performed using an RP C18 column, UV-Vis detection at 262 nm, and methanol-water (70 + 30, v/v) mobile phase at a flow rate of 1.2 mL/min. The method was validated in terms of specificity, linearity and range, LOQ, accuracy, precision, and robustness. The results obtained were within the acceptable ranges. The nanocapsules, made of poly(epsilon-caprolactone), were prepared by the solvent displacement technique and showed high entrapment efficiency. The entrapment efficiency was 97.6 and 98.2% for the nifedipine-loaded polymeric nanocapsules prepared from polyvinyl alcohol (PVA) and Pluronic F68 (PF68), respectively. The particle size and zeta potential of nanocapsules were found to be influenced by the nature of the stabilizer used. The mean diameter and zeta potential for nanocapsules with PVA and PF68 were 290.9 and 179.9 nm, and -17.7 mV and -32.7 mV, respectively. The two formulations prepared showed a drug release of up to 70% over 4 days. This behavior indicates the viability of this drug delivery system for use as a controlled-release system.

Entrapped cells-based-anaerobic membrane bioreactor treating domestic wastewater: Performances, fouling, and bacterial community structure.

PubMed

Juntawang, Chaipon; Rongsayamanont, Chaiwat; Khan, Eakalak

2017-11-01

A laboratory scale study on treatment performances and fouling of entrapped cells-based-anaerobic membrane bioreactor (E-AnMBR) in comparison with suspended cells-based-bioreactor (S-AnMBR) treating domestic wastewater was conducted. The difference between E-AnMBR and S-AnMBR was the uses of cells entrapped in phosphorylated polyvinyl alcohol versus planktonic cells. Bulk organic removal efficiencies by the two AnMBRs were comparable. Lower concentrations of suspended biomass, bound extracellular polymeric substances and soluble microbial products in E-AnMBR resulted in less fouling compared to S-AnMBR. S-AnMBR provided 7 days of operation time versus 11 days for E-AnMBR before chemical cleaning was required. The less frequent chemical cleaning potentially leads to a longer membrane life-span for E-AnMBR compared to S-AnMBR. Phyla Proteobacteria, Chloroflexi, Bacteroidetes and Acidobacteria were dominant in cake sludge from both AnMBRs but their abundances were different between the two AnMBRs, suggesting influence of cell entrapment on the bacteria community. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immobilization of Actinobacillus succinogenes by adhesion or entrapment for the production of succinic acid.

PubMed

Corona-González, Rosa Isela; Miramontes-Murillo, Ricardo; Arriola-Guevara, Enrique; Guatemala-Morales, Guadalupe; Toriz, Guillermo; Pelayo-Ortiz, Carlos

2014-07-01

The production of succinic acid was studied with entrapped and adsorbed Actinobacillus succinogenes. The adsorption of fermentation products (organic acids in the concentration range of 1-20 g/L) on different supports was evaluated. It was found that succinic acid was adsorbed in small quantities on diatomite and zeolite (12.6 mg/g support). The highest production of succinic acid was achieved with A. succinogenes entrapped in agar beads. Batch fermentations with immobilized cells were carried out with glucose concentrations ranging from 20 to 80 g/L. Succinic acid (43.4 g/L) was obtained from 78.3g/L glucose, and a high productivity (2.83 g/Lh) was obtained with a glucose concentration of 37.6g/L. For repeated batch fermentations (5 cycles in 72 h) with immobilized cells in agar, the total glucose consumed was 147.55 g/L, while the production of succinic acid was 107 g/L. Immobilized cells reduced significantly the fermentation time, yield, productivity and final concentration of succinic acid. Copyright © 2014 Elsevier Ltd. All rights reserved.

Use of CdSe/ZnS luminescent quantum dots incorporated within sol-gel matrix for urea detection.

PubMed

Duong, Hong Dinh; Rhee, Jong Il

2008-09-19

In this work, urea detection techniques based on the pH sensitivity of CdSe/ZnS QDs were developed using three types of sol-gel membranes: a QD-entrapped membrane, urease-immobilized membrane and double layer consisting of a QD-entrapped membrane and urease-immobilized membrane. The surface morphology of the sol-gel membranes deposited on the wells in a 24-well microtiter plate was investigated. The linear detection range of urea was in the range of 0-10mM with the three types of sol-gel membranes. The urea detection technique based on the double layer consisting of the QD-entrapped membrane and urease-immobilized membrane resulted in the highest sensitivity to urea due to the Michaelis-Menten kinetic parameters. That is, the Michaelis-Menten constant (K(m)=2.0745mM) of the free urease in the QD-entrapped membrane was about 4-fold higher than that (K(m)=0.549mM) of the immobilized urease in the urease-immobilized membrane and about 12-fold higher than that (K(m)=0.1698mM) of the immobilized urease in the double layer. The good stability of the three sol-gel membranes for urea sensing over 2 months showed that the use of sol-gel membranes immobilized with QDs or an enzyme is suitable for biomedical and environmental applications.

A highly efficient colorimetric immunoassay using a nanocomposite entrapping magnetic and platinum nanoparticles in ordered mesoporous carbon.

PubMed

Kim, Moon Il; Ye, Youngjin; Woo, Min-Ah; Lee, Jinwoo; Park, Hyun Gyu

2014-01-01

Nanocomposite to achieve ultrafast immunoassay: a new synergistically integrated nanocomposite consisting of magnetic and platinum nanoparticles, simultaneously entrapped in mesoporous carbon, is developed as a promising enzyme mimetic candidate to achieve ultrafast colorimetric immunoassays. Using new assay system, clinically important target molecules, such as human epidermal growth factor receptor 2 (HER2) and diarrhea-causing rotavirus, can be detected in only 3 min at room temperature with high specificity and sensitivity. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Formulation optimization of gentamicin loaded Eudragit RS100 microspheres using factorial design study.

PubMed

Singh, Deependra; Saraf, Swarnlata; Dixit, Vinod Kumar; Saraf, Shailendra

2008-04-01

Gentamicin-Eudragit RS100 microspheres were prepared by modified double emulsion method. A 3(2) full factorial experiment was designed to study the effects of the composition of outer aqueous phase in terms of amount of glycerol (viscosity effect) and sodium chloride (osmotic pressure gradient effect) on the entrapment efficiency and % yield and microsphere size. The results of analysis of variance test for responses measured indicated that the test is significant (p>0.05). The contribution of sodium chloride concentration was found to be higher on entrapment efficiency and % yield, whereas glycerol produced significant effect on the mean diameter of microspheres. Microspheres demonstrated spherical particles in the size range of 33.24-60.43 microm. In vitro release profile of optimized formulation demonstrated sustained release for 24 h following Higuchi kinetics. Finally, drug bioactivity was found to remain intact after microencapsulation. Response surface graphs are presented to examine the effects of independent variables on the responses studied. Thus, by formulation design important parameters affecting formulation characteristics of gentamicin loaded Eudragit RS100 microspheres can be identified for controlled delivery with desirable characters in terms of maximum entrapment and yield.

Push-Pull Locomotion for Vehicle Extrication

NASA Technical Reports Server (NTRS)

Creager, Colin M.; Johnson, Kyle A.; Plant, Mark; Moreland, Scott J.; Skonieczny, Krzysztof

2014-01-01

For applications in which unmanned vehicles must traverse unfamiliar terrain, there often exists the risk of vehicle entrapment. Typically, this risk can be reduced by using feedback from on-board sensors that assess the terrain. This work addressed the situations where a vehicle has already become immobilized or the desired route cannot be traversed using conventional rolling. Specifically, the focus was on using push-pull locomotion in high sinkage granular material. Push-pull locomotion is an alternative mode of travel that generates thrust through articulated motion, using vehicle components as anchors to push or pull against. It has been revealed through previous research that push-pull locomotion has the capacity for generating higher net traction forces than rolling, and a unique optical flow technique indicated that this is the result of a more efficient soil shearing method. It has now been found that pushpull locomotion results in less sinkage, lower travel reduction, and better power efficiency in high sinkage material as compared to rolling. Even when starting from an "entrapped" condition, push-pull locomotion was able to extricate the test vehicle. It is the authors' recommendation that push-pull locomotion be considered as a reliable back-up mode of travel for applications where terrain entrapment is a possibility.

Preparation of solid lipid nanoparticles as drug carriers for levothyroxine sodium with in vitro drug delivery kinetic characterization.

PubMed

Rostami, E; Kashanian, S; Azandaryani, A H

2014-05-01

The aim of this work was to produce and characterize solid lipid nanoparticles (SLN) containing levothyroxine sodium for oral administration, and to evaluate the kinetic release of these colloidal carriers. SLNs were prepared by microemulsion method. The particle size and zeta potential of levothyroxine sodium-loaded SLNs were determined to be around 153 nm,-43 mV (negatively charged), respectively by photon correlation spectroscopy. The levothyroxine entrapment efficiency was over 98%. Shape and surface morphology were determined by TEM and SEM. They revealed fairly spherical shape of nanoparticles.SLN formulation was stable over a period of 6 months. There were no significant changes in particle size, zeta potential and polydispersity index and entrapment efficiency, indicating that the developed SLNs were fairly stable.

Development and optimization of enteric coated mucoadhesive microspheres of duloxetine hydrochloride using 32 full factorial design

PubMed Central

Setia, Anupama; Kansal, Sahil; Goyal, Naveen

2013-01-01

Background: Microspheres constitute an important part of oral drug delivery system by virtue of their small size and efficient carrier capacity. However, the success of these microspheres is limited due to their short residence time at the site of absorption. Objective: The objective of the present study was to formulate and systematically evaluate in vitro performance of enteric coated mucoadhesive microspheres of duloxetine hydrochloride (DLX), an acid labile drug. Materials and Methods: DLX microspheres were prepared by simple emulsification phase separation technique using chitosan as carrier and glutaraldehyde as a cross-linking agent. Microspheres prepared were coated with eudragit L-100 using an oil-in-oil solvent evaporation method. Eudragit L-100was used as enteric coating polymer with the aim to release the drug in small intestine The microspheres prepared were characterized by particle size, entrapment efficiency, swelling index (SI), mucoadhesion time, in vitro drug release and surface morphology. A 32 full factorial design was employed to study the effect of independent variables polymer-to-drug ratio (X1) and stirring speed (X2) on dependent variables, particle size, entrapment efficiency, SI, in vitro mucoadhesion and drug release up to 24 h (t24). Results: Microspheres formed were discrete, spherical and free flowing. The microspheres exhibited good mucoadhesive property and also showed high percentage entrapment efficiency. The microspheres were able to sustain the drug release up to 24 h. Conclusion: Thus, the prepared enteric coated mucoadhesive microspheres may prove to be a potential controlled release formulation of DLX for oral administration. PMID:24167786

Native and β-cyclodextrin-enclosed curcumin: entrapment within liposomes and their in vitro cytotoxicity in lung and colon cancer.

PubMed

Rahman, Shafiur; Cao, Siyu; Steadman, Kathryn J; Wei, Ming; Parekh, Harendra S

2012-01-01

With a view to improving the solubility and delivery characteristics of poorly water-soluble drugs, we prepared β-cyclodextrin-curcumin (βCD-C) inclusion complexes (hydrophilic curcumin) and entrapped both native curcumin (hydrophobic) and the complexes separately into liposomes; these were then assessed for in vitro cytotoxicity in lung and colon cancer cell lines. Optimization of curcumin entrapment within βCD was achieved, with the resultant βCD-C complexes prepared by methanol reflux. Inclusion complexes were confirmed using UV spectroscopy, Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction. The water solubility of βCD-C complexes improved markedly (c.f. native curcumin) and successful entrapment of complexes into liposomes, prepared using a thin-film hydration approach, was also achieved. All the liposomal formulations were characterized for curcumin and βCD-C complex entrapment efficiency, particle size, polydispersity and stability at 2-8°C. Curcumin, βCD-C complex and their optimized liposomal formulations were evaluated for anticancer activity in lung (A-459) and colon (SW-620) cancer cell lines. All curcumin-containing formulations tested were effective in inhibiting cell proliferation, as determined via an MTT assay. The median effective dose (EC(50)) for all curcumin formulations was found to be in the low µM range for both lung and colon cancer cell lines tested. Our results confirm that βCD inclusion complexes of poorly water soluble drugs, such as curcumin can be entrapped within biocompatible vesicles such as liposomes, and this does not preclude their anticancer activity.

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

Physical stability, centrifugation tests, and entrapment efficiency studies of carnauba wax-decyl oleate nanoparticles used for the dispersion of inorganic sunscreens in aqueous media.

PubMed

Villalobos-Hernández, J R; Müller-Goymann, C C

2006-06-01

Aqueous nanoscale lipid dispersions consisting of carnauba wax-decyl oleate mixtures acting as carriers or accompanying vehicles for inorganic sunscreens such as barium sulfate, strontium carbonate, and titanium dioxide were prepared by high pressure homogenization. For the manufacture of these nanosuspensions, three pigment concentrations (%wt), namely 2, 4, and 6, and two carnauba wax-decyl oleate ratios, 1:1 and 2:1, were used, being some of these combinations chosen for stability studies. Six-month physical stability tests at 4, 20, and 40 degrees C selecting the mean particle size and the polydispersity index of the nanosuspensions as reference parameters were performed. Centrifugation tests of the nanosuspensions assessed by transmission electron microscopy and by the determination of the content of pigments and carnauba wax in the separated fractions were done. The mean particle sizes and the polydispersity indices of the nanosuspensions were not altered after six-month storages at 20 and at 40 degrees C. However, the storage of those at 4 degrees C considerably increased the particle size and polydispersity of the systems, particularly when wax-oil ratios (2:1) were used for the entrapment of the pigments. Transmission electron micrographs of centrifuged samples denoted the presence of three major fractions showing the different types of particles integrated into the nanosuspensions. Furthermore, it was observed that not all the carnauba wax participated in the entrapment of the pigment. Regarding the amount of pigment being encapsulated or bonded by the wax-oil matrices, entrapment efficiencies higher than 85.52% were reported.

Inhibitory effect of liposome-entrapped lemongrass oil on the growth of Listeria monocytogenes in cheese.

PubMed

Cui, H Y; Wu, J; Lin, L

2016-08-01

Listeria monocytogenes infection in dairy products is of mounting public concern. To inhibit bacterial growth, we engineered stimuli-responsive liposomes containing lemongrass oil for this study. The controlled release of liposome-entrapped lemongrass oil is triggered by listerolysin O, secreted by L. monocytogenes. We investigated the antibiotic activities of lemongrass oil liposomes against L. monocytogenes in cheese. We also assessed their possible effects on the quality of the cheese. Liposomes containing lemongrass oil (5.0mg/mL) presented the optimal polydispersity index (0.246), zeta-potential (-58.9mV) and entrapment efficiency (25.7%). The liposomes displayed satisfactory antibiotic activity against L. monocytogenes in cheese over the storage period at 4°C. We observed no effects on the physical and sensory properties of the cheese after the liposome treatment. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Formulation of resveratrol entrapped niosomes for topical use.

PubMed

Pando, Daniel; Matos, María; Gutiérrez, Gemma; Pazos, Carmen

2015-04-01

A new approach to the formulation of resveratrol (RSV) entrapped niosomes for topical use is proposed in this work. Niosomes were formulated with Gelot 64 (G64) as surfactant, and two skin-compatible unsaturated fatty acids (oleic and linoleic acids), commonly used in pharmaceutical formulations, as penetration enhancers. Niosomes were prepared by two different methods: a thin film hydration method with minor modifications followed by a sonication stage (TFH-S), and an ethanol injection modified method (EIM). Niosomes prepared with the EIM method were in the range of 299-402 nm, while the TFH-S method produced larger niosomes in the range of 293-496 nm. Moreover, niosomes with higher RSV entrapment efficiency (EE) and better stability were generated by the EIM method. Ex vivo transdermal experiments, carried out in Franz diffusion cells on newborn pig skin, indicated that niosomes prepared by the EIM method were more effective for RSV penetration in epidermis and dermis (EDD), with values up to 21% for both penetration enhancers tested. The EIM method, which yielded the best RSV-entrapped niosomes, seems to be the most suitable for scaling up. Copyright © 2015 Elsevier B.V. All rights reserved.

Mutagenesis of diploid mammalian genes by gene entrapment

PubMed Central

Lin, Qing; Donahue, Sarah L.; Moore-Jarrett, Tracy; Cao, Shang; Osipovich, Anna B.; Ruley, H. Earl

2006-01-01

The present study describes a genome-wide method for biallelic mutagenesis in mammalian cells. Novel poly(A) gene trap vectors, which contain features for direct cloning vector–cell fusion transcripts and for post-entrapment genome engineering, were used to generate a library of 979 mutant ES cells. The entrapment mutations generally disrupted gene expression and were readily transmitted through the germline, establishing the library as a resource for constructing mutant mice. Cells homozygous for most entrapment loci could be isolated by selecting for enhanced expression of an inserted neomycin-resistance gene that resulted from losses of heterozygosity (LOH). The frequencies of LOH measured at 37 sites in the genome ranged from 1.3 × 10−5 to 1.2 × 10−4 per cell and increased with increasing distance from the centromere, implicating mitotic recombination in the process. The ease and efficiency of obtaining homozygous mutations will (i) facilitate genetic studies of gene function in cultured cells, (ii) permit genome-wide studies of recombination events that result in LOH and mediate a type of chromosomal instability important in carcinogenesis, and (iii) provide new strategies for phenotype-driven mutagenesis screens in mammalian cells. PMID:17062627

Microparticulate drug delivery system containing tramadol hydrochloride for pain treatment.

PubMed

Ciurba, Adriana; Todoran, Nicoleta; Vari, C E; Lazăr, Luminita; Al Hussein, Stela; Hancu, G

2014-01-01

The current trend of replacing conventional pharmaceutical forms is justified because most substances administered in this form give fluctuations of therapeutic concentrations and often outside the therapeutic range. In addition, these formulations offer a reduction in the dose or the number of administrations, thus increasing patient compliance. In the experiment, we developed an appropriate technology for the preparation of gelatin microspheres containing tramadol hydrochloride by emulsification/cross-linking method. The formulated microspheres were characterized by product yield, size distribution, encapsulation efficiency and in vitro release of tramadol hydrochloride. Data obtained from in vitro release studies were fitted to various mathematical models to elucidate the transport mechanisms. The kinetic models used were zero-order, first-order, Higuchi Korsmeyer-Peppas and Hopfenberg. Spherical microspheres were obtained, with free-flowing properties. The entrapment efficiency of tramadol hydrochloride in microparticles was 79.91% and product yield -94.92%. As the microsphere size was increased, the entrapment efficiency increased. This was 67.56, 70.03, 79.91% for formulations MT80-250, MT8-500 and, MT250-500. High entrapment efficiency was observed for MT250-500 formulation. The gelatin microspheres had particle sizes ranging from 80 to 500 microm. The drug was released for a period of 12 hours with a maximum release of 96.02%. Of the three proposed formulations, MT250-500 presented desirable properties and optimal characteristics for the therapy of pain. Release of tramadol hydrochloridi was best fitted to Korsmeyer-Peppas equation because the Akaike Information Criterion had the lowest values for this kinetic model. These results suggest the opportunity to influence the therapeutic characteristics of gelatin microspheres to obtain a suitable drug delivery system for the oral administration of tramadol hydrochloride.

Topical Delivery of Erythromycin Through Cubosomes for Acne.

PubMed

Khan, Sana; Jain, Poorva; Jain, Sourabh; Jain, Richa; Bhargava, Saurabh; Jain, Aakanchha

2018-01-01

Topical delivery is an attractive route for local and systemic treatment. The novel topical application has many advantages like averting the GI-irritation, preventing the metabolism of drugs in the liver and increasing the bioavailability of the drug over the conventional dosage forms. The aim of present work was to prepare and characterized erythromycin encapsulated cubosomes using different concentrations of glyceryl monooleate and poloxamer 407 by the emulsification method. The prepared dispersion of cubosomes was characterized for surface morphology, particle size, entrapment efficiency and in vitro release. Further, optimized formulation was converted to cubosomal gel by incorporating carbopol 934 at different concentrations. The prepared gel was characterized for homogeneity, pH, viscosity, spreadibility, drug content and in vitro drug release study. The result of optimized cubosomes showed average particle size of 264.5±2.84nm and entrapment efficiency about 95.29±1.32 % and the pH of optimized cubosomal was found to be 6.5, viscosity 2475-8901(cp), drug content 95.29% and the spreadability was found to be 11.74 gm.cm/sec. The in vitro drug release kinetics of optimized formulation was found to follow Korsmeyer peppas model having highest R2 value 0.835 and in vitro drug release of optimized erythromycin loaded cubosomal gel and plain drug gel in 24 hr was found to be 89.91±0.73 and 88.64±2.16, while in 36 hr plain drug gel and cubosomal gel showed drug release about 87.64±0.97 and 91.55±1.09, and sustained release was obtained after 24 hr in case of cubosomal gel. Thus, as a whole it can be concluded that erythromycin loaded cubosomes are effective in topically delivering drug in sustained and non-invasive manner for treatment and prevention of acne. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Amyloglucosidase enzymatic reactivity inside lipid vesicles

PubMed Central

Li, Mian; Hanford, Michael J; Kim, Jin-Woo; Peeples, Tonya L

2007-01-01

Efficient functioning of enzymes inside liposomes would open new avenues for applications in biocatalysis and bioanalytical tools. In this study, the entrapment of amyloglucosidase (AMG) (EC 3.2.1.3) from Aspergillus niger into dipalmitoylphosphatidylcholine (DPPC) multilamellar vesicles (MLVs) and large unilamellar vesicles (LUVs) was investigated. Negative-stain, freeze-fracture, and cryo-transmission electron microscopy images verified vesicle formation in the presence of AMG. Vesicles with entrapped AMG were isolated from the solution by centrifugation, and vesicle lamellarity was identified using fluorescence laser confocal microscopy. The kinetics of starch hydrolysis by AMG was modeled for two different systems, free enzyme in aqueous solution and entrapped enzyme within vesicles in aqueous suspension. For the free enzyme system, intrinsic kinetics were described by a Michaelis-Menten kinetic model with product inhibition. The kinetic constants, Vmax and Km, were determined by initial velocity measurements, and Ki was obtained by fitting the model to experimental data of glucose concentration-time curves. Predicted concentration-time curves using these kinetic constants were in good agreement with experimental measurements. In the case of the vesicles, the time-dependence of product (glucose) formation was experimentally determined and simulated by considering the kinetic behavior of the enzyme and the permeation of substrate into the vesicle. Experimental results demonstrated that entrapped enzymes were much more stable than free enyzme. The entrapped enzyme could be recycled with retention of 60% activity after 3 cycles. These methodologies can be useful in evaluating other liposomal catalysis operations. PMID:18271982

Bypassing multidrug resistant ovarian cancer using ultrasound responsive doxorubicin/curcumin co-deliver alginate nanodroplets.

PubMed

Baghbani, Fatemeh; Moztarzadeh, Fathollah

2017-05-01

Ultrasound-responsive perfluorocarbon nanoemulsions are a class of new multifunctional smart nanocarriers which combine diagnostic properties with therapeutic properties and release their drug payload in a controlled manner in response to ultrasound. Therefore, combination therapy using chemotherapeutic and chemosensitizing agents co-entrapped in these nanocarriers seems beneficial for cancer treatment. In the present study, multifunctional smart alginate/perfluorohexane nanodroplets were developed for co-delivery of doxorubicin and curcumin (a strong chemosensitizer). The nanodroplets with the average particle size of 55.1nm were synthesized via nanoemulsion process. The entrapment efficiency of doxorubicin was 92.3%. To improve curcumin entrapment into the alginate shell, Span 60 was added to the formulation as a co-surfactant and finally curcumin entrapment of about 40% was achieved. Ultrasound-mediated drug release kinetic was evaluated at two different frequencies of 28kHz (low frequency) and 1MHz (high frequency). Low frequency ultrasound resulted in higher triggered drug release from nanodroplets. The nanodroplets showed strong ultrasound contrast via droplet to bubble transition as confirmed via B-mode ultrasound imaging. Enhanced cytotoxicity in adriamycin-resistant A2780 ovarian cancer cells was observed for Dox-Cur-NDs compared to Dox-NDs because of the synergistic effects of doxorubicin and curcumin. However, ultrasound irradiation significantly increased the cytotoxicity of Dox-Cur-NDs. Finally, in vivo ovarian cancer treatment using Dox/Cur-NDs combined with ultrasound irradiation resulted in efficient tumor regression. According to the present study, nanotherapy of multidrug resistant human ovarian cancer using ultrasound responsive doxorubicin/curcumin co-loaded alginate-shelled nanodroplets combined with ultrasound irradiation could be a promising modality for the future of cancer treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Coulombic interactions on the deposition and rotational mobility distributions of dyes in polyelectrolyte multilayer thin films.

PubMed

Li, Ye; Yip, Wai Tak

2004-12-07

We employed negatively charged fluorescein (FL), positively charged rhodamine 6G (R6G), and neutral Nile Red (NR) as molecular probes to investigate the influence of Coulombic interaction on their deposition into and rotational mobility inside polyelectrolyte multilayer (PEM) films. The entrapment efficiency of the dyes reveals that while Coulombic repulsion has little effect on dye deposition, Coulombic attraction can dramatically enhance the loading efficiency of dyes into a PEM film. By monitoring the emission polarization of single dye molecules in polyethylenimine (PEI) films, the percentages of mobile R6G, NR, and FL were determined to be 87 +/- 4%, 76 +/- 5%, and 68 +/- 3%, respectively. These mobility distributions suggest that cationic R6G enjoys the highest degree of rotational freedom, whereas anionic FL shows the least mobility because of Coulombic attraction toward cationic PEI. Regardless of charges, this high percentage of mobile molecules is in stark contrast to the 5-40% probe mobility reported from spun-cast polymer films, indicating that our PEI films contain more free volume and display richer polymer dynamics. These observations demonstrate the potential of using isolated fluorescent probes to interrogate the internal structure of a PEM film at a microscopic level.

Physico-chemical characterisation, cytotoxic activity, and biocompatibility studies of tamoxifen-loaded solid lipid nanoparticles prepared via a temperature-modulated solidification method.

PubMed

Lakkadwala, Sushant; Nguyen, Sanko; Lawrence, Joseph; Nauli, Surya M; Nesamony, Jerry

2014-01-01

Solid lipid nanoparticles (SLNs) can efficiently and efficaciously incorporate anti-cancer agents. To prepare and characterise tamoxifen (TAM)-loaded SLNs. Glyceryl monostearate, Tween-80, and trehalose were used in SLNs. SLNs were tested via dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). Characterisation studies revealed SLNs of about 540 nm with a negative surface charge and confirmed the entrapment of TAM in the SLNs. The entrapment efficiency was estimated to be 60%. The in vitro drug release profile demonstrated a gradual increase followed by a release plateau for several days. A drug concentration-dependent increase in cytotoxic activity was observed when the SLNs were evaluated in cell cultures. Biocompatible and stable lyophilised SLNs were successfully prepared and found to possess properties that may be utilised in an anti-cancer drug delivery system.

Nitric oxide-releasing porous silicon nanoparticles

NASA Astrophysics Data System (ADS)

Kafshgari, Morteza Hasanzadeh; Cavallaro, Alex; Delalat, Bahman; Harding, Frances J.; McInnes, Steven JP; Mäkilä, Ermei; Salonen, Jarno; Vasilev, Krasimir; Voelcker, Nicolas H.

2014-07-01

In this study, the ability of porous silicon nanoparticles (PSi NPs) to entrap and deliver nitric oxide (NO) as an effective antibacterial agent is tested against different Gram-positive and Gram-negative bacteria. NO was entrapped inside PSi NPs functionalized by means of the thermal hydrocarbonization (THC) process. Subsequent reduction of nitrite in the presence of d-glucose led to the production of large NO payloads without reducing the biocompatibility of the PSi NPs with mammalian cells. The resulting PSi NPs demonstrated sustained release of NO and showed remarkable antibacterial efficiency and anti-biofilm-forming properties. These results will set the stage to develop antimicrobial nanoparticle formulations for applications in chronic wound treatment.

Nitric oxide-releasing porous silicon nanoparticles.

PubMed

Kafshgari, Morteza Hasanzadeh; Cavallaro, Alex; Delalat, Bahman; Harding, Frances J; McInnes, Steven Jp; Mäkilä, Ermei; Salonen, Jarno; Vasilev, Krasimir; Voelcker, Nicolas H

2014-01-01

In this study, the ability of porous silicon nanoparticles (PSi NPs) to entrap and deliver nitric oxide (NO) as an effective antibacterial agent is tested against different Gram-positive and Gram-negative bacteria. NO was entrapped inside PSi NPs functionalized by means of the thermal hydrocarbonization (THC) process. Subsequent reduction of nitrite in the presence of d-glucose led to the production of large NO payloads without reducing the biocompatibility of the PSi NPs with mammalian cells. The resulting PSi NPs demonstrated sustained release of NO and showed remarkable antibacterial efficiency and anti-biofilm-forming properties. These results will set the stage to develop antimicrobial nanoparticle formulations for applications in chronic wound treatment.

PEGylated non-ionic surfactant vesicles as drug delivery systems for Gambogenic acid.

PubMed

Lin, Tongyuan; Fang, Qingying; Peng, Daiyin; Huang, Xia; Zhu, Tingting; Luo, Qing; Zhou, Kai; Chen, Weidong

2013-01-01

Gambogenic acid (GNA), a popular Chinese traditional medicine, has its limitations of coming into use due to its low aqueous solubility and poor bioavailability. In this study, therefore, the PEGylated non-ionic surfactant vesicles drug delivery systems were prepared from biocompatible non-ionic surfactant of Span60, cholesterol and dicetyl phosphate (DCP) by the improved ethanol injection method, and were modified with a polyethylene glycol monostearate15 (PEG15-SA). PEG15-SA, as a biocompatible, non-toxic and non-immunogenic hydrophilic segment, was grafted onto the surface of colloidal niosomes carries to reduce the uptake by the reticuloendothelial system (RES), prolonging the circulation time and attaining higher entrapment efficiency. To our knowledge, this work is the first to report that PEG15-SA was applied to coating of niosomes for encapsulation of GNA. The optimized PEG-GNA-NISVs (P-GNA-NISVs) were characterized in terms of mean vesicles size, polydispersity index (PDI), Zeta potential and entrapment efficiency of the P-GNA-NISVs. The results showed that the mean diameter, PDI, Zeta potential, and the entrapment efficiency of the P-GNA-NISVs were 70.1 nm, 0.166, -44.3 mV and 87.74%, respectively. Furthermore, the release studies of GNA from PEGylated niosomes in vitro and the pharmacokinetics in vivo exhibited a prolonged release profile as studied over 24 h. In conclusion, the result suggests that P-GNA-NISVs prepared in this way not only have higher encapsulation capacity, more colloidal stability but also offer an approach that the PEGylated niosomes is a promising carrier for anticancer GNA.

Formulation and in vitro assessment of minoxidil niosomes for enhanced skin delivery.

PubMed

Balakrishnan, Prabagar; Shanmugam, Srinivasan; Lee, Won Seok; Lee, Won Mo; Kim, Jong Oh; Oh, Dong Hoon; Kim, Dae-Duk; Kim, Jung Sun; Yoo, Bong Kyu; Choi, Han-Gon; Woo, Jong Soo; Yong, Chul Soon

2009-07-30

Niosomes have been reported as a possible approach to improve the low skin penetration and bioavailability characteristics shown by conventional topical vehicle for minoxidil. Niosomes formed from polyoxyethylene alkyl ethers (Brij) or sorbitan monoesters (Span) with cholesterol molar ratios of 0, 1 and 1.5 were prepared with varying drug amount 20-50mg using thin film-hydration method. The prepared systems were characterized for entrapment efficiency, particle size, zeta potential and stability. Skin permeation studies were performed using static vertical diffusion Franz cells and hairless mouse skin treated with either niosomes, control minoxidil solution (propylene glycol-water-ethanol at 20:30:50, v/v/v) or a leading topical minoxidil commercial formulation (Minoxyl). The results showed that the type of surfactant, cholesterol and incorporated amount of drug altered the entrapment efficiency of niosomes. Higher entrapment efficiency was obtained with the niosomes prepared from Span 60 and cholesterol at 1:1 molar ratio using 25mg drug. Niosomal formulations have shown a fairly high retention of minoxidil inside the vesicles (80%) at refrigerated temperature up to a period of 3 months. It was observed that both dialyzed and non-dialyzed niosomal formulations (1.03+/-0.18 to 19.41+/-4.04%) enhanced the percentage of dose accumulated in the skin compared to commercial and control formulations (0.11+/-0.03 to 0.48+/-0.17%) except dialyzed Span 60 niosomes. The greatest skin accumulation was always obtained with non-dialyzed vesicular formulations. Our results suggest that these niosomal formulations could constitute a promising approach for the topical delivery of minoxidil in hair loss treatment.

Dual crosslinked pectin-alginate network as sustained release hydrophilic matrix for repaglinide.

PubMed

Awasthi, Rajendra; Kulkarni, Giriraj T; Ramana, Malipeddi Venkata; de Jesus Andreoli Pinto, Terezinha; Kikuchi, Irene Satiko; Molim Ghisleni, Daniela Dal; de Souza Braga, Marina; De Bank, Paul; Dua, Kamal

2017-04-01

Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half-life of approximately 1h. Developing a controlled and prolonged release delivery system is required to maintain its therapeutic plasma concentration and to eliminate its adverse effects particularly hypoglycemia. The present study aimed to develop controlled release repaglinide loaded beads using sodium alginate and pectin with dual cross-linking for effective control of drug release. The prepared beads were characterized for size, percentage drug entrapment efficiency, in vitro drug release and the morphological examination using scanning electron microscope. For the comparative study, the release profile of a marketed conventional tablet of repaglinide (Prandin ® tablets 2mg, Novo Nordisk) was determined by the same procedure as followed for beads. The particle size of beads was in the range of 698±2.34-769±1.43μm. The drug entrapment efficiency varied between 55.24±4.61 to 82.29±3.42%. The FTIR results suggest that there was no interaction between repaglinide and excipients. The XRD and DSC results suggest partial molecular dispersion and amorphization of the drug throughout the system. These results suggest that repaglinide did not dissolve completely in the polymer composition and seems not to be involved in the cross-linking reaction. The percent drug release was decreased with higher polymer concentrations. In conclusion, the developed beads could enhance drug entrapment efficiency, prolong the drug release and enhance bioavailability for better control of diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

Optimizing novel penetration enhancing hybridized vesicles for augmenting the in-vivo effect of an anti-glaucoma drug.

PubMed

Naguib, Sarah S; Hathout, Rania M; Mansour, Samar

2017-11-01

Usually the topical delivery of ocular drugs poses a great challenge. Accordingly, the work in this study comprised the use of different hybrids of generally regarded as safe (GRAS) oils and surfactants in order to develop and optimize novel acetazolamide (AZD) entrapped-vesicular systems aiming at improving its ocular delivery and reaching better therapeutic outcomes in the treatment of glaucoma. The phospholipid/cholesterol bilayer of the vesicles was enriched with hybrids of Tween 80, Labrasol, Transcutol and Labrafac lipophile WL in different masses and proportions according to a mixture design viz. D-optimal mixture design. Three models were generated comprising three responses: particles size, percentage of entrapment efficiency and amount of drug released after 24 hours (Q24h). The results demonstrated the ability of the penetration enhancing hybrids in modulating the three responses compared to the conventional liposomes. Transmission electron microscope was used to characterize the selected formulations. Sterilization of selected formulations was carried out using gamma radiation and the effect of gamma radiations on entrapment, particle size and in vitro release were studied. The selected sterilized formulations were tested in-vivo on the eyes of albino rabbits in order to evaluate the efficiency of the novel delivery systems on the intra-ocular pressure reduction (IOP) compared to drug solution and the conventional liposomes. The novel formulations proved their efficiency in reducing the IOP to lower values compared to the conventional liposomes, which pose new successful platform for ocular delivery of AZD and other anti-glaucoma drug analogs.

Impact of plant growth-promoting rhizobacteria on root colonization potential and life cycle of Rhizophagus irregularis following co-entrapment into alginate beads.

PubMed

Loján, P; Demortier, M; Velivelli, S L S; Pfeiffer, S; Suárez, J P; de Vos, P; Prestwich, B D; Sessitsch, A; Declerck, S

2017-02-01

This study aimed at evaluating the impact of seven plant growth-promoting rhizobacteria (PGPR) on root colonization and life cycle of Rhizophagus irregularis MUCL 41833 when co-entrapped in alginate beads. Two in vitro experiments were conducted. The first consisted of the immobilization of R. irregularis and seven PGPR isolates into alginate beads to assess the effect of the bacteria on the pre-symbiotic growth of the fungus. In the second experiment, the best performing PGPR from experiment 1 was tested for its ability to promote the symbiotic development of the AMF in potato plantlets from three cultivars. Results showed that only one isolate identified as Pseudomonas plecoglossicida (R-67094) promoted germ tube elongation and hyphal branching of germinated spores during the pre-symbiotic phase of the fungus. This PGPR further promoted the symbiotic development of the AMF in potato plants. The co-entrapment of Ps. plecoglossicida R-67094 and R. irregularis MUCL 41833 in alginate beads improved root colonization by the AMF and its further life cycle under the experimental conditions. Co-entrapment of suitable AMF-PGPR combinations within alginate beads may represent an innovative technology that can be fine-tuned for the development of efficient consortia-based bioformulations. © 2016 The Society for Applied Microbiology.

Characterization of drug release from liposomal formulations in ocular fluid.

PubMed

Jafari, M R; Jones, A B; Hikal, A H; Williamson, J S; Wyandt, C M

1998-01-01

The successful application of liposomes in topical ophthalmic drug delivery requires knowledge of vesicle stabilization in the presence of tear fluid. The release of procaine hydrochloride (PCH) from large unilamellar liposomes in the presence of simulated tear fluid was studied in vitro as a function of bilayer lipid content and tear protein composition. Reverse-phase evaporation vesicles were prepared from egg phosphatidylcholine, stearylamine or dicetyl phosphate, and cholesterol. The relationship between lipid composition and encapsulation efficiency, vesicle size, drug leakage upon storage at 4 degrees C, and the release of PCH-loaded liposomes was studied. The encapsulation efficiency was found to be dependent upon the lipid composition used in the liposome preparation. In particular, phosphatidylcholine vesicles containing cholesterol and/or charged lipids had a lower entrapment efficiency than liposomes prepared with phosphatidylcholine alone. However, the drug release rate was reduced significantly by inclusion of cholesterol and/or charged lipids in the liposomes. The release kinetics of the entrapped agent seemed to be a biphasic process and the drug-release in both simulated tear fluid (STF) and pH 7.4 phosphate buffered saline (PBS) solutions followed pseudo first-order kinetics in the early stage of the release profile. The drug-release appeared to be diffusion and/or partition controlled. Drug release from liposomes into STF, pH 7.4 PBS, and five different modified tear formulations was also evaluated. While serum-induced leakage is attributed to high-density lipoprotein-mediated destabilization, it was determined that lactoferrin might be the protein component in tear fluid that has the primary influence on the liposome-entrapped drug release rate. Five local anesthetics, benoxinate, proparacaine, procaine, tetracaine, and benzocaine were entrapped in liposomal vesicles by a reverse-phase evaporation (REV) technique. The release of these structurally similar topical anesthetics entrapped in positively charged liposomes (egg phosphatidylcholine, stearylamine, and cholesterol in a 7:2:1 molar ratio) was evaluated in a simulated tear fluid and pH 7.4 phosphate buffered saline solution. The liposomes appeared to be useful carriers for these drugs to retard their in vitro release in tear fluid and perhaps sustain or control their release in the eye for better therapeutic efficacy. An analysis of the release data demonstrated that for this series of drugs, drug partition coefficient has the largest effect on release rate, with molecular weight exhibiting a smaller effect. Release rate was found to decrease with increased lipophilicity or increased molecular weight.

Catechin-loaded Eudragit microparticles for the management of diabetes: formulation, characterization and in vivo evaluation of antidiabetic efficacy.

PubMed

Meena, Kedar Prasad; Vijayakumar, Mahalingam Rajamanickam; Dwibedy, Priti S

2017-06-01

Catechin (CT) is natural molecule proved for antidiabetic activity. Clinical application of CT is highly restricted because of its low bioavailability and ineffectiveness in in vivo conditions. Therefore, the main objective of the present investigation was to formulate CT-loaded Eudragit RS 100 microparticles and evaluated for its potential against diabetes. CT microparticles showing highest entrapment efficiency of 92.3 ± 6.5% and higher percentage yield of 63.46 ± 4.3% was selected as optimised formulation. CT microparticles treated rats showed significantly lower blood glucose, cholesterol, LDL, free fatty acid and triglyceride concentrations in comparison to pristine CT-treated rats. The glucose and lipid profiles of microparticle formulation were akin to normal rats. Moreover, CT microparticles did not produce obesity even after 60 days which is a comment side effect of antidiabetic drugs. These results indicate that the CT microparticles can be applied as potential and safe carrier for the treatment of diabetes.

Novel galactosylated biodegradable nanoparticles for hepatocyte-delivery of oridonin.

PubMed

Wang, Ying; Liu, Xinquan; Liu, Guangpu; Guo, Hejian; Li, Caiyun; Zhang, Yongchun; Zhang, Fang; Zhao, Zhongxi; Cheng, Huiling

2016-04-11

Nanoparticles based on the newly synthesized copolymers of linear PLGA blocked with two TPGS ends and galactosylated TPGS were successfully constructed as carriers of oridonin for liver-targeting. The novel copolymers were characterized by (1)H-NMR and TGA. The drug-loaded nanoparticles were prepared by a nanoprecipitation technique and characterized in terms of physicochemical properties, such as particle size, zeta potential, morphology, encapsulation efficiency, in vitro drug release behavior and physical state of the entrapped drug. The ORI-Gal-PT NPs were found to have the highest antitumor efficacy in comparison with the oridonin solution and non-galactosylated nanoparticles and induced a higher apoptotic rate of tumor cells. The targeting nanoparticles could enhance the therapeutic effect of oridonin by increasing uptake of the nanoparticles through asialoglycoprotein receptor-mediated endocytosis. The ORI-Gal-PT NPs system could be a highly promising drug delivery system to be used in liver cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation of curcumin-loaded PCL-PEG-PCL triblock copolymeric nanoparticles by a microchannel technology.

PubMed

Guo, Fangyuan; Guo, Dingjia; Zhang, Wei; Yan, Qinying; Yang, Yan; Hong, Weiyong; Yang, Gensheng

2017-03-01

Biodegradable polymeric nanoparticles (NPs) have potential therapeutic applications; however, preparing NPs of a specific diameter and uniform size distribution is a challenge. In this work, we fabricated a microchannel system for the preparation of curcumin (Cur)-loaded NPs by the interfacial precipitation method, which rapidly and consistently generated stable NPs with a relatively smaller diameter, narrow size distribution, and higher drug-loading capacity and entrapment efficiency. Poly(ε-caprolactone)-poly(ethylene glycol)-poly (ε-caprolactone) triblock copolymers(PCEC) used as the carrier material was synthesized and characterized. Cur-loaded PCEC NPs had an average size of 167.2nm with a zeta potential of -29.23mV, and showed a loading capacity and drug entrapment efficiency of 15.28%±0.23% and 96.11%±0.13%, respectively. Meanwhile, the NPs demonstrated good biocompatibility and bioavailability, efficient cellular uptake, and long circulation time and a possible liver targeting effect in vivo. These results indicate that the Cur-loaded PCEC NPs can be used as drug carriers in controlled delivery systems and other biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Development of repaglinide microspheres using novel acetylated starches of bitter and Chinese yams as polymers.

PubMed

Okunlola, Adenike; Adebayo, Amusa Sarafadeen; Adeyeye, Moji Christianah

2017-01-01

Tropical starches from Dioscorea dumetorum (bitter) and Dioscorea oppositifolia (Chinese) yams were acetylated with acetic anhydride in pyridine medium and utilized as polymers for the delivery of repaglinide in microsphere formulations in comparison to ethyl cellulose. Acetylated starches of bitter and Chinese yams with degrees of substitution of 2.56 and 2.70 respectively were obtained. Acetylation was confirmed by FTIR, 1 H NMR spectroscopy. A 3 2 factorial experimental design was performed using polymer type and drug-polymer ratio as independent variables. Particle size, swelling, entrapment and time for 50% drug release (t 50 ) were dependent variables. Contour plots showed the relationship between the independent factors and the response variables. All variables except swelling increased with drug: polymer ratio. Entrapment efficiency was generally in the rank of Bitter yam>Ethyl cellulose>Chinese yam. Repaglinide microspheres had size 50±4.00 to 350±18.10μm, entrapment efficiency 75.30±3.03 to 93.10±2.75% and t 50 3.20±0.42 to 7.20±0.55h. Bitter yam starch gave longer dissolution times than Chinese yam starch at all drug-polymer ratios. Drug release fitted Korsmeyer-Peppas and Hopfenberg models. Acetylated bitter and Chinese yam starches were found suitable as polymers to prolong release of repaglinide in microsphere formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

Electrospun Zein/PCL Fibrous Matrices Release Tetracycline in a Controlled Manner, Killing Staphylococcus aureus Both in Biofilms and Ex Vivo on Pig Skin, and are Compatible with Human Skin Cells.

PubMed

Alhusein, Nour; Blagbrough, Ian S; Beeton, Michael L; Bolhuis, Albert; De Bank, Paul A

2016-01-01

To investigate the destruction of clinically-relevant bacteria within biofilms via the sustained release of the antibiotic tetracycline from zein-based electrospun polymeric fibrous matrices and to demonstrate the compatibility of such wound dressing matrices with human skin cells. Zein/PCL triple layered fibrous dressings with entrapped tetracycline were electrospun. The successful entrapment of tetracycline in these dressings was validated. The successful release of bioactive tetracycline, the destruction of preformed biofilms, and the viability of fibroblast (FEK4) cells were investigated. The sustained release of tetracycline from these matrices led to the efficient destruction of preformed biofilms from Staphylococcus aureus MRSA252 in vitro, and of MRSA252 and ATCC 25923 bacteria in an ex vivo pig skin model using 1 × 1 cm square matrices containing tetracycline (30 μg). Human FEK4 cells grew normally in the presence of these matrices. The ability of the zein-based matrices to destroy bacteria within increasingly complex in vitro biofilm models was clearly established. An ex vivo pig skin assay showed that these matrices, with entrapped tetracycline, efficiently kill bacteria and this, combined with their compatibility with a human skin cell line suggest these matrices are well suited for applications in wound healing and infection control.

Potential application of immobilized streptokinase extracted from Streptococcus equinus VIT_VB2.

PubMed

Vaishnavi, B; Subathra Devi, C

2017-11-26

Streptokinase purified from Streptococcus equinus VIT_VB2 isolated from bovine milk sample was immobilized in various solid supports namely entrapment in agarose gel, calcium alginate beads and gelatin gel by cross-linking with formaldehyde. Immobilization of streptokinase in calcium alginate beads showed maximum efficiency (81.8 ± 1.06%) when compared with entrapment with agarose gel (55.6 ± 2.17%) and cross-linked gelatin formaldehyde gel (71.0 ± 1.54%). The purified SK activity was expressed maximum in calcium alginate (1%) and gelatin gel (0.25%) with 1292.68 ± 1.33 and 1121.9 ± 1.2 U mL -1 , respectively. Similarly, SK entrapped in gelatin gel and calcium alginate showed maximum in vitro blood clot lysis activity with 77.67 ± 2.64% and 76.16 ± 2.72%, respectively. The immobilized SK in gelatin gel showed complete clot lysis within 15 min; hence, this application of the study could be used in the treatment of superficial thrombophlebitis, phlebitis, and venous thrombosis. These beads were used for three repeated cycles to check the conversion of substrates into their products, and we concluded that SK can be immobilized in the suitable matrices. Therefore, this helps in the drug-delivery strategies in highly efficient way, moreover, economically competent process in the pharmaceutics.

Air-stable superparamagnetic metal nanoparticles entrapped in graphene oxide matrix

NASA Astrophysics Data System (ADS)

Tuček, Jiří; Sofer, Zdeněk; Bouša, Daniel; Pumera, Martin; Holá, Kateřina; Malá, Aneta; Poláková, Kateřina; Havrdová, Markéta; Čépe, Klára; Tomanec, Ondřej; Zbořil, Radek

2016-09-01

Superparamagnetism is a phenomenon caused by quantum effects in magnetic nanomaterials. Zero-valent metals with diameters below 5 nm have been suggested as superior alternatives to superparamagnetic metal oxides, having greater superspin magnitudes and lower levels of magnetic disorder. However, synthesis of such nanometals has been hindered by their chemical instability. Here we present a method for preparing air-stable superparamagnetic iron nanoparticles trapped between thermally reduced graphene oxide nanosheets and exhibiting ring-like or core-shell morphologies depending on iron concentration. Importantly, these hybrids show superparamagnetism at room temperature and retain it even at 5 K. The corrected saturation magnetization of 185 Am2 kg-1 is among the highest values reported for iron-based superparamagnets. The synthetic concept is generalized exploiting functional groups of graphene oxide to stabilize and entrap cobalt, nickel and gold nanoparticles, potentially opening doors for targeted delivery, magnetic separation and imaging applications.

Air-stable superparamagnetic metal nanoparticles entrapped in graphene oxide matrix.

PubMed

Tuček, Jiří; Sofer, Zdeněk; Bouša, Daniel; Pumera, Martin; Holá, Kateřina; Malá, Aneta; Poláková, Kateřina; Havrdová, Markéta; Čépe, Klára; Tomanec, Ondřej; Zbořil, Radek

2016-09-15

Superparamagnetism is a phenomenon caused by quantum effects in magnetic nanomaterials. Zero-valent metals with diameters below 5 nm have been suggested as superior alternatives to superparamagnetic metal oxides, having greater superspin magnitudes and lower levels of magnetic disorder. However, synthesis of such nanometals has been hindered by their chemical instability. Here we present a method for preparing air-stable superparamagnetic iron nanoparticles trapped between thermally reduced graphene oxide nanosheets and exhibiting ring-like or core-shell morphologies depending on iron concentration. Importantly, these hybrids show superparamagnetism at room temperature and retain it even at 5 K. The corrected saturation magnetization of 185 Am(2) kg(-1) is among the highest values reported for iron-based superparamagnets. The synthetic concept is generalized exploiting functional groups of graphene oxide to stabilize and entrap cobalt, nickel and gold nanoparticles, potentially opening doors for targeted delivery, magnetic separation and imaging applications.

Air-stable superparamagnetic metal nanoparticles entrapped in graphene oxide matrix

PubMed Central

Tuček, Jiří; Sofer, Zdeněk; Bouša, Daniel; Pumera, Martin; Holá, Kateřina; Malá, Aneta; Poláková, Kateřina; Havrdová, Markéta; Čépe, Klára; Tomanec, Ondřej; Zbořil, Radek

2016-01-01

Superparamagnetism is a phenomenon caused by quantum effects in magnetic nanomaterials. Zero-valent metals with diameters below 5 nm have been suggested as superior alternatives to superparamagnetic metal oxides, having greater superspin magnitudes and lower levels of magnetic disorder. However, synthesis of such nanometals has been hindered by their chemical instability. Here we present a method for preparing air-stable superparamagnetic iron nanoparticles trapped between thermally reduced graphene oxide nanosheets and exhibiting ring-like or core-shell morphologies depending on iron concentration. Importantly, these hybrids show superparamagnetism at room temperature and retain it even at 5 K. The corrected saturation magnetization of 185 Am2 kg–1 is among the highest values reported for iron-based superparamagnets. The synthetic concept is generalized exploiting functional groups of graphene oxide to stabilize and entrap cobalt, nickel and gold nanoparticles, potentially opening doors for targeted delivery, magnetic separation and imaging applications. PMID:27628898

Removal of chlorinated organic solvents from hydraulic fracturing wastewater by bare and entrapped nanoscale zero-valent iron.

PubMed

Lei, Cheng; Sun, Yuqing; Khan, Eakalak; Chen, Season S; Tsang, Daniel C W; Graham, Nigel J D; Ok, Yong Sik; Yang, Xin; Lin, Daohui; Feng, Yujie; Li, Xiang-Dong

2018-04-01

With the increasing application of hydraulic fracturing, it is urgent to develop an effective and economically feasible method to treat the large volumes of fracturing wastewater. In this study, bare and entrapped nanoscale zero-valent iron (nZVI) were introduced for the removal of carbon tetrachloride (CT) and 1,1,2-trichloroethane (TCA) in model high-salinity fracturing wastewater. With increasing ionic strength (I) from Day-1 (I = 0.35 M) to Day-90 (I = 4.10 M) wastewaters, bare nZVI presented significantly lower removal efficiency of CT (from 53.5% to 38.7%) and 1,1,2-TCA (from 71.1% to 21.7%) and underwent more serious Fe dissolution from 1.31 ± 1.19% in Day-1 to 5.79 ± 0.32% in Day-90 wastewater. Particle aggregation induced by high ionic strength was primarily responsible for the lowered performance of nZVI due to less available reactive sites on nZVI surface. The immobilization of nZVI in alginate with/without polyvinyl alcohol provided resistance to particle aggregation and contributed to the superior performance of entrapped nZVI in Day-90 wastewater for 1,1,2-TCA removal (62.6-72.3%), which also mitigated Fe dissolution (4.00-4.69%). Both adsorption (by polymer matrix) and reduction (by immobilized nZVI) were involved in the 1,1,2-TCA removal by entrapped nZVI. However, after 1-month immersion in synthetic fracturing wastewater, a marked drop in the reactivity of entrapped nZVI for 1,1,2-TCA removal from Day-90 wastewater was observed with significant release of Na and total organic carbon. In summary, bare nZVI was sensitive to the nature of the fracturing wastewater, while the use of environmentally benign entrapped nZVI was more promising for wastewater treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nitric oxide-releasing porous silicon nanoparticles

PubMed Central

2014-01-01

In this study, the ability of porous silicon nanoparticles (PSi NPs) to entrap and deliver nitric oxide (NO) as an effective antibacterial agent is tested against different Gram-positive and Gram-negative bacteria. NO was entrapped inside PSi NPs functionalized by means of the thermal hydrocarbonization (THC) process. Subsequent reduction of nitrite in the presence of d-glucose led to the production of large NO payloads without reducing the biocompatibility of the PSi NPs with mammalian cells. The resulting PSi NPs demonstrated sustained release of NO and showed remarkable antibacterial efficiency and anti-biofilm-forming properties. These results will set the stage to develop antimicrobial nanoparticle formulations for applications in chronic wound treatment. PMID:25114633

Development and optimization of apigenin-loaded transfersomal system for skin cancer delivery: in vitro evaluation.

PubMed

Jangdey, Manmohan Singh; Gupta, Anshita; Saraf, Shailendra; Saraf, Swarnlata

2017-11-01

The aim of this work is to apply Box-Behnken design to optimize the transfersomes were formulated by modified rotary evaporation sonication technique using surfactant Tween 80. The response surface methodology was used having three-factored with three levels. The prepared formulations were characterized for vesicle shape, size, entrapment efficiency (%), stability, and in vitro permeation. The result showed that drug entrapment of 84.24% with average vesicle size of 35.41 nm and drug loading of 8.042%. Thus, optimized formulation was found good stability and is a promising approach to improve the permeability of apigenin in sustained release for prolonged period of time.

Magnetic nanoparticles entrapped in siliceous mesocellular foam: a new catalyst support.

PubMed

Lee, Su Seong; Riduan, Siti Nurhanna; Erathodiyil, Nandanan; Lim, Jaehong; Cheong, Jian Liang; Cha, Junhoe; Han, Yu; Ying, Jackie Y

2012-06-11

γ-Fe(2)O(3) nanoparticles were formed inside the cage-like pores of mesocellular foam (MCF). These magnetic nanoparticles showed a uniform size distribution that could be easily controlled by the MCF pore size, as well as by the hydrocarbon chain length used for MCF surface modification. Throughout the entrapment process, the pore structure and surface area of the MCF remained intact. The resulting magnetic MCF facilitated the immobilization of biocatalysts, homogeneous catalysts, and nanoclusters. Moreover, the MCF allowed for facile catalyst recovery by using a simple magnet. The supported catalysts exhibited excellent catalytic efficiencies that were comparable to their homogeneous counterparts. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development, characterization and in vivo evaluation of benzocaine-loaded liposomes.

PubMed

Mura, Paola; Maestrelli, Francesca; González-Rodríguez, Maria Luisa; Michelacci, Ilaria; Ghelardini, Carla; Rabasco, Antonio M

2007-08-01

This study reports the development and in vivo evaluation of a liposomal formulation of the local anaesthetic benzocaine. Multi-lamellar (MLV) and small uni-lamellar (SUV) vesicles entrapping benzocaine were prepared using 50:50 w/w phosphatidylcholine-cholesterol as lipophilic phase and 50:50 v/v ethanol-water as hydrophilic phase. Liposome size, Zeta-potential, encapsulation efficiency and skin penetration properties were determined. Drug permeation from liposomal dispersions, as such or formulated in Carbopol gel, was evaluated through artificial lipophilic membranes and excised abdominal rat skin, whereas in vivo anaesthetic effect was tested on rabbits. Interestingly, addition of the drug into the hydrophilic phase, rather than into the lipophilic one, during liposome preparation enabled an improvement of the MLV's entrapment efficiency from 29.7% to 82.3%. On the other hand, sonication conditions to obtain SUV influenced size and polydispersity index of the vesicles and reduced the entrapment efficiency by about 30%. All liposomal-benzocaine formulations showed sustained release properties and a more intense anaesthetic effect than plain drug. Permeation experiments from drug solutions in gel containing the same amount of ethanol as in the liposomal formulations made it possible to exclude a possible enhancer effect of this solvent, at least when not used in liposomal formulations. MLV with the drug added into the hydrophilic phase gave the most effective formulation, showing a permeability coefficient value 2.5 times higher than that of the plain drug and allowing a significant improvement (P<0.01) not only of intensity but also of duration of anaesthetic effect of benzocaine. These results suggest that a suitably developed liposomal formulation of benzocaine can be of actual value for improving its clinical effectiveness in topical anaesthesia.

Does stone entrapment with ″Uro-Net″ improve Ho:YAG laser lithotripsy efficiency in percutaneous nephrolithotomy and cystolithopaxy?: an in vitro study.

PubMed

Marchini, Giovanni Scala; Rai, Aayushi; De, Shubha; Sarkissian, Carl; Monga, Manoj

2013-01-01

to test the effect of stone entrapment on laser lithotripsy efficiency. Spherical stone phantoms were created using the BegoStone® plaster. Lithotripsy of one stone (1.0 g) per test jar was performed with Ho:YAG laser (365 µm fiber; 1 minute/trial). Four laser settings were tested: I-0.8 J,8 Hz; II-0.2J,50 Hz; III-0.5 J,50 Hz; IV-1.5 J,40 Hz. Uro-Net (US Endoscopy) deployment was used in 3/9 trials. Post-treatment, stone fragments were strained though a 1mm sieve; after a 7-day drying period fragments and unfragmented stone were weighed. Uro-Net nylon mesh and wire frame resistance were tested (laser fired for 30s). All nets used were evaluated for functionality and strength (compared to 10 new nets). Student's T test was used to compare the studied parameters; significance was set at p < 0.05. Laser settings I and II caused less damage to the net overall; the mesh and wire frame had worst injuries with setting IV; setting III had an intermediate outcome; 42% of nets were rendered unusable and excluded from strength analysis. There was no difference in mean strength between used functional nets and non-used devices (8.05 vs. 7.45 lbs, respectively; p = 0.14). Setting IV was the most efficient for lithotripsy (1.9 ± 0.6 mg/s; p < 0.001) with or without net stabilization; setting III was superior to I and II only if a net was not used. Laser lithotripsy is not optimized by stone entrapment with a net retrieval device which may be damaged by high energy laser settings.

Brain targeted oral delivery of doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles against ketamine induced psychosis: behavioral, biochemical, neurochemical and histological alterations in mice.

PubMed

Yadav, Monu; Parle, Milind; Sharma, Nidhi; Dhingra, Sameer; Raina, Neha; Jindal, Deepak Kumar

2017-11-01

To develop statistically optimized brain targeted Tween 80 coated chitosan nanoparticulate formulation for oral delivery of doxycycline hydrochloride for the treatment of psychosis and to evaluate its protective effect on ketamine induced behavioral, biochemical, neurochemical and histological alterations in mice. 3 2 full factorial design was used to optimize the nanoparticulate formulation to minimize particle size and maximize entrapment efficiency, while independent variables chosen were concentration of chitosan and Tween 80. The optimized formulation was characterized by particle size, drug entrapment efficiency, Fourier transform infrared, Transmission electron microscopy analysis and drug release behavior. Pure doxycycline hydrochloride (25 and 50 mg/kg, p.o.) and optimized doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles (DCNP opt ) (equivalent to 25 mg/kg doxycycline hydrochloride, p.o.) were explored against ketamine induced psychosis in mice. The experimental studies for DCNP opt , with mean particle size 237 nm and entrapment efficiency 78.16%, elucidated that the formulation successfully passed through blood brain barrier and exhibited significant antipsychotic activity. The underlying mechanism of action was further confirmed by behavioral, biochemical, neurochemical estimations and histopathological study. Significantly enhanced GABA and GSH level and diminished MDA, TNF-α and dopamine levels were observed after administration of DCNP opt at just half the dose of pure doxycycline hydrochloride, showing better penetration of doxycyline hydrochloride in the form of Tween 80 coated nanoparticles through blood brain barrier. This study demonstrates the hydrophilic drug doxycycline hydrochloride, loaded in Tween 80 coated chitosan nanoparticles, can be effectively brain targeted through oral delivery and therefore represents a suitable approach for the treatment of psychotic symptoms.

Optimization and Evaluation of Gastroretentive Ranitidine HCl Microspheres by Using Factorial Design with Improved Bioavailability and Mucosal Integrity in Ulcer Model.

PubMed

Khattab, Abeer; Zaki, Nashwah

2017-05-01

The purpose of our investigation was to develop and optimize the drug entrapment efficiency and bioadhesion properties of mucoadhesive chitosan microspheres containing ranitidine HCl prepared by an ionotropic gelation method as a gastroretentive delivery system; thus, we improved their protective and therapeutic gastric effects in an ulcer model. A 3 × 2 2 full factorial design was adopted to study the effect of three different factors, i.e., the type of polymer at three levels (chitosan, chitosan/hydroxypropylmethylcellulose, and chitosan/methylcellulose), the type of solvent at two levels (acetic acid and lactic acid), and the type of chitosan at two levels (low molecular weight (LMW) and high molecular weight (HMW)). The studied responses were particle size, swelling index, drug entrapment efficiency, bioadhesion (as determined by wash-off and rinsing tests), and T 80% of drug release. Studies of the in vivo mucoadhesion and in vivo protective and healing effects of the optimized formula against gastric ulcers were carried out using albino rats (with induced gastric ulceration) and were compared to the effects of free ranitidine powder. A pharmacokinetic study in rabbits showed a significant, 2.1-fold increase in theAUC 0-24 of the ranitidine microspheres compared to free ranitidine after oral administration. The optimized formula showed higher drug entrapment efficiency and mucoadhesion properties and had more protective and healing effects on induced gastric ulcers in rats than ranitidine powder. In conclusion, the prolonged gastrointestinal residence time and the stability of the mucoadhesive microspheres of ranitidine as well as the synergistic healing effect of chitosan could contribute to increasing the potential of its anti-gastric ulcer activity.

Theory of vibratory mobilization and break-up of non-wetting fluids entrapped in pore constrictions

NASA Astrophysics Data System (ADS)

Beresnev, I.; Li, W.; Vigil, D.

2006-12-01

Quantitative dynamics of a non-wetting (e. g., NAPL) ganglion entrapped in a pore constriction and subjected to vibrations can be approximated by the equation of motion of an oscillator moving under the effect of the external pressure gradient, inertial oscillatory force, and restoring capillary force. The solution of the equation provides the conditions under which the droplet experiences forced oscillations without being mobilized or is liberated upon the acceleration of the wall exceeding an "unplugging" threshold. This solution provides a quantitative tool for the estimation of the parameters of vibratory fields needed to liberate entrapped non-wetting fluids. For typical pore sizes encountered in reservoirs and aquifers, wall accelerations must exceed at least several m/sec2 and even higher levels to mobilize the droplets of NAPL; however, in the populations of ganglia entrapped in natural porous environments, many may reside very near their mobilization thresholds and may be mobilized by extremely low accelerations as well. For given acceleration, lower seismic frequencies are more efficient. The ganglia may also break up into smaller pieces when passing through pore constrictions. The snap-off is governed by the geometry only; for constrictions with sinusoidal profile (spatial wavelength of L and maximum and minimum radii of rmax and rmin, the break-up occurs if L > 2π(rmin rmax)1/2. Computational fluid dynamics shows the details of the break-up process.

A vertically aligned carbon nanotube-based impedance sensing biosensor for rapid and high sensitive detection of cancer cells.

PubMed

Abdolahad, Mohammad; Taghinejad, Mohammad; Taghinejad, Hossein; Janmaleki, Mohsen; Mohajerzadeh, Shams

2012-03-21

A novel vertically aligned carbon nanotube based electrical cell impedance sensing biosensor (CNT-ECIS) was demonstrated for the first time as a more rapid, sensitive and specific device for the detection of cancer cells. This biosensor is based on the fast entrapment of cancer cells on vertically aligned carbon nanotube arrays and leads to mechanical and electrical interactions between CNT tips and entrapped cell membranes, changing the impedance of the biosensor. CNT-ECIS was fabricated through a photolithography process on Ni/SiO(2)/Si layers. Carbon nanotube arrays have been grown on 9 nm thick patterned Ni microelectrodes by DC-PECVD. SW48 colon cancer cells were passed over the surface of CNT covered electrodes to be specifically entrapped on elastic nanotube beams. CNT arrays act as both adhesive and conductive agents and impedance changes occurred as fast as 30 s (for whole entrapment and signaling processes). CNT-ECIS detected the cancer cells with the concentration as low as 4000 cells cm(-2) on its surface and a sensitivity of 1.7 × 10(-3)Ω cm(2). Time and cell efficiency factor (TEF and CEF) parameters were defined which describe the sensor's rapidness and resolution, respectively. TEF and CEF of CNT-ECIS were much higher than other cell based electrical biosensors which are compared in this paper.

Brushed block copolymer micelles with pH-sensitive pendant groups for controlled drug delivery.

PubMed

Lee, Hyun Jin; Bae, Younsoo

2013-08-01

To investigate the effects of small aliphatic pendent groups conjugated through an acid-sensitive linker to the core of brushed block copolymer micelles on particle properties. The brushed block copolymers were synthesized by conjugating five types of 2-alkanone (2-butanone, 2-hexanone, 2-octanone, 2-decanone, and 2-dodecanone) through an acid-labile hydrazone linker to poly(ethylene glycol)-poly(aspartate hydrazide) block copolymers. Only block copolymers with 2-hexanone and 2-octanone (PEG-HEX and PEG-OCT) formed micelles with a clinically relevant size (< 50 nm in diameter), low critical micelle concentration (CMC, < 20 μM), and drug entrapment yields (approximately 5 wt.%). Both micelles degraded in aqueous solutions in a pH-dependent manner, while the degradation was accelerated in an acidic condition (pH 5.0) in comparison to pH 7.4. Despite these similar properties, PEG-OCT micelles controlled the entrapment and pH-dependent release of a hydrophobic drug most efficiently, without altering particle size, shape, and stability. The molecular weight of PEG (12 kDa vs 5 kDa) induced no change in pH-controlled drug release rates of PEG-OCT micelles. Acid-labile small aliphatic pendant groups are useful to control the entrapment and release of a hydrophobic drug physically entrapped in the core of brushed block copolymer micelles.

Preparation of Curcumin Loaded Egg Albumin Nanoparticles Using Acetone and Optimization of Desolvation Process.

PubMed

Aniesrani Delfiya, D S; Thangavel, K; Amirtham, D

2016-04-01

In this study, acetone was used as a desolvating agent to prepare the curcumin-loaded egg albumin nanoparticles. Response surface methodology was employed to analyze the influence of process parameters namely concentration (5-15%w/v) and pH (5-7) of egg albumin solution on solubility, curcumin loading and entrapment efficiency, nanoparticles yield and particle size. Optimum processing conditions obtained from response surface analysis were found to be the egg albumin solution concentration of 8.85%w/v and pH of 5. At this optimum condition, the solubility of 33.57%, curcumin loading of 4.125%, curcumin entrapment efficiency of 55.23%, yield of 72.85% and particles size of 232.6 nm were obtained and these values were related to the values which are predicted using polynomial model equations. Thus, the model equations generated for each response was validated and it can be used to predict the response values at any concentration and pH.

Targeted salinomycin delivery with EGFR and CD133 aptamers based dual-ligand lipid-polymer nanoparticles to both osteosarcoma cells and cancer stem cells.

PubMed

Chen, Fangyi; Zeng, Yibin; Qi, Xiaoxia; Chen, Yanchao; Ge, Zhe; Jiang, Zengxin; Zhang, Xinchao; Dong, Yinmei; Chen, Huaiwen; Yu, Zuochong

2018-06-10

We previously developed salinomycin (sali)-entrapped nanoparticles labeled with CD133 aptamers which could efficiently eliminate CD133 + osteosarcoma cancer stem cells (CSCs). However, sufficient evidences suggest that the simultaneous targeting both CSCs and cancer cells is pivotal in achieving preferable cancer therapeutic efficacy, due to the spontaneous conversion between cancer cells and CSCs. We hereby constructed sali-entrapped lipid-polymer nanoparticles labeled with CD133 and EGFR aptamers (CESP) to target both osteosarcoma cells and CSCs. The cytotoxicity of CESP in osteosarcoma cells and CSCs was superior to that of single targeting or nontargeted sali-loaded nanoparticles. Administration of CESP in vivo showed the best efficacy in inhibiting tumor growth than other controls in osteosarcoma-bearing mice. Thus, CESP was demonstrated to be capable of efficiently targeting both osteosarcoma CSCs and cancer cells, and it represents an effective potential approach to treat osteosarcoma. Copyright © 2018 Elsevier Inc. All rights reserved.

Preparation of surface multiple-coated polylactide acid drug-loaded nanoparticles for intranasal delivery and evaluation on its brain-targeting efficiency.

PubMed

Bian, Junjie; Yuan, Zhixiang; Chen, Xiaoliang; Gao, Yuan; Xu, Chaoqun; Shi, Jianyou

2016-01-01

To prepare a mixture of multiple-coated aniracetam nasal polylactic-acid nanoparticles (M-C-PLA-NP) and evaluate its stability preliminarily in vitro and its brain-targeting efficiency in vivo. The solvent diffusion-evaporation combined with magnetic stirring method has been chosen for the entrapment of aniracetam. The M-C-PLA-NP was characterized with respect to its morphology, particle size, size distribution and aniracetam entrapment efficiency. The in vivo distribution was studied in male SD rats after an intranasal administration. In vitro release of M-C-PLA-NP showed two components with an initial rapid release due to the surface-associated drug and followed by a slower exponential release of aniracetam, which was dissolved in the core. The AUC0 → 30 min of M-C-PLA-NP in brain tissues resulted in a 5.19-fold increase compared with aniracetam solution. The ratios of AUC in brain to that in other tissues obtained after nasal application of M-C-PLA-NP were significantly higher than those of aniracetam solution. Therefore, it can be concluded that M-C-PLA-NP demonstrated its potential on increasing the brain-targeting efficiency of drugs and will be used as novel brain-targeting agent for nasal drug delivery.

A facile approach to manufacturing non-ionic surfactant nanodipsersions using proniosome technology and high-pressure homogenization.

PubMed

Najlah, Mohammad; Hidayat, Kanar; Omer, Huner K; Mwesigwa, Enosh; Ahmed, Waqar; AlObaidy, Kais G; Phoenix, David A; Elhissi, Abdelbary

2015-03-01

In this study, a niosome nanodispersion was manufactured using high-pressure homogenization following the hydration of proniosomes. Using beclometasone dipropionate (BDP) as a model drug, the characteristics of the homogenized niosomes were compared with vesicles prepared via the conventional approach of probe-sonication. Particle size, zeta potential, and the drug entrapment efficiency were similar for both size reduction mechanisms. However, high-pressure homogenization was much more efficient than sonication in terms of homogenization output rate, avoidance of sample contamination, offering a greater potential for a large-scale manufacturing of noisome nanodispersions. For example, high-pressure homogenization was capable of producing small size niosomes (209 nm) using a short single-step of size reduction (6 min) as compared with the time-consuming process of sonication (237 nm in >18 min) and the BDP entrapment efficiency was 29.65% ± 4.04 and 36.4% ± 2.8. In addition, for homogenization, the output rate of the high-pressure homogenization was 10 ml/min compared with 0.83 ml/min using the sonication protocol. In conclusion, a facile, applicable, and highly efficient approach for preparing niosome nanodispersions has been established using proniosome technology and high-pressure homogenization.

Polymeric micelles for potentiated antiulcer and anticancer activities of naringin

PubMed Central

Mohamed, Elham Abdelmonem; Abu Hashim, Irhan Ibrahim; Yusif, Rehab Mohammad; Shaaban, Ahmed Abdel Aziz; El-Sheakh, Ahmed Ramadan; Hamed, Mohammed Fawzy; Badria, Farid Abd Elreheem

2018-01-01

Naringin is one of the most interesting phytopharmaceuticals that has been widely investigated for various biological actions. Yet, its low water solubility, limited permeability, and suboptimal bioavailability limited its use. Therefore, in this study, polymeric micelles of naringin based on pluronic F68 (PF68) were developed, fully characterized, and optimized. The optimized formula was investigated regarding in vitro release, storage stability, and in vitro cytotoxicity vs different cell lines. Also, cytoprotection against ethanol-induced ulcer in rats and antitumor activity against Ehrlich ascites carcinoma in mice were investigated. Nanoscopic and nearly spherical 1:50 micelles with the mean diameter of 74.80±6.56 nm and narrow size distribution were obtained. These micelles showed the highest entrapment efficiency (EE%; 96.14±2.29). The micelles exhibited prolonged release up to 48 vs 10 h for free naringin. The stability of micelles was confirmed by insignificant changes in drug entrapment, particle size, and retention (%) (91.99±3.24). At lower dose than free naringin, effective cytoprotection of 1:50 micelles against ethanol-induced ulcer in rat model has been indicated by significant reduction in mucosal damage, gastric level of malondialdehyde, gastric expression of tumor necrosis factor-alpha, caspase-3, nuclear factor kappa-light-chain-enhancer of activated B cells, and interleukin-6 with the elevation of gastric reduced glutathione and superoxide dismutase when compared with the positive control group. As well, these micelles provoked pronounced antitumor activity assessed by potentiated in vitro cytotoxicity particularly against colorectal carcinoma cells and tumor growth inhibition when compared with free naringin. In conclusion, 1:50 naringin–PF68 micelles can be represented as a potential stable nanodrug delivery system with prolonged release and enhanced antiulcer as well as antitumor activities. PMID:29497294

Polymeric micelles for potentiated antiulcer and anticancer activities of naringin.

PubMed

Mohamed, Elham Abdelmonem; Abu Hashim, Irhan Ibrahim; Yusif, Rehab Mohammad; Shaaban, Ahmed Abdel Aziz; El-Sheakh, Ahmed Ramadan; Hamed, Mohammed Fawzy; Badria, Farid Abd Elreheem

2018-01-01

Naringin is one of the most interesting phytopharmaceuticals that has been widely investigated for various biological actions. Yet, its low water solubility, limited permeability, and suboptimal bioavailability limited its use. Therefore, in this study, polymeric micelles of naringin based on pluronic F68 (PF68) were developed, fully characterized, and optimized. The optimized formula was investigated regarding in vitro release, storage stability, and in vitro cytotoxicity vs different cell lines. Also, cytoprotection against ethanol-induced ulcer in rats and antitumor activity against Ehrlich ascites carcinoma in mice were investigated. Nanoscopic and nearly spherical 1:50 micelles with the mean diameter of 74.80±6.56 nm and narrow size distribution were obtained. These micelles showed the highest entrapment efficiency (EE%; 96.14±2.29). The micelles exhibited prolonged release up to 48 vs 10 h for free naringin. The stability of micelles was confirmed by insignificant changes in drug entrapment, particle size, and retention (%) (91.99±3.24). At lower dose than free naringin, effective cytoprotection of 1:50 micelles against ethanol-induced ulcer in rat model has been indicated by significant reduction in mucosal damage, gastric level of malondialdehyde, gastric expression of tumor necrosis factor-alpha, caspase-3, nuclear factor kappa-light-chain-enhancer of activated B cells, and interleukin-6 with the elevation of gastric reduced glutathione and superoxide dismutase when compared with the positive control group. As well, these micelles provoked pronounced antitumor activity assessed by potentiated in vitro cytotoxicity particularly against colorectal carcinoma cells and tumor growth inhibition when compared with free naringin. In conclusion, 1:50 naringin-PF68 micelles can be represented as a potential stable nanodrug delivery system with prolonged release and enhanced antiulcer as well as antitumor activities.

Floating capsules containing alginate-based beads of salbutamol sulfate: In vitro-in vivo evaluations.

PubMed

Malakar, Jadupati; Datta, Prabir Kumar; Purakayastha, Saikat Das; Dey, Sanjay; Nayak, Amit Kumar

2014-03-01

The present study deals with the development and evaluations of stomach-specific floating capsules containing salbutamol sulfate-loaded oil-entrapped alginate-based beads. Salbutamol sulfate-loaded oil-entrapped beads were prepared and capsulated within hard gelatin capsules (size 1). The effects of HPMC K4M and potato starch weight masses on drug encapsulation efficiency (DEE) of beads and cumulative drug release at 10h (R10 h) from capsules was analyzed by 3(2) factorial design. The optimization results indicate increasing of DEE in the oil-entrapped beads and decreasing R10 h from capsules with increment of HPMC K4M and potato starch weight masses. The optimized formulation showed DEE of 70.02 ± 3.16% and R10 h of 56.96 ± 2.92%. These capsules showed floatation over 6h and sustained drug release over 10h in gastric pH (1.2). In vivo X-ray imaging study of optimized floating capsules in rabbits showed stomach-specific gastroretention over a prolonged period. Copyright © 2013 Elsevier B.V. All rights reserved.

Development and optimization of oil-filled lipid nanoparticles containing docetaxel conjugates designed to control the drug release rate in vitro and in vivo

PubMed Central

Feng, Lan; Wu, Huali; Ma, Ping; Mumper, Russell J; Benhabbour, S Rahima

2011-01-01

Three docetaxel (DX) lipid conjugates: 2′-lauroyl-docetaxel (C12-DX), 2′-stearoyl-docetaxel (C18-DX), and 2′-behenoyl-docetaxel (C22-DX) were synthesized to enhance drug loading, entrapment, and retention in liquid oil-filled lipid nanoparticles (NPs). The three conjugates showed ten-fold higher solubility in the liquid oil phase Miglyol 808 than DX. To further increase the drug entrapment efficiency in NPs, orthogonal design was performed. The optimized formulation was composed of Miglyol 808, Brij 78, and Vitamin E tocopheryl polyethylene glycol succinate (TPGS). The conjugates were successfully entrapped in the reduced-surfactant NPs with entrapment efficiencies of about 50%–60% as measured by gel permeation chromatography (GPC) at a final concentration of 0.5 mg/mL. All three conjugates showed 45% initial burst release in 100% mouse plasma. Whereas C12-DX showed another 40% release over the next 8 hours, C18-DX and C22-DX in NPs showed no additional release after the initial burst of drug. All conjugates showed significantly lower cytotoxicity than DX in human DU-145 prostate cancer cells. The half maximal inhibitory concentration values (IC50) of free conjugates and conjugate NPs were comparable except for C22-DX, which was nontoxic in the tested concentration range and showed only vehicle toxicity when entrapped in NPs. In vivo, the total area under the curve (AUC0–∞) values of all DX conjugate NPs were significantly greater than that of Taxotere, demonstrating prolonged retention of drug in the blood. The AUC0–∞ value of DX in Taxotere was 8.3-fold, 358.0-fold, and 454.5-fold lower than that of NP-formulated C12-DX, C18-DX, and C22-DX, respectively. The results of these studies strongly support the idea that the physical/chemical properties of DX conjugates may be fine-tuned to influence the affinity and retention of DX in oil-filled lipid NPs, which leads to very different pharmacokinetic profiles and blood exposure of an otherwise potent chemo-therapeutic agent. These studies and methodologies may allow for improved and more potent nanoparticle-based formulations. PMID:22072889

Development and optimization of oil-filled lipid nanoparticles containing docetaxel conjugates designed to control the drug release rate in vitro and in vivo.

PubMed

Feng, Lan; Wu, Huali; Ma, Ping; Mumper, Russell J; Benhabbour, S Rahima

2011-01-01

THREE DOCETAXEL (DX) LIPID CONJUGATES: 2'-lauroyl-docetaxel (C12-DX), 2'-stearoyl-docetaxel (C18-DX), and 2'-behenoyl-docetaxel (C22-DX) were synthesized to enhance drug loading, entrapment, and retention in liquid oil-filled lipid nanoparticles (NPs). The three conjugates showed ten-fold higher solubility in the liquid oil phase Miglyol 808 than DX. To further increase the drug entrapment efficiency in NPs, orthogonal design was performed. The optimized formulation was composed of Miglyol 808, Brij 78, and Vitamin E tocopheryl polyethylene glycol succinate (TPGS). The conjugates were successfully entrapped in the reduced-surfactant NPs with entrapment efficiencies of about 50%-60% as measured by gel permeation chromatography (GPC) at a final concentration of 0.5 mg/mL. All three conjugates showed 45% initial burst release in 100% mouse plasma. Whereas C12-DX showed another 40% release over the next 8 hours, C18-DX and C22-DX in NPs showed no additional release after the initial burst of drug. All conjugates showed significantly lower cytotoxicity than DX in human DU-145 prostate cancer cells. The half maximal inhibitory concentration values (IC(50)) of free conjugates and conjugate NPs were comparable except for C22-DX, which was nontoxic in the tested concentration range and showed only vehicle toxicity when entrapped in NPs. In vivo, the total area under the curve (AUC(0-∞)) values of all DX conjugate NPs were significantly greater than that of Taxotere, demonstrating prolonged retention of drug in the blood. The AUC(0-∞) value of DX in Taxotere was 8.3-fold, 358.0-fold, and 454.5-fold lower than that of NP-formulated C12-DX, C18-DX, and C22-DX, respectively. The results of these studies strongly support the idea that the physical/chemical properties of DX conjugates may be fine-tuned to influence the affinity and retention of DX in oil-filled lipid NPs, which leads to very different pharmacokinetic profiles and blood exposure of an otherwise potent chemo-therapeutic agent. These studies and methodologies may allow for improved and more potent nanoparticle-based formulations.

Aminopropyl-modified mesoporous molecular sieves as efficient adsorbents for removal of auxins

NASA Astrophysics Data System (ADS)

Moritz, Michał; Geszke-Moritz, Małgorzata

2015-03-01

In the present study, mesoporous siliceous materials grafted with 3-aminopropyltriethoxysilane (APTES) were examined as sorbents for removal of chosen plant growth factors (auxins) such as 1-naphthaleneacetic acid (NAA), indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA). Four different types of mesoporous molecular sieves including SBA-15, PHTS, SBA-16 and MCF have been prepared via non-ionic surfactant-assisted soft templating method. Silica molecular sieves were thoroughly characterized by nitrogen adsorption-desorption analysis, powder X-ray diffraction (XRD), transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FT-IR). The maximum adsorption capacity (Qmax) for NAA, IAA and IBA was in the range from 51.0 to 140.8 mg/g and from 4.3 to 7.3 mg/g for aminopropyl-modified adsorbents and pure silicas, respectively. The best adsorption performance was observed for IAA entrapment using both APTES-functionalized SBA-15 and MCF matrices (Qmax of 140.8 and 137.0 mg/g, respectively) which can be ascribed to their larger pore volumes and pore diameters. Moreover, these silicas were characterized by the highest adsorption efficiency exceeding 90% at low pollutant concentration. The experimental points for adsorption of plant growth factors onto aminopropyl-modified mesoporous molecular sieves fitted well to the Langmuir equation.

Design and characterization of plasmids encoding antigenic peptides of Aha1 from Aeromonas hydrophila as prospective fish vaccines.

PubMed

Rauta, Pradipta R; Nayak, Bismita; Monteiro, Gabriel A; Mateus, Marília

2017-01-10

The current investigation aimed at designing DNA vaccines against Aeromonas hydrophila infections. The DNA vaccine candidates were designed to express two antigenic outer membrane protein (Aha1) peptides and to be delivered by a nanoparticle-based delivery system. Gene sequences of conserved regions of antigenic Aha1 [aha1(211-381), aha1(211-381)opt, aha1(703-999) and aha1(703-999)opt] were cloned into pVAX-GFP expression vector. The selected DNA vaccine candidates were purified from E. coli DH5α and transfected into Chinese hamster ovary cells. The expression of the antigenic peptides was measured in cells along post-transfection time, through the fluorescence intensity of the reporter GFP. The lipofection efficiency of aha-pVAX-GFP was highest after 24h incubation. Formulated PLGA-chitosan nanoparticle/plasmid DNA complexes were characterized in terms of size, size distribution and zeta potential. Nanocomplexes with average diameters in the range of 150-170nm transfected in a similar fashion into CHO cells confirmed transfection efficiency comparable to that of lipofection. DNA entrapment and further DNase digestion assays demonstrated ability for pDNA protection by the nanoparticles against enzymatic digestion. Copyright © 2016 Elsevier B.V. All rights reserved.

Formulation, characterization and pharmacokinetics of Morin hydrate niosomes prepared from various non-ionic surfactants.

PubMed

Waddad, Ayman Y; Abbad, Sarra; Yu, Fan; Munyendo, Were L L; Wang, Jing; Lv, Huixia; Zhou, Jianping

2013-11-18

Morin hydrate (MH), a bioflavonoid with antioxidant and anticancer activity as well as the ability to improve the bioavailability of other drugs on their concurrent use. Three differently optimized niosomal formulations using three different non-ionic surfactants (Span 60, Span 80 and Tween 60) were achieved by (L9 (3(4))) Taguchi orthogonal array (TOA). The analysis of TOA revealed that Tween 60 Niosomes had the highest entrapment efficiency (93.4%) compared to other optimized Niosomal formulations (71-79%). In terms of MH remaining %, Tween 60 Niosomes were found to be the most stable (89%) at 4 °C over one month compared to Span 60 (56%) and Span 80 (57%) Niosomes. The release pattern in all Niosomal formulations was found to follow the Weibull model and Tween 60 Niosomes had the highest release rate. The molecular modeling simulation explained the binding of MH to the human serum albumin (HSA) by hydrogen bonds during the in vitro release process. As for the bioavailability, the AUC0-8 showed 1.3-2.7 fold increase compared to the MH solution. Ex vivo images of the excised organs showed that MH could accumulate in brain which indicates that MH-Tween 60 Niosomes might be a possible candidate to deliver hydrophobic drugs and overcome the blood-brain barrier (BBB) penetration. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

Development and validation of an efficient ultrasound assisted extraction of phenolic compounds from flax (Linum usitatissimum L.) seeds.

PubMed

Corbin, Cyrielle; Fidel, Thibaud; Leclerc, Emilie A; Barakzoy, Esmatullah; Sagot, Nadine; Falguiéres, Annie; Renouard, Sullivan; Blondeau, Jean-Philippe; Ferroud, Clotilde; Doussot, Joël; Lainé, Eric; Hano, Christophe

2015-09-01

Flaxseed accumulates in its seedcoat a macromolecular complex composed of lignan (secoisolariciresinol diglucoside, SDG), flavonol (herbacetin diglucoside, HDG) and hydroxycinnamic acids (p-couramic, caffeic and ferulic acid glucosides). Their antioxidant and/or cancer chemopreventive properties support their interest in human health and therefore, the demand for their extraction. In the present study, ultrasound-assisted extraction (UAE) of flaxseed phenolic compounds was investigated. Scanning Electron Microscopy imaging and histochemical analysis revealed the deep alteration of the seedcoat ultrastructure and the release of the mucilage following ultrasound treatment. Therefore, this method was found to be very efficient for the reduction of mucilage entrapment of flaxseed phenolics. The optimal conditions for UAE phenolic compounds extraction from flaxseeds were found to be: water as solvent supplemented with 0.2N of sodium hydroxide for alkaline hydrolysis of the SDG-HMG complex, an extraction time of 60 min at a temperature of 25°C and an ultrasound frequency of 30 kHz. Under these optimized and validated conditions, highest yields of SDG, HDG and hydroxycinnamic acid glucosides were detected in comparison to other published methods. Therefore, the procedure presented herein is a valuable method for efficient extraction and quantification of the main flaxseed phenolics. Moreover, this UAE is of particular interest within the context of green chemistry in terms of reducing energy consumption and valuation of flaxseed cakes as by-products resulting from the production of flax oil. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of novel bioactive edible coatings based on jujube gum and nettle oil-loaded nanoemulsions on the shelf-life of Beluga sturgeon fillets.

PubMed

Gharibzahedi, Seyed Mohammad Taghi; Mohammadnabi, Sara

2017-02-01

Effect of jujube gum (JG; 4, 8 and 12% wt)-based nanoemulsions (NEs) containing nettle essential oil (NEO; 2, 3.5 and 5% wt) as new edible coatings was investigated to preserve Beluga sturgeon fillets (BSFs) during 15 day-refrigerated storage at 4°C. Physical (weight loss, cooking loss, color and texture), chemical (pH, FFA, PV, TBARS and TVB-N), microbiological (total and psychrotrophic bacterial counts), and sensorial characteristics of BSFs were kinetically analyzed. Preliminary studies showed that the NEs formulated with NEO lower than 5% at all JG concentrations were able to form stable coating solutions owing to the highest short-term stability (>90%) and entrapment efficiency (94.4-98.3%). Edible NE coating formulated with 12% JG and 3.5% NEO as a novel antimicrobial and antioxidant biomaterial exhibited the lowest weight and cooking losses, pH changes, textural and color deterioration, lipid oxidation and microbial growth in BSFs refrigerated over a period of 15days (P<0.05). Copyright © 2016 Elsevier B.V. All rights reserved.

Magnetic bionanoparticles of Penicillium sp. yz11-22N2 doped with Fe3O4 and encapsulated within PVA-SA gel beads for atrazine removal.

PubMed

Yu, Jiaping; He, Huijun; Yang, William L; Yang, Chunping; Zeng, Guangming; Wu, Xin

2018-07-01

A novel magnetic bionanomaterial, Penicillium sp. yz11-22N2 doped with nano Fe 3 O 4 entrapped in polyvinyl alcohol-sodium alginate gel beads (PFEPS), was successfully synthesized. The factors including nutrient substance, temperature, pH, initial concentrations of atrazine and rotational speeds were presented and discussed in detail. Results showed that the highest removal efficiency of atrazine by PFEPS was 91.2% at 8.00 mg/L atrazine. The maximum removal capacity for atrazine was 7.94 mg/g. Meanwhile, it has been found that most of atrazine were removed by metabolism and degradation of Penicillium sp. yz11-22N2, which could use atrazine as the sole source of either carbon or nitrogen. Degradation kinetics of atrazine conformed to first-order kinetics model. The intermediates indicated that the possible pathway for atrazine degradation by PFEPS mainly included hydrolysis dechlorination, dealkylation, side-chain oxidation and ring-opening. Copyright © 2018 Elsevier Ltd. All rights reserved.

Loteprednol Etabonate Nanoparticles: Optimization via Box-Behnken Design Response Surface Methodology and Physicochemical Characterization.

PubMed

Sah, Abhishek K; Suresh, Preeti K

2017-01-01

Abstract: The objective of the present work was to prepare and optimize the loteprednoletabonate (LE) loaded poly (D,L-lactide co-glycolide) (PLGA) polymer based nanoparticle carrier. The review on recent patents (US9006241, US20130224302A1, US2012/0028947A1) assisted in the selection of drug and polymer for designing nanoparticles for ocular delivery applications. The nanoparticles were prepared by solvent evaporation followed by high speed homogenization. Biodegradable polymer PLGA (50:50) grade was utilized to develop various formulations with different drug:polymer ratio. A Box-Behnken design with 33 factorial design was selected for the present study and 17 runs were carried out in totality. The influence of various process variables (viz., polymer concentration, homogenization speed and sonication time) on the characteristics of nanoparticles including the in vitro drug release profile were studied. The nanoparticulate formulations were evaluated for mean spherical diameter, polydispersity index (PDI), zeta potential, surface morphology, drug entrapment and in-vitro drug release profile. The entrapment efficiency, drug loading and mean particle size were found to be 96.31±1.68 %, 35.46±0.35 % and 167.6±2.1 nm respectively. The investigated process and formulation variables were found to have significant effect on the particle size, drug loading (DL), entrapment efficiency (EE), and in vitro drug release profile. A biphasic in vitro drug release profile was apparent from the optimized nanoparticles (NPs) for 24 hours. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Advance and application of the stratigraphic simulation model 2D- SedFlux: From tank experiment to geological scale simulation

NASA Astrophysics Data System (ADS)

Kubo, Yu'suke; Syvitski, James P. M.; Hutton, Eric W. H.; Paola, Chris

2005-07-01

The stratigraphic simulation model 2D- SedFlux is further developed and applied to a turbidite experiment in a subsiding minibasin. The new module dynamically simulates evolving hyperpycnal flows and their interaction with the basin bed. Comparison between the numerical results and the experimental results verifies the ability of 2D- SedFlux to predict the distribution of the sediments and the possible feedback from subsidence. The model was subsequently applied to geological-scale minibasins such as are located in the Gulf of Mexico. Distance from the sediment source is determined to be more influential than the sediment entrapment in upstream minibasin. The results suggest that efficiency of sediment entrapment by a basin was not influenced by the distance from the sediment source.

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.

Enhanced Ungual Permeation of Terbinafine HCl Delivered Through Liposome-Loaded Nail Lacquer Formulation Optimized by QbD Approach.

PubMed

Shah, Viral H; Jobanputra, Amee

2018-01-01

The present investigation focused on developing, optimizing, and evaluating a novel liposome-loaded nail lacquer formulation for increasing the transungual permeation flux of terbinafine HCl for efficient treatment of onychomycosis. A three-factor, three-level, Box-Behnken design was employed for optimizing process and formulation parameters of liposomal formulation. Liposomes were formulated by thin film hydration technique followed by sonication. Drug to lipid ratio, sonication amplitude, and sonication time were screened as independent variables while particle size, PDI, entrapment efficiency, and zeta potential were selected as quality attributes for liposomal formulation. Multiple regression analysis was employed to construct a second-order quadratic polynomial equation and contour plots. Design space (overlay plot) was generated to optimize a liposomal system, with software-suggested levels of independent variables that could be transformed to desired responses. The optimized liposome formulation was characterized and dispersed in nail lacquer which was further evaluated for different parameters. Results depicted that the optimized terbinafine HCl-loaded liposome formulation exhibited particle size of 182 nm, PDI of 0.175, zeta potential of -26.8 mV, and entrapment efficiency of 80%. Transungual permeability flux of terbinafine HCl through liposome-dispersed nail lacquer formulation was observed to be significantly higher in comparison to nail lacquer with a permeation enhancer. The developed formulation was also observed to be as efficient as pure drug dispersion in its antifungal activity. Thus, it was concluded that the developed formulation can serve as an efficient tool for enhancing the permeability of terbinafine HCl across human nail plate thereby improving its therapeutic efficiency.

Nano-transfersomes as a novel carrier for transdermal delivery.

PubMed

Chaudhary, Hema; Kohli, Kanchan; Kumar, Vikash

2013-09-15

The aim of this study was to design and optimize a nano-transfersomes of Diclofenac diethylamine (DDEA) and Curcumin (CRM). A 3(3) factorial design (Box-Behnken) was used to derive a polynomial equation (second order) to construct 2-D (contour) and 3-D (Response Surface) plots for prediction of responses. The ratio of lipid to surfactant (X1), weight of lipid to surfactant (X2) and sonication time (X3) (independent variables) and dependent variables [entrapment efficiency of DDEA (Y1), entrapment efficiency of CRM (Y2), effect on particle size (Y3), flux of DDEA (Y4), and flux of CRM (Y5)] were studied. The 2-D and 3-D plots were drawn and a statistical validity of the polynomials was established to find the compositions of optimized formulation. The design established the role of the derived polynomial equation, 2-D and 3-D plots in predicting the values of dependent variables for the preparation and optimization of nano-transfersomes for transdermal drug release. Copyright © 2013 Elsevier B.V. All rights reserved.

Impact of mild alkali dosage on immobilized Exiguobacterium spp. mediated cost and energy efficient sludge disintegration.

PubMed

Rajesh Banu, J; Ushani, U; Rajkumar, M; Naresh Kumar, R; Parthiba Karthikeyan, O

2017-12-01

Approaches to (extracellular polymeric substance) EPS removal were studied with major aim to enhance the biodegradability and sludge solubilization. In this study, a novel approach of entrapment of bacterial strain was carried out to achieve long term activity of protease secreting bacteria Exiguobacterium sp. A mild treatment of potassium hydroxide (KOH) was applied to remove EPS which was followed by entrapment under the biological pretreatment. The efficiency of Exiguobacterium was predicted through dissolvable organic and suspended solids (SS) reduction. The maximum dissolvable organic matter released was 2300mg/L with the solubilization of 23% which was obtained for sludge without EPS (SWOE). For dissolvable organic release, SWOE showed higher final methane production of 232mL/g COD at the production rate of 16.2mL/g COD.d. The SWOE pretreatment was found to be cost effective and less energy intensive beneficial in terms of energy and cost (43.9KWh and -8.2USD) when compared to sludge with EPS (SWE) pretreatment (-177.6KWh and -91.23USD). Copyright © 2017 Elsevier Ltd. All rights reserved.

Improvement of Oral Bioavailability of Lopinavir Without Co-administration of Ritonavir Using Microspheres of Thiolated Xyloglucan.

PubMed

Madgulkar, Ashwini R; Bhalekar, Mangesh R; Kadam, Ashwini A

2018-01-01

Lopinavir is a BCS Class IV drug exhibiting poor bioavailability due to P-gp efflux and limited permeation. The aim of this research was to formulate and characterize microspheres of lopinavir using thiolated xyloglucan (TH-MPs) as carrier to improve its oral bioavailability without co-administration of ritonavir. Thiomeric microspheres were prepared by ionotropic gelation between alginic acid and calcium ions. Interaction studies were performed using Fourier transform infrared spectroscopy (FT-IR). The thiomeric microspheres were characterized for its entrapment efficiency, T 80 , surface morphology, and mucoadhesion employing in vitro wash off test. The microspheres were optimized by 3 2 factorial design. The optimized thiomeric microsphere formulation revealed 93.12% entrapment efficiency, time for 80% drug release (T 80 ) of 358.1 min, and 88% mucoadhesion after 1 h. The permeation of lopinavir from microspheres was enhanced 3.15 times as determined by ex vivo study using everted chick intestine and increased relative bioavailability over 3.22-fold over combination of lopinavir and ritonavir as determined by in vivo study in rat model.

Treatment of acetone waste gases using slurry-phase airlift embedded with polyacrylamide-entrapped cell beads.

PubMed

Hwang, Sz-Chwun John; Lin, Yun-Huin; Huang, Ku Shu; Lyuu, Jyuhn-Yih; Hou, Cheng-Ting; Chen, Hsin-Hua; He, Sin-Yi

2009-10-01

Acetone is the most common chemical used in the Hsin-chu Science Park in Taiwan. The three-phase airlift bioreactor was designed to absorb acetone into the 39 L of medium solution and then degraded by 2-L polyacrylamide (PAA)-entrapped Thiosphaera pantotropha cell beads. The airlift medium was successfully regenerated and circulated for more than 5 months. The elimination capacity of 350-part per million (ppm) acetone at 10 L x min(-1) was 258.4 g x m(-3) hr(-1) (160.4 g-C x m(-3) hr(-1)) with 100% removal efficiency in Stage II, higher than previously reported biofiltration results. The maximum chemical oxygen demand:nitrogen ratio of 100:2.9 is achieved, and a balanced nutrient state was indicated by the change in redox potential. The pH of the system was maintained at neutral because of the strong buffer agent added to the medium (final buffer intensity, beta = 1.18 x 10(-2) M). The PAA-entrapped cell beads could also provide a good barrier for high salinity gradient environment and the inoculum source to maintain steady operation of the system.

A Role for Peptides in Overcoming Endosomal Entrapment in siRNA Delivery – A Focus on Melittin

PubMed Central

Hou, Kirk K.; Pan, Hua; Schlesinger, Paul H.; Wickline, Samuel A.

2015-01-01

siRNA has the possibility to revolutionize medicine by enabling highly specific and efficient silencing of proteins involved in disease pathogenesis. Despite nearly 20 years of research dedicated to translating siRNA from a research tool into a clinically relevant therapeutic, minimal success has been had to date. Access to RNA interference machinery located in the cytoplasm is often overlooked, but must be considered when designing the next generation of siRNA delivery strategies. Peptide transduction domains (PTD) have demonstrated moderate siRNA transfection, which is primarily limited by endosomal entrapment. Strategies aimed at overcoming endosomal entrapment associated with peptide vectors are reviewed here, including osmotic methods, lipid conjugation, and fusogenic peptides. As an alternative to traditional PTD, the hemolytic peptide melittin exhibits the native capacity for endosomal disruption but causes cytotoxicity. However, appropriate packaging and protection of melittin with activation and release in the endosomal compartment has allowed melittin-based strategies to demonstrate both in vitro and in vivo safety and efficacy. These data suggest that melittin's membrane disruptive properties can enable safe and effective endosomolysis, building a case for melittin as a key component in a new generation of siRNA therapeutics. PMID:26025036

Ultrasound-responsive nanobubbles contained with peptide-camptothecin conjugates for targeted drug delivery.

PubMed

Xie, Xiangyang; Lin, Wen; Liu, Hui; Deng, Jianping; Chen, Ying; Liu, Hong; Fu, Xudong; Yang, Yang

2016-10-01

To improve the targeting delivery efficiency of anticancer drug to tumor sites, a new strategy combining cell-permeable peptide (CPP) and ultrasound was reported in this article. In this study, we devised and tested a strategy for functional payload delivery to cells by loading CPP-camptothecin conjugate (CPP-CPT) into nanobubble (CPP-CPT NB). Here, CPP existing in the conjugation form of CPP and CPT was hidden in nanobubble to cloak the penetration activity of CPP. Meanwhile, local tumor ultrasound was utilized to achieve specific targeting of CPP-CPT to the tumor cells. The mean particle size of the prepared CPP-CPT NB was ∼200 nm, and the drug entrapment efficiency was >80%. Stimulated by ultrasound, over 90% of the entrapped CPP-CPTs would release from the nanobubbles. Subsequent research demonstrated that the CPP-CPT NB showed effective cellular uptake and significant cytotoxic activity in HeLa cells in vitro. Additionally, after systemic administration in mice, CPP-CPT NB with ultrasound showed a higher tumor inhibition effect in nude mice xenografted HeLa cells tumors and excellent body safety when compared with normal CPT injection group. In conclusion, the carrier constructed in this study would be a safe and efficiently drug delivery system for specific cancer treatment.

Application of Box-Behnken design for preparation of levofloxacin-loaded stearic acid solid lipid nanoparticles for ocular delivery: Optimization, in vitro release, ocular tolerance, and antibacterial activity.

PubMed

Baig, Mirza Salman; Ahad, Abdul; Aslam, Mohammed; Imam, Syed Sarim; Aqil, Mohd; Ali, Asgar

2016-04-01

The aim of the present study was to develop and optimize levofloxacin loaded solid lipid nanoparticles for the treatment of conjunctivitis. Box-Behnken experimental design was applied for optimization of solid lipid nanoparticles. The independent variables were stearic acid as lipid (X1), Tween 80 as surfactant (X2) and sodium deoxycholate as co-surfactant (X3) while particle size (Y1) and entrapment efficiency (Y2) were the dependent variables. Further in vitro release and antibacterial activity in vitro were also performed. The optimized formulation of levofloxacin provides particle size of 237.82 nm and showed 78.71% entrapment efficiency and achieved flux 0.2,493 μg/cm(2)/h across excised goat cornea. In vitro release study showed prolonged drug release from the optimized formulation following Korsmeyer-Peppas model. Antimicrobial study revealed that the developed formulation possesses antibacterial activity against Staphylococcus aureus, and Escherichia coli equivalent to marketed eye drops. HET-CAM test demonstrated that optimized formulation was found to be non-irritant and safe for topical ophthalmic use. Our results concluded that solid lipid nanoparticles are an efficient carrier for ocular delivery of levofloxacin and other drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of nanovesicular systems for dermal imiquimod delivery: physicochemical characterization and in vitro/in vivo evaluation.

PubMed

Ma, Man; Wang, Jinping; Guo, Fang; Lei, Mingzhu; Tan, Fengping; Li, Nan

2015-06-01

The aim of the current investigation was to develop and statistically evaluate nanovesicular systems for dermal imiquimod delivery. To this purpose, transethosomes were prepared with phospholipid, ethanol and different permeation enhancers. Conventional ethosomes, with soy phospholipid and ethanol, were used as control. The prepared vesicles were characterized for size, zeta potential, stability and entrapment efficiency. The optimal transethosomal formulation with mean particle size of 82.3 ± 9.5 nm showed the higher entrapment efficiency (68.69 ± 1.7%). In vitro studies, permeation results of accumulated drug and local accumulation efficiency were significantly higher for transethosomes (24.64 µg/cm(2) and 6.70, respectively) than control (14.45 µg/cm(2) and 3.93, respectively). Confocal laser scanning microscopy of rhodamine 6G-loaded transethosomes revealed an enhanced retention into the deeper skin layers as compared to conventional ethosomes. Besides, Fourier-transform infra-red spectroscopy studies were also performed to understand the mechanism of interaction between skin and carriers. What's more, results of in vivo studies indicated the transethosomes of imiquimod providing the most effectiveness for dermal delivery among all of the formulations. These results suggested that transethosomes would be a promising dermal carrier for imiquimod in actinic keratose treatment.

Development of a novel niosomal system for oral delivery of Ginkgo biloba extract

PubMed Central

Jin, Ye; Wen, Jingyuan; Garg, Sanjay; Liu, Da; Zhou, Yulin; Teng, Lirong; Zhang, Weiyu

2013-01-01

Background The aim of this study was to develop an optimal niosomal system to deliver Ginkgo biloba extract (GbE) with improved oral bioavailability and to replace the conventional GbE tablets. Methods In this study, the film dispersion-homogenization method was used to prepare GbE niosomes. The resulting GbE niosome suspension was freeze-dried or spray-dried to improve the stability of the niosomes. GbE-loaded niosomes were formulated and characterized in terms of their morphology, particle size, zeta potential, entrapment efficiency, and angle of repose, and differential scanning calorimetry analysis was performed. In vitro release and in vivo distribution studies were also carried out. Results The particle size of the optimal delivery system prepared with Tween 80, Span 80, and cholesterol was about 141 nm. There was a significant difference (P < 0.05) in drug entrapment efficiency between the spray-drying method (about 77.5%) and the freeze-drying method (about 50.1%). The stability study revealed no significant change in drug entrapment efficiency for the GbE niosomes at 4°C and 25°C after 3 months. The in vitro release study suggested that GbE niosomes can prolong the release of flavonoid glycosides in phosphate-buffered solution (pH 6.8) for up to 48 hours. The in vivo distribution study showed that the flavonoid glycoside content in the heart, lung, kidney, brain, and blood of rats treated with the GbE niosome carrier system was greater than in the rats treated with the oral GbE tablet (P < 0.01). No flavonoid glycosides were detected in the brain tissue of rats given the oral GbE tablets, but they were detected in the brain tissue of rats given the GbE niosomes. Conclusion Niosomes are a promising oral system for delivery of GbE to the brain. PMID:23378764

Folic acid conjugated cross-linked acrylic polymer (FA-CLAP) hydrogel for site specific delivery of hydrophobic drugs to cancer cells.

PubMed

Pillai, Jisha Jayadevan; Thulasidasan, Arun Kumar Theralikattu; Anto, Ruby John; Chithralekha, Devika Nandan; Narayanan, Ashwanikumar; Kumar, Gopalakrishnapillai Sankaramangalam Vinod

2014-07-15

The hydrogel based system is found to be rarely reported for the delivery of hydrophobic drug due to the incompatibility of hydrophilicity of the polymer network and the hydrophobicity of drug. This problem can be solved by preparing semi-interpenetrating network of cross-linked polymer for tuning the hydrophilicity so as to entrap the hydrophobic drugs. The current study is to develop a folic acid conjugated cross-linked pH sensitive, biocompatible polymeric hydrogel to achieve a site specific drug delivery. For that, we have synthesized a folic acid conjugated PEG cross-linked acrylic polymer (FA-CLAP) hydrogel and investigated its loading and release of curcumin. The formed polymer hydrogel was then conjugated with folic acid for the site specific delivery of curcumin to cancer cells and then further characterized and conducted the cell uptake and cytotoxicity studies on human cervical cancer cell lines (HeLa). In this study, we synthesized folic acid conjugated cross-linked acrylic hydrogel for the delivery of hydrophobic drugs to the cancer site. Poly (ethyleneglycol) (PEG) diacrylate cross-linked acrylic polymer (PAA) was prepared via inverse emulsion polymerization technique and later conjugated it with folic acid (FA-CLAP). Hydrophobic drug curcumin is entrapped into it and investigated the entrapment efficiency. Characterization of synthesized hydogel was done by using Fourier Transform-Infrared spectroscopy (FT-IR), Transmission Electron Microscopy (TEM), Differential Scanning Calorimetry (DSC). Polymerization and folate conjugation was confirmed by FT-IR spectroscopy. The release kinetics of drug from the entrapped form was studied which showed initial burst release followed by sustained release due to swelling and increased cross-linking. In vitro cytotoxicity and cell uptake studies were conducted in human cervical cancer (HeLa) cell lines. Results showed that curcumin entrapped folate conjugated cross-linked acrylic polymer (FA-CLAP) hydrogel showed higher cellular uptake than the non folate conjugated form. So this can be suggested as a better delivery system for site specific release of hydrophobic cancer drugs.

Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer's disease management: preparation and detection in rat brain.

PubMed

Hanafy, Amira S; Farid, Ragwa M; ElGamal, Safaa S

2015-01-01

Complexation was investigated as an approach to enhance the entrapment of the cationic neurotherapeutic drug, galantamine hydrobromide (GH) into cationic chitosan nanoparticles (CS-NPs) for Alzheimer's disease management intranasally. Biodegradable CS-NPs were selected due to their low production cost and simple preparation. The effects of complexation on CS-NPs physicochemical properties and uptake in rat brain were examined. Placebo CS-NPs were prepared by ionic gelation, and the parameters affecting their physicochemical properties were screened. The complex formed between GH and chitosan was detected by the FT-IR study. GH/chitosan complex nanoparticles (GH-CX-NPs) were prepared by ionic gelation, and characterized in terms of particle size, zeta potential, entrapment efficiency, in vitro release and stability for 4 and 25 °C for 3 months. Both placebo CS-NPs and GH-CX-NPs were visualized by transmission electron microscopy. Rhodamine-labeled GH-CX-NPs were prepared, administered to male Wistar rats intranasally, and their delivery to different brain regions was detected 1 h after administration using fluorescence microscopy and software-aided image processing. Optimized placebo CS-NPs and GH-CX-NPs had a diameter 182 and 190 nm, and a zeta potential of +40.4 and +31.6 mV, respectively. GH encapsulation efficiency and loading capacity were 23.34 and 9.86%, respectively. GH/chitosan complexation prolonged GH release (58.07% ± 6.67 after 72 h), improved formulation stability at 4 °C in terms of drug leakage and particle size, and showed insignificant effects on the physicochemical properties of the optimized placebo CS-NPs (p > 0.05). Rhodamine-labeled GH-CX-NPs were detected in the olfactory bulb, hippocampus, orbitofrontal and parietal cortices. Complexation is a promising approach to enhance the entrapment of cationic GH into the CS-NPs. It has insignificant effect on the physicochemical properties of CS-NPs. GH-CX-NPs were successfully delivered to different brain regions shortly after intranasal administration suggesting their potential as a delivery system for Alzheimer's disease management.

Influence of Hydrostatic Pressure on the Corrosion Behavior of Superhydrophobic Surfaces on Bare and Oxidized Aluminum Substrates.

PubMed

Ou, J F; Fang, X Z; Zhao, W J; Lei, S; Xue, M S; Wang, F J; Li, C Q; Lu, Y L; Li, W

2018-05-22

It is generally recognized that superhydrophobic surfaces in water may be used for corrosion resistance due to the entrapped air in the solid/liquid interface and could find potential applications in the protection of ship hull. For a superhydrophobic surface, as its immersion depth into water increases, the resultant hydrostatic pressure is also increased, and the entrapped air can be squeezed out much more easily. It is therefore predicted that high hydrostatic pressure would cause an unexpected decrease in corrosion resistance for the vessels in deep water (e.g., submarines) because of the unstable entrapped air. In this work, in order to clarify the role of hydrostatic pressure in the corrosion behavior of superhydrophobic surfaces, two typical superhydrophobic surfaces (SHSs) were prepared on bare and oxidized aluminum substrates, respectively, and then were immersed into the NaCl aqueous solutions with different depths of ∼0 cm (hydrostatic pressure ∼0 kPa), 10 cm (1 kPa), and 150 cm (15 kPa). It was found out for the SHSs on the oxidized Al, as the hydrostatic pressure increased, the corrosion behavior became severe. However, for the SHSs on the bare Al, their corrosion behavior was complex due to hydrostatic pressure. It was found that the corrosion resistance under 1 kPa was the highest. Further mechanism analysis revealed that this alleviated corrosion behavior under 1 kPa resulted from suppressing the oxygen diffusion through the liquid and reducing the subsequent corrosion rate as compared with 0 kPa, whereas the relatively low hydrostatic pressure (HP) could stabilize the entrapped air and hence enhance the corrosion resistance, compared with 15 kPa. The present study therefore provided a fundamental understanding for the applications of SHSs to prevent the corrosion, especially for various vessels in deep water.

Entrapment of curcumin into monoolein-based liquid crystalline nanoparticle dispersion for enhancement of stability and anticancer activity

PubMed Central

Baskaran, Rengarajan; Madheswaran, Thiagarajan; Sundaramoorthy, Pasupathi; Kim, Hwan Mook; Yoo, Bong Kyu

2014-01-01

Despite the promising anticancer potential of curcumin, its therapeutic application has been limited, owing to its poor solubility, bioavailability, and chemical fragility. Therefore, various formulation approaches have been attempted to address these problems. In this study, we entrapped curcumin into monoolein (MO)-based liquid crystalline nanoparticles (LCNs) and evaluated the physicochemical properties and anticancer activity of the LCN dispersion. The results revealed that particles in the curcumin-loaded LCN dispersion were discrete and monodispersed, and that the entrapment efficiency was almost 100%. The stability of curcumin in the dispersion was surprisingly enhanced (about 75% of the curcumin survived after 45 days of storage at 40°C), and the in vitro release of curcumin was sustained (10% or less over 15 days). Fluorescence-activated cell sorting (FACS) analysis using a human colon cancer cell line (HCT116) exhibited 99.1% fluorescence gating for 5 μM curcumin-loaded LCN dispersion compared to 1.36% for the same concentration of the drug in dimethyl sulfoxide (DMSO), indicating markedly enhanced cellular uptake. Consistent with the enhanced cellular uptake of curcumin-loaded LCNs, anticancer activity and cell cycle studies demonstrated apoptosis induction when the cells were treated with the LCN dispersion; however, there was neither noticeable cell death nor significant changes in the cell cycle for the same concentration of the drug in DMSO. In conclusion, entrapping curcumin into MO-based LCNs may provide, in the future, a strategy for overcoming the hurdles associated with both the stability and cellular uptake issues of the drug in the treatment of various cancers. PMID:25061290

Entrapment of curcumin into monoolein-based liquid crystalline nanoparticle dispersion for enhancement of stability and anticancer activity.

PubMed

Baskaran, Rengarajan; Madheswaran, Thiagarajan; Sundaramoorthy, Pasupathi; Kim, Hwan Mook; Yoo, Bong Kyu

2014-01-01

Despite the promising anticancer potential of curcumin, its therapeutic application has been limited, owing to its poor solubility, bioavailability, and chemical fragility. Therefore, various formulation approaches have been attempted to address these problems. In this study, we entrapped curcumin into monoolein (MO)-based liquid crystalline nanoparticles (LCNs) and evaluated the physicochemical properties and anticancer activity of the LCN dispersion. The results revealed that particles in the curcumin-loaded LCN dispersion were discrete and monodispersed, and that the entrapment efficiency was almost 100%. The stability of curcumin in the dispersion was surprisingly enhanced (about 75% of the curcumin survived after 45 days of storage at 40°C), and the in vitro release of curcumin was sustained (10% or less over 15 days). Fluorescence-activated cell sorting (FACS) analysis using a human colon cancer cell line (HCT116) exhibited 99.1% fluorescence gating for 5 μM curcumin-loaded LCN dispersion compared to 1.36% for the same concentration of the drug in dimethyl sulfoxide (DMSO), indicating markedly enhanced cellular uptake. Consistent with the enhanced cellular uptake of curcumin-loaded LCNs, anticancer activity and cell cycle studies demonstrated apoptosis induction when the cells were treated with the LCN dispersion; however, there was neither noticeable cell death nor significant changes in the cell cycle for the same concentration of the drug in DMSO. In conclusion, entrapping curcumin into MO-based LCNs may provide, in the future, a strategy for overcoming the hurdles associated with both the stability and cellular uptake issues of the drug in the treatment of various cancers.

Nanoparticle-Based Topical Ophthalmic Gel Formulation for Sustained Release of Hydrocortisone Butyrate.

PubMed

Yang, Xiaoyan; Trinh, Hoang M; Agrahari, Vibhuti; Sheng, Ye; Pal, Dhananjay; Mitra, Ashim K

2016-04-01

This study was conducted to develop formulations of hydrocortisone butyrate (HB)-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NP) suspended in thermosensitive gel to improve ocular bioavailability of HB for the treatment of bacterial corneal keratitis. PLGA NP with different surfactants such as polyvinyl alcohol (PVA), pluronic F-108, and chitosan were prepared using oil-in-water (O/W) emulsion evaporation technique. NP were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential, and crystallinity. In vitro release of HB from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when nanoparticles were suspended in thermosensitive gels and zero-order release kinetics was observed. In HCEC cell line, chitosan-emulsified NP showed the highest cellular uptake efficiency over PVA- and pluronic-emulsified NP (59.09 ± 6.21%, 55.74 ± 6.26%, and 62.54 ± 3.30%, respectively) after 4 h. However, chitosan-emulsified NP indicated significant cytotoxicity of 200 and 500 μg/mL after 48 h, while PVA- and pluronic-emulsified NP exhibited no significant cytotoxicity. PLGA NP dispersed in thermosensitive gels can be considered as a promising drug delivery system for the treatment of anterior eye diseases.

Development and characterization of polymer-coated liposomes for vaginal delivery of sildenafil citrate.

PubMed

Refai, Hanan; Hassan, Doaa; Abdelmonem, Rehab

2017-11-01

Vaginal administration of sildenafil citrate has shown recently to develop efficiently the uterine lining with subsequent successful embryo implantation following in vitro fertilization. The aim of the present study was to develop sildenafil-loaded liposomes coated with bioadhesive polymers for enhanced vaginal retention and improved drug permeation. Three liposomal formulae were prepared by thin-film method using different phospholipid:cholesterol ratios. The optimal liposomal formulation was coated with bioadhesive polymers (chitosan and HPMC). A marked increase in liposomal size and zeta potential was observed for all coated liposomal formulations. HPMC-coated liposomes showed the greater bioadhesion and higher entrapment efficiency than chitosan-coated formulae. The in vitro release studies showed prolonged release of sildenafil from coated liposomes as compared to uncoated liposomes and sildenafil solution. Ex vivo permeation study revealed the enhanced permeation of coated relative to uncoated liposomes. Chitosan-coated formula demonstrated highest drug permeation and was thus selected for further investigations. Transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR) confirmed the successful coating of the liposomes by chitosan. Histopathological in vivo testing proved the efficacy of chitosan-coated liposomes to improve blood flow to the vaginal endometrium and to increase endometrial thickness. Chitosan-coated liposomes can be considered as potential novel drug delivery system intended for the vaginal administration of sildenafil, which would prolong system's retention at the vaginal site and enhance the permeation of sildenafil to uterine blood circulation.

Ulnar nerve entrapment in a French horn player.

PubMed

Hoppmann, R A

1997-10-01

Nerve entrapment syndromes are frequent among musicians. Because of the demands on the musculoskeletal system and the great agility needed to per-form, musicians often present with vague complaints early in the course of entrapment, which makes the diagnosis a challenge for the clinician. Presented here is such a case of ulnar nerve entrapment at the left elbow of a French horn player. This case points out some of the difficulties in establishing a diagnosis of nerve entrapment in musicians. It also supports the theory that prolonged elbow flexion and repetitive finger movement contribute to the development of ulnar entrapment at the elbow. Although surgery is not required for most of the musculoskeletal problems of musicians, release of an entrapped nerve refractory to conservative therapy may be career-saving for the musician.

Kinetic analysis of beer primary fermentation using yeast cells immobilized by ceramic support adsorption and alginate gel entrapment.

PubMed

Zhang, Yongming; Kennedy, John F; Knill, Charles J; Panesar, Parmjit S

2006-01-01

Yeast cells were immobilized by absorption onto porous ceramic support and evaluated for continuous beer primary fermentation using a bioreactor in comparison to yeast cells immobilized by entrapment in calcium alginate gel. The effects of temperature and flow rate as a function of reaction/fermentation time on fermentation rate were investigated. The fermentation reaction (in terms of loss of total soluble solids in the beer wort as a function of time) was first-order with half-lifes in the range of approximately 9-11 hours at approximately 10-12 degrees C at beer wort linear flow rates of approximately 0.8-1.6 cm/minute for ceramic support, compared with approximately 16 hours for Ca-alginate gel, the former support matrix being more efficient and demonstrating greater potential for future commercial application.

Polyamidoamine (PAMAM) dendrimers as potential release modulators and oral bioavailability enhancers of vardenafil hydrochloride.

PubMed

Tawfik, Mai Ahmed; Tadros, Mina Ibrahim; Mohamed, Magdy Ibrahim

2018-05-21

Vardenafil hydrochloride (VAR) is an erectile dysfunction treating drug. VAR has a short elimination half-life (4-5 h) and suffers low oral bioavailability (15%). This work aimed to explore the dual potential of VAR-dendrimer complexes as drug release modulators and oral bioavailability enhancers. VAR-dendrimer complexes were prepared by solvent evaporation technique using four dendrimer generations (G4.5, G5, G5.5 and G6) at three concentrations (190 nM, 380 nM and 950 nM). The systems were evaluated for intermolecular interactions, particle size, zeta potential, drug entrapment efficiency percentages (EE%) and drug released percentages after 2 h (Q 2h ) and 24 h (Q 24h ). The results were statistically analyzed, and the system showing the highest desirability was selected for further pharmacokinetic studies in rabbits, in comparison to Levitra ® tablets. The highest desirability (0.82) was achieved with D10 system comprising VAR (10 mg) and G6 (190 nM). It possessed small particle size (113.85 nm), low PDI (0.19), positive zeta potential (+21.53), high EE% (75.24%), promising Q 2 h (41.45%) and Q 24 h (74.05%). Compared to Levitra ® tablets, the significantly (p < 0.01) delayed T max , prolonged MRT (0-∞) and higher relative bioavailability (3.7-fold) could clarify the dual potential of D10 as a sustained release system capable of enhancing VAR oral bioavailability.

pH responsive cylindrical MSN for oral delivery of insulin-design, fabrication and evaluation.

PubMed

Guha, Arijit; Biswas, Nikhil; Bhattacharjee, Kaustav; Sahoo, Nityananda; Kuotsu, Ketousetuo

2016-11-01

The objective of the present study was to develop novel PMV [poly (methacrylic acid-co-vinyl triethoxylsilane)]-coated mesoporous silica nanoparticles (MSN) with improved hypoglycemic effect for oral insulin (INS) delivery. MSN was synthesized under acidic condition using Pluronic® P 123 and Tetra ethoxy orthosilane. Surfactant was removed by calcination. Calcined MSN was coated with pH sensitive polymer PMV. Cytotoxicity of this coated MSN was evaluated by MTT assay using CHO-K1 cell line. Different MSN samples were characterized with BET surface area analyzer, FESEM, TEM, FT-IR, XRD, TG-DTA. In vivo study was performed using male rats. Pharmacokinetic study was conducted using HPLC. Highest surface area (304.3921 m 2 /g) was observed in case of calcined sample. Adsorption pore width of final coated sample was highest (64.7844 nm) compared with others. No noticeable cytotoxicity was observed for this coated support. The entrapment efficiency of insulin was found to be 39.39%. In vitro studies were done at different pH using Franz-diffusion cell. Results showed significant release at pH 7.4. Cumulative drug release over a period of 6 h was more than 48% at this systemic pH. Effect of this MSN-PMV-INS on blood glucose level was retained for 16 h. This novel formulation has shown 73.10% relative bioavailability of insulin. A novel-coated mesoporous silica support was successfully developed for delivery of insulin through oral route.

6-mercaptopurine and daunorubicin double drug liposomes-preparation, drug-drug interaction and characterization.

PubMed

Agrawal, Vineet; Paul, Manash K; Mukhopadhyay, Anup K

2005-01-01

This article addresses and investigates the dual incorporation of daunorubicin (DR) and 6-mercaptopurine (6-MP) in liposomes for better chemotherapy. These drugs are potential candidates for interaction due to the quinone (H acceptor) and hydroxyl (H donor) groups on DR and 6-MP, respectively. Interactions between the two drugs in solution were monitored by UV/Vis and fluorescence spectroscopy. Interaction between the two drugs inside the liposomes was evaluated by HPLC (for 6-MP) and by fluorescence spectroscopy (for daunorubicin) after phospholipase-mediated liposome lysis. Our results provide evidence for the lack of interaction between the two drugs in solution and in liposomes. The entrapment efficiencies of 6-MP in the neutral Phosphatidyl choline (PC):Cholesterol (Chol):: 2:1 and anionic PC:Chol:Cardiolipin (CL) :: 4:5:1 single and double drug liposomes were found to be 0.4% and 1.5% (on average), respectively. The entrapment efficiencies of DR in the neutral and anionic double drug liposomes were found to be 55% and 31%, respectively. The corresponding entrapment of daunorubicin in the single drug liposomes was found to be 62% on average. Our thin layer chromatography (TLC) and transmission electron microscopy (TEM) results suggest stability of lipid and liposomes, thus pointing plausible existence of double drug liposomes. Cytotoxicity experiments were performed by using both single drug and double drug liposomes. By comparing the results of phase contrast and fluorescence microscopy, it was observed that the double drug liposomes were internalized in the jurkat and Hut78 (highly resistant cell line) leukemia cells as viewed by the fluorescence of daunorubicin. The cytotoxicity was dose dependent and had shown a synergistic effect when double drug liposome was used.

Preparation and physicochemical characteristics of polylactide microspheres of emamectin benzoate by modified solvent evaporation/extraction method.

PubMed

Zhang, Shao Fei; Chen, Peng Hao; Zhang, Fei; Yang, Yan Fang; Liu, De Kun; Wu, Gang

2013-12-18

Emamectin benzoate is highly effective against insect pests and widely used in the world. However, its biological activity is limited because of high resistance of target insects and rapid degradation speed in fields. Preparation and physicochemical characterization of degradable microcapsules of emamectin benzoate were studied by modified solvent evaporation/extraction method using polylactide (PLA) as wall material. The influence of different compositions of the solvent in internal organic phase and external aqueous phase on diameter, span, pesticide loading, and entrapment rate of the microspheres was investigated. The results indicated that the process of solvent extraction and the formation of the microcapsules would be accelerated by adding water-miscible organic solvents such as ethyl ether, acetone, ethyl acetate, or n-butanol into internal organic phase and external aqueous phase. Accelerated formation of the microcapsules would result in entrapment rates of emamectin benzoate increased to as high as 97%. In addition, by adding ethanol into the external aqueous phase, diameters would reduce to 6.28 μm, whereas the loading efficiency of emamectin benzoate did not increase. The PLA microspheres prepared under optimum conditions were smoother and more spherical. The degradation rate in PLA microspheres of emamectin benzoate on the 10th day was 4.29 ± 0.74%, whereas the degradation rates of emamectin benzoate in methanol solution and solid technical material were 46.3 ± 2.11 and 22.7 ± 1.51%, respectively. The PLA skeleton had combined with emamectin benzoate in an amorphous or molecular state by using differential scanning calorimetry (DSC) determination. The results indicated that PLA microspheres of emamectin benzoate with high entrapment rate, loading efficiency, and physicochemical characteristics could be obtained by adding water-miscible organic solvents into the internal organic phase and external aqueous phase.

Optimization of methazolamide-loaded solid lipid nanoparticles for ophthalmic delivery using Box-Behnken design.

PubMed

Wang, Fengzhen; Chen, Li; Jiang, Sunmin; He, Jun; Zhang, Xiumei; Peng, Jin; Xu, Qunwei; Li, Rui

2014-09-01

The purpose of the present study was to optimize methazolamide (MTZ)-loaded solid lipid nanoparticles (SLNs) which were used as topical eye drops by evaluating the relationship between design factors and experimental data. A three factor, three-level Box-Behnken design (BBD) was used for the optimization procedure, choosing the amount of GMS, the amount of phospholipid, the concentration of surfactant as the independent variables. The chosen dependent variables were entrapment efficiency, dosage loading, and particle size. The generated polynomial equations and response surface plots were used to relate the dependent and independent variables. The optimal nanoparticles were formulated with 100 mg GMS, 150 mg phospholipid, and 1% Tween80 and PEG 400 (1:1, w/v). A new formulation was prepared according to these levels. The observed responses were close to the predicted values of the optimized formulation. The particle size was 197.8 ± 4.9 nm. The polydispersity index of particle size was 0.239 ± 0.01 and the zeta potential was 32.7 ± 2.6 mV. The entrapment efficiency and dosage loading were about 68.39% and 2.49%, respectively. Fourier transform infrared spectroscopy (FT-IR) study indicated that the drug was entrapped in nanoparticles. The optimized formulation showed a sustained release followed the Peppas model. MTZ-SLNs showed significant prolonged decreasing intraocular pressure effect comparing with MTZ solution in vivo pharmacodynamics studies. The results of acute eye irritation study indicated that MTZ-SLNs and AZOPT both had no eye irritation. Furthermore, the MTZ-SLNs were suitable to be stored at low temperature (4 °C).

Alginate Nanoparticles Containing Curcumin and Resveratrol: Preparation, Characterization, and In Vitro Evaluation Against DU145 Prostate Cancer Cell Line.

PubMed

Saralkar, Pushkar; Dash, Alekha K

2017-10-01

Curcumin and resveratrol are naturally occurring polyphenolic compounds having anti-cancer potential. However, their poor aqueous solubility and bioavailability limit their clinical use. Entrapment of hydrophobic drugs into hydrophilic nanoparticles such as calcium alginate presents a means to deliver these drugs to their target site. Curcumin and resveratrol-loaded calcium alginate nanoparticles were prepared by emulsification and cross-linking process. The nanoparticles were characterized for particle size, zeta potential, moisture content, physical state of the drugs, physical stability, and entrapment efficiency. An UPLC method was developed and validated for the simultaneous analysis of curcumin and resveratrol. Alginate nanoformulation was tested for in vitro efficacy on DU145 prostate cancer cells. The particle size of the nanosuspension and freeze-dried nanoparticles was found to be 12.53 ± 1.06 and 60.23 ± 15 nm, respectively. Both DSC and powder XRD studies indicated that curcumin as well as resveratrol were present in a non-crystalline state, in the nanoparticles. The entrapment efficiency for curcumin and resveratrol was found to be 49.3 ± 4.3 and 70.99 ± 6.1%, respectively. Resveratrol showed a higher percentage of release than curcumin (87.6 ± 7.9 versus 16.3 ± 3.1%) in 24 h. Curcumin was found to be taken up by the cells from solution as well as the nanoparticles. Resveratrol had a poor cellular uptake. The drug-loaded nanoparticles exhibit cytotoxic effects on DU145 cells. At high concentration, drug solution exhibited greater toxicity than nanoparticles. The alginate nanoformulation was found to be safe for intravenous administration.

Encapsulating fatty acid esters of bioactive compounds in starch

NASA Astrophysics Data System (ADS)

Lay Ma, Ursula Vanesa

Interest in the use of many bioactive compounds in foods is growing in large part because of the apparent health benefits of these molecules. However, many of these compounds can be easily degraded during processing, storage, or their passage through the gastrointestinal tract before reaching the target site. In addition, they can be bitter, acrid, or astringent, which may negatively affect the sensory properties of the product. Encapsulation of these molecules may increase their stability during processing, storage, and in the gastrointestinal tract, while providing controlled release properties. The ability of amylose to form inclusion complexes and spherulites while entrapping certain compounds has been suggested as a potential method for encapsulation of certain molecules. However, complex formation and spherulitic crystallization are greatly affected by the type of inclusion molecules, type of starch, and processing conditions. The objectives of the present investigation were to: (a) study the effect of amylose, amylopectin, and intermediate material on spherulite formation and its microstructure; (b) investigate the formation of amylose and high amylose starch inclusion complexes with ascorbyl palmitate, retinyl palmitate, and phytosterol esters; (c) evaluate the ability of spherulites to form in the presence of fatty acid esters and to entrap ascorbyl palmitate, retinyl palmitate, and phytosterol esters; and (d) evaluate the effect of processing conditions on spherulite formation and fatty acid ester entrapment. Higher ratios of linear to branched molecules resulted in the formation of more and rounder spherulites with higher heat stability. In addition to the presence of branches, it appears that spherulitic crystallization is also affected by other factors, such as degree of branching, chain length, and chain length distribution. Amylose and Hylon VII starch formed inclusion complexes with fatty acid esters of ascorbic acid, retinol, or phytosterols. However, only retinyl palmitate formed a complex with amylopectin. In general, ascorbyl palmitate resulted in the highest complexation, followed by retinyl palmitate and phytosterol ester. The presence of native lipids in Hylon VII starch did not inhibit complex formation. On the contrary, native lipids appear to increase the complexation yield and thermal stability of the starch-fatty acid ester inclusion complexes, possibly due to the formation of ternary complexes. From the three fatty acid esters studied, only ascorbyl palmitate was entrapped in starch spherulites. Various structures including round spherulites, various sizes of torus-shape spherulites, non-spherulitic birefringent and non-birefringent particles, "balloon" morphologies, and gel-like material were formed depending on processing conditions. However, only the torus-shape spherulites, and some non-spherulitic birefringent and non-birefringent particles showed ascorbyl palmitate entrapment. The % yield of the precipitate increased with higher % of added Hylon VII, and decreased with higher heating temperature and faster cooling rates. The amount of entrapped ascorbyl palmitate in the starch precipitate seems to be governed by the amount of this compound added during processing. This study showed that starch can form inclusion complexes with fatty acid esters which may be used for the delivery of certain bioactive molecules. In addition, encapsulation of fatty acid esters in starch spherulites may be a good potential delivery system for water soluble bioactive molecules. However, further research is necessary to gain a better understanding of the type of molecules that can be entrapped in starch spherulites, and the factors affecting spherulitic crystallization and bioactive compound entrapment.

Entrapment of anaerobic thermophilic and hyperthermophilic marine micro-organisms in a gellan/xanthan matrix.

PubMed

Landreau, M; Duthoit, F; Claeys-Bruno, M; Vandenabeele-Trambouze, O; Aubry, T; Godfroy, A; Le Blay, G

2016-06-01

The aims of this study were (i) to develop a protocol for the entrapment of anaerobic (hyper)thermophilic marine micro-organisms; (ii) to test the use of the chosen polymers in a range of physical and chemical conditions and (iii) to validate the method with batch cultures. The best conditions for immobilization were obtained at 80°C with gellan and xanthan gums. After 5-week incubation, beads showed a good resistance to all tested conditions except those simultaneously including high temperature (100°C), low NaCl (<0∙5 mol l(-1) ) and extreme pH (4/8). To confirm the method efficiency, batch cultures with immobilized Thermosipho sp. strain AT1272 and Thermococcus kodakarensis strain KOD1 showed an absence of detrimental effect on cell viability and a good growth within and outside the beads. This suggests that entrapment in a gellan-xanthan matrix could be employed for the culture of anaerobic (hyper)thermophilic marine micro-organisms. (Hyper)thermophilic marine micro-organisms possess a high biotechnological potential. Generally microbial cells are grown as free-cell cultures. The use of immobilized cells may offer several advantages such as protection against phage attack, high cell biomass and better production rate of desired metabolites. © 2016 The Society for Applied Microbiology.

Electrospun polylactic acid and polyvinyl alcohol fibers as efficient and stable nanomaterials for immobilization of lipases.

PubMed

Sóti, Péter Lajos; Weiser, Diana; Vigh, Tamás; Nagy, Zsombor Kristóf; Poppe, László; Marosi, György

2016-03-01

Electrospinning was applied to create easy-to-handle and high-surface-area membranes from continuous nanofibers of polyvinyl alcohol (PVA) or polylactic acid (PLA). Lipase PS from Burkholderia cepacia and Lipase B from Candida antarctica (CaLB) could be immobilized effectively by adsorption onto the fibrous material as well as by entrapment within the electrospun nanofibers. The biocatalytic performance of the resulting membrane biocatalysts was evaluated in the kinetic resolution of racemic 1-phenylethanol (rac-1) and 1-phenylethyl acetate (rac-2). Fine dispersion of the enzymes in the polymer matrix and large surface area of the nanofibers resulted in an enormous increase in the activity of the membrane biocatalyst compared to the non-immobilized crude powder forms of the lipases. PLA as fiber-forming polymer for lipase immobilization performed better than PVA in all aspects. Recycling studies with the various forms of electrospun membrane biocatalysts in ten cycles of the acylation and hydrolysis reactions indicated excellent stability of this forms of immobilized lipases. PLA-entrapped lipases could preserve lipase activity and enantiomer selectivity much better than the PVA-entrapped forms. The electrospun membrane forms of CaLB showed high mechanical stability in the repeated acylations and hydrolyses than commercial forms of CaLB immobilized on polyacrylamide beads (Novozyme 435 and IMMCALB-T2-150).

Inhalational system for Etoposide liposomes: formulation development and in vitro deposition.

PubMed

Parmar, J J; Singh, D J; Lohade, A A; Hegde, Darshana D; Soni, P S; Samad, A; Menon, Mala D

2011-11-01

Etoposide is a semisynthetic compound, widely used in treatment of non small cell lung cancer. However, frequent dosing and adverse effects remain a major concern in the use of etoposide. Liposomal systems for pulmonary drug delivery have been particularly attractive because of their compatibility with lung surfactant components. In the present investigation, pulmonary liposomal delivery system of etoposide was prepared by film hydration method. Various parameters were optimized with respect to entrapment efficiency as well as particle size of etoposide liposomes. For better shelf life of etoposide liposomes, freeze drying using trehalose as cryoprotectant was carried out. The liposomes were characterized for entrapment efficiency, particle size, surface topography, and in vitro drug release was carried out in simulated lung fluid at 37° at pH 7.4. The respirable or fine particle fraction was determined by using twin stage impinger. The stability study of freeze dried as well as aqueous liposomal systems was carried out at 2-8° and at ambient temperature (28±4°). The freeze dried liposomes showed better fine particle fraction and drug content over the period of six months at ambient as well as at 2-8° storage condition compared to aqueous dispersion of liposomes.

Folate Conjugated Hybrid Nanocarrier for Targeted Letrozole Delivery in Breast Cancer Treatment.

PubMed

Hemati Azandaryani, Abbas; Kashanian, Soheila; Derakhshandeh, Katayoun

2017-12-01

Letrozole as a steroidal anticancer drug with hydrophobic nature is usually administrated by oral route for patient treatment and the injectable formulation for this drug has not still been reported. In this study, a new letrozole incorporated folate-conjugated polymer - lipid hybrid nanoparticles - is introduced for cancer treatment. Nanoparticles were fabricated via modified oil in water ionic gelation method using optimization parameters and then were coupled to folic acid using carbodiimide activation. The physicochemical characterization in vitro drug release, cytotoxicity, and then ex vivo study of obtained carrier was investigated. Both thermal and crystallography studies proved the amorphous loading of drug in the nanocarrier. The cytotoxicity investigation with an average IC 50 value of 79 ± 2.40 nM proved the efficiency of the coupled folic acid carrier for the intracellular uptake of letrozole on the breast cancer line. Ex vivo, the study proved the positive effect of the letrozole entrapment on the drug bioavailability. The obtained targeted nanocarrier could overcome the limitations associated with the LTZ as a potent non-steroidal drug. Both the entrapment and therapeutic efficiency of letrozole in the amphiphilic carrier were increased using the lipid nanoparticles and the surface modification, respectively.

Fabrication of Apigenin loaded gellan gum-chitosan hydrogels (GGCH-HGs) for effective diabetic wound healing.

PubMed

Shukla, Rajesh; Kashaw, Sushil K; Jain, Alok Pal; Lodhi, Santram

2016-10-01

The Apigenin (APN) was isolated from ethanolic extract of M. alba leaves and screened by in-vivo wound models (Diabetic and Dead space) in rats. Apigenin loaded hydrogel (HGs) was prepared using gellan gum-chitosan (GGCH) with PEG as a cross linker and characterized for various parameter like AFM, swelling property, entrapment efficiency and drug release. Further performance of hydrogel was evaluated by wound healing activity tested against wound contraction, collagen content, dried granuloma weights and antioxidant activity. The percent entrapment efficiency of optimized hydrogel found to be 87.15±1.20. APN loaded GGCH-HGs were able to release 96.11% APN in 24h. The level of superoxide dismutase (SOD) and catalase were found increased significantly in granuloma tissue of APN treated group. APN GGCH-HGs found higher wound healing effect in diabetic as well as normal wound tissues with significant antioxidant activity. Results proven the utility of prepared hydrogel (APN loaded GGCH-HGs) seems to be highly suitable for wound healing due to its unique properties of biocompatibility, biodegradability, moist nature and antioxidant effectiveness. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation of redispersible liposomal dry powder using an ultrasonic spray freeze-drying technique for transdermal delivery of human epithelial growth factor

PubMed Central

Yin, Fei; Guo, Shiyan; Gan, Yong; Zhang, Xinxin

2014-01-01

In this work, an ultrasonic spray freeze-drying (USFD) technique was used to prepare a stable liposomal dry powder for transdermal delivery of recombinant human epithelial growth factor (rhEGF). Morphology, particle size, entrapment efficiency, in vitro release, and skin permeability were systematically compared between rhEGF liposomal dry powder prepared using USFD and that prepared using a conventional lyophilization process. Porous and spherical particles with high specific area were produced under USFD conditions. USFD effectively avoided formation of ice crystals, disruption of the bilayer structure, and drug leakage during the liposome drying process, and maintained the stability of the rhEGF liposomal formulation during storage. The reconstituted rhEGF liposomes prepared from USFD powder did not show significant changes in morphology, particle size, entrapment efficiency, or in vitro release characteristics compared with those of rhEGF liposomes before drying. Moreover, the rhEGF liposomal powder prepared with USFD exhibited excellent enhanced penetration in ex vivo mouse skin compared with that for powder prepared via conventional lyophilization. The results suggest that ultrasonic USFD is a promising technique for the production of stable protein-loaded liposomal dry powder for application to the skin. PMID:24729702

Preparation of redispersible liposomal dry powder using an ultrasonic spray freeze-drying technique for transdermal delivery of human epithelial growth factor.

PubMed

Yin, Fei; Guo, Shiyan; Gan, Yong; Zhang, Xinxin

2014-01-01

In this work, an ultrasonic spray freeze-drying (USFD) technique was used to prepare a stable liposomal dry powder for transdermal delivery of recombinant human epithelial growth factor (rhEGF). Morphology, particle size, entrapment efficiency, in vitro release, and skin permeability were systematically compared between rhEGF liposomal dry powder prepared using USFD and that prepared using a conventional lyophilization process. Porous and spherical particles with high specific area were produced under USFD conditions. USFD effectively avoided formation of ice crystals, disruption of the bilayer structure, and drug leakage during the liposome drying process, and maintained the stability of the rhEGF liposomal formulation during storage. The reconstituted rhEGF liposomes prepared from USFD powder did not show significant changes in morphology, particle size, entrapment efficiency, or in vitro release characteristics compared with those of rhEGF liposomes before drying. Moreover, the rhEGF liposomal powder prepared with USFD exhibited excellent enhanced penetration in ex vivo mouse skin compared with that for powder prepared via conventional lyophilization. The results suggest that ultrasonic USFD is a promising technique for the production of stable protein-loaded liposomal dry powder for application to the skin.

[Optimization of Formulation and Process of Paclitaxel PEGylated Liposomes by Box-Behnken Response Surface Methodology].

PubMed

Shi, Ya-jun; Zhang, Xiao-feil; Guo, Qiu-ting

2015-12-01

To develop a procedure for preparing paclitaxel encapsulated PEGylated liposomes. The membrane hydration followed extraction method was used to prepare PEGylated liposomes. The process and formulation variables were optimized by "Box-Behnken Design (BBD)" of response surface methodology (RSM) with the amount of Soya phosphotidylcholine (SPC) and PEG2000-DSPE as well as the rate of SPC to drug as independent variables and entrapment efficiency as dependent variables for optimization of formulation variables while temperature, pressure and cycle times as independent variables and particle size and polydispersion index as dependent variables for process variables. The optimized liposomal formulation was characterized for particle size, Zeta potential, morphology and in vitro drug release. For entrapment efficiency, particle size, polydispersion index, Zeta potential, and in vitro drug release of PEGylated liposomes was found to be 80.3%, (97.15 ± 14.9) nm, 0.117 ± 0.019, (-30.3 ± 3.7) mV, and 37.4% in 24 h, respectively. The liposomes were found to be small, unilamellar and spherical with smooth surface as seen in transmission electron microscopy. The Box-Behnken response surface methodology facilitates the formulation and optimization of paclitaxel PEGylated liposomes.

Pravastatin chitosan nanogels-loaded erythrocytes as a new delivery strategy for targeting liver cancer.

PubMed

Harisa, Gamaleldin I; Badran, Mohamed M; AlQahtani, Saeed A; Alanazi, Fars K; Attia, Sabry M

2016-01-01

Chitosan nanogels (CNG) are developed as one of the most promising carriers for cancer targeting. However, these carriers are rapidly eliminated from circulation by reticuloendothelial system (RES), which limits their application. Therefore, erythrocytes (ER) loaded CNG as multifunctional carrier may overcome the massive elimination of nanocarriers by RES. In this study, erythrocytes loaded pravastatin-chitosan nanogels (PR-CNG-ER) were utilized as a novel drug carrier to target liver cancer. Thus, PR-CNG formula was developed in nanosize, with good entrapment efficiency, drug loading and sustained release over 48 h. Then, PR-CNG loaded into ER were prepared by hypotonic preswelling technique. The resulting PR-CNG-ER showed 36.85% of entrapment efficiency, 66.82% of cell recovery and release consistent to that of hemoglobin over 48 h. Moreover, PR-CNG-ER exhibited negative zeta potential, increasing of hemolysis percent, marked phosphatidylserine exposure and stomatocytes shape compared to control unloaded erythrocytes. PR-CNG-ER reduced cells viability of HepG2 cells line by 28% compared to unloaded erythrocytes (UER). These results concluded that PR-CNG-ER are promising drug carriers to target liver cancer.

Pravastatin chitosan nanogels-loaded erythrocytes as a new delivery strategy for targeting liver cancer

PubMed Central

Harisa, Gamaleldin I.; Badran, Mohamed M.; AlQahtani, Saeed A.; Alanazi, Fars K.; Attia, Sabry M.

2015-01-01

Chitosan nanogels (CNG) are developed as one of the most promising carriers for cancer targeting. However, these carriers are rapidly eliminated from circulation by reticuloendothelial system (RES), which limits their application. Therefore, erythrocytes (ER) loaded CNG as multifunctional carrier may overcome the massive elimination of nanocarriers by RES. In this study, erythrocytes loaded pravastatin–chitosan nanogels (PR–CNG–ER) were utilized as a novel drug carrier to target liver cancer. Thus, PR–CNG formula was developed in nanosize, with good entrapment efficiency, drug loading and sustained release over 48 h. Then, PR–CNG loaded into ER were prepared by hypotonic preswelling technique. The resulting PR–CNG–ER showed 36.85% of entrapment efficiency, 66.82% of cell recovery and release consistent to that of hemoglobin over 48 h. Moreover, PR–CNG–ER exhibited negative zeta potential, increasing of hemolysis percent, marked phosphatidylserine exposure and stomatocytes shape compared to control unloaded erythrocytes. PR–CNG–ER reduced cells viability of HepG2 cells line by 28% compared to unloaded erythrocytes (UER). These results concluded that PR–CNG–ER are promising drug carriers to target liver cancer. PMID:26903771

Development and validation of a fast RP-HPLC method for determination of methotrexate entrapment efficiency in polymeric nanocapsules.

PubMed

Sartori, Tatiane; Seigi Murakami, Fabio; Pinheiro Cruz, Ariane; Machado de Campos, Angela

2008-07-01

A rapid and effective isocratic chromatographic procedure is successfully developed to determinate methotrexate (MTX) entrapment efficiency (EE) in polymeric nanocapsules using reversed-phase high-performance liquid chromatography. The method employed a RP-C(18) Shimadzu Shim-pack CLC-ODS (150 mm x 4.6 mm, 5 microm) column with mobile phase constituted by a mixture of water-acetonitrile-tetrahydrofuran (65:30:5 v/v/v; pH 3.0) at a flow rate of 0.8 mL/min. The eluate is monitored with a UV detector set at 313 nm. The parameters used in the validation process are: linearity, specificity, precision, accuracy, and limit of quantitation (LOQ). The linearity is evaluated by a calibration curve in the concentration range of 10-50 microg/mL and presented a correlation coefficient of 0.9998. The polymers (PLA or PLA-PEG), oil, and surfactants used in the nanocapsule formulation did not interfere with analysis and the recovery was quantitative. The intra and inter-day assay relative standard deviation were less than 0.72%. Results are satisfactory, and the method proved to be adequate for the determination of methotrexate in nanocapsules formulations.

Characterization, stabilization and activity of uricase loaded in lipid vesicles.

PubMed

Tan, Q Y; Wang, N; Yang, H; Zhang, L K; Liu, S; Chen, L; Liu, J; Zhang, L; Hu, N N; Zhao, C J; Zhang, J Q

2010-01-15

Uricase-containing lipid vesicles (UOXLVs) were prepared by reverse-phase evaporation method with high efficiency and the characteristics of UOXLVs were described. The average size and zeta potential of UOXLVs obtained by the optimized formulation were 205.47 nm and -37.33 mV, respectively. Uricase was encapsulated in the alkaline aqueous phase of the lipid vesicle and the stability of its tetrameric structure was thus improved and its activity preserved. The storage stability of uricase in lipid vesicles was significantly increased compared to that of free uricase at 4 degrees C in borate buffer of pH 8.5. At 55 degrees C, free uricase was deactivated much more quickly especially at lower concentration predominantly due to enhanced dissociation of uricase into subunits. An intrinsic tryptophan of uricase recovered from the lipid vesicle thermally treated at 55 degrees C revealed that a partially denatured uricase molecule was stabilized through its hydrophobic interaction with lipid vesicle membrane. This interaction was depressed mainly by dissociation of uricase into subunits. At the physiological pH, significant increase of enzyme activity was found for the uricase entrapped in the lipid vesicles (1.8 times that of free uricase) at their respective optimum pH. The shift of optimum pH and increased uricolytic activity suggested the conformation change of the uricase during the entrapment process. The stability to proteolytic digestion was increased obviously by entrapping the uricase in the lipid vesicles. UOXLVs also showed relatively slower loss in activity compared with free uricase when treated with some chemical reagents. Lastly, in vitro study explicitly indicated that the uricase entrapped by UOXLVs possessed higher uricolytic activity than that of native uricase solution.

Reversible entrapment of plasmid deoxyribonucleic acid on different chromatographic supports.

PubMed

Gabor, Boštjan; Černigoj, Urh; Barut, Miloš; Štrancar, Aleš

2013-10-11

HPLC based analytical assay is a powerful technique that can be used to efficiently monitor plasmid DNA (pDNA) purity and quantity throughout the entire purification process. Anion exchange monolithic and non-porous particle based stationary phases were used to study the recovery of the different pDNA isoforms from the analytical column. Three differently sized pDNA molecules of 3.0kbp, 5.2kbp and 14.0kbp were used. Plasmid DNA was injected onto columns under the binding conditions and the separation of the isoforms took place by increasing the ionic strength of the elution buffer. While there was no substantial decrease of the recovered supercoiled and linear isoforms of the pDNA with the increase of the plasmid size and with the increase of the flow rate (recoveries in all cases larger than 75%), a pronounced decrease of the oc isoform recovery was observed. The entrapment of the oc pDNA isoform occurred under non-binding conditions as well. The partial oc isoform elution from the column could be achieved by decreasing the flow rate of the elution mobile phase. The results suggested a reversible entrapment of the oc isoform in the restrictions within the pores of the monolithic material as well as within the intra-particle space of the non-porous particles. This phenomenon was observed on both types of the stationary phase morphologies and could only be connected to the size of a void space through which the pDNA needs to migrate. A prediction of reversible pDNA entrapment was successfully estimated with the calculation of Peclet numbers, Pe, which defines the ratio between a convective and diffusive mass transport. Copyright © 2013 Elsevier B.V. All rights reserved.

Gamma-oryzanol-loaded calcium pectinate microparticles reinforced with chitosan: optimization and release characteristics.

PubMed

Lee, Ji-Soo; Kim, Jong Soo; Lee, Hyeon Gyu

2009-05-01

Response surface methodology was used to optimize microparticle preparation conditions, including the ratio of pectin:gamma-oryzanol (OZ) (X(1)), agitation speed (X(2)), and the concentration of emulsifier (X(3)), for maximal entrapment efficiency (EE) of OZ-loaded Ca pectinate microparticles. The optimized values of X(1), X(2), and X(3) were found to be 2.72:5.28, 1143.5 rpm, and 2.61%, respectively. Experimental results obtained for the optimum formulation agreed favorably with the predicted results, indicating the usefulness of predicting models for EE. In order to evaluate the effect of chitosan-coating and blending on the release pattern of the entrapped OZ from microparticles, chitosan-coated and blended Ca pectinate microparticles were prepared. Release studies revealed that the chitosan treatments, especially the chitosan-coating, were effective in suppressing the release in both simulated gastric fluid (SGF) and intestinal fluid (SIF).

Optimisation of entrapped activated carbon conditions to remove coloured compounds from winery wastewaters.

PubMed

Devesa-Rey, R; Bustos, G; Cruz, J M; Moldes, A B

2011-06-01

The objective of this work was to study the entrapped conditions of activated carbon in calcium-alginate beads for the clarification of winery wastewaters. An incomplete 3(3) factorial design was carried out to study the efficiency of activated carbon (0.5-2%); sodium alginate (1-5%); and calcium chloride (0.050-0.900 M), on the following dependent variables: colour reduction at 280, 465, 530 and 665 nm. The activated carbon and calcium chloride were the most influential variables in the colour reduction. Nearly 100% colour reductions were found for the wavelengths assayed when employing 2% of activated carbon, 5% of sodium alginate and intermediate concentrations of calcium chloride (0.475 M). Instead, other conditions like, 2% of activated carbon, 4% of sodium alginate and 0.580 M of calcium chloride can also give absorbance reductions close to 100%. Copyright © 2011 Elsevier Ltd. All rights reserved.

Solid lipid nanoparticles for delivery of Calendula officinalis extract.

PubMed

Arana, Lide; Salado, Clarisa; Vega, Sandra; Aizpurua-Olaizola, Oier; de la Arada, Igor; Suarez, Tatiana; Usobiaga, Aresatz; Arrondo, José Luis R; Alonso, Alicia; Goñi, Félix M; Alkorta, Itziar

2015-11-01

Solid lipid nanoparticles (SLN) composed of long-chain fatty acids (palmitic acid, stearic acid or arachidic acid), Epikuron 200 (purified phosphatidylcholine), and bile salts (cholate, taurocholate or taurodeoxycholate) have been prepared by dilution of a microemulsion. A total of five different systems were prepared, and characterized by photon correlation spectroscopy, transmission electron microscopy, differential scanning calorimetry, and infrared spectroscopy. The SLN formulation showing optimal properties (lowest size and polydispersity index and highest zeta potential) was obtained with stearic acid and taurodeoxycholate as cosurfactant. This formulation was loaded with Calendula officinalis extract, a natural compound used on ophthalmic formulations given its anti-inflammatory, emollient, and wound repairing activity. Calendula-loaded SLN preparations were characterized in order to determine loading capacity and entrapment efficiency. In vitro cytotoxicity and wound healing efficacy of Calendula-loaded SLN compared to that of a free plant extract were evaluated on a conjunctival epithelium cell line WKD. Our results suggest that this SLN formulation is a safe and solvent-free Calendula extract delivery system which could provide a controlled therapeutic alternative for reducing disease-related symptoms and improving epithelium repair in ocular surface. Copyright © 2015 Elsevier B.V. All rights reserved.

Application of bioflocculating property of Pseudomonas aeruginosa strain IASST201 in treatment of oil-field formation water.

PubMed

Pathak, Mihirjyoti; Devi, Arundhuti; Sarma, Hridip Kumar; Lal, Banwari

2014-07-01

A bioflocculating activity of 89.8% was depicted by an activated sludge-borne bacteria Pseudomonas aeruginosa strain IASST201 with a yield of bioflocculant of 2.68 g L(-1) obtained from production media broth after optimization of different parameters. The highest bioflocculation efficiency was found at the pre-stationary phase of the bacterial growth period in the production media broth at 96th hour examined from a growth-flocculation kinetics study. 85.67% of bioflocculation was observed in oil-field formation water, with a separation of 68.7% of aliphatic hydrocarbon contents of the formation water after the application of the bacterial bioflocculant by entrapment mechanism with formation of flocs which was analyzed and examined comparatively through gas-chromatography. Extensive removal of heavy metal contents of the oil-field formation water due to bioflocculation was estimated by Atomic Absorption Spectrophotometer (AAS). The SEM and AFM studies declare the extracellular polymeric nature of the bioflocculant produced by this bacterium clumped within bacterial biofilm supported with FTIR study of the extracted bioflocculant. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Depression status of academic high school students in Seoul: mediating role of entrapment].

PubMed

Park, Young-Joo; Shin, Nah-Mee; Han, Kuem-Sun; Kang, Hyun-Cheol; Cheon, Sook-Hee; Shin, Hyunjeong

2011-10-01

Purpose of this study was to investigate the status of depression in academic high school students and path analysis model for exploring the mediating role of entrapment to depression in relation to academic stress and perceived social support. Measurements were four reliable questionnaires measuring academic stress, social support, entrapment, and depression. Data were collected from students in 17 high schools in Seoul. Students (n=5,346) completing the questionnaires indicated depression & entrapment from academic stress. Depression was more prevalent in girls, those whose parents' household income was less than two million won, who did not live with father or mother or both due to divorce, separation, or death, and those who smoked or used alcohol. Entrapment was more prevalent in students similar to cases of depression and in seniors. According to the proposed path model, 48.6% of depression was explained by academic stress, social support, and entrapment. The indirect effect of entrapment as a mediator between academic stress and depression was verified and larger than the direct effect of academic stress on depression. Considering levels of depression and entrapment demonstrated by these students, better mental health programs with diverse strategies should be developed for their psychological well-being.

Study on acceleration processes of the radiation belt electrons through interaction with sub-packet chorus waves in parallel propagation

NASA Astrophysics Data System (ADS)

Hiraga, R.; Omura, Y.

2017-12-01

By recent observations, chorus waves include fine structures such as amplitude fluctuations (i.e. sub-packet structure), and it has not been verified in detail yet how energetic electrons are efficiently accelerated under the wave features. In this study, we firstly focus on the acceleration process of a single electron: how it experiences the efficient energy increase by interaction with sub-packet chorus waves in parallel propagation along the Earth's magnetic field. In order to reproduce the chorus waves as seen by the latest observations by Van Allen Probes (Foster et al. 2017), the wave model amplitude in our simulation is structured such that when the wave amplitude nonlinearly grows to reach the optimum amplitude, it starts decreasing until crossing the threshold. Once it crosses the threshold, the wave dissipates and a new wave rises to repeat the nonlinear growth and damping in the same manner. The multiple occurrence of this growth-damping cycle forms a saw tooth-like amplitude variation called sub-packet. This amplitude variation also affects the wave frequency behavior which is derived by the chorus wave equations as a function of the wave amplitude (Omura et al. 2009). It is also reasonable to assume that when a wave packet diminishes and the next wave rises, it has a random phase independent of the previous wave. This randomness (discontinuity) in phase variation is included in the simulation. Through interaction with such waves, dynamics of energetic electrons were tracked. As a result, some electrons underwent an efficient acceleration process defined as successive entrapping, in which an electron successfully continues to surf the trapping potential generated by consecutive wave packets. When successive entrapping occurs, an electron trapped and de-trapped (escape the trapping potential) by a single wave packet falls into another trapping potential generated by the next wave sub-packet and continuously accelerated. The occurrence of successive entrapping is influenced by some factors such as the magnitude of wave amplitude or inhomogeneity of the Earth's dipole magnetic field. In addition, an energy range of electrons is also a major factor. In this way, it has been examined in detail how and under which conditions electrons are efficiently accelerated in the formation process of the radiation belts.

Evaluation of support matrices for immobilization of anaerobic consortia for efficient carbon cycling in waste regeneration.

PubMed

Chauhan, Ashvini; Ogram, Andrew

2005-02-18

Efficient metabolism of fatty acids during anaerobic waste digestion requires development of consortia that include "fatty acid consuming H(2) producing bacteria" and methanogenic bacteria. The objective of this research was to optimize methanogenesis from fatty acids by evaluating a variety of support matrices for use in maintaining efficient syntrophic-methanogenic consortia. Tested matrices included clays (montmorillonite and bentonite), glass beads (106 and 425-600mum), microcarriers (cytopore, cytodex, cytoline, and cultispher; conventionally employed for cultivation of mammalian cell lines), BioSep beads (powdered activated carbon), and membranes (hydrophilic; nylon, polysulfone, and hydrophobic; teflon, polypropylene). Data obtained from headspace methane (CH(4)) analyses as an indicator of anaerobic carbon cycling efficiency indicated that material surface properties were important in maintenance and functioning of the anaerobic consortia. Cytoline yielded significantly higher CH(4) than other matrices as early as in the first week of incubation. 16S rRNA gene sequence analysis from crushed cytoline matrix showed the presence of Syntrophomonas spp. (butyrate oxidizing syntrophs) and Syntrophobacter spp. (propionate oxidizing syntrophs), with Methanosaeta spp. (acetate utilizing methanogen), and Methanospirillum spp. (hydrogen utilizing methanogen) cells. It is likely that the more hydrophobic surfaces provided a suitable surface for adherence of cells of syntrophic-methanogenic consortia. Cytoline also appeared to protect entrapped consortia from air, resulting in rapid methanogenesis after aerial exposure. Our study suggests that support matrices can be used in anaerobic digestors, pre-seeded with immobilized or entrapped consortia on support matrices, and may be of value as inoculant-adsorbents to rapidly initiate or recover proper system functioning following perturbation.

Stability of cardamom (Elettaria cardamomum) essential oil in microcapsules made of whey protein isolate, guar gum, and carrageenan.

PubMed

Mehyar, Ghadeer F; Al-Ismail, Khalid M; Al-Isamil, Khalid M; Al-Ghizzawi, Hana'a M; Holley, Richard A

2014-10-01

The effects of microencapsulating cardamom essential oil (CEO) in whey protein isolate (WPI) alone and combined with guar gum (GG) and carrageen (CG) on microencapsulation efficiency, oil chemical stability, and microcapsule structure were investigated. Freeze-dried microcapsules were prepared from emulsions containing (w/w): 15% and 30% WPI; 0.1% GG, and 0.2% CG as wall materials with CEO (at 10% of polymer concentration) as core material, and physical properties and chemical stability were compared. Bulk density of microcapsules was highest in WPI without GG or CG and in 30% WPI + GG microcapsules, and was more affected by moisture content (r = -0.6) than by mean particle diameter (d43 ; r = -0.2) and span (r = 0.1). Microcapsules containing only WPI had the highest entrapped oil (7.5%) and microencapsulation efficiency (98.5%). The concentrations of 1,8-cineole and d-limonene were used as indicators for microcapsule chemical stability since they were the main components of CEO. Microcapsules retained higher (P ≤ 0.05) concentrations of both components than non-microencapsulated CEO during 16 wk storage at 20 ºC, but higher loss of both components was noted at 35 ºC. Microencapsulated d-limonene was reduced faster than 1,8-cineole regardless of temperature. The 30% WPI and 30% WPI + GG microcapsules retained CEO best throughout storage at both storage temperatures. Scanning electron micrographs revealed that WPI microcapsules had smooth surfaces, were relatively homogenous and regular in shape, whereas GG and CG addition increased visual surface porosity and reduced shape regularity. It was concluded that the best formulation for encapsulating CEO was 30% WPI. Encapsulating cardamom essential oil in whey protein isolate alone or combined with guar gum produced dried powders that effectively retained and chemically stabilized CEO, and therefore enhanced its handling and storability. © 2014 Institute of Food Technologists®

Preparation, characterization and relative bioavailability of oral elemene o/w microemulsion.

PubMed

Zeng, Zhaowu; Zhou, Guanglin; Wang, Xiaoli; Huang, Eric Zhijian; Zhan, Xiaori; Liu, Jun; Wang, Shuling; Wang, Anming; Li, Haifeng; Pei, Xiaolin; Xie, Tian

2010-09-07

The objective was to develop an elemene oil/water (o/w) microemulsion and evaluate its characteristics and oral relative bioavailability in rats. Elemene was used as the oil phase and drug, polysorbate 80 as a surfactant along with ethanol, propylene glycol, and glycerol as the cosurfactants. The microemulsion was prepared by mixing method, or ultrasonication method in an ultrasonic bath. Its three-dimensional response surface diagram was drawn by Mathcad software. The microemulsion was characterized by visual observation, cross-polarized microscopy, size, zeta potential, acidity, viscosity, and surface tension measurement. The drug content and entrapment efficiency were determined by ultra fast liquid chromatography (UFLC) and liquid surface method. Blood was drawn from rats at different time points after oral administration of an elemene microemulsion or a commercial elemene emulsion for measurement of the drug in plasma by UFLC to establish the pharmacokinetic parameters and relative bioavailability. The elemene microemulsion as a clarified and isotropic system containing 1% elemene (w/v), 5% ethanol (v/v), 15% propylene glycol (v/v), 15% glycerol (v/v), and 5% polysorbate 80 (w/v), was characterized as (57.7 ± 2.8) nm in size, 0.485 ± 0.032 in polydispersity index, (3.2 ± 0.4) mv in zeta potential, (5.19 ± 0.08) in pH, 6 mpa·s in viscosity, (31.8 ± 0.3) mN·m(-1) in surface tension, (8.273 ± 0.018) mg·mL(-1) in content of β-elemene, and (99.81 ± 0.24)% in average entrapment efficiency. The area under the concentration-time curves from 0 h to 24 h (AUC(0→24h)) of the elemene microemulsion and commercial elemene emulsion were integrated to be 3.092 mg·h·L(-1) and 1.896 mg·h·L(-1) respectively, yielding a relative bioavailability of 163.1%. The present study demonstrates the elemene microemulsion as a new formulation with ease of preparation, high entrapment efficiency, excellent clarity, good stability, and improved bioavailability.

Preparation, characterization and relative bioavailability of oral elemene o/w microemulsion

PubMed Central

Zeng, Zhaowu; Zhou, Guanglin; Wang, Xiaoli; Huang, Eric Zhijian; Zhan, Xiaori; Liu, Jun; Wang, Shuling; Wang, Anming; Li, Haifeng; Pei, Xiaolin; Xie, Tian

2010-01-01

The objective was to develop an elemene oil/water (o/w) microemulsion and evaluate its characteristics and oral relative bioavailability in rats. Elemene was used as the oil phase and drug, polysorbate 80 as a surfactant along with ethanol, propylene glycol, and glycerol as the cosurfactants. The microemulsion was prepared by mixing method, or ultrasonication method in an ultrasonic bath. Its three-dimensional response surface diagram was drawn by Mathcad software. The microemulsion was characterized by visual observation, cross-polarized microscopy, size, zeta potential, acidity, viscosity, and surface tension measurement. The drug content and entrapment efficiency were determined by ultra fast liquid chromatography (UFLC) and liquid surface method. Blood was drawn from rats at different time points after oral administration of an elemene microemulsion or a commercial elemene emulsion for measurement of the drug in plasma by UFLC to establish the pharmacokinetic parameters and relative bioavailability. The elemene microemulsion as a clarified and isotropic system containing 1% elemene (w/v), 5% ethanol (v/v), 15% propylene glycol (v/v), 15% glycerol (v/v), and 5% polysorbate 80 (w/v), was characterized as (57.7 ± 2.8) nm in size, 0.485 ± 0.032 in polydispersity index, (3.2 ± 0.4) mv in zeta potential, (5.19 ± 0.08) in pH, 6 mpa·s in viscosity, (31.8 ± 0.3) mN·m−1 in surface tension, (8.273 ± 0.018) mg·mL−1 in content of β-elemene, and (99.81 ± 0.24)% in average entrapment efficiency. The area under the concentration-time curves from 0 h to 24 h (AUC0→24h) of the elemene microemulsion and commercial elemene emulsion were integrated to be 3.092 mg·h·L−1 and 1.896 mg·h·L−1 respectively, yielding a relative bioavailability of 163.1%. The present study demonstrates the elemene microemulsion as a new formulation with ease of preparation, high entrapment efficiency, excellent clarity, good stability, and improved bioavailability. PMID:20856831

Preparation and evaluation of cyclosporin A-containing proliposomes: a comparison of the supercritical antisolvent process with the conventional film method

PubMed Central

Karn, Pankaj Ranjan; Jin, Su-Eon; Lee, Benjamin Joon; Sun, Bo Kyung; Kim, Min-Soo; Sung, Jong-Hyuk; Hwang, Sung-Joo

2014-01-01

Objectives The objectives of this study were to prepare cyclosporin A (CsA)-containing proliposomes using the supercritical antisolvent (SAS) process and the conventional thin film method for the comparative study of proliposomal formulations and to evaluate the physicochemical properties of these proliposomes. Methods CsA-containing proliposomes were prepared by the SAS process and the conventional film method, composed of natural and synthetic phospholipids. We investigated particle size, polydispersity index, and zeta potential of CsA-containing proliposomes. In addition, both production yield and entrapment efficiency of CsA in different proliposomes were analyzed. Physicochemical properties of CsA-containing proliposomes were also evaluated, using differential scanning calorimetry and X-ray diffraction. The morphology and size of CsA-containing proliposomes were confirmed, using scanning electron microscopy. We checked the in vitro release of CsA from CsA-containing proliposomes prepared by different preparation methods, comparing them with Restasis® as a positive control and the stability of SAS-mediated proliposomes was also studied. Results CsA-containing proliposomes formed by the SAS process had a relatively smaller particle size, with a narrow size distribution and spherical particles compared with those of conventionally prepared proliposomes. The yield and entrapment efficiency of CsA in all proliposomes varied from 85% to 92% and from 86% to 89%, respectively. Differential scanning calorimetry and X-ray diffraction studies revealed that the anhydrous lactose powder used in this formulation retained its crystalline form and that CsA was present in an amorphous form. Proliposome powders were rapidly converted to liposomes on contact with water. The in vitro release study of proliposomal formulations demonstrated a similar pattern to Restasis®. The SAS-mediated CsA-containing proliposomes were stable on storage, with no significant changes in particle size, polydispersity index, and entrapment efficiency. Conclusion These results show promising features of CsA-containing proliposomal formulations, using the SAS process for the large-scale industrial application. PMID:25395846

Entrapment of hepatocyte spheroids in a hollow fiber bioreactor as a potential bioartificial liver.

PubMed

Wu, F J; Peshwa, M V; Cerra, F B; Hu, W S

1995-01-01

A bioartificial liver (BAL) employing xenogeneic hepatocytes has been developed as a potential interim support for patients in hepatic failure. For application in human therapy, the BAL requires a substantial increase in liver-specific functions. Cultivation of hepatocytes as spheroids leads to enhanced liver specific functions. We explored the possibility of entrapping spheroids into the BAL in order to improve device performance. Rat hepatocyte spheroids were entrapped in collagen gel within the lumen fibers of the BAL. The morphology and ultrastructure of collagen-entrapped spheroids resembled those of suspended spheroids formed on petri dishes. Albumin synthesis and P-450 enzyme activity were measured as markers of liver specific functions of spheroids entrapped in the BAL. At least a 4-fold improvement in these functions was observed compared to BAL devices entrapped with dispersed hepatocytes in collagen gels.

The prospective role of defeat and entrapment in depression and anxiety: a 12-month longitudinal study.

PubMed

Griffiths, Alys Wyn; Wood, Alex M; Maltby, John; Taylor, Peter J; Tai, Sara

2014-04-30

The concepts of "defeat" (representing failed social struggle) and "entrapment" (representing an inability to escape from a situation) have emerged from the animal literature, providing insight into the health consequences of low social rank. Evolutionary models suggest that these constructs co-occur and can lead to the development of mental disorders, although there is limited empirical evidence supporting these predictions. Participants (N=172) were recruited from economically deprived areas in North England. Over half of participants (58%) met clinical cut-offs for depression and anxiety, therefore we conducted analyses to establish whether participant outcomes were dependent on baseline defeat and entrapment levels. Participants completed measures of defeat, entrapment, depression and anxiety at two time-points twelve months apart. Factor analysis demonstrated that defeat and entrapment were best defined as one factor, suggesting that the experiences co-occurred. Regression analyses demonstrated that changes in depression and anxiety between T1 and T2 were predicted from baseline levels of defeat and entrapment; however, changes in defeat and entrapment were also predicted from baseline depression and anxiety. There are implications for targeting perceptions of defeat and entrapment within psychological interventions for people experiencing anxiety and depression and screening individuals to identify those at risk of developing psychopathology. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Pharmacokinetics and analgesic effect of ketorolac floating delivery system.

PubMed

Radwan, Mahasen A; Abou El Ela, Amal El Sayeh F; Hassan, Maha A; El-Maraghy, Dalia A

2015-05-01

The efficacy of ketorolac tromethamine (KT) floating alginate beads as a drug delivery system for better control of KT release was investigated. The formulation with the highest drug loading, entrapment efficiency, swelling, buoyancy, and in vitro release would be selected for further in vivo analgesic effect in the mice and pharmacokinetics study in rats compared to the tablet dosage form. KT floating alginate beads were prepared by extrusion congealing technique. KT in plasma samples was analyzed using a UPLC MS/MS assay. The percentage yield, drug loading and encapsulation efficiency were increased proportionally with the hydroxypropylmethyl cellulose (HPMC) polymer amount in the KT floating beads. A reverse relationship was observed between HPMC amount in the beads and the KT in vitro release rate. F3-floating beads were selected, due to its better in vitro results (continued floating for >8 h) than others. A longer analgesic effect was observed for F3 in fed mice as compared to the tablets. After F3 administration to rats, the Cmax (2.2 ± 0.3 µg/ml) was achieved at ∼2 h and the decline in KT concentration was slower. F3 showed a significant increase in the AUC (1.89 fold) in rats as compared to the tablets. KT was successfully formulated as floating beads with prolonged in vitro release extended to a better in vivo characteristic with higher bioavailability in rats. KT in floating beads shows a superior analgesic effect over tablets, especially in fed mice.

NERVE ENTRAPMENT IN THE HIP REGION: CURRENT CONCEPTS REVIEW.

PubMed

Martin, RobRoy; Martin, Hal David; Kivlan, Benjamin R

2017-12-01

The purpose of this clinical commentary is to review the anatomy, etiology, evaluation, and treatment techniques for nerve entrapments of the hip region. Nerve entrapment can occur around musculotendinous, osseous, and ligamentous structures because of the potential for increased strain and compression on the peripheral nerve at those sites. The sequela of localized trauma may also result in nerve entrapment if normal nerve gliding is prevented. Nerve entrapment can be difficult to diagnose because patient complaints may be similar to and coexist with other musculoskeletal conditions in the hip and pelvic region. However, a detailed description of symptom location and findings from a comprehensive physical examination can be used to determine if an entrapment has occurred, and if so where. The sciatic, pudendal, obturator, femoral, and lateral femoral cutaneous are nerves that can be entrapped and serve a source of hip pain in the athletic population. Manual therapy, stretching and strengthening exercises, aerobic conditioning, and cognitive-behavioral education are potential interventions. When conservative treatment is ineffective at relieving symptoms surgical treatment with neurolysis or neurectomy may be considered. 5.

NERVE ENTRAPMENT IN THE HIP REGION: CURRENT CONCEPTS REVIEW

PubMed Central

Martin, Hal David; Kivlan, Benjamin R.

2017-01-01

The purpose of this clinical commentary is to review the anatomy, etiology, evaluation, and treatment techniques for nerve entrapments of the hip region. Nerve entrapment can occur around musculotendinous, osseous, and ligamentous structures because of the potential for increased strain and compression on the peripheral nerve at those sites. The sequela of localized trauma may also result in nerve entrapment if normal nerve gliding is prevented. Nerve entrapment can be difficult to diagnose because patient complaints may be similar to and coexist with other musculoskeletal conditions in the hip and pelvic region. However, a detailed description of symptom location and findings from a comprehensive physical examination can be used to determine if an entrapment has occurred, and if so where. The sciatic, pudendal, obturator, femoral, and lateral femoral cutaneous are nerves that can be entrapped and serve a source of hip pain in the athletic population. Manual therapy, stretching and strengthening exercises, aerobic conditioning, and cognitive-behavioral education are potential interventions. When conservative treatment is ineffective at relieving symptoms surgical treatment with neurolysis or neurectomy may be considered. Level of Evidence 5 PMID:29234567

Occipital Neuralgia Diagnosis and Treatment: The Role of Ultrasound.

PubMed

Narouze, Samer

2016-04-01

Occipital neuralgia is a form of neuropathic type of pain in the distribution of the greater, lesser, or third occipital nerves. Patients with intractable occipital neuralgia do not respond well to conservative treatment modalities. This group of patients represents a significant therapeutic challenge and may require interventional or invasive therapeutic approaches. Occipital neuralgia frequently occurs as a result of nerve entrapment or irritation by a tight muscle or vascular structure, or nerve trauma during whiplash injury. Although the entrapment theory is most commonly accepted, it lacks strong clinical evidence to support it. Accordingly, the available interventional approaches have been targeting the accessible part of the occipital nerve rather than the entrapped part. Bedside sonography is an excellent imaging modality for soft tissue structures. Ultrasound not only allows distinguishing normal from abnormal entrapped occipital nerves, it can identify the level and the cause of entrapment as well. Ultrasound guidance allows precise occipital nerve blocks and interventions at the level of the "specific" entrapment location rather than into the site of "presumed" entrapment. © 2016 American Headache Society.

Novel durable bio-photocatalyst purifiers, a non-heterogeneous mechanism: accelerated entrapped dye degradation into structural polysiloxane-shield nano-reactors.

PubMed

Dastjerdi, Roya; Montazer, Majid; Shahsavan, Shadi; Böttcher, Horst; Moghadam, M B; Sarsour, Jamal

2013-01-01

This research has designed innovative Ag/TiO(2) polysiloxane-shield nano-reactors on the PET fabric to develop novel durable bio-photocatalyst purifiers. To create these very fine nano-reactors, oppositely surface charged multiple size nanoparticles have been applied accompanied with a crosslinkable amino-functionalized polysiloxane (XPs) emulsion. Investigation of photocatalytic dye decolorization efficiency revealed a non-heterogeneous mechanism including an accelerated degradation of entrapped dye molecules into the structural polysiloxane-shield nano-reactors. In fact, dye molecules can be adsorbed by both Ag and XPs due to their electrostatic interactions and/or even via forming a complex with them especially with silver NPs. The absorbed dye and active oxygen species generated by TiO(2) were entrapped by polysiloxane shelter and the presence of silver nanoparticles further attract the negative oxygen species closer to the adsorbed dye molecules. In this way, the dye molecules are in close contact with concentrated active oxygen species into the created nano-reactors. This provides an accelerated degradation of dye molecules. This non-heterogeneous mechanism has been detected on the sample containing all of the three components. Increasing the concentration of Ag and XPs accelerated the second step beginning with an enhanced rate. Further, the treated samples also showed an excellent antibacterial activity. Copyright © 2012 Elsevier B.V. All rights reserved.

Versatile polyion complex micelles for peptide and siRNA vectorization to engineer tolerogenic dendritic cells.

PubMed

Mebarek, Naila; Vicente, Rita; Aubert-Pouëssel, Anne; Quentin, Julie; Mausset-Bonnefont, Anne-Laure; Devoisselle, Jean-Marie; Jorgensen, Christian; Bégu, Sylvie; Louis-Plence, Pascale

2015-05-01

Dendritic cells (DCs) are professional antigen-presenting cells that play a critical role in maintaining the balance between immunity and tolerance and, as such are a promising immunotherapy tool to induce immunity or to restore tolerance. The main challenge to harness the tolerogenic properties of DCs is to preserve their immature phenotype. We recently developed polyion complex micelles, formulated with double hydrophilic block copolymers of poly(methacrylic acid) and poly(ethylene oxide) blocks and able to entrap therapeutic molecules, which did not induce DC maturation. In the current study, the intrinsic destabilizing membrane properties of the polymers were used to optimize endosomal escape property of the micelles in order to propose various strategies to restore tolerance. On the first hand, we showed that high molecular weight (Mw) copolymer-based micelles were efficient to favor the release of the micelle-entrapped peptide into the endosomes, and thus to improve peptide presentation by immature (i) DCs. On the second hand, we put in evidence that low Mw copolymer-based micelles were able to favor the cytosolic release of micelle-entrapped small interfering RNAs, dampening the DCs immunogenicity. Therefore, we demonstrate the versatile use of polyionic complex micelles to preserve tolerogenic properties of DCs. Altogether, our results underscored the potential of such micelle-loaded iDCs as a therapeutic tool to restore tolerance in autoimmune diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Lung Entrapment between the Pectus Bar and Chest Wall after Pectus Surgery: An Incidental Finding during Video-Assisted Thoracoscopic Surgery

PubMed Central

Kim, Kyung Soo; Hyun, Kwanyong; Kim, Do Yeon; Choi, Kukbin; Choi, Hahng Joon; Park, Hyung Joo

2015-01-01

We report a case of an entrapped lung after the pectus bar repair of a pectus deformity. The entrapped lung was found incidentally during video-assisted thoracoscopic surgery (VATS) for pneumothorax. Based on VATS exploration, multiple bullae seemed to be the cause of the pneumothorax, but the entrapped lung was suspected to have been a cause of the air leakage. PMID:26509135

Nerve Entrapment Syndromes at the Wrist and Elbow by Sonography.

PubMed

Klauser, Andrea S; Buzzegoli, Tommaso; Taljanovic, Mihra S; Strobl, Sylvia; Rauch, Stefan; Teh, James; Wanschitz, Julia; Löscher, Wolfgang; Martinoli, Carlo

2018-07-01

Nerve entrapment syndromes of the upper extremity are associated with structural abnormalities or by an intrinsic abnormality of the nerve. Nerve entrapment syndromes generally have a typical clinical presentation, and findings on physical examination and in conjunction with electrodiagnostic studies imaging is used to evaluate the cause, severity, and etiology of the entrapment. With the development of high-frequency linear array transducers (12-24 MHz), ultrasound (US) is incomparable in terms of spatial resolution to depict morphological aspects and changes in nerves. US can identify the abnormalities causing entrapment, such as fibrous bands, ganglia, anomalous muscles, and osseous deformities, with the advantage of dynamic assessment under active and passive examination. US is a unique diagnostic modality that allows superb visualization of both large and small peripheral terminal nerve branches of the upper extremity and enables the correct diagnosis of various nerve entrapment syndromes. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Solid lipid nanoparticles for nose to brain delivery of haloperidol: in vitro drug release and pharmacokinetics evaluation

PubMed Central

Yasir, Mohd; Sara, Udai Vir Singh

2014-01-01

In the present study, haloperidol (HP)-loaded solid lipid nanoparticles (SLNs) were prepared to enhance the uptake of HP to brain via intranasal (i.n.) delivery. SLNs were prepared by a modified emulsification–diffusion technique and evaluated for particle size, zeta potential, drug entrapment efficiency, in vitro drug release, and stability. All parameters were found to be in an acceptable range. In vitro drug release was found to be 94.16±4.78% after 24 h and was fitted to the Higuchi model with a very high correlation coefficient (R2=0.9941). Pharmacokinetics studies were performed on albino Wistar rats and the concentration of HP in brain and blood was measured by high performance liquid chromatography. The brain/blood ratio at 0.5 h for HP-SLNs i.n., HP sol. i.n. and HP sol. i.v. was 1.61, 0.17 and 0.031, respectively, indicating direct nose-to-brain transport, bypassing the blood–brain barrier. The maximum concentration (Cmax) in brain achieved from i.n. administration of HP-SLNs (329.17±20.89 ng/mL, Tmax 2 h) was significantly higher than that achieved after i.v. (76.95±7.62 ng/mL, Tmax 1 h), and i.n. (90.13±6.28 ng/mL, Tmax 2 h) administration of HP sol. The highest drug-targeting efficiency (2362.43%) and direct transport percentage (95.77%) was found with HP-SLNs as compared to the other formulations. Higher DTE (%) and DTP (%) suggest that HP-SLNs have better brain targeting efficiency as compared to other formulations. PMID:26579417

Development of β-cyclodextrin-based hydrogel microparticles for solubility enhancement of rosuvastatin: an in vitro and in vivo evaluation

PubMed Central

Sarfraz, Rai Muhammad; Ahmad, Mahmood; Mahmood, Asif; Akram, Muhammad Rouf; Abrar, Asad

2017-01-01

The aim of this study was to enhance the solubility of rosuvastatin (RST) calcium by developing β-cyclodextrin-g-poly(2-acrylamido-2-methylpropane sulfonic acid [AMPS]) hydrogel microparticles through aqueous free-radical polymerization technique. Prepared hydrogel microparticles were characterized for percent entrapment efficiency, solubility studies, Fourier transform infrared spectroscopy, differential scanning calorimetry, thermal gravimetric analysis, powder X-ray diffraction, scanning electron microscopy, zeta size and potential, swelling and release studies. Formulations (HS1–HS9) have shown entrapment efficiency between 83.50%±0.30% and 88.50%±0.25%, and optimum release was offered by formulation HS7 at both pH levels, ie, 1.2 (89%) and 7.4 (92%). The majority of microparticles had a particle size of less than 500 µm and zeta potential of −37 mV. Similarly, optimum solubility, ie, 10.66-fold, was determined at pH 6.8 as compared to pure RST calcium, ie, 7.30-fold. In vivo studies on fabricated hydrogel microparticulate system in comparison to pure drug were carried out, and better results regarding pharmacokinetic parameters were seen in the case of hydrogel microparticles. A potential approach for solubility enhancement of RST calcium and other hydrophobic moieties was successfully developed. PMID:29123380

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.

Inhalational System for Etoposide Liposomes: Formulation Development and In Vitro Deposition

PubMed Central

Parmar, J. J.; Singh, D. J.; Lohade, A. A.; Hegde, Darshana D.; Soni, P. S.; Samad, A.; Menon, Mala D.

2011-01-01

Etoposide is a semisynthetic compound, widely used in treatment of non small cell lung cancer. However, frequent dosing and adverse effects remain a major concern in the use of etoposide. Liposomal systems for pulmonary drug delivery have been particularly attractive because of their compatibility with lung surfactant components. In the present investigation, pulmonary liposomal delivery system of etoposide was prepared by film hydration method. Various parameters were optimized with respect to entrapment efficiency as well as particle size of etoposide liposomes. For better shelf life of etoposide liposomes, freeze drying using trehalose as cryoprotectant was carried out. The liposomes were characterized for entrapment efficiency, particle size, surface topography, and in vitro drug release was carried out in simulated lung fluid at 37° at pH 7.4. The respirable or fine particle fraction was determined by using twin stage impinger. The stability study of freeze dried as well as aqueous liposomal systems was carried out at 2-8° and at ambient temperature (28±4°). The freeze dried liposomes showed better fine particle fraction and drug content over the period of six months at ambient as well as at 2-8° storage condition compared to aqueous dispersion of liposomes. PMID:23112400

Development and evaluation of inhalational liposomal system of budesonide for better management of asthma.

PubMed

Parmar, J J; Singh, D J; Hegde, Darshana D; Lohade, A A; Soni, P S; Samad, A; Menon, Mala D

2010-07-01

Budesonide is a corticosteroid used by inhalation in the prophylactic management of asthma. However, frequent dosing and adverse effects (local and systemic) remain a major concern in the use of budesonide. Liposomal systems for sustained pulmonary drug delivery have been particularly attractive because of their compatibility with lung surfactant components. In the present investigation, pulmonary liposomal delivery system of budesonide was prepared by film hydration method and evaluated for sustained release. Various parameters were optimized with respect to entrapment efficiency as well as particle size of budesonide liposomes. For better shelf life of budesonide liposomes, they were freeze dried using trehalose as cryoprotectant. The liposomes were characterized for entrapment efficiency, particle size, and surface topography; in vitro drug release was evaluated out in simulated lung fluid at 37° at pH 7.4. The respirable or fine particle fraction was determined by using twin stage impinger. The stability study of freeze dried as well as aqueous liposomal systems was carried out at 2-8° and at ambient temperature (28±40). The freeze dried liposomes showed better fine particle fraction and drug content over the period of six months at ambient as well as at 2-8° storage condition compared to aqueous dispersion of liposomes.

Development and Evaluation of Inhalational Liposomal System of Budesonide for Better Management of Asthma

PubMed Central

Parmar, J. J.; Singh, D. J.; Hegde, Darshana D.; Lohade, A. A.; Soni, P. S.; Samad, A.; Menon, Mala D.

2010-01-01

Budesonide is a corticosteroid used by inhalation in the prophylactic management of asthma. However, frequent dosing and adverse effects (local and systemic) remain a major concern in the use of budesonide. Liposomal systems for sustained pulmonary drug delivery have been particularly attractive because of their compatibility with lung surfactant components. In the present investigation, pulmonary liposomal delivery system of budesonide was prepared by film hydration method and evaluated for sustained release. Various parameters were optimized with respect to entrapment efficiency as well as particle size of budesonide liposomes. For better shelf life of budesonide liposomes, they were freeze dried using trehalose as cryoprotectant. The liposomes were characterized for entrapment efficiency, particle size, and surface topography; in vitro drug release was evaluated out in simulated lung fluid at 37° at pH 7.4. The respirable or fine particle fraction was determined by using twin stage impinger. The stability study of freeze dried as well as aqueous liposomal systems was carried out at 2-8° and at ambient temperature (28±40). The freeze dried liposomes showed better fine particle fraction and drug content over the period of six months at ambient as well as at 2-8° storage condition compared to aqueous dispersion of liposomes. PMID:21218054

Systematic Approach for the Formulation and Optimization of Solid Lipid Nanoparticles of Efavirenz by High Pressure Homogenization Using Design of Experiments for Brain Targeting and Enhanced Bioavailability

PubMed Central

Gupta, Shweta; Kesarla, Rajesh; Chotai, Narendra; Misra, Ambikanandan

2017-01-01

The nonnucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections, are reported to have low bioavailability pertaining to high first-pass metabolism, high protein binding, and enzymatic metabolism. They also show low permeability across blood brain barrier. The CNS is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective of providing increased permeability and protection of drug due to biocompatible lipidic content and nanoscale size and thus developing formulation having potential for enhanced bioavailability and brain targeting. Solid lipid nanoparticles were prepared by high pressure homogenization technique using a systematic approach of design of experiments (DoE) and evaluated for particle size, polydispersity index, zeta potential, and entrapment efficiency. Particles of average size 108.5 nm having PDI of 0.172 with 64.9% entrapment efficiency were produced. Zeta potential was found to be −21.2 mV and the formulation was found stable. The in-vivo pharmacokinetic studies revealed increased concentration of the drug in brain, as desired, when administered through intranasal route indicating its potential for an attempt towards complete eradication of HIV and cure of HIV-infected patients. PMID:28243600

Recombinant Spider Silk Functionalized with a Motif from Fibronectin Mediates Cell Adhesion and Growth on Polymeric Substrates by Entrapping Cells During Self-Assembly.

PubMed

Tasiopoulos, Christos Panagiotis; Widhe, Mona; Hedhammar, My

2018-05-02

In vitro endothelialization of synthetic grafts or engineered vascular constructs is considered a promising alternative to overcome shortcomings in the availability of autologous vessels and in-graft complications with synthetics. A number of cell-seeding techniques have been implemented to render vascular grafts accessible for cells to attach, proliferate, and spread over the surface area. Nonetheless, seeding efficiency and the time needed for cells to adhere varies dramatically. Herein, we investigated a novel cell-seeding approach (denoted co-seeding) that enables cells to bind to a motif from fibronectin included in a recombinant spider silk protein. Entrapment of cells occurs at the same time as the silk assembles into a nanofibrillar coating on various substrates. Cell adhesion analysis showed that the technique can markedly improve cell-seeding efficiency to nonfunctionalized polystyrene surfaces, as well as establish cell attachment and growth of human dermal microvascular endothelial cells on bare polyethylene terephthalate and polytetrafluoroethylene (PTFE) substrates. Scanning electron microscopy images revealed a uniform endothelial cell layer and cell-substratum compliance with the functionalized silk protein to PTFE surfaces. The co-seeding technique holds a great promise as a method to reliably and quickly cellularize engineered vascular constructs as well as to in vitro endothelialize commercially available cardiovascular grafts.

Preparation and evaluation of miconazole nitrate-loaded solid lipid nanoparticles for topical delivery.

PubMed

Bhalekar, Mangesh R; Pokharkar, Varsha; Madgulkar, Ashwini; Patil, Nilam; Patil, Nilkanth

2009-01-01

The purpose of this study was to prepare miconazole nitrate (MN) loaded solid lipid nanoparticles (MN-SLN) effective for topical delivery of miconazole nitrate. Compritol 888 ATO as lipid, propylene glycol (PG) to increase drug solubility in lipid, tween 80, and glyceryl monostearate were used as the surfactants to stabilize SLN dispersion in the SLN preparation using hot homogenization method. SLN dispersions exhibited average size between 244 and 766 nm. All the dispersions had high entrapment efficiency ranging from 80% to 100%. The MN-SLN dispersion which showed good stability for a period of 1 month was selected. This MN-SLN was characterized for particle size, entrapment efficiency, and X-ray diffraction. The penetration of miconazole nitrate from the gel formulated using selected MN-SLN dispersion as into cadaver skins was evaluated ex-vivo using franz diffusion cell. The results of differential scanning calorimetry (DSC) showed that MN was dispersed in SLN in an amorphous state. The MN-SLN formulations could significantly increase the accumulative uptake of MN in skin over the marketed gel and showed a significantly enhanced skin targeting effect. These results indicate that the studied MN-SLN formulation with skin targeting may be a promising carrier for topical delivery of miconazole nitrate.

The study on the entrapment efficiency and in vitro release of puerarin submicron emulsion.

PubMed

Yue, Peng-Fei; Lu, Xiu-Yun; Zhang, Zeng-Zhu; Yuan, Hai-Long; Zhu, Wei-Feng; Zheng, Qin; Yang, Ming

2009-01-01

The entrapment efficiency (EE) and release in vitro are very important physicochemical characteristics of puerarin submicron emulsion (SME). In this paper, the performance of ultrafiltration (UF), ultracentrifugation (UC), and microdialysis (MD) for determining the EE of SME were evaluated, respectively. The release study in vitro of puerarin from SME was studied by using MD and pressure UF technology. The EE of SME was 86.5%, 72.8%, and 55.8% as determined by MD, UF, and UC, respectively. MD was not suitable for EE measurements of puerarin submicron oil droplet, which could only determine the total EE of submicron oil droplet and liposomes micelles, but it could be applied to determine the amount of free drug in SMEs. Although UC was the fastest and simplest to use, its results were the least reliable. UF was still the relatively accurate method for EE determination of puerarin SME. The release of puerarin SME could be evaluated by using MD and pressure UF, but MD seemed to be more suitable for the release study of puerarin emulsion. The drug release from puerarin SME at three drug concentrations was initially rapid, but reached a plateau value within 30 min. Drug release of puerarin from the SME occurred via burst release.

HPLC method for determination of SN-38 content and SN-38 entrapment efficiency in a novel liposome-based formulation, LE-SN38.

PubMed

Xuan, Tong; Zhang, J Allen; Ahmad, Imran

2006-05-03

A simple HPLC method was developed for quantification of SN-38, 7-ethyl-10-hydroxycamptothecin, in a novel liposome-based formulation (LE-SN38). The chromatographic separation was achieved on an Agilent Zorbax SB-C18 (4.6 mmx250 mm, 5 microm) analytical column using a mobile phase consisting of a mixture of NaH2PO4 (pH 3.1, 25 mM) and acetonitrile (50:50, v/v). SN-38 was detected at UV wavelength of 265 nm and quantitatively determined using an external calibration method. The limit of detection (LOD) and limit of quantitation (LOQ) were found to be 0.05 and 0.25 microg/mL, respectively. The individual spike recovery of SN-38 ranged from 100 to 101%. The percent of relative standard deviation (%R.S.D.) of intra-day and inter-day analyses were less than 1.6%. The method validation results confirmed that the method is specific, linear, accurate, precise, robust and sensitive for its intended use. The current method was successfully applied to the determination of SN-38 content and drug entrapment efficiency in liposome-based formulation, LE-SN38 during early stage formulation development.

Fracturing fluid cleanup by controlled release of enzymes from polyelectrolyte complex nanoparticles

NASA Astrophysics Data System (ADS)

Barati Ghahfarokhi, Reza

Guar-based polymer gels are used in the oil and gas industry to viscosify fluids used in hydraulic fracturing of production wells, in order to reduce leak-off of fluids and pressure, and improve the transport of proppants. After fracturing, the gel and associated filter cake must be degraded to very low viscosities using breakers to recover the hydraulic conductivity of the well. Enzymes are widely used to achieve this but injecting high concentrations of enzyme may result in premature degradation, or failure to gel; denaturation of enzymes at alkaline pH and high temperature conditions can also limit their applicability. In this study, application of polyelectrolyte nanoparticles for entrapping, carrying, releasing and protecting enzymes for fracturing fluids was examined. The objective of this research is to develop nano-sized carriers capable of carrying the enzymes to the filter cake, delaying the release of enzyme and protecting the enzyme against pH and temperature conditions inhospitable to native enzyme. Polyethylenimine-dextran sulfate (PEI-DS) polyelectrolyte complexes (PECs) were used to entrap two enzymes commonly used in the oil industry in order to obtain delayed release and to protect the enzyme from conditions inhospitable to native enzyme. Stability and reproducibility of PEC nanoparticles was assured over time. An activity measurement method was used to measure the entrapment efficiency of enzyme using PEC nanoparticles. This method was confirmed using a concentration measurement method (SDS-PAGE). Entrapment efficiencies of pectinase and a commercial high-temperature enzyme mixture in polyelectrolyte complex nanoparticles were maximized. Degradation, as revealed by reduction in viscoelastic moduli of borate-crosslinked hydroxypropyl guar (HPG) gel by commercial enzyme loaded in polyelectrolyte nanoparticles, was delayed, compared to equivalent systems where the enzyme mixture was not entrapped. This indicates that PEC nanoparticles delay the activity of enzymes by entrapping them. It was also observed that control PEC nanoparticles decreased both viscoelastic moduli, but with a slower rate compared to the PEC nanoparticles loaded with enzyme. Preparation shear and applied shear showed no significant effect on activity of enzyme-loaded PEC nanoparticles mixed with HPG solutions. However, fast addition of chemicals during the preparations showed smaller particle size compared to the drop-wise method. PEC nanoparticles (PECNPs) also protected both enzymes from denaturation at elevated temperature and pH. Following preparation, enzyme-loaded PEC nanoparticles were mixed with borate crosslinked HPG and the mixture was injected through a shear loop. Pectinase-loaded nanoparticles mixed with gelled HPG showed no sensitivity to shear applied along the shear loop at 25 °C. However, EL2X-loaded PEC nanoparticles showed sensitivity to shear applied along the shear loop at 40 °C. Filter cake was formed and degraded in a fluid loss cell for borate crosslinked HPG solutions mixed with either enzymes or enzyme-loaded PEC nanoparticles. Cleanup slopes of filter cake degraded using enzyme-loaded PEC nanoparticles and systems with enzymes mixed with HPG gel were significantly higher than for the filter cake formed with HPG gel mixed with no enzyme. In a different application, enzyme-loaded PEC nanoparticles showed significantly slower reduction in viscosity of HPG solution over time compared to the HPG systems mixed with enzyme. Increasing the viscosity of low concentration HPG, used as slick-water, decreases the proppant settling velocity. This is of specific interest in fracturing fluids used for unconventional reservoirs.

Attachment style and suicide behaviors in high risk psychiatric inpatients following hospital discharge: The mediating role of entrapment.

PubMed

Li, Shuang; Galynker, Igor I; Briggs, Jessica; Duffy, Molly; Frechette-Hagan, Anna; Kim, Hae-Joon; Cohen, Lisa J; Yaseen, Zimri S

2017-11-01

Insecure attachment is associated with suicidal behavior. This relationship and its possible mediators have not been examined in high-risk psychiatric inpatients with respect to the critical high-risk period following hospital discharge. Attachment styles and perception of entrapment were assessed in 200 high-risk adult psychiatric inpatients hospitalized following suicidal ideation or suicide attempt. Suicidal behaviors were evaluated with the Columbia Suicide Severity Rating Scale at 1-2 months post-discharge. Associations between different attachment styles and suicidal behaviors were assessed and mediation of attachment effects by entrapment was modeled. Fearful attachment was associated with post-discharge suicidal behavior and there was a trend-level negative association for secure attachment. In addition, entrapment mediated the relationship between fearful attachment and suicidal behavior. The current study highlights the mediating role of perceptions of entrapment in the contribution of fearful attachment to suicidal behavior in high-risk patients, suggesting entrapment as potential therapeutic target to prevent suicidal behavior in these individuals. Further research is warranted to establish the mechanisms by which entrapment experiences emerge in patients with insecure attachment styles. Copyright © 2017 Elsevier B.V. All rights reserved.

A study on characteristic of different sample pretreatment methods to evaluate the entrapment efficiency of liposomes.

PubMed

Ran, Congcong; Chen, Dan; Xu, Meng; Du, Chaohui; Li, Qinglian; Jiang, Ye

2016-08-15

To examine how methods affect the evaluation of entrapment efficiency (EE) of liposomes, four different sample pretreatment methods were adopted in the experiment. The four sample pretreatment methods were size-exclusion chromatography (SEC), solid-phase extraction (SPE), centrifugation ultrafiltration (CF-UF) and hollow fiber centrifugal ultrafiltration (HF-CF-UF). Amphotericin B (AmB), which could self-associate to form aggregates in water is adopted as the model drugs in this paper. In the present work, it was found that the characterization results of four methods were quite different. The EE of liposome by SEC was about 93%, only 5-13% using C18 or HLB columns, and approximately 100% by CF-UF. The EE of HF-CF-UF reached up to nearly 99.0%. Further, this paper revealed the reasons making the difference of EE among four methods. Conventional SEC may distort the authentic of EE of liposomes with mainly employing some small liposomes or excessive water as eluent. For SPE, cholesterol on liposome surface could interact with the stationary phase making it hard to elute with water, and increase the risk of liposome leakage. While for CF-UF, concentration polarization was a main limitation hindering unentrapped drug to pass through membrane, making unentrapped drug undetectable in liposome. HF-CF-UF could truly reflect EE of liposomes with the concentration of unentrapped AmB lower than 25.0μg/mL. However, when the concentration was higher than 25.0μg/mL, AmB aggregates could be entrapped by hollow fiber. From the above analysis, this paper came to the conclusion that each method had its own feature in characterization. This study provided a reasonable guideline for choosing methods to character the EE of liposome. Copyright © 2016 Elsevier B.V. All rights reserved.

[Entrapment of herbal extracts in biodegradable microcapsules].

PubMed

Borodina, T N; Rumsh, L D; Kunizhev, S M; Sukhorukov, G B; Vorozhtsov, G N; Fel'dman, B M; Rusanova, A V; Vasil'eva, T V; Strukova, S M; Markvicheva, E A

2007-01-01

The microcapsules with entrapped herbal water-soluble extracts Plantago major and Calendula officinalis L. (HE) were prepared by LbL-adsorption of carrageenan and modificated chitosan onto CaCO3 microparticles with their subsequent dissolving after the treatment of EDTA. Entrapment of HE was performed by adsorption and co-precipitation techniques. The co-precipitation provided better entrapment of HE compared to adsorption. In vitro release kinetics in an artificial gastric juice (AGJ) was studied. The HE release was shown to accelerate gastric ulcer treatment in a rat model.

Patterns of entrapped air dissolution in a two-dimensional pilot-scale synthetic aquifer.

PubMed

McLeod, Heather C; Roy, James W; Smith, James E

2015-01-01

Past studies of entrapped air dissolution have focused on one-dimensional laboratory columns. Here the multidimensional nature of entrapped air dissolution was investigated using an indoor tank (180 × 240 × 600 cm(3) ) simulating an unconfined sand aquifer with horizontal flow. Time domain reflectometry (TDR) probes directly measured entrapped air contents, while dissolved gas conditions were monitored with total dissolved gas pressure (PTDG ) probes. Dissolution occurred as a diffuse wedge-shaped front from the inlet downgradient, with preferential dissolution at depth. This pattern was mainly attributed to increased gas solubility, as shown by PTDG measurements. However, compression of entrapped air at greater depths, captured by TDR and leading to lower quasi-saturated hydraulic conductivities and thus greater velocities, also played a small role. Linear propagation of the dissolution front downgradient was observed at each depth, with both TDR and PTDG , with increasing rates with depth (e.g, 4.1 to 5.7× slower at 15 cm vs. 165 cm depth). PTDG values revealed equilibrium with the entrapped gas initially, being higher at greater depth and fluctuating with the barometric pressure, before declining concurrently with entrapped air contents to the lower PTDG of the source water. The observed dissolution pattern has long-term implications for a wide variety of groundwater management issues, from recharge to contaminant transport and remediation strategies, due to the persistence of entrapped air near the water table (potential timescale of years). This study also demonstrated the utility of PTDG probes for simple in situ measurements to detect entrapped air and monitor its dissolution. © 2014 Her Majesty the Queen in Right of Canada Groundwater © 2014, National Ground Water Association.

Enhanced anticancer activity and oral bioavailability of ellagic acid through encapsulation in biodegradable polymeric nanoparticles.

PubMed

Mady, Fatma M; Shaker, Mohamed A

2017-01-01

Despite the fact that various studies have investigated the clinical relevance of ellagic acid (EA) as a naturally existing bioactive substance in cancer therapy, little has been reported regarding the efficient strategy for improving its oral bioavailability. In this study, we report the formulation of EA-loaded nanoparticles (EA-NPs) to find a way to enhance its bioactivity as well as bioavailability after oral administration. Poly(ε-caprolactone) (PCL) was selected as the biodegradable polymer for the formulation of EA-NPs through the emulsion-diffusion-evaporation technique. The obtained NPs have been characterized by measuring particle size, zeta potential, Fourier transform infrared, differential scanning calorimetry, and X-ray diffraction. The entrapment efficiency and the release profile of EA was also determined. In vitro cellular uptake and cytotoxicity of the obtained NPs were evaluated using Caco-2 and HCT-116 cell lines, respectively. Moreover, in vivo study has been performed to measure the oral bioavailability of EA-NPs compared to free EA, using New Zealand white rabbits. NPs with distinct shape were obtained with high entrapment and loading efficiencies. Diffusion-driven release profile of EA from the prepared NPs was determined. EA-NP-treated HCT-116 cells showed relatively lower cell viability compared to free EA-treated cells. Fluorometric imaging revealed the cellular uptake and efficient localization of EA-NPs in the nuclear region of Caco-2 cells. In vivo testing revealed that the oral administration of EA-NPs produced a 3.6 times increase in the area under the curve compared to that of EA. From these results, it can be concluded that incorporation of EA into PCL as NPs enhances its oral bioavailability and activity.

Enhanced anticancer activity and oral bioavailability of ellagic acid through encapsulation in biodegradable polymeric nanoparticles

PubMed Central

Mady, Fatma M; Shaker, Mohamed A

2017-01-01

Despite the fact that various studies have investigated the clinical relevance of ellagic acid (EA) as a naturally existing bioactive substance in cancer therapy, little has been reported regarding the efficient strategy for improving its oral bioavailability. In this study, we report the formulation of EA-loaded nanoparticles (EA-NPs) to find a way to enhance its bioactivity as well as bioavailability after oral administration. Poly(ε-caprolactone) (PCL) was selected as the biodegradable polymer for the formulation of EA-NPs through the emulsion–diffusion–evaporation technique. The obtained NPs have been characterized by measuring particle size, zeta potential, Fourier transform infrared, differential scanning calorimetry, and X-ray diffraction. The entrapment efficiency and the release profile of EA was also determined. In vitro cellular uptake and cytotoxicity of the obtained NPs were evaluated using Caco-2 and HCT-116 cell lines, respectively. Moreover, in vivo study has been performed to measure the oral bioavailability of EA-NPs compared to free EA, using New Zealand white rabbits. NPs with distinct shape were obtained with high entrapment and loading efficiencies. Diffusion-driven release profile of EA from the prepared NPs was determined. EA-NP-treated HCT-116 cells showed relatively lower cell viability compared to free EA-treated cells. Fluorometric imaging revealed the cellular uptake and efficient localization of EA-NPs in the nuclear region of Caco-2 cells. In vivo testing revealed that the oral administration of EA-NPs produced a 3.6 times increase in the area under the curve compared to that of EA. From these results, it can be concluded that incorporation of EA into PCL as NPs enhances its oral bioavailability and activity. PMID:29066891

Effects of inoculum type and bulk dissolved oxygen concentration on achieving partial nitrification by entrapped-cell-based reactors.

PubMed

Rongsayamanont, Chaiwat; Limpiyakorn, Tawan; Khan, Eakalak

2014-07-01

An entrapment of nitrifiers into gel matrix is employed as a tool to fulfill partial nitrification under non-limiting dissolved oxygen (DO) concentrations in bulk solutions. This study aims to clarify which of these two attributes, inoculum type and DO concentration in bulk solutions, is the decisive factor for partial nitrification in an entrapped-cell based system. Four polyvinyl alcohol entrapped inocula were prepared to have different proportions of nitrite-oxidizing bacteria (NOB) and nitrite-oxidizing activity. At a DO concentration of 3 mg l(-1), the number of active NOB cells in an inoculum was the decisive factor for partial nitrification enhancement. However, when the DO concentration was reduced to 2 mg l(-1), all entrapped cell inocula showed similar degrees of partial nitrification. The results suggested that with the lower bulk DO concentration, the preparation of entrapped cell inocula is not useful as the DO level becomes the decisive factor for achieving partial nitrification. Copyright © 2014 Elsevier Ltd. All rights reserved.

No Way Out: Entrapment as a Moderator of Suicide Ideation Among Military Personnel.

PubMed

Shelef, Leah; Levi-Belz, Yossi; Fruchter, Eyal; Santo, Yoav; Dahan, Eyal

2016-10-01

Suicide is a leading and growing cause of death in the military during peacetime. This study sought to examine the psychological mechanisms relating to entrapment, stress, and psychological protective factors facilitating suicide ideation among military personnel. The study population comprised 168 soldiers (aged 18-21) divided into 3 groups: suicide attempters (n = 58), those receiving treatment by a mental health professional, reporting no suicidal behavior (n = 58), and controls (n = 50). In general, the suicidal group scored higher than the 2 other groups in stress levels and entrapment but lower than the other 2 groups in perceived problem-solving abilities and perceived social support. Moreover, the interaction of stress and entrapment predict suicide ideation beyond stress, protective factors, and entrapment alone. Entrapment is an important predictor of suicide ideation and can serve as a moderator, in that its presence may exacerbate the harsh situation of subjective stress within the military context and intensify it into a suicide risk. © 2016 Wiley Periodicals, Inc.

Amphotericin-B entrapped lecithin/chitosan nanoparticles for prolonged ocular application.

PubMed

Chhonker, Yashpal S; Prasad, Yarra Durga; Chandasana, Hardik; Vishvkarma, Akhilesh; Mitra, Kalyan; Shukla, Praveen K; Bhatta, Rabi S

2015-01-01

Fungal keratitis is the major cause of vision loss worldwide. Amphotericin-B is considered as the drug of choice for fungal infections. However, its use in ophthalmic drug delivery is limited by the low precorneal residence at ocular surface as a result of blinking reflex, tear turnover and nasopharyngeal drainage. We report Amphotericin-B loaded lecithin/chitosan nanoparticles for prolonged ocular application. The prepared nanoparticles were in the size range of 161.9-230.5 nm, entrapment efficiency of 70-75%, theoretical drug loading of 5.71% with positive zeta potential of 26.6-38.3 mV. As demonstrated by antifungal susceptibility against Candida albicans and Aspergillus fumigatus, nanoparticles were more effective than marketed formulation. They exhibited pronounced mucoadhesive properties. In-vivo pharmacokinetic studies in New Zealand albino rabbit eyes indicated improved bioavailablity (∼ 2.04 fold) and precorneal residence time (∼ 3.36 fold) by nanoparticles prepared from low molecular weight chitosan as compared with marketed formulation. Copyright © 2014. Published by Elsevier B.V.

Enzymatic Conversion of CO2 to Bicarbonate in Functionalized Mesoporous Silica

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

Yu, Yuehua; Chen, Baowei; Qi, Wen N.

2012-05-01

We report here that carbonic anhydrase (CA), the fastest enzyme that can covert carbon dioxide to bicarbonate, can be spontaneously entrapped in functionalized mesoporous silica (FMS) with super-high loading density (up to 0.5 mg of protein/mg of FMS) due to the dominant electrostatic interaction. The binding of CA to HOOC-FMS can result in the protein’s conformational change comparing to the enzyme free in solution, but can be overcome with increased protein loading density. The higher the protein loading density, the less conformational change, hence the higher enzymatic activity and the higher enzyme immobilization efficiency. The electrostatically bound CA can bemore » released by changing pH. The released enzyme still displayed the native conformational structure and the same high enzymatic activity as that prior to the enzyme entrapment. This work opens up a new approach converting carbon dioxide to biocarbonate in a biomimetic nanoconfiguration that can be integrated with the other part of biosynthesis process for the assimilation of carbon dioxide.« less

Preparation and evaluation of microspheres of xyloglucan and its thiolated xyloglucan derivative.

PubMed

Sonawane, Savita; Bhalekar, Mangesh; Shimpi, Shamkant

2014-08-01

Xyloglucan is a natural polymer reported to possess mucoadhesive properties. To enhance the mucoadhesion potential, xyloglucan was thiolated with cysteine. The microspheres of xyloglucan were prepared using a biocompatible crosslinker sodium trimetaphosphate and it was optimized for formulation variables, namely polymer concentration, internal:external phase ratio and stirring speed using a Box-Behnken experimental design. The formulation was also optimized for performance parameters like entrapment, t80 and % mucoadhesion. The microspheres were characterized by Fourier transform infrared spectroscopy, DSC and SEM for the optimum formula and then were reproduced by replacing the xyloglucan with thiomer. The microspheres formed showed entrapment efficiency of about 80%, t80 of about 400min and % mucoadhesion of 60% while same for thiomer were 90%, 500min and 80% respectively. In oral glucose tolerance test protocol the thiomer microspheres showed significant reduction in blood glucose levels. Thus thiolated xyloglucan offers a better polymer for multiparticulate drug delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

Spray drying of lipid-based systems loaded with Camellia sinensis polyphenols.

PubMed

Secolin, Vanessa A; Souza, Claudia R F; Oliveira, Wanderley P

2017-03-01

In this work, spray-dried lipid systems based on soy phosphatidylcholine, cholesterol and lauroyl polyoxylglycerides for entrapping Green tea polyphenols were produced. The aim was to study the effects of the encapsulating composition and spray drying conditions on the system performance and physicochemical product properties. The spray dryer powder production yield falls around 50.7 ± 2.8%, which is typical for lab scale spray dryers. Wrinkled and rounded particles, with low surface porosities were generated, independent of the drying carriers (trehalose or lactose) used. The product showed high encapsulation efficiency of Green tea polyphenols, which was promptly redispersible in water. It presented low density, and good compressive and flow properties. The results herein reported confirm the feasibility of the entrapment of Green tea polyphenols in lipid-based compositions by spray drying in presence of the drying carriers evaluated. The spray-dried microparticles show high potential to be used as additive in food, nutraceutical and pharmaceutical products.

Effect of sterilization on the physical stability of brimonidine-loaded solid lipid nanoparticles and nanostructured lipid carriers.

PubMed

El-Salamouni, Noha S; Farid, Ragwa M; El-Kamel, Amal H; El-Gamal, Safaa S

2015-12-30

Nanoparticulate delivery systems have recently been under consideration for topical ophthalmic drug delivery. Brimonidine base-loaded solid lipid nanoparticles and nanostructured lipid carrier formulations were prepared using glyceryl monostearate as solid lipid and were evaluated for their physical stability following sterilization by autoclaving at 121°C for 15min. The objective of this work was to evaluate the effect of autoclaving on the physical appearance, particle size, polydispersity index, zeta potential, entrapment efficiency and particle morphology of the prepared formulations, compared to non-autoclaved ones. Results showed that, autoclaving at 121°C for 15min allowed the production of physically stable formulations in nanometric range, below 500nm suitable for ophthalmic application. Moreover, the autoclaved samples appeared to be superior to non-autoclaved ones, due to their increased zeta potential values, indicating a better physical stability. As well as, increased amount of brimonidine base entrapped in the tested formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

Far beyond Phagocytosis: Phagocyte-Derived Extracellular Traps Act Efficiently against Protozoan Parasites In Vitro and In Vivo.

PubMed

Silva, Liliana M R; Muñoz-Caro, Tamara; Burgos, Rafael A; Hidalgo, Maria A; Taubert, Anja; Hermosilla, Carlos

2016-01-01

Professional mononuclear phagocytes such as polymorphonuclear neutrophils (PMN), monocytes, and macrophages are considered as the first line of defence against invasive pathogens. The formation of extracellular traps (ETs) by activated mononuclear phagocytes is meanwhile well accepted as an effector mechanism of the early host innate immune response acting against microbial infections. Recent investigations showed evidence that ETosis is a widely spread effector mechanism in vertebrates and invertebrates being utilized to entrap and kill bacteria, fungi, viruses, and protozoan parasites. ETs are released in response to intact protozoan parasites or to parasite-specific antigens in a controlled cell death process. Released ETs consist of nuclear DNA as backbone adorned with histones, antimicrobial peptides, and phagocyte-specific granular enzymes thereby producing a sticky extracellular matrix capable of entrapping and killing pathogens. This review summarizes recent data on protozoa-induced ETosis. Special attention will be given to molecular mechanisms of protozoa-induced ETosis and on its consequences for the parasites successful reproduction and life cycle accomplishment.

Viper and Cobra Venom Neutralization by Alginate Coated Multicomponent Polyvalent Antivenom Administered by the Oral Route

PubMed Central

Bhattacharya, Sourav; Chakraborty, Mousumi; Mukhopadhyay, Piyasi; Kundu, P. P.; Mishra, Roshnara

2014-01-01

Background Snake bite causes greater mortality than most of the other neglected tropical diseases. Snake antivenom, although effective in minimizing mortality in developed countries, is not equally so in developing countries due to its poor availability in remote snake infested areas as, and when, required. An alternative approach in this direction could be taken by making orally deliverable polyvalent antivenom formulation, preferably under a globally integrated strategy, for using it as a first aid during transit time from remote trauma sites to hospitals. Methodology/Principal Findings To address this problem, multiple components of polyvalent antivenom were entrapped in alginate. Structural analysis, scanning electron microscopy, entrapment efficiency, loading capacity, swelling study, in vitro pH sensitive release, acid digestion, mucoadhesive property and venom neutralization were studied in in vitro and in vivo models. Results showed that alginate retained its mucoadhesive, acid protective and pH sensitive swelling property after entrapping antivenom. After pH dependent release from alginate beads, antivenom (ASVS) significantly neutralized phospholipaseA2 activity, hemolysis, lactate dehydrogenase activity and lethality of venom. In ex vivo mice intestinal preparation, ASVS was absorbed significantly through the intestine and it inhibited venom lethality which indicated that all the components of antivenom required for neutralization of venom lethality were retained despite absorption across the intestinal layer. Results from in vivo studies indicated that orally delivered ASVS can significantly neutralize venom effects, depicted by protection against lethality, decreased hemotoxicity and renal toxicity caused by russell viper venom. Conclusions/Significance Alginate was effective in entrapping all the structural components of ASVS, which on release and intestinal absorption effectively reconstituted the function of antivenom in neutralizing viper and cobra venom. Further research in this direction can strategize to counter such dilemma in snake bite management by promoting control release and oral antivenom rendered as a first aid. PMID:25102172

Minimally invasive percutaneous management of large bladder stones with a laparoscopic entrapment bag.

PubMed

Tan, Yung K; Gupta, Dilan M; Weinberg, Aaron; Matteis, August J; Kotwal, Sunny; Gupta, Mantu

2014-01-01

The treatment of large volume bladder stones is a management conundrum. Transurethral methods are plagued by long operative times, trauma to the bladder mucosa, and the need for a postoperative urethral catheter. Open cystolithotomy has higher morbidity. We present the percutaneous management of bladder stones with the novel use of a laparoscopic entrapment bag. Twenty-five patients (mean age 65.7), including 22 men and 3 women, 4 with a neurogenic bladder and 21 with a prior diagnosis of benign prostatic hyperplasia, underwent our novel technique. The mean number of stones was 6.8±8.0 (range, 1 to 30) and total stone burden 10.4±10.5 cm (range, 3.0 to 50.0 cm). Using regional or general anesthesia and flexible cystoscopic guidance, percutaneous bladder access was achieved. The tract was balloon dilated to 30F and stones captured in a laparoscopic entrapment bag. The bag's opening was exteriorized and stone fragmentation and comminution were achieved using a nephroscope and pneumatic or ultrasonic lithotripters. The bag was extracted and a 22F suprapubic catheter was inserted into the bladder; the patient was discharged the next day after a voiding trial. The procedure was done without fluoroscopy. No foley catheter was necessary. All patients were rendered stone free. The mean estimated blood loss was 11.1±3.93 mL (range, 10 to 25 mL). The mean operative time was 102.3 minutes. There was minimal trauma to the bladder mucosa and no complications of fluid extravasation, hematuria, or urethral trauma were noted. All patients were discharged within 24 hours of the operation. Percutaneous cystolithotomy with the use of an entrapment bag is an efficient, safe technique for treating large volume bladder calculi. We recommend this technique as an alternative to open surgery for patients with too large a stone burden to remove transurethrally.

Method to produce nanocrystalline powders of oxide-based phosphors for lighting applications

DOEpatents

Loureiro, Sergio Paulo Martins; Setlur, Anant Achyut; Williams, Darryl Stephen; Manoharan, Mohan; Srivastava, Alok Mani

2007-12-25

Some embodiments of the present invention are directed toward nanocrystalline oxide-based phosphor materials, and methods for making same. Typically, such methods comprise a steric entrapment route for converting precursors into such phosphor material. In some embodiments, the nanocrystalline oxide-based phosphor materials are quantum splitting phosphors. In some or other embodiments, such nanocrystalline oxide based phosphor materials provide reduced scattering, leading to greater efficiency, when used in lighting applications.

Development of a topical niosomal preparation of acetazolamide: preparation and evaluation.

PubMed

Aggarwal, Deepika; Garg, Alka; Kaur, Indu P

2004-12-01

Orally administered acetazolamide has a limited use in glaucoma due to the systemic side effects associated with its use. No topical formulation of acetazolamide is available, mainly because of it having a limited aqueous solubility and poor corneal permeation. To enhance the bioavailability of acetazolamide by the topical route and to improve the corneal permeability of the drug, niosomes of acetazolamide were prepared (employing span 60 and cholesterol) by different methods. Transmission electron microscopy (TEM) of the selected formulation was carried out to study the morphology. Niosomes were also prepared in the presence of dicetyl phosphate and stearylamine to obtain negatively and positively charged vesicles, respectively. It was found that the reverse-phase evaporation method (REV) gave the maximum drug entrapment efficiency (43.75%) as compared with ether injection (39.62%) and film hydration (31.43%) techniques. Drug entrapment efficiency varied with the charge and the percent entrapment efficiency for the REV method was 43.75, 51.23 and 36.26% for neutral, positively charged and negatively charged niosomes, respectively. Corneal permeability studies, however, showed that the percent permeation and the apparent permeability coefficient for the charged niosomes were less than for the neutral ones. A bioadhesive niosomal formulation of acetazolamide was also prepared and compared with the positively charged formulation, considering that both of them would have a prolonged stay in the cul-de-sac because of their expected interactions with mucin. The formulations were also compared based on their intraocular pressure (IOP)-lowering capacity. The positively charged niosomes (REV2), although showing good corneal permeability and pharmacodynamics, were however found to be inappropriate in terms of the corneal cell toxicity. The bioadhesive coated formulation (REV1bio) compared well with REV2 and also showed a much lesser toxicity. Further, the IOP-lowering effect of the developed formulations was compared with that of a marketed formulation of dorzolamide 2%, a topical carbonic anhydrase inhibitor. The developed niosomal formulations of acetazolamide showed a comparable physiological effect (33% reduction of IOP in REV1bio and 37% reduction in dorzolamide) with a duration of up to 6 h (the duration being 3 h for dorzolamide). Results of the study indicate that it is possible to develop a safe (as indicated by corneal toxicity studies) and physiologically active topical niosomal formulation of acetazolamide relative in efficiency to the newer local carbonic anhydrase inhibitor, dorzolamide. The developed formulations can form a cost effective treatment plan, which is especially important in the treatment of glaucoma, a chronic ailment affecting middle-aged to old patients.

Drug release patterns and cytotoxicity of PEG-poly(aspartate) block copolymer micelles in cancer cells.

PubMed

Eckman, Allison M; Tsakalozou, Eleftheria; Kang, Nayon Y; Ponta, Andrei; Bae, Younsoo

2012-07-01

To test physicochemical and biological properties of PEG-poly(aspartate) [PEG-p(Asp)] block copolymer micelles entrapping doxorubicin hydrochloride (DOX) through ionic interaction. PEG-p(Asp) was synthesized from 5 kDa PEG and 20 Asp units. Carboxyl groups of p(Asp) were present as benzyl ester [PEG-p(Asp/Bz)], sodium salt [PEG-p(Asp/Na)] or free acid [PEG-p(Asp/H)]. Block copolymers and DOX were mixed at various ratios to prepare polymer micelles, which were subsequently characterized to determine particle size, drug loading and release patterns, and cytotoxicity against prostate (PC3 and DU145) and lung (A549) cancer cell lines. PEG-p(Asp/Bz), Na- and H-micelles entrapped 1.1, 56.8 and 40.6 wt.% of DOX, respectively. Na- and H-micelles (<100 nm) showed time-dependent DOX release at pH 7.4, which was accelerated at pH 5.0. Na-micelles were most stable at pH 7.4, retaining 31.8% of initial DOX for 48 h. Cytotoxicity of Na-micelles was 23.2% (A549), 28.5% (PC3) and 45.9% (DU145) more effective than free DOX. Ionic interaction appeared to entrap DOX efficiently in polymer micelles from PEG-p(Asp) block copolymers. Polymer micelles possessing counter ions (Na) of DOX in the core were the most stable, releasing drugs for prolonged time in a pH-dependent manner, and suppressing cancer cells effectively.

Numerical Simulation of Slag Eye Formation and Slag Entrapment in a Bottom-Blown Argon-Stirred Ladle

NASA Astrophysics Data System (ADS)

Liu, Wei; Tang, Haiyan; Yang, Shufeng; Wang, Minghui; Li, Jingshe; Liu, Qing; Liu, Jianhui

2018-06-01

A transient mathematical model is developed for simulating the bubble-steel-slag-top gas four-phase flow in a bottom-blown argon-stirred ladle with a 70-ton capacity. The Lagrangian discrete phase model (DPM) is used for describing the moving behavior of bubbles in the steel and slag. To observe the formation process of slag eye, the volume of fluid (VOF) model is used to track the interfaces between three incompressible phases: metal/slag, metal/gas, and slag/gas. The complex multiphase turbulent flow induced by bubble-liquid interactions is solved by a large eddy simulation (LES) model. Slag eye area and slag droplet dispersion are investigated under different gas flow rates. The results show that the movement of bubbles, formation and collapse of slag eye, volatility of steel/slag interface and behavior of slag entrapment can be properly predicted in the current model. When the gas flow rate is 300 L/min, the circulation driven by the bubble plume will stir the entire ladle adequately and form a slag eye of the right size. At the same time, it will not cause strong erosion to the ladle wall, and the fluctuation of the interface is of adequate intensity, which will be helpful for improving the desulfurization efficiency; the slag entrapment behavior can also be decreased. Interestingly, with the motion of liquid steel circulation, the collision and coalescence of dispersed slag droplets occur during the floating process in the vicinity of the wall.

Formulation and evaluation of optimized oxybenzone microsponge gel for topical delivery.

PubMed

Pawar, Atmaram P; Gholap, Aditya P; Kuchekar, Ashwin B; Bothiraja, C; Mali, Ashwin J

2015-01-01

Background. Oxybenzone, a broad spectrum sunscreen agent widely used in the form of lotion and cream, has been reported to cause skin irritation, dermatitis, and systemic absorption. Aim. The objective of the present study was to formulate oxybenzone loaded microsponge gel for enhanced sun protection factor with reduced toxicity. Material and Method. Microsponge for topical delivery of oxybenzone was successfully prepared by quasiemulsion solvent diffusion method. The effects of ethyl cellulose and dichloromethane were optimized by the 3(2) factorial design. The optimized microsponges were dispersed into the hydrogel and further evaluated. Results. The microsponges were spherical with pore size in the range of 0.10-0.22 µm. The optimized formulation possesses the particle size and entrapment efficiency of 72 ± 0.77 µm and 96.9 ± 0.52%, respectively. The microsponge gel showed the controlled release and was nonirritant to the rat skin. In creep recovery test it had shown highest recovery indicating elasticity. The controlled release of oxybenzone from microsponge and barrier effect of gel result in prolonged retention of oxybenzone with reduced permeation activity. Conclusion. Evaluation study revealed remarkable and enhanced topical retention of oxybenzone for prolonged period of time. It also showed the enhanced sun protection factor compared to the marketed preparation with reduced irritation and toxicity.

Enhanced Cellular Cytotoxicity and Antibacterial Activity of 18-β-Glycyrrhetinic Acid by Albumin-conjugated PLGA Nanoparticles.

PubMed

Darvishi, B; Manoochehri, S; Esfandyari-Manesh, M; Samadi, N; Amini, M; Atyabi, F; Dinarvand, R

2015-12-01

The aim of the present work was to encapsulate 18-β-Glycyrrhetinic acid (GLA) in albumin conjugated poly(lactide-co-glycolide) (PLGA) nanoparticles by a modified nanoprecipitation method. Nanoparticles (NPs) were prepared by different drug to polymer ratios, human serum albumin (HSA) content, dithiothreitol (as producer of free thiol groups) content, and acetone (as non-solvent in nanoprecipitation). NPs with a size ranging from 126 to 174 nm were achieved. The highest entrapment efficiency (89.4±4.2%) was achieved when the ratio of drug to polymer was 1:4. The zeta potential of NPs was fairly negative (-8 to -12). Fourier transform infrared spectroscopy and differential scanning calorimetry proved the conjugation of HSA to PLGA NPs. In vitro release profile of NPs showed 2 phases: an initial burst for 4 h (34-49%) followed by a slow release pattern up to the end. The antibacterial effects of NPs against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa were studied by microdilution method. The GLA-loaded NPs showed more antibacterial effect than pure GLA (2-4 times). The anticancer MTT test revealed that GLA-loaded NPs were approximately 9 times more effective than pure GLA in Hep G2 cells. © Georg Thieme Verlag KG Stuttgart · New York.

Methyl trypsin loaded poly(D,L-lactide-coglycolide) nanoparticles for contact lens care.

PubMed

Jimenez, N; Galan, J; Vallet, A; Egea, M A; Garcia, M L

2010-03-01

The need of an enzymatic cleaner for soft contact lens care with an improved ocular safety and stability profile led us to evaluate the use of nanoparticles (NPs) of poly(D,L-lactide-coglycolide) (PLGA) and methyl trypsin (MT). NPs were prepared by double emulsion-solvent evaporation technique. A factorial design was performed to select the lactic acid proportion in the copolymer and conditions of the second sonication. The increment in proportion of lactic acid provided higher particle size results. When the time of second sonication was decreased, the entrapment efficiency (EE) increased. PLGA 50:50 NPs were chosen for further development since PLGA 50:50H NPs settled fast with different particle size in the sediment and PLGA 75:25 NPs led to form aggregates. The addition of glycerol to the NPs provided the highest EE of MT (>90%) while the addition of Tetronic 1304 promoted the fast release of enzyme initially and decreased the zeta potential (zeta) up to neutral values after gamma irradiation. NPs are expected to be effective as a lens care cleaner after 3 days or even longer with a very low quantity of enzyme released. Formulations showed an acceptable irritation ocular tolerance after in vitro HET-CAM test and in vivo Draize test. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

Novel use of pleural ultrasound can identify malignant entrapped lung prior to effusion drainage.

PubMed

Salamonsen, Matthew R; Lo, Ada K C; Ng, Arnold C T; Bashirzadeh, Farzad; Wang, William Y S; Fielding, David I K

2014-11-01

The presence of entrapped lung changes the appropriate management of malignant pleural effusion from pleurodesis to insertion of an indwelling pleural catheter. No methods currently exist to identify entrapped lung prior to effusion drainage. Our objectives were to develop a method to identify entrapped lung using tissue movement and deformation (strain) analysis with ultrasonography and compare it to the existing technique of pleural elastance (PEL). Prior to drainage, 81 patients with suspected malignant pleural effusion underwent thoracic ultrasound using an echocardiogram machine. Images of the atelectatic lower lobe were acquired during breath hold, allowing motion and strain related to the cardiac impulse to be analyzed using motion mode (M mode) and speckle-tracking imaging, respectively. PEL was measured during effusion drainage. The gold-standard diagnosis of entrapped lung was the consensus opinion of two interventional pulmonologists according to postdrainage imaging. Participants were randomly divided into development and validation sets. Both total movement and strain were significantly reduced in entrapped lung. Using data from the development set, the area under the receiver-operating curves for the diagnosis of entrapped lung was 0.86 (speckle tracking), 0.79 (M mode), and 0.69 (PEL). Using respective cutoffs of 6%, 1 mm, and 19 cm H2O on the validation set, the sensitivity/specificity was 71%/85% (speckle tracking), 50%/85% (M mode), and 40%/100% (PEL). This novel ultrasound technique can identify entrapped lung prior to effusion drainage, which could allow appropriate choice of definitive management (pleurodesis vs indwelling catheter), reducing the number of interventions required to treat malignant pleural effusion.

Effects of stuttering severity and therapy involvement on role entrapment of people who stutter.

PubMed

Gabel, Rodney M; Hughes, Stephanie; Daniels, Derek

2008-01-01

The primary purpose of this study was to examine whether a group of university students would report role entrapment of people who stutter (PWS) in the form of occupational stereotyping. The study also examined whether severity of stuttering (mild or severe) and level of therapy involvement (choosing or not choosing to attend therapy) affected the perceptions of role entrapment. To examine these issues, 260 students completed the Vocational Advice Scale (VAS) [Gabel, R. M., Blood, G. W., Tellis, G., & Althouse, M. T. (2004). Measuring role entrapment of people who stutter. Journal of Fluency Disorders, 29, 27-49]. Results suggested that stuttering severity and the level of therapy involvement did not appear alter the judges' reports for all of the careers except for the career of speech therapist. For the career of speech therapist, therapy involvement improved the participants' reports and stuttering severity had no effect. Additionally, findings suggested that university students reported that 16 of the careers listed on the VAS were appropriate choices for people who stutter and were less certain about advising for 27 of the careers. Thus, the findings from this study do not support the notion that stuttering leads to role entrapment in the form vocational stereotyping and variations in therapy involvement or stuttering severity do not change perceptions of role entrapment. LEARNER OUTCOMES: The reader will be able to (1) identify common stereotypes of PWS, (2) describe the possible effects of stereotyping and role entrapment, and (3) describe the effects of severity and therapy involvement of role entrapment of PWS.

Defeat and entrapment: more than meets the eye? Applying network analysis to estimate dimensions of highly correlated constructs.

PubMed

Forkmann, Thomas; Teismann, Tobias; Stenzel, Jana-Sophie; Glaesmer, Heide; de Beurs, Derek

2018-01-25

Defeat and entrapment have been shown to be of central relevance to the development of different disorders. However, it remains unclear whether they represent two distinct constructs or one overall latent variable. One reason for the unclarity is that traditional factor analytic techniques have trouble estimating the right number of clusters in highly correlated data. In this study, we applied a novel approach based on network analysis that can deal with correlated data to establish whether defeat and entrapment are best thought of as one or multiple constructs. Explanatory graph analysis was used to estimate the number of dimensions within the 32 items that make up the defeat and entrapment scales in two samples: an online community sample of 480 participants, and a clinical sample of 147 inpatients admitted to a psychiatric hospital after a suicidal attempt or severe suicidal crisis. Confirmatory Factor analysis (CFA) was used to test whether the proposed structure fits the data. In both samples, bootstrapped exploratory graph analysis suggested that the defeat and entrapment items belonged to different dimensions. Within the entrapment items, two separate dimensions were detected, labelled internal and external entrapment. Defeat appeared to be multifaceted only in the online sample. When comparing the CFA outcomes of the one, two, three and four factor models, the one factor model was preferred. Defeat and entrapment can be viewed as distinct, yet, highly associated constructs. Thus, although replication is needed, results are in line with theories differentiating between these two constructs.

Preparation of an efficient and safe polymeric-magnetic nanoparticle delivery system for sorafenib in hepatocellular carcinoma.

PubMed

Tom, Greeshma; Philip, Sheena; Isaac, Rimal; Praseetha, P K; Jiji, S G; Asha, V V

2018-08-01

Superparamagnetic iron oxide nanoparticles (SPIONs), as drug delivery vehicles, offer to eliminate the concerns associated with hydrophobic anti-cancer agents. The current study was intended to fabricate a SPION based delivery system for sorafenib that can simultaneously enable targeted delivery of sorafenib and expand its therapeutic index against hepatocellular carcinoma (HCC). Co-precipitation and physical entrapment methods were employed for the synthesis of sorafenib loaded PVA coated SPIONs. Physicochemical characterizations were done using TEM, XRD, FTIR, Raman spectra and VSM measurements. The superior activity of nanoconjugate was demonstrated by AO/EB staining, FACS, immunofluorescence and Western blot. The safety of the sorafenib conjugated nanoparticles were verified in Wistar rats. The synthesized nanoparticles were in the size range of 5-15 nm. The adsorption of PVA to the SPIONs and the conjugation of sorafenib to the nanocarrier were confirmed by XRD, FTIR and Raman spectra analyses. VSM study ascertained the superparamagnetic nature of the nanoconjugate. Cellular uptake studies suggested its efficient entrapment in HepG2 cells. MTT assay showed that the cytotoxicity of sorafenib loaded PVA/SPIONs was comparable or higher than free sorafenib. The activation of apoptosis and autophagy pathways in HepG2 by the nanoconjugate was evidenced. Acute toxicity testing in Wistar rats supported the safe administration of the nanoconjugate and established its localization in animal tissues by Perl's Prussian Blue reaction. The novel combination of sorafenib with PVA/SPIONs showed better anticancer efficiency than free sorafenib demonstrative of its potential in cancer chemotherapy. Copyright © 2018 Elsevier Inc. All rights reserved.

A directional entrapment modification on the polyethylene surface by the amphiphilic modifier of stearyl-alcohol poly(ethylene oxide) ether

NASA Astrophysics Data System (ADS)

Lu, Qiang; Chen, Yi; Huang, Juexin; Huang, Jian; Wang, Xiaolin; Yao, Jiaying

2018-05-01

A novel entrapment modification method involving directional implantation of the amphiphilic modifier of stearyl-alcohol poly(ethylene oxide) ether (AEO) into the high-density polyethylene (HDPE) surface is proposed. This modification technique allows the AEO modifier to be able to spontaneously attain and subsequently penetrate into the swollen HDPE surface with its hydrophobic stearyl segment, while its hydrophilic poly(ethylene oxide) (PEO) segment spontaneously points to water. The AEO modifier with a HLB number below 8.7 was proved appropriate for the directional entrapment, Nevertheless, AEOs with larger HLB numbers were also effective modifiers in the presence of salt additives. In addition, a larger and hydrophobic micelle, induced respectively by the AEO concentration above 1.3 × 10-2 mol/L and the entrapping temperature above the cloud point of AEO, could lead to a sharp contact angle decline of the modified surface. Finally, a hydrophilic HDPE surface with the modifier coverage of 38.9% was reached by the directional entrapment method, which is far larger than that of 19.2% by the traditional entrapment method.

Protection of enzymes from photodegradation by entrapment within alumina.

PubMed

Shapovalova, Olga E; Levy, David; Avnir, David; Vinogradov, Vladimir V

2016-10-01

Most enzymes are highly sensitive to UV-light in all of its ranges and their activity can irreversibly drop even after a short time of exposure. Here we report a solution of this problem by using sol-gel matrices as effective protectors against this route of enzyme inactivation and denaturation. The concept presented here utilizes several modes of action: First, the entrapment within the rigid ceramic sol-gel matrix, inhibits denaturation motions, and the hydration shell around the entrapped protein provides extra protection. Second, the matrix itself - alumina in this report - absorbs UV light. And third, sol-gel materials have been shown to be quite universal in their ability to entrap small molecules, and so co-entrapment with well documented sun-screening molecules (2-hydroxybenzophenone, 2,2'-dihydroxybenzophenone, and 2,2'-dihydroxy-4-methoxybenzophenone) is an additional key protective tool. Three different enzymes as models were chosen for the experiments: carbonic anhydrase, acid phosphatase and horseradish peroxidase. All showed greatly enhanced UV (regions UV-A, UV-B, and UV-C) stabilization after entrapment within the doped sol-gel alumina matrices. Copyright © 2016 Elsevier B.V. All rights reserved.

The effect of entrapped nonaqueous phase liquids on tracer transport in heterogeneous porous media: Laboratory experiments at the intermediate scale

USGS Publications Warehouse

Barth, Gilbert R.; Illangasekare, T.H.; Rajaram, H.

2003-01-01

This work considers the applicability of conservative tracers for detecting high-saturation nonaqueous-phase liquid (NAPL) entrapment in heterogeneous systems. For this purpose, a series of experiments and simulations was performed using a two-dimensional heterogeneous system (10??1.2 m), which represents an intermediate scale between laboratory and field scales. Tracer tests performed prior to injecting the NAPL provide the baseline response of the heterogeneous porous medium. Two NAPL spill experiments were performed and the entrapped-NAPL saturation distribution measured in detail using a gamma-ray attenuation system. Tracer tests following each of the NAPL spills produced breakthrough curves (BTCs) reflecting the impact of entrapped NAPL on conservative transport. To evaluate significance, the impact of NAPL entrapment on the conservative-tracer breakthrough curves was compared to simulated breakthrough curve variability for different realizations of the heterogeneous distribution. Analysis of the results reveals that the NAPL entrapment has a significant impact on the temporal moments of conservative-tracer breakthrough curves. ?? 2003 Elsevier B.V. All rights reserved.

Effective cellular internalization, cell cycle arrest and improved pharmacokinetics of Tamoxifen by cholesterol based lipopolymeric nanoparticles.

PubMed

Mazumdar, Samrat; Italiya, Kishan S; Sharma, Saurabh; Chitkara, Deepak; Mittal, Anupama

2018-05-30

The present study aims at the development of cholesterol based lipopolymeric nanoparticles for improved entrapment, better cell penetration and improved pharmacokinetics of Tamoxifen (TMX). Self-assembling cholesterol grafted lipopolymer, mPEG-b-(CB-{g-chol}-co-LA) was synthesized from poly(ethyleneglycol)-block-2-methyl-2-carboxyl-propylenecarboxylic acid-co-poly (l-lactide) [mPEG-b-(CB-{g-COOH}-co-LA)] copolymer followed by carbodiimide coupling for attaching cholesterol. Lipopolymeric nanoparticles were prepared using o/w solvent evaporation technique, which were subsequently characterized to determine its particle size, entrapment efficiency, release pattern and compared with mPEG-PLA nanoparticles. Further, in order to assess the in vitro efficacy, cytotoxicity studies, uptake, apoptosis assay and cell cycle analysis were performed in breast cancer cell lines (MCF-7 and 4T1). Finally, the pharmacokinetic profile of TMX loaded mPEG-b-(CB-{g-chol}-co-LA) lipopolymeric nanoparticles was also performed. TMX loaded lipopolymeric nanoparticles of particle size 151.25 ± 3.74 (PDI 0.123) and entrapment efficiency of 73.62 ± 3.08% were formulated. The haemolytic index, protein binding and in vitro drug release of the optimized nanoparticles were found to be comparable to that of the TMX loaded mPEG-PLA nanoparticles. Lipopolymeric nanoparticles demonstrated improved IC 50 values in breast cancer cells (22.2 μM in 4T1; 18.8 μM in MCF-7) than free TMX (27.6 μM and 23.5 μM respectively) and higher uptake efficiency. At IC 50 values, TMX loaded lipopolymeric nanoparticles induced apoptosis and cell cycle arrest (G 0 /G 1 phase) to similar extent as that of free drug. Pharmacokinetic studies indicated ∼2.5-fold increase in the half-life (t 1/2 ) (p < 0.001) and ∼2.7-fold (p < 0.001) increase in the mean residence time (MRT) of TMX following incorporation into lipopolymeric nanoparticles. Thus, mPEG-b-(CB-{g-chol}-co-LA) lipopolymeric nanoparticles offer a more promising approach for delivery of Tamoxifen in breast cancer by improving drug internalization and prolonging the mean residence time of the drug indicating possibility of dose reduction and hence bypassing the adverse effects of TMX therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Efficient delivery of recombinant human bone morphogenetic protein (rhBMP-2) with dextran sulfate-chitosan microspheres.

PubMed

Xia, Yuan-Jun; Xia, Hong; Chen, Ling; Ying, Qing-Shui; Yu, Xiang; Li, Li-Hua; Wang, Jian-Hua; Zhang, Ying

2018-04-01

Bone morphogenetic protein-2 (BMP-2) serves an important role in the development of bone and cartilage. However, administration of BMP-2 protein alone by intravenous delivery is not very effective. Sustained delivery of stabilized BMP-2 by carriers has been proven necessary to improve the osteogenesis effect of BMP-2. The present study constructed a novel drug delivery system using dextran sulfate (DS)-chitosan (CS) microspheres and investigated the efficiency of the delivery system on recombinant human bone morphogenetic protein (rhBMP-2). The microsphere morphology, optimal ratio of DS/CS/rhBMP-2, and drug loading rate and entrapment efficiency of rhBMP-2 CS nanoparticles were determined. L929 cells were used to evaluate the cytotoxicity and effect of DS/CS/rhBMP-2 microspheres on cell proliferation. Differentiation study was conducted using bone marrow mesenchymal stem cells (BMSCs-C57) cells treated with DS/CS/rhBMP-2 microspheres or the control microspheres. The DS/CS/rhBMP-2 microspheres delivery system was successfully established. Subsequent complexation of rhBMP-2-bound DS with polycations afforded well defined microspheres with a diameter of ~250 nm. High protein entrapment efficiency (85.6%) and loading ratio (47.245) µg/mg were achieved. Release of rhBMP-2 from resultant microspheres persisted for over 20 days as determined by ELISA assay. The bioactivity of rhBMP-2 encapsulated in the CS/DS microsphere was observed to be well preserved as evidenced by the alkaline phosphatase activity assay and calcium nodule formation of BMSCs-C57 incubated with rhBMP-2-loaded microspheres. The results demonstrated that microspheres based on CS-DS polyion complexes were a highly efficient vehicle for delivery of rhBMP-2 protein. The present study may provide novel orientation for bone tissue engineering for repairing and regenerating bone defects.

Modified mesoporous silica nanoparticles for enhancing oral bioavailability and antihypertensive activity of poorly water soluble valsartan.

PubMed

Biswas, Nikhil

2017-03-01

The aim was to improve the oral bioavailability and antihypertensive activity of poorly soluble drug valsartan (VAL) by modifying the design and delivery of mesoporous silica nanoparticles (MSNs). The synthesized MSNs were functionalized with aminopropyl groups (AP-MSN) through postsynthesis and coated with pH sensitive polymer Eudragit L100-55 (AP-MSN-L100-55) for pH dependant sustain release of anionic VAL. MSNs were characterized by Brauner-Emmett-Teller (BET) surface area analyzer, zeta sizer, Field Emission Scanning Electron Microscope (FESEM), Powder X-Ray Diffraction (PXRD) and Differential Scanning Calorimetry (DSC). Functionalized MSNs showed highest entrapment efficiency (59.77%) due to strong ionic interaction with VAL. In vitro dissolution of M-MSN [MSN-VAL and AP-MSN-VAL-L100-55 mixed equally] at physiological conditions demonstrated immediate release (MSN-VAL fraction) followed by sustained release (AP-MSN-VAL-L100-55 fraction) of 96% VAL in 960min. The dramatic improvement in dissolution was attributed to the amorphization of crystalline VAL by MSNs as evidenced by DSC and PXRD studies. No noticeable cytotoxicity was observed for MSN, AP-MSN and AP-MSN-L100-55 in MTT assay. Pharmacokinetic study of M-MSN confirmed 1.82 fold increases in bioavailability compared to commercial Diovan tablet in fasted male rabbits. Blood pressure monitoring in rats showed that the morning dosing of Diovan tablet efficiently controlled BP for just over 360min whereas the effect of M-MSN lasted for >840min. Copyright © 2016 Elsevier B.V. All rights reserved.

'Flash-forwards' and suicidal ideation: A prospective investigation of mental imagery, entrapment and defeat in a cohort from the Hong Kong Mental Morbidity Survey.

PubMed

Ng, Roger M K; Di Simplicio, Martina; McManus, Freda; Kennerley, Helen; Holmes, Emily A

2016-12-30

'Flash-forwards' - mental images of suicide - have been reported in selected Caucasian samples. Perceptions of defeat and entrapment are considered to be associated with suicidal ideation. We aimed to investigate (1) the presence of suicidal flash-forwards in people with recent suicidal ideation versus those without such ideation in an Asian sample, and (2) associations between suicidal flash-forwards, and perceptions of entrapment accounting for suicidal ideation. Eighty two suicidal and 80 non-suicidal participants from the Hong Kong Mental Morbidity Survey completed questionnaires including suicidal ideation, presence of suicidal flash-forward images, defeat and entrapment, at baseline and seven weeks later. Suicidal 'flash-forwards' were present only in suicidal cases. People with recent suicidal ideation and suicidal flash-forwards had more severe suicidal ideation than those without flash-forwards. Compared to those without suicidal ideation, people with recent suicidal ideation reported higher entrapment and defeat levels. Resolution of suicidal ideation over time was associated with fewer suicidal flash-forwards and reduced entrapment perceptions. At baseline and seven weeks, suicidal ideation was predicted by an interaction between suicidal flash-forwards presence and perceptions of entrapment. Mental imagery of suicide appears to be associated with suicidal ideation, and may represent a novel target in suicidal risk assessment and prevention. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Sol-Gel Entrapped Levonorgestrel Antibodies: Activity and Structural Changes as a Function of Different Polymer Formats

PubMed Central

Shalev, Moran; Miriam, Altstein

2011-01-01

The paper describes development of a sol-gel based immunoaffinity method for the steroid hormone levonorgestrel (LNG) and the effects of changes in the sol-gel matrix format on the activity of the entrapped antibodies (Abs) and on matrix structure. The best sol-gel format for Ab entrapment was found to be a tetramethoxysilane (TMOS) based matrix at a TMOS:water ratio of 1:8, containing 10% polyethylene glycol (PEG) of MW 0.4 kDa. Addition of higher percentages of PEG or a higher MW PEG did not improve activity. No activity was obtained with a TMOS:water ratio of 1:12, most likely because of the very dense polymer that resulted from these polymerization conditions. Only minor differences in the non-specific binding were obtained with the various formats. TMOS was found to be more effective than tetrakis (2-hydroxyethyl)orthosilicate (THEOS) for entrapment of anti-levonorgestrel (LNG) Abs. However, aging the THEOS-based sol-gel for a few weeks at 4 °C stabilized the entrapped Abs and increased its binding capacity. Confocal fluorescent microscopy with fluorescein isothiocyanate (FITC) labeled immunoglobulines (IgGs) entrapped in the sol-gel matrix showed that the entrapped Abs were distributed homogenously within the gel. Scanning electron microscopy (SEM) images have shown the diverse structures of the various sol-gel formats and precursors. PMID:28880001

Development of Octyl Methoxy Cinnamates (OMC)/Silicon Dioxide (SiO₂) Nanoparticles by Sol-Gel Emulsion Method.

PubMed

Wu, Pey-Shiuan; Lee, Yi-Ching; Kuo, Yi-Ching; Lin, Chih-Chien

2017-12-07

Although octyl methoxy cinnamates (OMC) is the most used Ultraviolet B (UVB) filter in sunscreen, it has poor light stability in emulsion system. In this study, OMC/SiO₂ nanoparticles were prepared via sol-gel emulsion method. Tetraethoxy silane (TEOS) was used as the silica source to encapsulate OMC. Modification of experimental parameters such as stirring speed of condensation reaction and emulsion condition, pH value of acid-catalyzed, surfactant and different percentage of TEOS and OMC, adding of OMC and surfactant to different phase may affect the particle size, and yield and entrapment efficiency in preparation process of OMC/SiO₂ nanoparticles. Concluding all the parameter, we found that when condensation reaction and emulsion conditions are at 1000 rpm, pH 1.5, Span 80/Tween 20, TEOS/OMC ratios 1:1, OMC and surfactants added in oil phase, resulting in smaller particle sizes 476.5 nm, higher yield 95.8%, and higher entrapment efficiency 61.09%. Fourier transform infrared (FTIR) analysis demonstrated that OMC/SiO₂ nanoparticles were successfully prepared. In vitro release profile supposed that OMC/SiO₂ nanoparticles can delay OMC releasing and had 60.83% decreasing of cumulative amount. Therefore, the OMC/SiO₂ nanoparticles have the potential to develop as new sunscreen materials in the use for cosmetics field in the future.

Vincristine-sulphate-loaded liposome-templated calcium phosphate nanoshell as potential tumor-targeting delivery system.

PubMed

Thakkar, Hetal Paresh; Baser, Amit Kumar; Parmar, Mayur Prakashbhai; Patel, Ketul Harshadbhai; Ramachandra Murthy, Rayasa

2012-06-01

Vincristine-sulfate-loaded liposomes were prepared with an aim to improve stability, reduce drug leakage during systemic circulation, and increase intracellular uptake. Liposomes were prepared by the thin-film hydration method, followed by coating with calcium phosphate, using the sequential addition approach. Prepared formulations were characterized for size, zeta potential, drug-entrapment efficiency, morphology by transmission electron microscopy (TEM), in vitro drug-release profile, and in vitro cell cytotoxicity study. Effect of formulation variables, such as drug:lipid ratio as well as nature and volume of hydration media, were found to affect drug entrapment, and the concentration of calcium chloride in coating was found to affect size and coating efficiency. Size, zeta potential, and TEM images confirmed that the liposomes were effectively coated with calcium phosphate. The calcium phosphate nanoshell exhibited pH-dependent drug release, showing significantly lower release at pH 7.4, compared to the release at pH 4.5, which is the pH of the tumor interstitium. The in vitro cytotoxicity study done on the lung cancer cell line indicated that coated liposomes are more cytotoxic than plain liposomes and drug solution, indicating their potential for intracellular drug delivery. The cell-uptake study done on the lung cancer cell line indicated that calcium-phosphate-coated liposomes show higher cell uptake than uncoated liposomes.

A poly (lactide-co-glycolide) film loaded with abundant bone morphogenetic protein-2: A substrate promoting osteoblast attachment, proliferation and differentiation in bone tissue engineering.

PubMed

Qu, Xiangyang; Cao, Yujiang; Chen, Cong; Die, Xiaohong; Kang, Quan

2014-12-10

We explored a novel biodegradable poly (lactide-co-glycolide) (PLGA) film loaded with over 80 wt% bone morphogenetic protein (BMP-2), which was regarded as a substrate promoting osteoblast attachment, proliferation and differentiation for application of bone tissue engineering. Using phospholipid as a surfactant, BMP-2 was modified as a complex (PBC) for dispersing in PLGA/dichloromethane solution. The PLGA film loaded with BMP-2 and phospholipid complex (PBC-PF) showed rough and draped morphology with high entrapment efficiency exceeding 80% and good hydrophilicity respectively. The in-vitro release study of BMP-2 showed that about 50% BMP-2 was slowly and continuously released from PBC-PF within 5 weeks and had a short initial burst release only in the last 1.5 days, which was better than serious burst release of PLGA film loaded with pure BMP-2 without phospholipid (BMP-PF) controlling. By comparison with other PLGA films and tissue culture plates, it was confirmed that PBC-PF significantly promoted the attachment, proliferation and differentiation of osteoblasts with higher entrapment efficiency and better sustained release. These advantages illustrated that PBC-PF could be a potential substrate providing long-term requisite growth factors for osteoblasts, which might be applied in bone tissue engineering. This article is protected by copyright. All rights reserved. Copyright © 2014 Wiley Periodicals, Inc., A Wiley Company.

A poly(lactide-co-glycolide) film loaded with abundant bone morphogenetic protein-2: A substrate-promoting osteoblast attachment, proliferation, and differentiation in bone tissue engineering.

PubMed

Qu, Xiangyang; Cao, Yujiang; Chen, Cong; Die, Xiaohong; Kang, Quan

2015-08-01

We explored a novel biodegradable poly(lactide-co-glycolide) (PLGA) film loaded with over 80 wt % bone morphogenetic protein (BMP)-2, which was regarded as a substrate-promoting osteoblast attachment, proliferation, and differentiation for application of bone tissue engineering. Using phospholipid as a surfactant, BMP-2 was modified as a complex (PBC) for dispersing in PLGA/dichloromethane solution. The PLGA film loaded with BMP-2 and phospholipid complex (PBC-PF) showed rough and draped morphology with high entrapment efficiency exceeding 80% and good hydrophilicity, respectively. The in vitro release study of BMP-2 showed that about 50% BMP-2 was slowly and continuously released from PBC-PF within 5 weeks and had a short initial burst release only in the last 1.5 days, which was better than serious burst release of PLGA film loaded with pure BMP-2 without phospholipid (BMP-PF) as control. By comparison with other PLGA films and tissue culture plates, it was confirmed that PBC-PF significantly promoted the attachment, proliferation, and differentiation of osteoblasts with higher entrapment efficiency and better sustained release. These advantages illustrated that PBC-PF could be a potential substrate providing long-term requisite growth factors for osteoblasts, which might be applied in bone tissue engineering. © 2015 Wiley Periodicals, Inc.

Design of composite microparticle systems based on pectin and waste material of propolis for modified l-alanyl-l-glutamine release and with immunostimulant activity.

PubMed

Villa Nova, Mônica; Ratti, Bianca A; Herculano, Leandro S; Bittencourt, Paulo R S; Novello, Cláudio R; Bazotte, Roberto Barbosa; Lautenschlager, Sueli de Oliveira Silva; Bruschi, Marcos Luciano

2017-12-12

Catabolic conditions like acquired immunodeficiency syndrome, cancer, and burn can cause immunosuppression. Amino acids such as alanine and glutamine are essential for the activity of the immune system. Propolis is immunostimulant and the waste of propolis extraction has been reused with technological and therapeutic purposes. Therefore, this study describes the association of propolis byproduct extract (BPE) with pectin to prepare spray-dried microparticles containing the dipeptide l-alanyl-l-glutamine as stimulant systems of neutrophils. The use of a factorial design allowed selecting the best formulation, which was characterized by morphology, size, and entrapment efficiency analyses. In addition, the systems were characterized by thermal and X-ray diffraction analysis, Fourier-transform infrared spectroscopy, in vitro drug release, and in vitro cytotoxicity and stimulation test of neutrophils. Small well-structured microparticles with good entrapment efficiency values were achieved. Thermal stability of formulation was observed, and it was proved that pectin, BPE and l-alanyl-l-glutamine were dispersed throughout the matrix. The drug was released from the microparticles during 24 h governed by swelling and diffusion. The drug-loaded formulations showed a significant stimulating effect on neutrophils. These structures could increase the activity of immune cells, and other in vitro and in vivo studies should be performed in the future.

Development of transethosomes formulation for dermal fisetin delivery: Box-Behnken design, optimization, in vitro skin penetration, vesicles-skin interaction and dermatokinetic studies.

PubMed

Moolakkadath, Thasleem; Aqil, Mohd; Ahad, Abdul; Imam, Syed Sarim; Iqbal, Babar; Sultana, Yasmin; Mujeeb, Mohd; Iqbal, Zeenat

2018-05-07

The present study was conducted for the optimization of transethosomes formulation for dermal fisetin delivery. The optimization of the formulation was carried out using "Box-Behnken design". The independent variables were Lipoid S 100, ethanol and sodium cholate. The prepared formulations were characterized for vesicle size, entrapment efficiency and in vitro skin penetration study. The vesicles-skin interaction, confocal laser scanning microscopy and dermatokinetic studies were performed with optimized formulation. Results of the present study demonstrated that the optimized formulation presented vesicle size of 74.21 ± 2.65 nm, zeta potential of -11.0 mV, entrapment efficiency of 68.31 ± 1.48% and flux of 4.13 ± 0.17 µg/cm 2 /h. The TEM image of optimized formulation exhibited sealed and spherical shape vesicles. Results of thermoanalytical techniques demonstrated that the prepared transethosomes vesicles formulation had fluidized the rigid membrane of rat's skin for smoother penetration of fisetin transethosomes. The confocal study results presented well distribution and penetration of Rhodamine B loaded transethosomes vesicles formulation up to deeper layers of the rat's skin as compared to the Rhodamine B-hydro alcoholic solution. Present study data revealed that the developed transethosomes vesicles formulation was found to be a potentially useful drug carrier for fisetin dermal delivery.

Ultrasonic Processing Technique as a Green Preparation Approach for Diacerein-Loaded Niosomes.

PubMed

Khan, Muhammad Imran; Madni, Asadullah; Hirvonen, Jouni; Peltonen, Leena

2017-07-01

In this study, the feasibility of ultrasonic processing (UP) technique as green preparation method for production of poorly soluble model drug substance, diacerein, loaded niosomes was demonstrated. Also, the effects of different surfactant systems on niosomes' characteristics were analyzed. Niosomes were prepared using both the green UP technique and traditional thin-film hydration (TFH) technique, which requires the use of environmentally hazardous organic solvents. The studied surfactant systems were Span 20, Pluronic L64, and their mixture (Span 20 and Pluronic L64). Both the production techniques produced well-defined spherical vesicles, but the UP technique produced smaller and more monodisperse niosomes than TFH. The entrapment efficiencies with the UP method were lower than with TFH, but still at a feasible level. All the niosomal formulations released diacerein faster than pure drug, and the drug release rates from the niosomes produced by the UP method were higher than those from the TFH-produced niosomes. With UP technique, the optimum process conditions for small niosomal products with low PDI values and high entrapment efficiencies were obtained when 70% amplitude and 45-min sonication time were used. The overall results demonstrated the potency of UP technique as an alternative fast, cost-effective, and green preparation approach for production of niosomes, which can be utilized as drug carrier systems for poorly soluble drug materials.

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.

Development of ketoconazole nanovesicular system using 1,2-hexanediol and 1,4-cyclohexanediol for dermal targeting delivery: physicochemical characterization and in vitro/in vivo evaluation

NASA Astrophysics Data System (ADS)

Wang, Jinping; Guo, Fang; Ma, Man; Li, Nan; Tan, Fengping

2014-07-01

The present study was aimed at the encapsulation of ketoconazole (KCZ) in the novel modified nanovesicles for dermal targeting delivery. To this purpose, innovative modified vesicles were prepared with soy phospholipid and aqueous solutions containing different concentrations of two targeting modifiers, 1,2-hexanediol and 1,4-cyclohexanediol. Conventional liposomes, with soy phospholipid and cholesterol, were used as control. The prepared formulations were characterized in terms of entrapment efficiency, size distribution, morphology, and stability. Dermal KCZ targeting delivery from modified vesicles was investigated in vitro and in vivo through newborn pig and rat skin, respectively. All vesicles showed a mean size ranging from 58 to 147 nm with fairly narrow size distribution and drug entrapment efficiency between 20 and 75 %. Results of in vitro and in vivo studies indicated that modified vesicles provided an improved KCZ targeting delivery into skin layers. Images of the confocal laser scanning microscopy analyses supported the conclusion that modified vesicles could enhance the drug deposition into the skin strata and reduce the drug permeation into the blood, due to a synergic effect of phospholipid and modifiers. Finally, histological evaluation showed that KCZ-loaded modified vesicles caused no irritation to the skin. The results obtained encouraged the use of the KCZ-loaded modified vesicles as the formulation for the potential topical treatment of fungal infections.

Sulfacetamide loaded Eudragit® RL100 nanosuspension with potential for ocular delivery.

PubMed

Mandal, Bivash; Alexander, Kenneth S; Riga, Alan T

2010-01-01

Polymeric nanosuspension was prepared from an inert polymer resin (Eudragit® RL100) with the aim of improving the availability of sulfacetamide at the intraocular level to combat bacterial infections. Nanosuspensions were prepared by the solvent displacement method using acetone and Pluronic® F108 solution. Drug to polymer ratio was selected as formulation variable. Characterization of the nanosupension was performed by measuring particle size, zeta potential, Fourier Transform infrared spectra (FTIR), Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD), drug entrapment efficiency and in vitro release. In addition, freeze drying, redispersibility and short term stability study at room temperature and at 4(0)C were performed. Spherical, uniform particles (size below 500 nm) with positive zeta potential were obtained. No significant chemical interactions between drug and polymer were observed in the solid state characterization of the freeze dried nanosuspension (FDN). Drug entrapment efficiency of the selected batch was increased by changing the pH of the external phase and addition of polymethyl methacrylate in the formulation. The prepared nanosuspension exhibited good stability after storage at room temperature and at 4(0)C. Sucrose and Mannitol were used as cryoprotectants and exhibited good water redispersibility of the FDN. The results indicate that the formulation of sulfacetamide in Eudragit® RL100 nanosuspension could be utilized as potential delivery system for treating ocular bacterial infections.

Diacerein niosomal gel for topical delivery: development, in vitro and in vivo assessment.

PubMed

El-Say, Khalid M; Abd-Allah, Fathy I; Lila, Ahmed E; Hassan, Abd El-Saboor A; Kassem, Alaa Eldin A

2016-01-01

The purpose of this study was to load diacerein (DCR) in niosomes by applying response surface methodology and incorporate these niosomes in gel base for topical delivery. Box-Behnken design was used to investigate the effect of charge-inducing agent (X1), surfactant HLB (X2) and sonication time (X3) on the vesicle size (Y1), entrapment efficiency (Y2) and cumulative drug released (Y3). DCR niosomal formulations were prepared by thin film hydration method. The optimized formula was incorporated in different gel bases. DCR niosomal gels were evaluated for homogeneity, rheological behavior; in vitro release and pharmacodynamic activity by carrageenan-induced hind paw edema method in the rat compared with DCR commercial gel. The results revealed that the mean vesicle sizes of the prepared niosomes ranged from 7.33 to 23.72 µm and the entrapment efficiency ranged from 9.52% to 58.43% with controlled release pattern over 8 h. DCR niosomal gels exhibited pseudoplastic flow with thixotropic behavior. The pharmacodynamic activity of DCR niosomal gel in 3% HPMC showed significant, 37.66%, maximum inhibition of edema size in comparison with 20.83% for the commercial gel (p < 0.05). These results recommended the incorporation of DCR niosomes in 3% HPMC for topical application as a potent anti-inflammatory drug for the treatment of osteoarthritis.

Nanovesicles for transdermal delivery of felodipine: Development, characterization, and pharmacokinetics

PubMed Central

Yusuf, Mohd; Sharma, Vijay; Pathak, Kamla

2014-01-01

Aim: The research traces development of nanovesicles to attain enhanced transdermal delivery of felodipine and also investigates parameters for optimization of variable membrane compositions containing soya- and egg lecithin and edge activator. Materials and Methods: Rotary evaporation sonication method was employed to obtain tranfersomal formulation that was characterized for vesicle shape and size, polydispersity index (PDI), zeta potential, entrapment and loading efficiency, deformability index and in vitro skin permeation. Results: Spherical nanovesicles of 75.71 ± 5.4 nm with PDI 0.228 and zeta potential of −49.8 were adjudged as the best formulation (MF8). MF8 displayed maximum entrapment and loading efficiency with a high deformability index of 119.68. In vitro permeation across rat skin by MF8 reported 256% enhancement in permeation (flux = 23.72 ± 0.64) when compared with transdermal control formulation and followed zero order kinetics (Case-II). Pharmacokinetic studies revealed that transdermal administration, in contrast to oral delivery provided relatively constant, sustained blood concentration with minimal plasma fluctuation, rapid and prolonged peak time. The relative bioavailability of felodipine was found 358.42% versus oral administration that was well supported by the outcomes of confocal laser scanning microscopic studies that suggested rapid permeation of drugs to across dermal layers. Conclusion: The results conclude that composition variation and method of preparation elicited significant effect on the vesicle characteristic and proved the transcendency of felodipine loaded transfersomes. PMID:25126525

PLGA nano/microparticles loaded with cresyl violet as a tracer for drug delivery: Characterization and in-situ hyperspectral fluorescence and 2-photon localization.

PubMed

Lunardi, Claure N; Gomes, Anderson J; Palepu, Sandeep; Galwaduge, P Thilanka; Hillman, Elizabeth M C

2017-01-01

Here we present the production, characterization and in-vivo assessment of cresyl violet-loaded biodegradable PLGA nano/microparticles (CV-NP and CV-MP). We demonstrate that the beneficial spectral characteristics of cresyl violet make it suitable as a tracer for particle-based drug delivery using both hyperspectral wide field and two-photon excited fluorescence microscopy. Particles were prepared using a cosolvent method, after which the physicochemical properties such as morphology, particle size, drug entrapment efficiency, drug loading and in vitro drug release behavior were measured in addition to spectroscopic properties, such as absorption, fluorescence and infrared spectra. The particles were then tested in an in vivo mouse model to assess their biodistribution characteristics. The location and integrity of particles after injection was determined using both hyperspectral fluorescence and two-photon microscopy within intact organs in situ. Our results show that cresyl violet is efficiently entrapped into PLGA particles, and that the particles are spherical in shape, ranging from 300 to 5070nm in diameter. Particle biodistribution in the mouse was found to depend on particle size, as expected. Cresyl violet is shown to be an ideal tracer to assess the properties PLGA particle-based drug delivery in combination with our novel multi-scale optical imaging techniques for in-situ particle localization. Copyright © 2016 Elsevier B.V. All rights reserved.

Development and biological evaluation of Gymnema sylvestre extract-loaded nonionic surfactant-based niosomes.

PubMed

Kamble, Bhagyashree; Talreja, Seema; Gupta, Ankur; Patil, Dada; Pathak, Deepa; Moothedath, Ismail; Duraiswamy, Basavan

2013-08-01

To develop and characterize Gymnema sylvestre extract-loaded niosomes using nonionic surfactants, and to evaluate their antihyperglycemic efficacy in comparison with the parent extract. Nonionic surfactant-based G. sylvestre extract-loaded niosomes were prepared using the thin-film hydration method. The optimized formulation was screened for entrapment efficiency of the constituents, as well as other parameters such as release kinetics, vesicle size, zeta-potential and stability studies. The parent extract and optimized niosomal formulation were evaluated for their antihyperglycemic potential in an alloxan-induced diabetic animal model. Niosomes prepared using Span™ 40 (SD Fine Chemicals Ltd, Mumbai, India) provided sterically stable vesicles 229.5 nm in size with zeta-potential and entrapment efficiency of 150.86 mV and 85.3 ± 4.5%, respectively. The surface morphology of vesicles was confirmed to be spherical by scanning electron microscopy studies. An in vitro release study demonstrated 77.4% of phytoconstituents release within 24 h. The niosome formulation demonstrated significant blood glucose level reduction in an oral glucose tolerance test, and increased antihyperglycemic activity compared with the parent extract in an alloxan-induced diabetic model. This study reveals the merits of G. sylvestre extract-loaded niosomes, and justifies the potential of niosomes for improving the efficacy of G. sylvestre extract as antidiabetic. Original submitted 30 March 2012; Revised submitted 29 August 2012; Published online 24 December 2012.

Phototoxicity free quantum dot-based niosome formulation for controlled drug release and its monitoring

NASA Astrophysics Data System (ADS)

Kumar, Sunil; Kang, T. W.; Bala, Suman; Kamboj, Sunil; Jeon, H. C.

2018-04-01

A novel niosomes-based system composed of Hypromellose (HPMC) functionalized fluorescent, biocompatible ZnS:Mn quantum dots (QDs), and anti-HIV drug Tenofovir disoproxil fumarate (TDF) was designed. An appropriate ratio of surfactant Sorbitan Monostearate (SPAN-60) and cholesterol was used to obtain an optimal entrapment efficiency. Initially, after observing the successful interaction of HPMC with SPAN-60, the noisome formulation including (QDs + drug) and HPMC-coated QDs was synthesized by a wet chemical route and characterized by X-ray diffraction (XRD), Transmission electron microscope (TEM) and Selected Electron Diffraction (SAED). Secondly, (QDs + drug) loaded niosome formulations were studied by varying the ratio of SPAN-60 and cholesterol. Multiple studies were done to characterize the shape, size, viscosity, colloidal stability, and entrapment efficiency of (QDs + drug) loaded niosomes. Lastly, pH-dependent (QDs + drug) release profiles were studied by a spectroscopic technique considering the pH of the human gastrointestinal region to obtain the formulation stability of (QDs + drug) release from the niosome vesicles. These studies also include pH-dependent photo-stability measurements based on laser-induced multiphoton excitation technique in the Infrared region. The multiphoton time-resolved studies were completed to avoid the UV induced phototoxicity in the drug delivery modules. Current studies on the formulation of niosomes-based (QDs + drug) system laid a foundation to make a complete phototoxicity free system for tracking controlled drug release and its imaging.

Preparation, characterization and evaluation of ranitidine hydrochloride-loaded mucoadhesive microspheres.

PubMed

Dhankar, Vandana; Garg, Garima; Dhamija, Koushal; Awasthi, Rajendra

2014-01-01

Mucoadhesion enables localization of drugs to a defined region of the gastrointestinal tract through attractive interactions between polymers composing the drug delivery devices and the mucin layer of the intestinal epithelium. Thus, this approach can be used for enhancement of the oral bioavailability of the drug. The current communication deals with the development of ranitidine hydrochloride-loaded chitosan-based mucoadhesive microspheres. Microspheres were prepared by water-in-oil emulsion technique, using glutaraldehyde as a cross-linking agent. The effect of independent variables like stirring speed and polymer-to-drug ratio on dependent variables, i.e. percentage mucoadhesion, percentage drug loading, particle size and swelling index, was examined using a 3(2); factorial design. The microspheres were discrete, spherical, free-flowing and also showed high percentage drug entrapment efficiency (43-70%). An in vitro mucoadhesion test showed that the microspheres adhered strongly to the mucous layer for an extended period of time. The RC 4 batch exhibited a high percentage of drug encapsulation (70%) and mucoadhesion (75%). The drug release was sustained for more than 12 h. The drug release kinetics were found to follow Peppas' kinetics for all the formulations and the drug release was diffusion controlled. The preliminary results of this study suggest that the developed microspheres containing ranitidine hydrochloride could enhance drug entrapment efficiency, reduce the initial burst release and modulate the drug release.

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

16 CFR Figure 2 to Part 1513 - Test Probe for Neck Entrapment

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Test Probe for Neck Entrapment 2 Figure 2 to Part 1513 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR BUNK BEDS Pt. 1513, Fig. 2 Figure 2 to Part 1513—Test Probe for Neck Entrapment...

16 CFR Figure 2 to Part 1513 - Test Probe for Neck Entrapment

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Test Probe for Neck Entrapment 2 Figure 2 to Part 1513 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR BUNK BEDS Pt. 1513, Fig. 2 Figure 2 to Part 1513—Test Probe for Neck Entrapment...

16 CFR Figure 2 to Part 1513 - Test Probe for Neck Entrapment

Code of Federal Regulations, 2014 CFR

2014-01-01

... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Test Probe for Neck Entrapment 2 Figure 2 to Part 1513 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR BUNK BEDS Pt. 1513, Fig. 2 Figure 2 to Part 1513—Test Probe for Neck Entrapment...

16 CFR Figure 2 to Part 1513 - Test Probe for Neck Entrapment

Code of Federal Regulations, 2013 CFR

2013-01-01

... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Test Probe for Neck Entrapment 2 Figure 2 to Part 1513 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR BUNK BEDS Pt. 1513, Fig. 2 Figure 2 to Part 1513—Test Probe for Neck Entrapment...

16 CFR Figure 2 to Part 1513 - Test Probe for Neck Entrapment

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Test Probe for Neck Entrapment 2 Figure 2 to Part 1513 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR BUNK BEDS Pt. 1513, Fig. 2 Figure 2 to Part 1513—Test Probe for Neck Entrapment...

The novel formulation design of self-emulsifying drug delivery systems (SEDDS) type O/W microemulsion III: the permeation mechanism of a poorly water soluble drug entrapped O/W microemulsion in rat isolated intestinal membrane by the Ussing chamber method.

PubMed

Araya, Hiroshi; Tomita, Mikio; Hayashi, Masahiro

2006-02-01

We used ibuprofen as a poorly water soluble model drug, to examine the influence of bile salts and mucin layers on the permeability of that entrapped in an O/W microemulsion, in a rat isolated intestinal membrane by the Ussing chamber method. Under the presence of 3 kinds of the primary bile salts such a sodium taurocholate, etc., or a secondary bile salt such a sodium taurochenodeoxycholate at 0.01 mmol/L concentration, a significant difference was not demonstrated in the permeation clearance of the ibuprofen entrapped O/W microemulsion, as compared with the case without the bile salts. Thus, the bile salts did not have a remarkable influence on the permeability of the drug entrapped in the O/W microemulsion, and it was verified that this O/W microemulsion was hardly influenced by the flow of the bile secretion. On the other hand, when N-acetyl-L-cysteine (NAC) with the removal ability of a mucin layer was combined with the ibuprofen entrapped O/W microemulsion at the concentration of 3 and 10 mmol/L, it was shown that the permeation clearance of free ibuprofen did not decrease, but that of ibuprofen entrapped in the O/W microemulsion decreased with the increase of the NAC concentration. Therefore, it is confirmed that the mucin layer participates in the permeability of the drug entrapped in the O/W microemulsion. From these results, the mechanism in which the drug entrapped in the O/W microemulsion is released in a mucin layer, without passing through the route of the mixed micelle formation by bile, thereafter the drug permeates an intestinal membrane, is supposed.

Chronic Localized Back Pain Due to Posterior Cutaneous Nerve Entrapment Syndrome (POCNES): A New Diagnosis.

PubMed

Boelens, Oliver B; Maatman, Robert C; Scheltinga, Marc R; van Laarhoven, Kees; Roumen, Rudi M

2017-03-01

Most patients with chronic back pain suffer from degenerative thoracolumbovertebral disease. However, the following case illustrates that a localized peripheral nerve entrapment must be considered in the differential diagnosis of chronic back pain. We report the case of a 26-year-old woman with continuous excruciating pain in the lower back area. Previous treatment for nephroptosis was to no avail. On physical examination the pain was present in a 2 x 2 cm area overlying the twelfth rib some 4 cm lateral to the spinal process. Somatosensory testing using swab and alcohol gauze demonstrated the presence of skin hypo- and dysesthesia over the painful area. Local pressure on this painful spot elicited an extreme pain response that did not irradiate towards the periphery. These findings were highly suggestive of a posterior version of the anterior cutaneous nerve entrapment syndrome (ACNES), a condition leading to a severe localized neuropathic pain in anterior portions of the abdominal wall. She demonstrated a beneficial albeit temporary response after lidocaine infiltration as dictated by an established diagnostic and treatment protocol for ACNES. She subsequently underwent a local neurectomy of the involved superficial branch of the intercostal nerve. This limited operation had a favorable outcome resulting in a pain-free return to normal activities up to this very day (follow-up of 24 months).We propose to name this novel syndrome "posterior cutaneous nerve entrapment syndrome" (POCNES). Each patient with chronic localized back pain should undergo simple somatosensory testing to detect the presence of overlying skin hypo- and dysesthesia possibly reflecting an entrapped posterior cutaneous nerve.Key words: Chronic pain, back pain, posterior cutaneous nerve entrapment, peripheral nerve entrapment, surgical treatment for pain, anterior cutaneous nerve entrapment.

Contributing Causes of Injury or Death in Grain Entrapment, Engulfment, and Extrication.

PubMed

Issa, Salah Fuad; Field, William E; Schwab, Charles V; Issa, Fadi S; Nauman, Eric A

2017-01-01

Grain entrapments and engulfments are one of most common hazards associated with grain storage facilities, with over 1,140 such entrapments/engulfments documented since the 1970s. The objective of the study was to determine the factors that contribute to injury or death in grain entrapment, engulfment, and extrication cases. A literature review, including data contained in the Purdue Agricultural Confined Spaces Incident Database (PACSID), was conducted to determine the conditions that the body experiences during an entrapment or engulfment in grains and during extrication efforts. Based on the review, the conditions a human body faces during an entrapment, engulfment, or extraction can be split into two broad categories-environmental and physiological/psychological. The environmental factors depend on the grain's properties, depth of entrapment or engulfment, position of the victim's body, and characteristics of the storage unit, which include the grain's lateral pressure, vertical pressure, and weight, as well as friction, oxygen availability and diffusion rate, and grain temperature. The physiological and psychological factors are related to the individual's age and physical and psychological conditions, and manifest themselves in terms of oxygen consumption, asphyxiation (including aspiration, lack of oxygen, compression or splinting of the thorax), blood flow, and heart rate. Of all the above factors, a review of fatality data contained in the PACSID indicate that aspiration, asphyxiation, grain weight, and lateral pressure are most likely the primary cause of death for most entrapment victims. Research gaps found by this study include an understanding of the impact of lateral pressure on lung expansion and oxygen availability and consumption rate, and the need for more case studies to accurately determine cause of death.

Microscopic Examination of Chitosan Polyphosphate Beads with Entrapped Spores of the Biocontrol Agent, Streptomyces melanosporofaciens EF-76

NASA Astrophysics Data System (ADS)

Jobin, Guy; Grondin, Gilles; Couture, Geneviève; Beaulieu, Carole

2005-04-01

Spores of the biocontrol agent, Streptomyces melanosporofaciens EF-76, were entrapped by complex coacervation in beads composed of a macromolecular complex (MC) of chitosan and polyphosphate. A proportion of spores entrapped in beads survived the entrapment procedure as shown by treating spores from chitosan beads with a dye allowing the differentiation of live and dead cells. The spore-loaded chitosan beads could be digested by a chitosanase, suggesting that, once introduced in soil, the beads would be degraded to release the biocontrol agent. Spore-loaded beads were examined by optical and scanning electron microscopy because the release of the biological agent depends on the spore distribution in the chitosan beads. The microscopic examination revealed that the beads had a porous surface and contained a network of inner microfibrils. Spores were entrapped in both the chitosan microfibrils and the bead lacuna.

Fluxgate magnetorelaxometry for characterization of hydrogel polymerization kinetics and physical entrapment capacity.

PubMed

Heim, E; Harling, S; Ludwig, F; Menzel, H; Schilling, M

2008-05-21

Hydrogels have the potential for providing drug delivery systems with long release rates. The polymerization kinetics and the physical entrapment capacity of photo-cross-linked hydroxyethyl methacrylate hydroxyethylstarch hydrogels are investigated with a non-destructive method. For this purpose, superparamagnetic nanoparticles as replacements for biomolecules are used as probes. By analyzing their magnetic relaxation behavior, the amounts of physically entrapped and mobile nanoparticles can be determined. The hydrogels were loaded with five different concentrations of nanoparticles. Different methods of analysis of the relaxation curves and the influence of the microviscosity are discussed. This investigation allows one to optimize the UV light irradiation time and to determine the amount of physically entrapped nanoparticles in the hydrogel network. It was found that the polymerization kinetics is faster for decreasing nanoparticle concentration but not all nanoparticles can be physically entrapped in the network.

A new diagnostic approach to popliteal artery entrapment syndrome

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

Williams, Charles; Kennedy, Dominic; Bastian-Jordan, Matthew

A new method of diagnosing and defining functional popliteal artery entrapment syndrome is described. By combining ultrasonography and magnetic resonance imaging techniques with dynamic plantarflexion of the ankle against resistance, functional entrapment can be demonstrated and the location of the arterial occlusion identified. This combination of imaging modalities will also define muscular anatomy for guiding intervention such as surgery or Botox injection.

Thermal stabilization of glucose oxidase and glucoamylase by physical entrapment.

PubMed Central

Basaveswara Rao, V; Sastri, N V; Subba Rao, P V

1981-01-01

Physical entrapment was used as an approach to achieve thermal stabilization of enzymes. The t 1/2 values for the thermoinactivation of glucose oxidase and glucoamylase were increased several-fold by their entrapment in polyacrylamide gels. In polyacrylate gels the individual enzymes behaved differently, probably owing to microenvironmental effects arising by the polyelectrolyte nature of the carrier. PMID:6796045

Environmental controls of wood entrapment in upper Midwestern streams

USGS Publications Warehouse

Merten, Eric C.; Finlay, Jacques; Johnson, Lucinda; Newman, Raymond; Stefan, Heinz; Vondracek, Bruce C.

2011-01-01

Wood deposited in streams provides a wide variety of ecosystem functions, including enhancing habitat for key species in stream food webs, increasing geomorphic and hydraulic heterogeneity and retaining organic matter. Given the strong role that wood plays in streams, factors that influence wood inputs, retention and transport are critical to stream ecology. Wood entrapment, the process of wood coming to rest after being swept downstream at least 10 m, is poorly understood, yet important for predicting stream function and success of restoration efforts. Data on entrapment were collected for a wide range of natural wood pieces (n = 344), stream geomorphology and hydraulic conditions in nine streams along the north shore of Lake Superior in Minnesota. Locations of pieces were determined in summer 2007 and again following an overbank stormflow event in fall 2007. The ratio of piece length to effective stream width (length ratio) and the weight of the piece were important in a multiple logistic regression model that explained 25% of the variance in wood entrapment. Entrapment remains difficult to predict in natural streams, and often may simply occur wherever wood pieces are located when high water recedes. However, this study can inform stream modifications to discourage entrapment at road crossings or other infrastructure by applying the model formula to estimate the effective width required to pass particular wood pieces. Conversely, these results could also be used to determine conditions (e.g. pre-existing large, stable pieces) that encourage entrapment where wood is valued for ecological functions.

Starch-entrapped microspheres show a beneficial fermentation profile and decrease in potentially harmful bacteria during in vitro fermentation in faecal microbiota obtained from patients with inflammatory bowel disease.

PubMed

Rose, Devin J; Venema, Koen; Keshavarzian, Ali; Hamaker, Bruce R

2010-05-01

The purpose of this research was to test the hypothesis that starch-entrapped microspheres would produce favourable fermentation profiles and microbial shifts during in vitro fermentation with the faecal microbiota from patients with inflammatory bowel disease (IBD). In vitro fermentation was carried out using a validated, dynamic, computer-controlled model of the human colon (Toegepast Natuurwetenschappelijk Onderzoek gastro-intestinal model-2) after inoculation with pooled faeces from healthy individuals, patients with inactive IBD (Crohn's disease (CD)) or patients with active IBD (ulcerative colitis (UC)). Starch-entrapped microspheres fermented more slowly and produced more butyrate than fructo-oligosaccharides (FOS) when fermented with the faecal microbiota from patients with active UC. When fermented with the microbiota from patients with inactive CD, starch-entrapped microspheres also fermented more slowly but produced similar amounts of butyrate compared with FOS. Starch-entrapped microspheres showed a greater ability to maintain a low pH during simulated-distal colon conditions compared with FOS. After fermentation with the microbiota from inactive CD patients, starch-entrapped microspheres resulted in lower concentrations of some potentially harmful gut bacteria, included in Bacteroides, Enterococcus, Fusobacterium and Veillonella, compared with FOS. These findings suggest that slow fermenting starch-entrapped microspheres may induce a favourable colonic environment in patients with IBD through high butyrate production, maintenance of low pH in the distal colon and inhibition of the growth of potentially harmful bacteria.

Cecal entrapment within the epiploic foramen in a mare.

PubMed

Grzeskowiak, Remigiusz M; Barrett, Elizabeth J; Rodgerson, Dwayne H

2017-08-01

An 11-year-old Thoroughbred mare with colic unresponsive to medical treatment underwent exploratory laparotomy. During surgery the cecum was found entrapped within the epiploic foramen from left to right. The entrapped cecum was reduced through the foramen by gentle traction. After reduction of the cecum, rupture of the portal vein was detected. Loss of a large amount of blood prompted euthanasia during surgery.

Chelators influenced synthesis of chitosan-carboxymethyl cellulose microparticles for controlled drug delivery

NASA Astrophysics Data System (ADS)

Samrot, Antony V.; Akanksha; Jahnavi, Tatipamula; Padmanaban, S.; Philip, Sheryl-Ann; Burman, Ujjala; Rabel, Arul Maximus

2016-11-01

In this study, polyphenolic curcumin is entrapped within microcomposites made of biopolymers chitosan (CS) and carboxymethyl cellulose (CMC) formulated by ionic gelation method. Here, different concentrations of two chelating agents, barium chloride and sodium tripolyphosphate, are used to make microcomposites. Thus, the synthesized microparticles were characterized by FTIR, and their surface morphology was studied by SEM. Drug encapsulation efficiency and the drug release kinetics of CS-CMC composites are also studied. The produced microcomposites were used to study antibacterial activity in vitro.

Development and optimization of locust bean gum and sodium alginate interpenetrating polymeric network of capecitabine.

PubMed

Upadhyay, Mansi; Adena, Sandeep Kumar Reddy; Vardhan, Harsh; Pandey, Sureshwar; Mishra, Brahmeshwar

2018-03-01

The objective of the study was to develop interpenetrating polymeric network (IPN) of capecitabine (CAP) using natural polymers locust bean gum (LBG) and sodium alginate (NaAlg). The IPN microbeads were optimized by Box-Behnken Design (BBD) to provide anticipated particle size with good drug entrapment efficiency. The comparative dissolution profile of IPN microbeads of CAP with the marketed preparation proved an excellent sustained drug delivery vehicle. Ionotropic gelation method utilizing metal ion calcium (Ca 2+ ) as a cross-linker was used to prepare IPN microbeads. The optimization study was done by response surface methodology based Box-Behnken Design. The effect of the factors on the responses of optimized batch was exhibited through response surface and contour plots. The optimized batch was analyzed for particle size, % drug entrapment, pharmacokinetic study, in vitro drug release study and further characterized by FTIR, XRD, and SEM. To study the water uptake capacity and hydrodynamic activity of the polymers, swelling studies and viscosity measurement were performed, respectively. The particle size and % drug entrapment of the optimized batch was 494.37 ± 1.4 µm and 81.39 ± 2.9%, respectively, closer to the value predicted by Minitab 17 software. The in vitro drug release study showed sustained release of 92% for 12 h and followed anomalous drug release pattern. The derived pharmacokinetic parameters of optimized batch showed improved results than pure CAP. Thus, the formed IPN microbeads of CAP proved to be an effective extended drug delivery vehicle for the water soluble antineoplastic drug.

Spectroscopic investigation of the pH controlled inclusion of doxycycline and oxytetracycline antibiotics in cationic micelles and their magnesium driven release.

PubMed

Cesaretti, Alessio; Carlotti, Benedetta; Gentili, Pier Luigi; Clementi, Catia; Germani, Raimondo; Elisei, Fausto

2014-07-24

This work presents a steady-state and time-resolved UV-visible spectroscopic investigation of two antibiotics belonging to the family of tetracyclines (doxycycline and oxytetracycline) in the micellar medium provided by p-dodecyloxybenzyltrimethylammonium bromide (pDoTABr). The spectroscopic analysis has been performed in absorption and emission with femtosecond time resolution, and at pH 5.0 and 8.7 where doxycycline and oxytetracycline are present in their neutral-zwitterionic and monoanionic forms, respectively. The experimental data have been processed by sophisticated data mining methods such as global/target analysis and the maximum entropy method. The results unambiguously indicate that, when doxycycline and oxytetracycline are in their zwitterionic form, they are entrapped within the micelle, while when they are in their monoanionic form, they preferentially show a strong one-to-one interaction with the positively charged surfactant heads. Thus, the pH of the solution controls the inclusion of the investigated drugs into the micelle. When the drugs are entrapped inside the micelles, their spectroscopic and dynamical properties after photoexcitation change appreciably. Interestingly, the entrapped drugs are still able to strongly bind Mg(2+) cations, crucial in determining the biological functioning of tetracyclines. The femtosecond resolved measurements reveal that the drugs are efficiently pulled out of the micelles by Mg(2+). In fact, magnesium-tetracycline complexes are detected in the aqueous phase. The present study suggests the potential promising use of ammonium surfactant micelles embedding doxycycline and oxytetracycline as "smart" drug delivery systems allowing their pH controlled inclusion and Mg(2+) induced release.

Physicochemical properties to determine the buoyancy of hollow microspheres (microballoons) prepared by the emulsion solvent diffusion method.

PubMed

Sato, Yasunori; Kawashima, Yoshiaki; Takeuchi, Hirofumi; Yamamoto, Hiromitsu

2003-05-01

Hollow microspheres (microballoons) floatable on JPXIII No.1 solution were developed as a dosage form capable of floating in the stomach. Hollow microspheres were prepared by the emulsion solvent diffusion method using enteric acrylic polymers with drug in a mixture of dichloromethane and ethanol. It was found that preparation temperature determined the formation of cavity inside the microsphere and the surface smoothness, determining the floatability and the drug release rate of the microballoon. The correlation between the buoyancy of microballoons and their physical properties, e.g. apparent density and roundness of microballoons were elucidated. The drug loading efficiency of microballoons with various types of drug was investigated and correlated to the distribution coefficient of drug between dichloromethane and water. The optimum loading amount of riboflavin in the microballoon was found to impart ideal floatable properties to the microballoons. On the other hand, little entrapment was observed for aspirin due to the low distribution coefficient; however, entrapment improved to some extent upon reduction of the pH of the process.

Assessing Atmospheric CO2 Entrapped in Clay Nanotubes using Residual Gas Analyzer.

PubMed

Das, Sankar; Maity, Abhijit; Pradhan, Manik; Jana, Subhra

2016-02-16

A residual gas analyzer (RGA) coupled with a high-vacuum chamber has been explored to measure atmospheric CO2 entrapped in aminosilane-modified clay nanotubes. Ambient CO2 uptake efficacy together with stability of these novel adsorbents composed of both primary and/or secondary amine sites has been demonstrated at standard ambient temperature and pressure. The unprecedented sensitivity and accuracy of the RGA-based mass spectrometry technique toward atmospheric CO2 measurement has been substantiated with a laser-based optical cavity-enhanced integrated cavity output spectroscopy. The adsorption kinetics of atmospheric CO2 on amine-functionalized clay nanotubes followed the fractional-order kinetic model compared to that of the pseudo-first-order or pseudo-second-order rate equations. The efficiency along with stability of these novel adsorbents has also been demonstrated by their repetitive use for CO2 capture in the oxidative environment. Our findings thus point to a fundamental study on the atmospheric CO2 adsorption by amine-loaded adsorbents using an easy handling and low-cost benchtop RGA-based mass spectrometer, opening a new strategy for CO2 capture and sequestering study.

Liposomal Encapsulation Enzymes: From Medical Applications to Kinetic Characteristics.

PubMed

Jahadi, M; Khosravi-Darani, K

2017-01-01

Liposomes and nanoliposomes as small vesicles composed of phospholipid bilayer (entrapping one or more hydrophilic or lipophilic components) have recently found several potential applications in medicine and food industry. These vesicles may protect the core materials from moisture, heat and other extreme conditions. They may also provide controlled release of various bioactive agents, including food ingredients at the right place and time. Potential applications of enzyme-loaded liposomes are in the medical or biomedical field, particularly for the enzymereplacement therapy, as well as cheese industry for production of functional foods with improved health beneficial impacts on the consumer. Encapsulation process has a recondite impact on enzymes. In fact, liposome preparation techniques may alter the pH and temperature optima, affinity of the enzyme to substrate (Km), and maximum rate of reaction (Vmax). In addition, in this paper, the impact of process variables on the kinetic characteristics of enzymes encapsulated in liposomes was investigated. Also, the effects of enzyme entrapment in liposomes, prepared by different methods, on the catalytic efficiency of enzyme, as well as its kinetic properties and stability compared to native (free) enzymes has been reviewed.

Conjugated polymers nanostructured as smart interfaces for controlling the catalytic properties of enzymes.

PubMed

Barbosa, Camila Gouveia; Caseli, Luciano; Péres, Laura Oliveira

2016-08-15

The search for new molecular architectures to improve the efficiency of enzymes entrapped in ultrathin films is useful to enhance the effectiveness of biosensors. In this present work, conjugated polymers, based on thiophene and fluorine, were investigated to verify their suitability as matrices for the immobilization of urease. The copolymer poly[(9,9-dioctylfluorene)-co-thiophene], PDOF-co-Th was spread on the air-water interface forming stable Langmuir monolayers as determined by surface pressure-area isotherms, polarization-modulation reflection-absorption infrared spectroscopy (PM-IRRAS), and Brewster angle microscopy (BAM). Urease was incorporated in the floating monolayers being further transferred to solid supports as mixed Langmuir-Blodgett (LB) films. These films were then characterized with transfer ratio, fluorescence spectroscopy, PM-IRRAS and atomic force microscopy, confirming the co-transfer of the enzyme as well as its structuring in β-sheets. The catalytic activity was detected for urease, with a lower reaction rate than that encountered for the homogeneous environment. This was attributed to conformational constraints imposed to the biomacromolecule entrapped in the polymeric matrix. Copyright © 2016 Elsevier Inc. All rights reserved.

Coupled acoustic-gravity field for dynamic evaluation of ion exchange with a single resin bead.

PubMed

Kanazaki, Takahiro; Hirawa, Shungo; Harada, Makoto; Okada, Tetsuo

2010-06-01

A coupled acoustic-gravity field is efficient for entrapping a particle at the position determined by its acoustic properties rather than its size. This field has been applied to the dynamic observation of ion-exchange reactions occurring in a single resin bead. The replacement of counterions in an ion-exchange resin induces changes in its acoustic properties, such as density and compressibility. Therefore, we can visually trace the advancement of an ion-exchange reaction as a time change in the levitation position of a resin bead entrapped in the field. Cation-exchange reactions occurring in resin beads with diameters of 40-120 microm are typically completed within 100-200 s. Ion-exchange equilibrium or kinetics is often evaluated with off-line chemical analyses, which require a batch amount of ion exchangers. Measurements with a single resin particle allow us to evaluate ion-exchange dynamics and kinetics of ions including those that are difficult to measure by usual off-line analyses. The diffusion properties of ions in resins have been successfully evaluated from the time change in the levitation positions of resin beads.

Surface-Cross-Linked Micelles as Multifunctionalized Organic Nanoparticles for Controlled Release, Light Harvesting, and Catalysis

PubMed Central

2016-01-01

Surfactant micelles are dynamic entities with a rapid exchange of monomers. By “clicking” tripropargylammonium-containing surfactants with diazide cross-linkers, we obtained surface-cross-linked micelles (SCMs) that could be multifunctionalized for different applications. They triggered membrane fusion through tunable electrostatic interactions with lipid bilayers. Antenna chromophores could be installed on them to create artificial light-harvesting complexes with efficient energy migration among tens to hundreds of chromophores. When cleavable cross-linkers were used, the SCMs could break apart in response to redox or pH signals, ejecting entrapped contents quickly as a result of built-in electrostatic stress. They served as caged surfactants whose surface activity was turned on by environmental stimuli. They crossed cell membranes readily. Encapsulated fluorophores showed enhanced photophysical properties including improved quantum yields and greatly expanded Stokes shifts. Catalytic groups could be installed on the surface or in the interior, covalently attached or physically entrapped. As enzyme mimics, the SCMs enabled rational engineering of the microenvironment around the catalysts to afford activity and selectivity not possible with conventional catalysts. PMID:27181610

Fluorescent Biosensor for Phosphate Determination Based on Immobilized Polyfluorene-Liposomal Nanoparticles Coupled with Alkaline Phosphatase.

PubMed

Kahveci, Zehra; Martínez-Tomé, Maria José; Mallavia, Ricardo; Mateo, C Reyes

2017-01-11

This work describes the development of a novel fluorescent biosensor based on the inhibition of alkaline phosphatase (ALP). The biosensor is composed of the enzyme ALP and the conjugated cationic polyfluorene HTMA-PFP. The working principle of the biosensor is based on the fluorescence quenching of this polyelectrolyte by p-nitrophenol (PNP), a product of the hydrolysis reaction of p-nitrophenyl phosphate (PNPP) catalyzed by ALP. Because HTMA-PFP forms unstable aggregates in buffer, with low fluorescence efficiency, previous stabilization of the polyelectrolyte was required before the development of the biosensor. HTMA-PFP was stabilized through its interaction with lipid vesicles to obtain stable blue-emitting nanoparticles (NPs). Fluorescent NPs were characterized, and the ability to be quenched by PNP was evaluated. These nanoparticles were coupled to ALP and entrapped in a sol-gel matrix to produce a biosensor that can serve as a screening platform to identify ALP inhibitors. The components of the biosensor were examined before and after sol-gel entrapment, and the biosensor was optimized to allow the determination of phosphate ion in aqueous medium.

Tissue-based standoff biosensors for detecting chemical warfare agents

DOEpatents

Greenbaum, Elias; Sanders, Charlene A.

2003-11-18

A tissue-based, deployable, standoff air quality sensor for detecting the presence of at least one chemical or biological warfare agent, includes: a cell containing entrapped photosynthetic tissue, the cell adapted for analyzing photosynthetic activity of the entrapped photosynthetic tissue; means for introducing an air sample into the cell and contacting the air sample with the entrapped photosynthetic tissue; a fluorometer in operable relationship with the cell for measuring photosynthetic activity of the entrapped photosynthetic tissue; and transmitting means for transmitting analytical data generated by the fluorometer relating to the presence of at least one chemical or biological warfare agent in the air sample, the sensor adapted for deployment into a selected area.

Polymeric nanoparticles loaded with the 3,5,3'-triiodothyroacetic acid (Triac), a thyroid hormone: factorial design, characterization, and release kinetics.

PubMed

Dos Santos, Karen C; da Silva, Maria Fatima Gf; Pereira-Filho, Edenir R; Fernandes, Joao B; Polikarpov, Igor; Forim, Moacir R

2012-01-01

This present investigation deals with the development and optimization of polymeric nanoparticle systems loaded with 3,5,3'-triiodothyroacetic acid (Triac). A 2(11-6) fractional factorial design and another 2(2) factorial design were used to study the contrasts on particle size distribution, morphology, surface charge, drug content, entrapment efficiency, and in vitro drug release profiles. The independent variables were the concentration of Triac, type and quantity of both polymer and oil, quantity of Span™ 60 and Tween® 80, volume of solvent and water, and velocity of both magnetic stirring and the transfer of the organic phase into the aqueous solution. The results of optimized formulations showed a narrow size distribution with a polydispersity index lower than 0.200. The particle sizes were on average 159.6 nm and 285.6 nm for nanospheres and nanocapsules, respectively. The zeta potential was higher than 20 mV (in module) and the entrapment efficiency was nearly 100%. A high-performance liquid chromatography method was developed, validated, and efficiently applied to Triac quantification in colloidal suspension. The main independent variables were the type and quantity of the polymer and oil. In vitro drug release profile depicted several features to sustain Triac release. Different formulations showed various release rates indicating an interaction between Triac and other formulation compounds such as polymer and/or oil quantity. Two different models were identified (biexponential and monoexponential) that allowed the control of both the release rate and Triac concentration. Thus, the prepared nanoparticles described here may be of clinical importance in delivering Triac for thyroid treatment.

Nano-transfersomal formulations for transdermal delivery of asenapine maleate: in vitro and in vivo performance evaluations.

PubMed

Shreya, A B; Managuli, Renuka S; Menon, Jyothsna; Kondapalli, Lavanya; Hegde, Aswathi R; Avadhani, Kiran; Shetty, Pallavi K; Amirthalingam, Muthukumar; Kalthur, Guruprasad; Mutalik, Srinivas

2016-09-01

Asenapine maleate (ASPM) is an antipsychotic drug for the treatment of schizophrenia and bipolar disorder. Extensive metabolism makes the oral route inconvenient for ASPM. The objective of this study is to increase ASPM bioavailability via transdermal route by improving the skin permeation using combined strategy of chemical and nano-carrier (transfersomal) based approaches. Transfersomes were prepared by the thin film hydration method using soy-phosphatidylcholine (SPC) and sodium deoxycholate (SDC). Transfersomes were characterized for particle size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, surface morphology, and in vitro skin permeation studies. Various chemical enhancers were screened for skin permeation enhancement of ASPM. Optimized transfersomes were incorporated into a gel base containing suitable chemical enhancer for efficient transdermal delivery. In vivo pharmacokinetic study was performed in rats to assess bioavailability by transdermal route against oral administration. Optimized transfersomes with drug:SPC:SDC weight ratio of 5:75:10 were spherical with an average size of 126.0 nm, PDI of 0.232, ZP of -43.7 mV, and entrapment efficiency of 54.96%. Ethanol (20% v/v) showed greater skin permeation enhancement. The cumulative amount of ASPM permeated after 24 h (Q24) by individual effect of ethanol and transfersome, and in combination was found to be 160.0, 132.9, and 309.3 μg, respectively, indicating beneficial synergistic effect of combined approach. In vivo pharmacokinetic study revealed significant (p < 0.05) increase in bioavailability upon transdermal application compared with oral route. Dual strategy of permeation enhancement was successful in increasing the transdermal permeation and bioavailability of ASPM.

Preparation, characterization, drug release and computational modelling studies of antibiotics loaded amorphous chitin nanoparticles.

PubMed

Gayathri, N K; Aparna, V; Maya, S; Biswas, Raja; Jayakumar, R; Mohan, C Gopi

2017-12-01

We present a computational investigation of binding affinity of different types of drugs with chitin nanocarriers. Understanding the chitn polymer-drug interaction is important to design and optimize the chitin based drug delivery systems. The binding affinity of three different types of anti-bacterial drugs Ethionamide (ETA) Methacycline (MET) and Rifampicin (RIF) with amorphous chitin nanoparticles (AC-NPs) were studied by integrating computational and experimental techniques. The binding energies (BE) of hydrophobic ETA, hydrophilic MET and hydrophobic RIF were -7.3kcal/mol, -5.1kcal/mol and -8.1kcal/mol respectively, with respect to AC-NPs, using molecular docking studies. This theoretical result was in good correlation with the experimental studies of AC-drug loading and drug entrapment efficiencies of MET (3.5±0.1 and 25± 2%), ETA (5.6±0.02 and 45±4%) and RIF (8.9±0.20 and 53±5%) drugs respectively. Stability studies of the drug encapsulated nanoparticles showed stable values of size, zeta and polydispersity index at 6°C temperature. The correlation between computational BE and experimental drug entrapment efficiencies of RIF, ETA and MET drugs with four AC-NPs strands were 0.999 respectively, while that of the drug loading efficiencies were 0.854 respectively. Further, the molecular docking results predict the atomic level details derived from the electrostatic, hydrogen bonding and hydrophobic interactions of the drug and nanoparticle for its encapsulation and loading in the chitin-based host-guest nanosystems. The present results thus revealed the drug loading and drug delivery insights and has the potential of reducing the time and cost of processing new antibiotic drug delivery nanosystem optimization, development and discovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

Topical phenytoin nanostructured lipid carriers: design and development.

PubMed

Motawea, Amira; Borg, Thanaa; Abd El-Gawad, Abd El-Gawad H

2018-01-01

Phenytoin (PHT) is an antiepileptic drug that was reported to exhibit high wound healing activity. Nevertheless, its limited solubility, bioavailability, and inefficient distribution during topical administration limit its use. Therefore, this study aims to develop, characterize nanostructured lipid carriers (NLCs), and evaluate their potential in topical delivery of PHT to improve the drug entrapment efficiency and sustained release. The NLCs were prepared by hot homogenization followed by ultra sonication method using 2 3 factorial design. NLC formulations were characterized regarding their particle size (PS), zeta potential (ZP), entrapment efficiency percent (%EE), surface morphology, physicochemical stability, and in vitro release studies. The optimized NLC (F7) was further incorporated in 1%w/v carbopol gel and then characterized for appearance, pH, viscosity, stability, and in vitro drug release. The prepared NLCs were spherical in shape and possessed an average PS of 121.4-258.2 nm, ZP of (-15.4)-(-32.2) mV, and 55.24-88.80 %EE. Solid-state characterization revealed that the drug is dispersed in an amorphous state with hydrogen bond interaction between the drug and the NLC components. NLC formulations were found to be stable at 25 °C for six months. The stored F7-hydrogel showed insignificant changes in viscosity and drug content (p>.05) up to six months at 25 °C that pave a way for industrial fabrication of efficient PHT products. In vitro release studies showed a sustained release from NLC up to 48 h at pH 7.4 following non-Fickian Higuchi kinetics model. These promising findings encourage the potential use of phenytoin loaded lipid nanoparticles for future topical application.

A novel drug delivery gel of terbinafine hydrochloride with high penetration for external use.

PubMed

Yang, Yan; Ou, Rujing; Guan, Shixia; Ye, Xiaoling; Hu, Bo; Zhang, Yi; Lu, Shufan; Zhou, Yubin; Yuan, Zhongwen; Zhang, Jun; Li, Qing-Guo

2015-12-01

Terbinafine hydrochloride is an antifungal drug for onychomycosis. Poor permeability of its external preparation leads to poor curative effect. Transfersomes, also known as flexible liposome, could improve transmission of drug for local external use. Terbinafine hydrochloride-loaded liposome is expected to become a breakthrough on the treatment of onychomycosis. This study is aimed to prepare high skin penetration terbinafine hydrochloride transfersomes with high encapsulation efficiency, appropriate drug loading and good stability. Taking entrapment efficiency as the main indicator, the formulations and the processes of preparation were investigated. Transfersomes with different surfactants were prepared in the optimization processes, and the formulations were optimized through the transdermal test in vitro. As a result, a gel contained transfersomes was obtained with a brief evaluation. Its pharmacokinetic properties of going through the skin were studied by using the micro dialysis technology and liquid chromatography-mass spectrometry to assay the penetration behavior of terbinafine. Mean particle size of the terbinafine hydrochloride transfersomes was 69.6 ± 1.23 nm, and the entrapment efficiency was 95.4% ± 0.51. The content of the gel was 4.45 ± 0.15 mg/g. The accumulated permeation of the transfersomes gel in 12 h was 88.52 ± 4.06 µg cm -2 and the intracutaneous drug detention was 94.38 ± 5.26 µg cm -2 . The results of pharmacokinetic studies showed the C max and area under the curve (AUC) were apparently higher than the commercial cream. The terbinafine hydrochloride transfersomes was highly absorbed by the skin. The absorption rate was significantly higher than that of the commercial cream either in the transdermal test in vitro or in the pharmacokinetic studies in vivo.

Development and biodistribution of a theranostic aluminum phthalocyanine nanophotosensitizer.

PubMed

Asem, Heba; El-Fattah, Ahmed Abd; Nafee, Noha; Zhao, Ying; Khalil, Labiba; Muhammed, Mamoun; Hassan, Moustapha; Kandil, Sherif

2016-03-01

Aluminum phthalocyanine (AlPc) is an efficient second generation photosensitizer (PS) with high fluorescence ability. Its use in photodynamic therapy (PDT) is hampered by hydrophobicity and poor biodistribution. AlPc was converted to a biocompatible nanostructure by incorporation into amphiphilic polyethylene glycol-polycaprolactone (PECL) copolymer nanoparticles, allowing efficient entrapment of the PS in the hydrophobic core, water dispersibility and biodistribution enhancement by PEG-induced surface characteristics. A series of synthesized PECL copolymers were used to prepare nanophotosensitizers with an average diameter of 66.5-99.1nm and encapsulation efficiency (EE%) of 66.4-78.0%. One formulation with favorable colloidal properties and relatively slow release over 7 days was selected for in vitro photophysical assessment and in vivo biodistribution studies in mice. The photophysical properties of AlPc were improved by encapsulating AlPc into PECL-NPs, which showed intense fluorescence emission at 687nm and no AlPc aggregation has been induced after entrapment into the nanoparticles. Biodistribution of AlPc loaded NPs (AlPc-NPs) and free AlPc drug in mice was monitored by in vivo whole body fluorescence imaging and ex vivo organ imaging, with in vivo imaging system (IVIS). Compared to a AlPc solution in aqueous TWEEN 80 (2 w/v%), the developed nanophotosensitizer showed targeted drug delivery to lungs, liver and spleen as monitored by the intrinsic fluorescence of AlPc at different time points (1h, 24h and 48h) post iv. administration. The AlPc-based copolymer nanoparticles developed offer potential as a single agent-multifunctional theranostic nanophotosensitizer for PDT coupled with imaging-guided drug delivery and biodistribution, and possibly also fluorescence diagnostics. Copyright © 2015 Elsevier B.V. All rights reserved.

Preparation and characterization of letrozole-loaded poly(d,l-lactide) nanoparticles for drug delivery in breast cancer therapy.

PubMed

Alemrayat, Bayan; Elhissi, Abdelbary; Younes, Husam M

2018-04-05

Letrozole (LTZ), an aromatase inhibitor used for the treatment of hormonally-positive breast cancer in postmenopausal women, has poor water solubility, rapid metabolism, and a range of side effects. In this study, polymer-based nanoparticles (NPs) incorporating the drug have been designed and characterized, aimed to control the release, potentially maximize the therapeutic efficiency, and minimize the side effects of the drug. LTZ was incorporated into poly(d,l-lactide) (PDLLA) NPs by employing the emulsion-solvent evaporation technique using a range of drug concentrations. Loaded drug and drug-polymer interactions were studied using X-ray diffraction and NPs morphology was evaluated using scanning electron microscopy (SEM). Particle size distribution (PSD) and zeta potential of the NPs were analyzed using dynamic light scattering (DLS) and laser Doppler velocimetry (LDV), respectively. Drug content and release profile studies were carried out and determined using ultra performance liquid chromatography (UPLC). The yield of LTZ-PDLLA NPs reached as high as 85%. The NPs were spherical and smooth, regardless of LTZ concentration in the formulation. However, particle size increased from 241.6 ± 1.2 to 348.7 ± 6.1 nm upon increasing LTZ concentration from 0 to 30% w/w, with entrapment efficiencies reaching up to 96.8%. Drug release from the polymeric matrix was best described by Higuchi model with a predominant diffusion-based mechanism. More than 15, 46, and 86% of LTZ was released in a controlled fashion over 30 d from the 10, 20, and 30% LTZ-PDLLA NPs, respectively. Overall, LTZ-PDLLA NPs were designed with appropriate size and surface charge, high drug loading, superior entrapment efficiency, and prolonged release profile.

Enzyme-entrapping behaviors in alginate fibers and their papers

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

Kobayashi, Y.; Matsuo, R.; Ohya, T.

1987-01-01

Enzyme immobilization in the form of fiber and paper was easily achieved by wet spinning of aqueous admixture of sodium alginate and enzymes into divalent metallic ion solution as a coagulating bath, followed by paper making of resultant shortly cut fibers. Entrapment yields of enzymes used, e.g., glucoamylase, cyclodextrin glucanotransferase, endo-polygalacturonase, and protease, were always higher in calcium alginate fibers and their papers than those in corresponding beads. It was found that the yields increased with an increase of the discharge rate through the spinning nozzle because the higher discharge rate could provide more highly oriented metal-chelate linear polymer moleculesmore » along the fiber axis for preventing leakage of entrapped enzymes. Divalent metallic ions affected greatly the entrapment of glucoamylase in alginate fibers, the order of which followed rougly the ionotropic series of Thiele. Entrapment of glucoamylase in bicomponent systems comprising alginate and other water-soluble polymers was also investigated. (Refs. 41).« less

Hydrodynamic Trapping of Swimming Bacteria by Convex Walls

NASA Astrophysics Data System (ADS)

Sipos, O.; Nagy, K.; Di Leonardo, R.; Galajda, P.

2015-06-01

Swimming bacteria display a remarkable tendency to move along flat surfaces for prolonged times. This behavior may have a biological importance but can also be exploited by using microfabricated structures to manipulate bacteria. The main physical mechanism behind the surface entrapment of swimming bacteria is, however, still an open question. By studying the swimming motion of Escherichia coli cells near microfabricated pillars of variable size, we show that cell entrapment is also present for convex walls of sufficiently low curvature. Entrapment is, however, markedly reduced below a characteristic radius. Using a simple hydrodynamic model, we predict that trapped cells swim at a finite angle with the wall and a precise relation exists between the swimming angle at a flat wall and the critical radius of curvature for entrapment. Both predictions are quantitatively verified by experimental data. Our results demonstrate that the main mechanism for wall entrapment is hydrodynamic in nature and show the possibility of inhibiting cell adhesion, and thus biofilm formation, using convex features of appropriate curvature.

Safety assessment of azelaic acid and its derivatives entrapped in nanovesicles.

PubMed

Panyosak, A; Manosroi, J; Rojanasakul, Y; Manosroi, A

2009-06-01

The aim of this study was to determine the safety of azelaic acid (AA) and its derivatives in nanovesicles for pharmaceutical and cosmetic uses. The hydrophilic property of AA was modified by complexing AA with hydroxypropyl-beta-cyclodextrin (AACD). The lipophilic property of AA was improved to diethyl azelate (DA) by esterification with Fischer reaction. AA, AACD and DA were entrapped in liposomes and niosomes with the compositions of L-alpha-dipalmitoyl phosphatidylcholine/cholesterol = 7:3 and Tween 61/cholesterol = 1:1, respectively, by chloroform film method with sonication. The size of the vesicles ranged from 50 to 200 nm, indicating nanosize characteristics. The cytotoxicity of AA, AACD and DA entrapped nanovesicular formulations on mouse epidermal cell lines (JB6, normal cell lines) by the sulforhodamine B assay was modest when compared with cisplatin. Blank liposomes and niosomes gave no growth inhibitory effect. The irritation of AA, AACD and DA entrapped and not entrapped in nanovesicles on rabbit skin was examined according to the Environmental Protection Agency health effect test guidelines. The results showed no signs of erythema or edema within 72 h. AA and its derivatives were safe for topical use when entrapped in nanovesicles because of no toxicity to normal cell lines and no allergy on rabbit skin.

Vascular entrapment of the sciatic plexus causing catamenial sciatica and urinary symptoms.

PubMed

Lemos, Nucelio; Marques, Renato Moretti; Kamergorodsky, Gil; Ploger, Christine; Schor, Eduardo; Girão, Manoel J B C

2016-02-01

Pelvic congestion syndrome is a well-known cause of cyclic pelvic pain (Ganeshan et al., Cardiovasc Intervent Radiol 30(6):1105-11, 2007). What is much less well known is that dilated or malformed branches of the internal or external iliac vessels can entrap the nerves of the sacral plexus against the pelvic sidewalls, producing symptoms that are not commonly seen in gynecological practice, such as sciatica, or refractory urinary and anorectal dysfunction (Possover et al., Fertil Steril 95(2):756-8. 2011). The objective of this video is to explain and describe the symptoms suggestive of vascular entrapment of the sacral plexus, as well as the technique for the laparoscopic decompression of these nerves. Two anecdotal cases of intrapelvic vascular entrapment are used to review the anatomy of the lumbosacral plexus and demonstrate the laparoscopic surgical technique for decompression at two different sites, one on the sciatic nerve and one on the sacral nerve roots. After surgery, the patient with the sciatic entrapment showed full recovery of the sciatica and partial recovery of the myofascial pain. The patient with sacral nerve root entrapment showed full recovery with resolution of symptoms. The symptoms suggestive of intrapelvic nerve entrapment are: perineal pain or pain irradiating to the lower limbs in the absence of a spinal disorder, and lower urinary tract symptoms in the absence of prolapse of a bladder lesion. In the presence of such symptoms, the radiologist should provide specific MRI sequences of the intrapelvic portion of the sacral plexus and a team and equipment to expose and decompress the sacral nerves should be prepared.

Changes in entrapped gas content and hydraulic conductivity with pressure.

PubMed

Marinas, Maricris; Roy, James W; Smith, James E

2013-01-01

Water table fluctuations continuously introduce entrapped air bubbles into the otherwise saturated capillary fringe and groundwater zone, which reduces the effective (quasi-saturated) hydraulic conductivity, K(quasi), thus impacting groundwater flow, aquifer recharge and solute and contaminant transport. These entrapped gases will be susceptible to compression or expansion with changes in water pressure, as would be expected with water table (and barometric pressure) fluctuations. Here we undertake laboratory experiments using sand-packed columns to quantify the effect of water table changes of up to 250 cm on the entrapped gas content and the quasi-saturated hydraulic conductivity, and discuss our ability to account for these mechanisms in ground water models. Initial entrapped air contents ranged between 0.080 and 0.158, with a corresponding K(quasi) ranging between 2 and 6 times lower compared to the K(s) value. The application of 250 cm of water pressure caused an 18% to 26% reduction in the entrapped air content, resulting in an increase in K(quasi) by 1.16 to 1.57 times compared to its initial (0 cm water pressure) value. The change in entrapped air content measured at pressure step intervals of 50 cm, was essentially linear, and could be modeled according to the ideal gas law. Meanwhile, the changes in K(quasi) with compression-expansion of the bubbles because of pressure changes could be adequately captured with several current hydraulic conductivity models. © Ground Water 2012 and © Her Majesty the Queen in Right of Canada 2012. Ground Water © 2012, National Ground Water Association.

Strategies for prevention of iatrogenic inferior vena cava filter entrapment and dislodgement during central venous catheter placement.

PubMed

Wu, Alex; Helo, Naseem; Moon, Eunice; Tam, Matthew; Kapoor, Baljendra; Wang, Weiping

2014-01-01

Iatrogenic migration of inferior vena cava (IVC) filters is a potentially life-threatening complication that can arise during blind insertion of central venous catheters when the guide wire becomes entangled with the filter. In this study, we reviewed the occurrence of iatrogenic migration of IVC filters in the literature and assessed methods for preventing this complication. A literature search was conducted to identify reports of filter/wire entrapment and subsequent IVC filter migration. Clinical outcomes and complications were identified. A total of 38 cases of filter/wire entrapment were identified. All of these cases involved J-tip guide wires. Filters included 23 Greenfield filters, 14 VenaTech filters, and one TrapEase filter. In 18 cases of filter/wire entrapment, there was migration of the filter to the heart and other central venous structures. Retrieval of the migrated filter was successful in only four of the 18 cases, and all of these cases were complicated by strut fracture and distant embolization of fragments. One patient required resuscitation during retrieval. Successful disengagement was possible in 20 cases without filter migration. Iatrogenic migration of an IVC filter is an uncommon complication related to wire/filter entrapment. This complication can be prevented with knowledge of the patient's history, use of proper techniques when placing a central venous catheter, identification of wire entrapment at an early stage, and use of an appropriate technique to disengage an entrapped wire. Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Ultrasonographic features of intestinal entrapment in dogs.

PubMed

Swift, Inar

2009-01-01

The clinical and ultrasonographic features of postoperative intestinal entrapment were assessed in five dogs. Four had vomiting and lethargy, and one had peracute collapse and hematochezia. Ultrasonographic findings in four of five dogs were similar, being characterized by focally hyperechoic mesentery and abdominal effusion, surrounding a single loop of amotile and dilated intestine. In some dogs, the affected intestinal loop had a thickened or corrugated wall, or alteration of wall layering. In one dog, the site of entrapment could be directly visualized. In the most severely affected dog, a large volume of echogenic peritoneal effusion was present, as well as fluid dilation of multiple intestinal loops. The ultrasonographic appearance of intestinal entrapment is similar to that of intestinal perforation or infarction by other causes.

Membrane-entrapped microperoxidase as a 'solid-state' promoter in the electrochemistry of soluble metalloproteins.

PubMed Central

Brunori, M; Santucci, R; Campanella, L; Tranchida, G

1989-01-01

Immobilization of biological systems in solid matrices is presently of great interest, in view of the many potential advantages associated with both the higher stability of the immobilized macromolecules and the potential utilization for biotechnology. In the present paper the electrochemical behaviour of the undecapeptide from cytochrome c (called microperoxidase) tightly entrapped in cellulose triacetate membrane is reported; its utilization as 'solid-state' promoter in the electrochemistry of soluble metalloproteins is presented. The results obtained indicate that: (i) membrane-entrapped microperoxidase undergoes rapid reversible electron transfer at a glassy carbon electrode; (ii) the electrochemical process is diffusion-controlled; (iii) entrapped microperoxidase acts as 'solid-state' promoter in the electrochemistry of soluble cytochrome c and of azurin. PMID:2557833

Entrapment of Ciliates at the Water-Air Interface

PubMed Central

Ferracci, Jonathan; Ueno, Hironori; Numayama-Tsuruta, Keiko; Imai, Yohsuke; Yamaguchi, Takami; Ishikawa, Takuji

2013-01-01

The importance of water-air interfaces (WAI) on microorganism activities has been recognized by many researchers. In this paper, we report a novel phenomenon: the entrapment of ciliates Tetrahymena at the WAI. We first characterized the behavior of cells at the interface and showed that the cells' swimming velocity was considerably reduced at the WAI. To verify the possible causes of the entrapment, we investigated the effects of positive chemotaxis for oxygen, negative geotaxis and surface properties. Even though the taxes were still effective, the entrapment phenomenon was not dependent on the physiological conditions, but was instead affected by the physical properties at the interface. This knowledge is useful for a better understanding of the physiology of microorganisms at interfaces in nature and in industry. PMID:24130692

Duloxetine HCl lipid nanoparticles: preparation, characterization, and dosage form design.

PubMed

Patel, Ketan; Padhye, Sameer; Nagarsenker, Mangal

2012-03-01

Solid lipid nanoparticles (SLNs) of duloxetine hydrochloride (DLX) were prepared to circumvent the problems of DLX, which include acid labile nature, high first-pass metabolism, and high-dosing frequency. The DLX-SLNs were prepared by using two different techniques, viz. solvent diffusion method and ultrasound dispersion method, and evaluated for particle size, zeta potential, entrapment efficiency, physical characteristics, and chemical stability. Best results were obtained when SLNs were prepared by ultrasound dispersion method using glyceryl mono stearate as solid lipid and DLX in ratio of 1:20 and mixture of polysorbate 80 and poloxamer 188 as surfactant in concentration of 3%. The mean particle size of formulation and entrapment efficiency was 91.7 nm and 87%, respectively, and had excellent stability in acidic medium. Differential scanning calorimetry and X-ray diffraction data showed complete amorphization of DLX in lipid. In vitro drug release from SLNs was observed for 48 h and was in accordance with Higuchi kinetics. In vivo antidepressant activity was evaluated in mice by forced swim test. DLX-SLNs showed significant enhancement in antidepressant activity at 24 h when administered orally in comparison to drug solution. These results confirm the potential of SLNs in enhancing chemical stability and improving the efficacy of DLX via oral route. The SLN dispersion was converted into solid granules by adsorbing on colloidal silicon dioxide and characterized for particle size after redispersion, morphology, and flow properties. Results indicated that nanoparticles were successfully adsorbed on the carrier and released SLNs when dispersed in water.

Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design.

PubMed

Hao, Jifu; Fang, Xinsheng; Zhou, Yanfang; Wang, Jianzhu; Guo, Fengguang; Li, Fei; Peng, Xinsheng

2011-01-01

The purpose of the present study was to optimize a solid lipid nanoparticle (SLN) of chloramphenicol by investigating the relationship between design factors and experimental data using response surface methodology. A Box-Behnken design was constructed using solid lipid (X(1)), surfactant (X(2)), and drug/lipid ratio (X(3)) level as independent factors. SLN was successfully prepared by a modified method of melt-emulsion ultrasonication and low temperature-solidification technique using glyceryl monostearate as the solid lipid, and poloxamer 188 as the surfactant. The dependent variables were entrapment efficiency (EE), drug loading (DL), and turbidity. Properties of SLN such as the morphology, particle size, zeta potential, EE, DL, and drug release behavior were investigated, respectively. As a result, the nanoparticle designed showed nearly spherical particles with a mean particle size of 248 nm. The polydispersity index of particle size was 0.277 ± 0.058 and zeta potential was -8.74 mV. The EE (%) and DL (%) could reach up to 83.29% ± 1.23% and 10.11% ± 2.02%, respectively. In vitro release studies showed a burst release at the initial stage followed by a prolonged release of chloramphenicol from SLN up to 48 hours. The release kinetics of the optimized formulation best fitted the Peppas-Korsmeyer model. These results indicated that the chloramphenicol-loaded SLN could potentially be exploited as a delivery system with improved drug entrapment efficiency and controlled drug release.

Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo oral bioavailability and in situ intestinal absorption of curcumin.

PubMed

Ji, Hongyu; Tang, Jingling; Li, Mengting; Ren, Jinmei; Zheng, Nannan; Wu, Linhua

2016-01-01

The present study was to formulate curcumin solid lipid nanoparticles (Cur-SLNs) with P-gp modulator excipients, TPGS and Brij78, to enhance the solubility and bioavailability of curcumin. The formulation was optimized by Plackett-Burman screening design and Box-Behnken experiment design. Then physiochemical properties, entrapment efficiency and in vitro release of Cur-SLNs were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of Cur-SLNs on the bioavailability and intestinal absorption of curcumin. The optimized formulations showed an average size of 135.3 ± 1.5 nm with a zeta potential value of -24.7 ± 2.1 mV and 91.09% ± 1.23% drug entrapment efficiency, meanwhile displayed a sustained release profile. In vivo pharmacokinetic study showed AUC0→t for Cur-SLNs was 12.27-folds greater than curcumin suspension and the relative bioavailability of Cur-SLNs was 942.53%. Meanwhile, Tmax and t(1/2) of curcumin for Cur-SLNs were both delayed comparing to the suspensions (p < 0.01). The in situ intestinal absorption study revealed that the effective permeability (Peff) value of curcumin for SLNs was significantly improved (p < 0.01) comparing to curcumin solution. Cur-SLNs with TPGS and Brij78 could improve the oral bioavailability and intestinal absorption of curcumin effectively.

Evaluation of bioavailability, efficacy, and safety profile of doxorubicin-loaded solid lipid nanoparticles

NASA Astrophysics Data System (ADS)

Patro, Nagaraju M.; Devi, Kshama; Pai, Roopa S.; Suresh, Sarasija

2013-12-01

We investigated the bioavailability, efficacy, and toxicity of doxorubicin-loaded solid lipid nanoparticles (DOX-SLNs) prepared by a simple modified double-emulsification method. A 3-factor, 3-level Box-Behnken statistical design was adopted in the optimization of DOX-SLN formulation considering dependent factors particle size and entrapment efficiency. Optimized SLN formulation composed of lipid (2 %) consisting of soya lecithin and Precirol ATO 5 (1:3) with Pluronic F68 (0.3 %) resulted in 217.36 ± 3.31 nm particle size and 59.45 ± 1.75 % entrapment efficiency. DOX-SLN exhibited significant enhancement ( p < 0.05) in bioavailability as compared with free DOX in Sprague-Dawley (SD) rats. DOX-SLN exhibited higher peak plasma concentration (6.761 ± 0.08 vs. 2.412 ± 0.04 μg/ml), increased AUC (61.368 ± 3.54 vs. 5.812 ± 0.49 μg/ml h), decreased clearance (36 ± 0.01 vs. 619 ± 0.005 mL/h kg), and volume of distribution (733 ± 0.092 vs. 2,064 ± 0.061 mL/kg) when compared to free DOX. The collective results of cardiac and kidney enzyme assay, antioxidant enzyme levels, hematological parameters, effect on body weight and tumor volume, tumor necrosis factor-α level, histopathological examination, and survival analysis confirmed the improved efficacy and safety profile of DOX-SLN in 7,12-dimethyl benzanthracene-induced breast cancer in SD rats.

Silymarin-Loaded Eudragit Nanoparticles: Formulation, Characterization, and Hepatoprotective and Toxicity Evaluation.

PubMed

El-Nahas, Amira E; Allam, Ahmed N; Abdelmonsif, Doaa A; El-Kamel, Amal H

2017-11-01

The objectives of this study were to formulate, characterize silymarin-loaded Eudragit nanoparticles (SNPs) and evaluate their hepatoprotective and cytotoxic effects after oral administration. SNPs were prepared by nanoprecipitation technique and were evaluated for particle size, entrapment efficiency, TEM, solid-state characterization, and in vitro drug release. The hepatoprotective activity was evaluated after oral administration of selected SNPs in carbon tetrachloride-intoxicated rats. Potential in vivo acute cytotoxicity study was also assessed. The selected SNPs contained 50 mg silymarin and 50 mg Eudragit polymers (1:1 w/w Eudragit RS 100 & Eudragit LS 100). Morphology of the selected SNPs (particle size of 84.70 nm and entrapment efficiency of 83.45% with 100% drug release after 12 h) revealed spherical and uniformly distributed nanoparticles. DSC and FT-IR studies suggested the presence of silymarin in an amorphous state and absence of chemical interaction. The hepatoprotective evaluation of the selected SNPs in CCl 4 -intoxicated rats revealed significant improvement in the activities of different biochemical parameters (P ≤ 0.01) compared to the marketed product. The histopathological studies suggested that the selected SNPs produced better hepatoprotective effect in CCl 4 -intoxicated rats compared with the commercially marketed product. Toxicity study revealed no evident toxic effect for blank or silymarin-loaded nanoparticles at the dose level of 50 mg/kg body weight. The obtained results suggested that the selected SNPs were safe and potentially offered enhancement in the pharmacological hepatoprotective properties of silymarin.

A study on ethosomes as mode for transdermal delivery of an antidiabetic drug.

PubMed

Bodade, Siddhodhan S; Shaikh, Karimunnisa Sameer; Kamble, Meghana S; Chaudhari, Praveen D

2013-01-01

A transdermal delivery system is warranted for repaglinide (RPG) which possesses half-life of 1 h and oral bioavailability of 56%. Ethosomes are useful tools for transdermal drug delivery. To prepare and evaluate ethosomes as mode for transdermal delivery of RPG. Ethosomes loaded with RPG were prepared from dipalmitoyl phosphatidylcholine and ethanol by the cold method. They were characterized using Fourier transform infrared spectroscopy and differential scanning calorimetry. They were evaluated for vesicle size, entrapment efficiency and ex-vivo skin permeation. Ethosomal composition was optimized using the 3(2) factorial design. Gel containing optimzsed ethosomes was studied for antidiabetic activity in rats. RPG ethosomes possessing the size of 0.171-1.727 µm and entrapment efficiency of 75-92% were obtained. They demonstrated a significantly higher permeation (64-97% of the administered dose) across excised rat skin when compared to free drug and its hydro alcoholic solution. In-vivo, RPG ethosomal system caused sustained antidiabetic effect. The lipid and ethanol concentration affected the physicochemical attributes and performance of ethosomes. The flexible ethosomes permeated the stratum corneum and improvized the availability of RPG for antidiabetic action. They prolonged the antidiabetic effect of RPG over a significantly longer period of time in comparison with the equivalent oral dose. Ethosomal system can successfully deliver RPG transdermally; sustain its effect and thus reduce its dosing frequency. Ethosomes are useful for enhancing the efficacy of RPG in the treatment of diabetes.

Development of New Lipid-Based Paclitaxel Nanoparticles Using Sequential Simplex Optimization

PubMed Central

Dong, Xiaowei; Mattingly, Cynthia A.; Tseng, Michael; Cho, Moo; Adams, Val R.; Mumper, Russell J.

2008-01-01

The objective of these studies was to develop Cremophor-free lipid-based paclitaxel (PX) nanoparticle formulations prepared from warm microemulsion precursors. To identify and optimize new nanoparticles, experimental design was performed combining Taguchi array and sequential simplex optimization. The combination of Taguchi array and sequential simplex optimization efficiently directed the design of paclitaxel nanoparticles. Two optimized paclitaxel nanoparticles (NPs) were obtained: G78 NPs composed of glyceryl tridodecanoate (GT) and polyoxyethylene 20-stearyl ether (Brij 78), and BTM NPs composed of Miglyol 812, Brij 78 and D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS). Both nanoparticles successfully entrapped paclitaxel at a final concentration of 150 μg/ml (over 6% drug loading) with particle sizes less than 200 nm and over 85% of entrapment efficiency. These novel paclitaxel nanoparticles were stable at 4°C over three months and in PBS at 37°C over 102 hours as measured by physical stability. Release of paclitaxel was slow and sustained without initial burst release. Cytotoxicity studies in MDA-MB-231 cancer cells showed that both nanoparticles have similar anticancer activities compared to Taxol®. Interestingly, PX BTM nanocapsules could be lyophilized without cryoprotectants. The lyophilized powder comprised only of PX BTM NPs in water could be rapidly rehydrated with complete retention of original physicochemical properties, in-vitro release properties, and cytotoxicity profile. Sequential Simplex Optimization has been utilized to identify promising new lipid-based paclitaxel nanoparticles having useful attributes. PMID:19111929

In situ generation of sodium alginate/hydroxyapatite nanocomposite beads as drug-controlled release matrices.

PubMed

Zhang, J; Wang, Q; Wang, A

2010-02-01

In order to find a new way to slow down the release of drugs and to solve the burst release problem of drugs from traditionally used hydrogel matrices, a series of novel pH-sensitive sodium alginate/hydroxyapatite (SA/HA) nanocomposite beads was prepared by the in situ generation of HA micro-particles in the beads during the sol-gel transition process of SA. The SA/HA nanocomposites were characterized by Fourier transform IR spectroscopy, X-ray fluorescence spectrometry, scanning electron microscopy and field emission SEM in order to reveal their composition and surface morphology as well as the role that the in situ generated HA micro-particles play. The factors influencing the swelling behavior, drug loading and controlled release behavior of the SA/HA nanocomposite beads were also investigated using diclofenac sodium (DS) as the model drug. The HA micro-particles act as inorganic crosslinkers in the nanocomposites, which could contract and restrict the movability of the SA polymer chains, and then change the surface morphology and decrease the swell ratio. Meanwhile, the entrapment efficiency of DS was improved, and the burst release of DS was overcome. The factors (including concentration of Ca(2+), reaction time and temperature) affecting the growth of HA micro-particles have a clear influence on the entrapment efficiency and release rate of DS. In this work, the nanocomposite beads prepared under optimum condition could prolong the release of DS for 8h more compared with the pristine SA hydrogel beads.

Development and optimization of solid lipid nanoparticle formulation for ophthalmic delivery of chloramphenicol using a Box-Behnken design

PubMed Central

Hao, Jifu; Fang, Xinsheng; Zhou, Yanfang; Wang, Jianzhu; Guo, Fengguang; Li, Fei; Peng, Xinsheng

2011-01-01

The purpose of the present study was to optimize a solid lipid nanoparticle (SLN) of chloramphenicol by investigating the relationship between design factors and experimental data using response surface methodology. A Box-Behnken design was constructed using solid lipid (X1), surfactant (X2), and drug/lipid ratio (X3) level as independent factors. SLN was successfully prepared by a modified method of melt-emulsion ultrasonication and low temperature-solidification technique using glyceryl monostearate as the solid lipid, and poloxamer 188 as the surfactant. The dependent variables were entrapment efficiency (EE), drug loading (DL), and turbidity. Properties of SLN such as the morphology, particle size, zeta potential, EE, DL, and drug release behavior were investigated, respectively. As a result, the nanoparticle designed showed nearly spherical particles with a mean particle size of 248 nm. The polydispersity index of particle size was 0.277 ± 0.058 and zeta potential was −8.74 mV. The EE (%) and DL (%) could reach up to 83.29% ± 1.23% and 10.11% ± 2.02%, respectively. In vitro release studies showed a burst release at the initial stage followed by a prolonged release of chloramphenicol from SLN up to 48 hours. The release kinetics of the optimized formulation best fitted the Peppas–Korsmeyer model. These results indicated that the chloramphenicol-loaded SLN could potentially be exploited as a delivery system with improved drug entrapment efficiency and controlled drug release. PMID:21556343

Cyclosporine a loaded solid lipid nanoparticles: optimization of formulation, process variable and characterization.

PubMed

Varia, Jigisha K; Dodiya, Shamsunder S; Sawant, Krutika K

2008-01-01

Solid lipid nanoparticles (SLNs) loaded with Cyclosporine A using glyceryl monostearate (GMS) and glyceryl palmitostearate (GPS) as lipid matrices were prepared by melt-homogenization using high-pressure homogenizer. Various process parameters such as homogenization pressure, homogenization cycles and formulation parameters such as ratio of drug: lipid, emulsifier: lipid and emulsifier: co-emulsifier were optimized using particle size and entrapment efficiencies as the dependent variables. The mean particle size of optimized batches of the GMS SLN and GPS SLN were found to be 131 nm and 158 nm and their entrapment efficiencies were 83 +/- 3.08% and 97 +/- 2.59% respectively. To improve the handling processing and stability of the prepared SLNs, the SLN dispersions were spray dried and its effect on size and reconstitution parameters were evaluated. The spray drying of SLNs did not significantly alter the size of SLNs and they exhibited good redispersibility. Solid state studies such as Infra Red Spectroscopy and Differential Scanning Calorimetry indicated absence of any chemical interaction between Cyclosporine A and the lipids. Scanning Electron Microscopy of optimized formulations showed spherical shape with smooth and non porous surface. In vitro release studies revealed that GMS based SLNs released the drug faster (41.12% in 20 hours) than GPS SLNs (7.958% in 20 hours). Release of Cyclosporine A from GMS SLN followed Higuchi equation better than first order while release from GPS SLN followed first order better than Higuchi model.

Nanostructured lipid carriers for oral bioavailability enhancement of raloxifene: Design and in vivo study.

PubMed

Shah, Nirmal V; Seth, Avinash K; Balaraman, R; Aundhia, Chintan J; Maheshwari, Rajesh A; Parmar, Ghanshyam R

2016-05-01

The objective of present work was to utilize potential of nanostructured lipid carriers (NLCs) for improvement in oral bioavailability of raloxifene hydrochloride (RLX). RLX loaded NLCs were prepared by solvent diffusion method using glyceryl monostearate and Capmul MCM C8 as solid lipid and liquid lipid, respectively. A full 3(2) factorial design was utilized to study the effect of two independent parameters namely solid lipid to liquid lipid ratio and concentration of stabilizer on the entrapment efficiency of prepared NLCs. The statistical evaluation confirmed pronounced improvement in entrapment efficiency when liquid lipid content in the formulation increased from 5% w/w to 15% w/w. Solid-state characterization studies (DSC and XRD) in optimized formulation NLC-8 revealed transformation of RLX from crystalline to amorphous form. Optimized formulation showed 32.50 ± 5.12 nm average particle size and -12.8 ± 3.2 mV zeta potential that impart good stability of NLCs dispersion. In vitro release study showed burst release for initial 8 h followed by sustained release up to 36 h. TEM study confirmed smooth surface discrete spherical nano sized particles. To draw final conclusion, in vivo pharmacokinetic study was carried out that showed 3.75-fold enhancements in bioavailability with optimized NLCs formulation than plain drug suspension. These results showed potential of NLCs for significant improvement in oral bioavailability of poorly soluble RLX.

Development and in vitro/in vivo evaluation of Zn-pectinate microparticles reinforced with chitosan for the colonic delivery of progesterone.

PubMed

Gadalla, Hytham H; Soliman, Ghareb M; Mohammed, Fergany A; El-Sayed, Ahmed M

2016-09-01

The colon is a promising target for drug delivery owing to its long transit time of up to 78 h, which is likely to increase the time available for drug absorption. Progesterone has a short elimination half-life and undergoes extensive first-pass metabolism, which results in very low oral bioavailability (∼25%). To overcome these shortcomings, we developed an oral multiparticulate system for the colonic delivery of progesterone. Zn-pectinate/chitosan microparticles were prepared by ionotropic gelation and characterized for their size, shape, weight, drug entrapment efficiency, mucoadhesion and swelling behavior. The effect of cross-linking pH, cross-linking time and chitosan concentration on progesterone release were also studied. Spherical microparticles having a diameter of 580-720 µm were obtained. Drug entrapment efficiency of ∼75-100% was obtained depending on the microparticle composition. Microparticle mucoadhesive properties were dependent on the pectin concentration, as well as the cross-linking pH. Progesterone release in simulated gastric fluids was minimal (3-9%), followed by burst release at pH 6.8 and a sustained phase at pH 7.4. The in vivo study revealed that the microparticles significantly increased progesterone residence time in the plasma and increased its relative bioavailability to ∼168%, compared to the drug alone. This study confirms the potential of Zn-pectinate/chitosan microparticles as a colon-specific drug delivery system able to enhance the oral bioavailability of progesterone or similar drugs.

Development of ionic-complex-based nanostructured lipid carriers to improve the pharmacokinetic profiles of breviscapine.

PubMed

Li, Mei; Zheng, Yong; Shan, Feng-ying; Zhou, Jing; Gong, Tao; Zhang, Zhi-rong

2013-08-01

Breviscapine isolated from the Chinese herb Erigeron breviscapus (Vant) Hand-Mazz is widely used to treat cardiovascular and cerebrovascular diseases. The aim of this study was to improve the pharmacokinetic profiles of breviscapine using nanostructured lipid carrier based on an ionic complex formation. Breviscapine nanostructured lipid carrier (Bre-NLC) was prepared using the thin film homogenization method. The morphology of Bre-NLCs was determined using transmission electron microscopy. The mean particle size, polydispersity index, zeta-potential analysis and entrapment efficiency were analized. In vitro release was studied using the dialysis method. In vitro stability was studied in fresh plasma and liver slurry of rats. In vivo pharmacokinetics was analyzed in rats after intravenous injection of a dose equivalent to breviscapine (10 mg/kg). The Bre-NLCs were spherical with a mean particle size of ~170 nm, a zeta potential of ∼20 mV and a high entrapment efficiency of ~89%. Compared with a commercially available solution, a substantial decrease in the cumulative release of breviscapine was found for the Bre-NLCs. The NLC has a significantly protective effect against the liver enzyme degradation of breviscapine. After intravenous administration in rats, the Bre-NLCs exhibited a 32 times increase in the AUC0-t and a 12 times increase in T1/2 as compared to the commercially available breviscapine solution. The results demonstrate that the NLC has great potential to use as a novel sustained release system for breviscapine.

Formulation and evaluation of voriconazole ophthalmic solid lipid nanoparticles in situ gel.

PubMed

Pandurangan, Dinesh Kumar; Bodagala, Prathima; Palanirajan, Vijayaraj Kumar; Govindaraj, Saravanan

2016-01-01

In the present investigation, solid lipid nanoparticles (SLNs)-loaded in situ gel with voriconazole drug was formulated. Further, the formulation was characterized for pH, gelling capacity, entrapment efficiency, in vitro drug release, drug content, and viscosity. Voriconazole is an antifungal drug used to treat various infections caused by yeast or other types of fungi. Film hydration technique was used to prepared SLNs from lecithin and cholesterol. Based on the entrapment efficiency 67.2-97.3% and drug release, the optimized formulation NF1 of SLNs was incorporated into in situ gels. The in situ gels were prepared using viscosity-enhancing polymers such as Carbopol and (hydroxypropyl)methyl cellulose (HPMC). Formulated SLN in situ gel formulations were characterized, which showed pH 4.9-7.1, drug content 65.69-96.3%, and viscosity (100 rpm) 120-620 cps. From the characterizations given above, F6 was optimized and evaluated for microbial assay and ocular irritation studies. Microbial assay was conducted by the cup-plate method using Candida albicans as the test organism. An ocular irritation study was conducted on albino rabbits. The results revealed that there was no ocular damage to the cornea, conjunctiva, or iris. Stability studies were carried out on the F6 formulation for 3 months, which showed that the formulation had good stability. These results indicate that the studied SLNs-loaded in situ gel is a promising vehicle for ocular delivery.

Combination of submicroemulsion and phospholipid complex for novel delivery of ursodeoxycholic acid.

PubMed

Ma, Yue-Qin; Li, Gang; Xu, Jiang-Hong; Zhang, Jing; Zhang, Zeng-Zhu; Xiao, Han-Yang; Li, Xian-Fei

2014-05-01

The objective of this study was to prepare and characterize ursodeoxycholic acid submicron emulsion (UA-SME) loaded with ursodeoxycholic acid phytosomes (UA-PS) and optimize the process variables. A screening experiment with response surface methodology with Box-Behnken design (BBD) was used to optimize the process parameters of UA-SME. The blood concentrations of UA after oral administration of UA-SME and UA coarse drug were assayed. The optimum process conditions were finally obtained by using a desirability function. It was found that stirring velocity, homogenization pressure and homogenization cycles were the most important variables that affected the particles size, polydispersity index and entrapment efficiency of UA-SME. Results showed that the optimum stirring velocity, homogenization pressure and cycles were 16 000 rpm, 60 MPa and 10 cycles, respectively. The mean diameter, polydispersity index and entrapment efficiency of UA-SME were 251.9 nm, 0.241 and 74.36%, respectively. Pharmacokinetic parameters of UA and UA-SME in rats were Tmax 2.215 and 1.489 h, Cmax 0.0364 and 0.1562 μg/mL, AUC0-∞ 3.682 and 13.756 μg h/mL, respectively. The bioavailability of UA in rats was significantly different (p < 0.05) after oral administration of UA-SME compared to those of UA coarse drug. This was due to improvement of the hydrophilicity and lipophilic property of UA-SME.

Albumin nanoparticles coated with polysorbate 80 as a novel drug carrier for the delivery of antiretroviral drug—Efavirenz

PubMed Central

Jenita, Josephine Leno; Chocalingam, Vijaya; Wilson, Barnabas

2014-01-01

Purpose of the study: The antiretroviral therapy (ART) has dramatically improved human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) treatment, prevention and also has been found to increase the lifespan of HIV/AIDS patients by providing durable control of the HIV replication in patients. Efavirenz is a non-nucleoside reverse transcriptase inhibitor of HIV-1. The purpose of this study is to formulate efavirenz-loaded bovine serum albumin nanoparticles to improve efavirenz delivery into various organs. Materials and Methods: Nanoparticles were prepared by desolvation technique and coated with polysorbate 80. Ethanol, glutaraldehyde, and mannitol were used as desolvating, cross linking agent, and cryoprotectant, respectively. Drug to polymer ratio was chosen at five levels from 1:2, 1:3, 1:4, 1:5, and 1:6 (by weight). The formulated nanoparticles were characterized for Fourier Transform Infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) studies, entrapment efficiency, particle size, surface charge, surface morphology, in vitro drug release, release kinetics, stability studies, and biodistribution studies. Results and Major Conclusion: The particle size of the prepared formulations was found below 250nm with narrow size distribution, spherical in shape and showed good entrapment efficiency (45.62-72.49%). The in vitro drug release indicated biphasic release and its data were fitted to release kinetics models and release pattern was Fickian diffusion controlled release profile. The prepared nanoparticles increased efavirenz delivery into various organs by several fold in comparison with the free drug. PMID:25126528

Quantitative determination of insulin entrapment efficiency in triblock copolymeric nanoparticles by high-performance liquid chromatography.

PubMed

Xu, Xiongliang; Fu, Yao; Hu, Haiyan; Duan, Yourong; Zhang, Zhirong

2006-04-11

A rapid and effective isocratic chromatographic procedure was described in this paper for the determination of insulin entrapment efficiency (EE) in triblock copolymeric nanoparticles using reversed-phase high-performance liquid chromatography (RP-HPLC) with an ultraviolet/visible detector at low flow rate. The method has been developed on a Shimadzu Shim-pack VP-ODS column (150 mm x 4.6 mm, 5 microm, Chiyoda-Ku, Tokyo, Japan) using a mixture of 0.2 M sodium sulfate anhydrous solution adjusted to pH 2.3 with phosphoric acid and acetonitrile (73:27, v/v) as mobile phase at the flow rate of 0.8 ml min(-1) and a 214 nm detection. The method was validated in terms of selectivity, linearity, precision, accuracy, solution stability, limit of detection (LOD) and limit of quantification (LOQ). The calibration curve was linear in the concentration range of 2.0-500.0 microg ml(-1), and the limits of detection and quantitation were 8 and 20 ng, respectively. The mean recovery of insulin from spiked samples, in a concentration range of 8-100 microg ml(-1), was 98.96% (R.S.D.= 2.51%, n = 9). The intra- and inter-assay coefficients of variation were less than 2.24%. The proposed method has the advantages of simple pretreatment, rapid isolation, high specificity and precision, which can be used for direct analysis of insulin in commercially available raw materials, formulations of nanoparticles, and drug release as well as stability studies.

Nanostructured lipid carriers for oral bioavailability enhancement of raloxifene: Design and in vivo study

PubMed Central

Shah, Nirmal V.; Seth, Avinash K.; Balaraman, R.; Aundhia, Chintan J.; Maheshwari, Rajesh A.; Parmar, Ghanshyam R.

2016-01-01

The objective of present work was to utilize potential of nanostructured lipid carriers (NLCs) for improvement in oral bioavailability of raloxifene hydrochloride (RLX). RLX loaded NLCs were prepared by solvent diffusion method using glyceryl monostearate and Capmul MCM C8 as solid lipid and liquid lipid, respectively. A full 32 factorial design was utilized to study the effect of two independent parameters namely solid lipid to liquid lipid ratio and concentration of stabilizer on the entrapment efficiency of prepared NLCs. The statistical evaluation confirmed pronounced improvement in entrapment efficiency when liquid lipid content in the formulation increased from 5% w/w to 15% w/w. Solid-state characterization studies (DSC and XRD) in optimized formulation NLC-8 revealed transformation of RLX from crystalline to amorphous form. Optimized formulation showed 32.50 ± 5.12 nm average particle size and −12.8 ± 3.2 mV zeta potential that impart good stability of NLCs dispersion. In vitro release study showed burst release for initial 8 h followed by sustained release up to 36 h. TEM study confirmed smooth surface discrete spherical nano sized particles. To draw final conclusion, in vivo pharmacokinetic study was carried out that showed 3.75-fold enhancements in bioavailability with optimized NLCs formulation than plain drug suspension. These results showed potential of NLCs for significant improvement in oral bioavailability of poorly soluble RLX. PMID:27222747

Formulation and Evaluation of Optimized Oxybenzone Microsponge Gel for Topical Delivery

PubMed Central

Pawar, Atmaram P.; Gholap, Aditya P.; Kuchekar, Ashwin B.; Bothiraja, C.; Mali, Ashwin J.

2015-01-01

Background. Oxybenzone, a broad spectrum sunscreen agent widely used in the form of lotion and cream, has been reported to cause skin irritation, dermatitis, and systemic absorption. Aim. The objective of the present study was to formulate oxybenzone loaded microsponge gel for enhanced sun protection factor with reduced toxicity. Material and Method. Microsponge for topical delivery of oxybenzone was successfully prepared by quasiemulsion solvent diffusion method. The effects of ethyl cellulose and dichloromethane were optimized by the 32 factorial design. The optimized microsponges were dispersed into the hydrogel and further evaluated. Results. The microsponges were spherical with pore size in the range of 0.10–0.22 µm. The optimized formulation possesses the particle size and entrapment efficiency of 72 ± 0.77 µm and 96.9 ± 0.52%, respectively. The microsponge gel showed the controlled release and was nonirritant to the rat skin. In creep recovery test it had shown highest recovery indicating elasticity. The controlled release of oxybenzone from microsponge and barrier effect of gel result in prolonged retention of oxybenzone with reduced permeation activity. Conclusion. Evaluation study revealed remarkable and enhanced topical retention of oxybenzone for prolonged period of time. It also showed the enhanced sun protection factor compared to the marketed preparation with reduced irritation and toxicity. PMID:25789176

Analysis of Lipid Phase Behavior and Protein Conformational Changes in Nanolipoprotein Particles upon Entrapment in Sol–Gel-Derived Silica

PubMed Central

2015-01-01

The entrapment of nanolipoprotein particles (NLPs) and liposomes in transparent, nanoporous silica gel derived from the precursor tetramethylorthosilicate was investigated. NLPs are discoidal patches of lipid bilayer that are belted by amphiphilic scaffold proteins and have an average thickness of 5 nm. The NLPs in this work had a diameter of roughly 15 nm and utilized membrane scaffold protein (MSP), a genetically altered variant of apolipoprotein A-I. Liposomes have previously been examined inside of silica sol–gels and have been shown to exhibit instability. This is attributed to their size (∼150 nm) and altered structure and constrained lipid dynamics upon entrapment within the nanometer-scale pores (5–50 nm) of the silica gel. By contrast, the dimensional match of NLPs with the intrinsic pore sizes of silica gel opens the possibility for their entrapment without disruption. Here we demonstrate that NLPs are more compatible with the nanometer-scale size of the porous environment by analysis of lipid phase behavior via fluorescence anisotropy and analysis of scaffold protein secondary structure via circular dichroism spectroscopy. Our results showed that the lipid phase behavior of NLPs entrapped inside of silica gel display closer resemblance to its solution behavior, more so than liposomes, and that the MSP in the NLPs maintain the high degree of α-helix secondary structure associated with functional protein–lipid interactions after entrapment. We also examined the effects of residual methanol on lipid phase behavior and the size of NLPs and found that it exerts different influences in solution and in silica gel; unlike in free solution, silica entrapment may be inhibiting NLP size increase and/or aggregation. These findings set precedence for a bioinorganic hybrid nanomaterial that could incorporate functional integral membrane proteins. PMID:25062385

The Effect of Tissue Entrapment on Screw Loosening at the Implant/Abutment Interface of External- and Internal-Connection Implants: An In Vitro Study.

PubMed

Zeno, Helios A; Buitrago, Renan L; Sternberger, Sidney S; Patt, Marisa E; Tovar, Nick; Coelho, Paulo; Kurtz, Kenneth S; Tuminelli, Frank J

2016-04-01

To compare the removal of torque values of machined implant abutment connections (internal and external) with and without soft tissue entrapment using an in vitro model. Thirty external- and 30 internal-connection implants were embedded in urethane dimethacrylate. Porcine tissue was prepared and measured to thicknesses of 0.5 and 1.0 mm. Six groups (n = 10) were studied: External- and internal-connection implants with no tissue (control), 0.5, and 1.0 mm of tissue were entrapped at the implant/abutment interface. Abutments were inserted to 20 Ncm for all six groups. Insertion torque values were recorded using a digital torque gauge. All groups were then immersed in 1 M NaOH for 48 hours to dissolve tissue. Subsequent reverse torque measurements were recorded. Mean and standard deviation were determined for each group, and one-way ANOVA and Bonferroni test were used for statistical analysis. All 60 specimens achieved a 20-Ncm insertion torque, despite tissue entrapment. Reverse torque measurements for external connection displayed a statistically significant difference (p < 0.05) between all groups with mean reverse torque values for the control (13.71 ± 1.4 Ncm), 0.5 mm (7.83 ± 2.4 Ncm), and 1.0 mm tissue entrapment (2.29 ± 1.4 Ncm) groups. Some statistically significant differences (p < 0.05) were found between internal-connection groups. In all specimens, tissue did not completely dissolve after 48 hours. External-connection implants were significantly affected by tissue entrapment; the thicker the tissue, the lower the reverse torque values noted. Internal-connection implants were less affected by tissue entrapment. © 2015 by the American College of Prosthodontists.

Results from the hydrodynamic element of the 1994 entrapment zone study in Suisun Bay

USGS Publications Warehouse

Burau, J.R.; Gartner, J.W.; Stacey, M.

1998-01-01

The entrapment zo as long been considered an important region of the San Francisco estuary. It has been the subject of several previous studies, and its location has been suggested as an index of condition of the estuarine ecosystem.A close correlate of this location, X2 1, is now used as a management objective on the basis that X2 is correlated with the abundance or survival of several estuarine-dependent species. X2 is a crude tool to use for this purpose, but it can be refined only through improved understanding of the various mechanisms underlying these correlations. These mechanisms probably differ among species, but for species resident in and near the entrapment zone, the correlation with X2 may be due to variations in intenSity oftrapping mechanisms with pOSition of the entrapment zone. Therefore, it is worthwhile to investigate these trapping mechanisms, the nature of the entrapment zone as habitat, and the responses of the entrapment zone to changes in X2 or outflow from the Sacramento-San Joaquin Delta. Studies ofthe entrapment zone ofthe San Francisco estuary have been conducted in springs of 1994, 1995, and 1996. These studies have been funded by the Interagency Ecological Program and conducted by scientists from IEP member agencies, the Romberg Tiburon Center for Environmental Studies, Bodega Marine Laboratory, and the University of California at Santa Cruz. This report presents results from 1994, a low-flow year. Subsequent reports will describe results from 1995 and 1996 and highlight differences among years. This report is organized in chapters that comprise more-or-Iess independent papers, with an introductory chapter for the entire study. This Executive Summary presents highlights of the overall study plan and summarizes the major findings.

Heterogeneously entrapped, vapor-rich melt inclusions record pre-eruptive magmatic volatile contents

NASA Astrophysics Data System (ADS)

Steele-MacInnis, Matthew; Esposito, Rosario; Moore, Lowell R.; Hartley, Margaret E.

2017-04-01

Silicate melt inclusions (MI) commonly provide the best record of pre-eruptive H2O and CO2 contents of subvolcanic melts, but the concentrations of CO2 and H2O in the melt (glass) phase within MI can be modified by partitioning into a vapor bubble after trapping. Melt inclusions may also enclose vapor bubbles together with the melt (i.e., heterogeneous entrapment), affecting the bulk volatile composition of the MI, and its post-entrapment evolution. In this study, we use numerical modeling to examine the systematics of post-entrapment volatile evolution within MI containing various proportions of trapped vapor from zero to 95 volume percent. Modeling indicates that inclusions that trap only a vapor-saturated melt exhibit significant decrease in CO2 and moderate increase in H2O concentrations in the melt upon nucleation and growth of a vapor bubble. In contrast, inclusions that trap melt plus vapor exhibit subdued CO2 depletion at equivalent conditions. In the extreme case of inclusions that trap mostly the vapor phase (i.e., CO2-H2O fluid inclusions containing trapped melt), degassing of CO2 from the melt is negligible. In the latter scenario, the large fraction of vapor enclosed in the MI during trapping essentially serves as a buffer, preventing post-entrapment modification of volatile concentrations in the melt. Hence, the glass phase within such heterogeneously entrapped, vapor-rich MI records the volatile concentrations of the melt at the time of trapping. These numerical modeling results suggest that heterogeneously entrapped MI containing large vapor bubbles represent amenable samples for constraining pre-eruptive volatile concentrations of subvolcanic melts.

Orbital Floor Fracture with Atypical Extraocular Muscle Entrapment Pattern and Intraoperative Asystole in an Adult

PubMed Central

Merali, Farhan I.; Grant, Michael P.; Mahoney, Nicholas R.

2015-01-01

Extraocular muscle entrapment in a nondisplaced orbital fracture, although a well-known entity in pediatric trauma, is atypical in adults. It can present with a triad of bradycardia, nausea, and in rare cases, syncope, and result in severe fibrosis of damaged and incarcerated muscle. We present a case of muscle entrapment in a partially nondisplaced two-wall orbital fracture with accompanying preoperative bradycardia and intraoperative asystole in an adult PMID:26576246

Establishing MICHCARB, a geological carbon sequestration research and education center for Michigan, implemented through the Michigan Geological Repository for Research and Education, part of the Department of Geosciences at Western Michigan University

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

Barnes, David A.; Harrison, William B.

The Michigan Geological Repository for Research and Education (MGRRE), part of the Department of Geosciences at Western Michigan University (WMU) at Kalamazoo, Michigan, established MichCarb—a geological carbon sequestration resource center by: • Archiving and maintaining a current reference collection of carbon sequestration published literature • Developing statewide and site-specific digital research databases for Michigan’s deep geological formations relevant to CO2 storage, containment and potential for enhanced oil recovery • Producing maps and tables of physical properties as components of these databases • Compiling all information into a digital atlas • Conducting geologic and fluid flow modeling to address specific predictivemore » uses of CO2 storage and enhanced oil recovery, including compiling data for geological and fluid flow models, formulating models, integrating data, and running the models; applying models to specific predictive uses of CO2 storage and enhanced oil recovery • Conducting technical research on CO2 sequestration and enhanced oil recovery through basic and applied research of characterizing Michigan oil and gas and saline reservoirs for CO2 storage potential volume, injectivity and containment. Based on our research, we have concluded that the Michigan Basin has excellent saline aquifer (residual entrapment) and CO2/Enhanced oil recovery related (CO2/EOR; buoyant entrapment) geological carbon sequestration potential with substantial, associated incremental oil production potential. These storage reservoirs possess at least satisfactory injectivity and reliable, permanent containment resulting from associated, thick, low permeability confining layers. Saline aquifer storage resource estimates in the two major residual entrapment, reservoir target zones (Lower Paleozoic Sandstone and Middle Paleozoic carbonate and sandstone reservoirs) are in excess of 70-80 Gmt (at an overall 10% storage efficiency factor; an approximately P50 probability range for all formations using DOE-NETL, 2010, storage resource estimation methodology). Incremental oil production resulting from successful implementation of CO2/EOR for the highest potential Middle Paleozoic reef reservoirs (Silurian, Northern Niagaran Reef trend) in Michigan is estimated at 130 to over 200 MMBO (22-33 Mm3). In addition, between 200 and 400 Mmt of CO2 could be sequestered in the course of successful deployment of CO2/EOR in the northern reef trend’s largest depleted (primary production) oil fields (those that have produced in excess of 500,000 BO; 80,000 m3of oil). • Effecting technology transfer to members of industry and governmental agencies by establishing an Internet Website at which all data, reports and results are accessible; publishing results in relevant journals; conducting technology transfer workshops as part of our role as the Michigan Center of the Petroleum Technology Transfer Council or any successor organization.« less

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.

Flexible, cathodoluminescent and free standing mesoporous silica films with entrapped quasi-2D perovskites

NASA Astrophysics Data System (ADS)

Vassilakopoulou, Anastasia; Papadatos, Dionysios; Koutselas, Ioannis

2017-04-01

The effective entrapment of hybrid organic-inorganic semiconductors (HOIS) into mesoporous polymer-silica hybrid matrices, formed as free standing flexible films, is presented for the first time. A blend of quasi-2D HOIS, simply synthesized by mixing two-dimensional (2D) and three dimensional (3D) HOIS, exhibiting strong photoluminescence, is embedded into porous silica matrices during the sol-gel synthesis, using tetraethylorthosilicate as precursor and Pluronic F-127 triblock copolymer as structure directing agent, under acidic conditions. The final nanostructure hybrid forms flexible, free standing films, presenting high cathodoluminescence and long stable excitonic luminescence, indicating the protective character of the hybrid matrix towards the entrapped perovskite. A significant result is that the photoluminescence of the entrapped HOIS is not affected even after films' prolonged exposure to water.

Development of scaffold architectures and heterotypic cell systems for hepatocyte transplantation

NASA Astrophysics Data System (ADS)

Alzebdeh, Dalia Abdelrahim

In vitro assembly of functional liver tissue is needed to enable the transplantation of tissue-engineered livers. In addition, there is an increasing demand for in vitro models that replicate complex events occurring in the liver. However, tissue engineering of sizable implantable liver systems is currently limited by the difficulty of assembling three dimensional hepatocyte cultures of a useful size, while maintaining full cell viability, an issue which is closely related to the high metabolic rate of hepatocytes. In this study, we first compared two designs of highly porous chitosan-heparin scaffolds seeded with hepatocytes in dynamic perfusion bioreactor systems. The aim was to promote cell seeding efficiency by effectively entrapping 100 million hepatocytes at high density. We found that scaffolds with radially tapering pore architecture had highly efficient cell entrapment that maximized donor hepatocyte utilization, compared to alternate pore structures. Hepatocytes showed higher seeding efficiency and metabolic function when seeded as single cell suspensions as opposed to pre-formed, 100microm aggregates. Seeding efficiency was found to increase with flow rate, with single cell and aggregate suspension exhibiting different optimal flow rates. However, metabolic performance results indicated significant shear damage to cells at high efficiency flow rates. To better maintain hepatocyte basement membrane and cell polarity, spheroid co-cultures with mesenchymal stem cells (MSC) were investigated. Hepatocytes and MSCs were seeded in three different architectures in an effort to optimize the spatial arrangement of the two cell types. MSC co-culture greatly enhanced hepatocyte metabolic function in agitated cultures. Interestingly, the effects of diffusion limitations in spheroid culture, coupled with shear damage and subsequent removal of outer hepatocyte layers produced a defined oscillation of urea production rates in certain co-culture arrangements. A mathematical model of urea synthesis in shear-exposed, co-culture spheroids reproduced the metabolic oscillations observed. This result together with culture observations suggests that MSCs can provide both physiological support and some direct shear protection to hepatocytes in perfused or shear-exposed culture environments. Finally, in order to reduce hepatocyte exposure to excessive shear forces in perfused scaffolds, a modular scaffold design based on polyelectrolyte fiber encapsulation was explored. Scaffolds with uniformly distributed, shear protected cells were achieved.

Engineering fibrin hydrogels to promote the wound healing potential of mesenchymal stem cell spheroids.

PubMed

Murphy, Kaitlin C; Whitehead, Jacklyn; Zhou, Dejie; Ho, Steve S; Leach, J Kent

2017-12-01

Mesenchymal stem cells (MSCs) secrete endogenous factors such as vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE 2 ) that promote angiogenesis, modulate the inflammatory microenvironment, and stimulate wound repair, and MSC spheroids secrete more trophic factors than dissociated, individual MSCs. Compared to injection of cells alone, transplantation of MSCs in a biomaterial can enhance their wound healing potential by localizing cells at the defect site and upregulating trophic factor secretion. To capitalize on the therapeutic potential of spheroids, we engineered a fibrin gel delivery vehicle to simultaneously enhance the proangiogenic and anti-inflammatory potential of entrapped human MSC spheroids. We used multifactorial statistical analysis to determine the interaction between four input variables derived from fibrin gel synthesis on four output variables (gel stiffness, gel contraction, and secretion of VEGF and PGE 2 ). Manipulation of the four input variables tuned fibrin gel biophysical properties to promote the simultaneous secretion of VEGF and PGE 2 by entrapped MSC spheroids while maintaining overall gel integrity. MSC spheroids in stiffer gels secreted the most VEGF, while PGE 2 secretion was highest in more compliant gels. Simultaneous VEGF and PGE 2 secretion was greatest using hydrogels with intermediate mechanical properties, as small increases in stiffness increased VEGF secretion while maintaining PGE 2 secretion by entrapped spheroids. The fibrin gel formulation predicted to simultaneously increase VEGF and PGE 2 secretion stimulated endothelial cell proliferation, enhanced macrophage polarization, and promoted angiogenesis when used to treat a wounded three-dimensional human skin equivalent. These data demonstrate that a statistical approach is an effective strategy to formulate fibrin gel formulations that enhance the wound healing potential of human MSCs. Mesenchymal stem cells (MSCs) are under investigation for wound healing applications due to their secretion of bioactive factors that enhance granulation tissue formation, blood vessel ingrowth, and reduce inflammation. However, the effectiveness of cell-based therapies is reduced due to poor engraftment and high rates of cell death when transplanted into harsh environments characteristic of large wounds. Compared to dissociated cells, MSCs exhibit increased overall function when aggregated into three-dimensional spheroids, and transplantation of cells using biomaterials is one strategy for guiding cell function in the defect site. The present study demonstrates that the biophysical properties of fibrin hydrogels, designed for use as a cell carrier, can be engineered to dictate the secretion of bioactive factors by entrapped MSC spheroids. This strategy enables MSCs to contribute to wound healing by synergistically promoting neovascularization and modulating the inflammatory milieu. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Intra-Articular Entrapment of the Medial Epicondyle following a Traumatic Fracture Dislocation of the Elbow in an Adult

PubMed Central

Hassan, Youssef G.; Joukhadar, Nabih I.

2018-01-01

Medial epicondyle entrapment after an acute fracture dislocation of the elbow is a common finding in the pediatric population, but a rare finding in adults. We present a case of an adult patient diagnosed with a traumatic fracture dislocation of the elbow joint with intra-articular entrapment of the medial epicondyle. After initial evaluation, closed reduction was done. Stability testing after reduction showed an unstable joint; thus, open reduction and internal fixation was decided. PMID:29666736

A novel amperometric alcohol biosensor developed in a 3rd generation bioelectrode platform using peroxidase coupled ferrocene activated alcohol oxidase as biorecognition system.

PubMed

Chinnadayyala, Somasekhar R; Kakoti, Ankana; Santhosh, Mallesh; Goswami, Pranab

2014-05-15

Alcohol oxidase (AOx) with a two-fold increase in efficiency (Kcat/Km) was achieved by physical entrapment of the activator ferrocene in the protein matrix through a simple microwave based partial unfolding technique and was used to develop a 3rd generation biosensor for improved detection of alcohol in liquid samples. The ferrocene molecules were stably entrapped in the AOx protein matrix in a molar ratio of ~3:1 through electrostatic interaction with the Trp residues involved in the functional activity of the enzyme as demonstrated by advanced analytical techniques. The sensor was fabricated by immobilizing ferrocene entrapped alcohol oxidase (FcAOx) and sol-gel chitosan film coated horseradish peroxidase (HRP) on a multi-walled carbon nanotube (MWCNT) modified glassy carbon electrode through layer-by-layer technique. The bioelectrode reactions involved the formation of H2O2 by FcAOx biocatalysis of substrate alcohol followed by HRP-catalyzed reduction of the liberated H2O2 through MWCNT supported direct electron transfer mechanism. The amperometric biosensor exhibited a linear response to alcohol in the range of 5.0 × 10(-6) to 30 × 10(-4)mol L(-1) with a detection limit of 2.3 × 10(-6) mol L(-1), and a sensitivity of 150 µA mM(-1) cm(-2). The biosensor response was steady for 28 successive measurements completed in a period of 5h and retained ~90% of the original response even after four weeks when stored at 4 °C. The biosensor was successfully applied for the determination of alcohol in commercial samples and its performance was validated by comparing with the data obtained by GC analyses of the samples. © 2013 Published by Elsevier B.V.

Evaluation of possible reasons for the low phenylalanine ammonia lyase activity in cellulose nitrate membrane microcapsules.

PubMed

Habibi-Moini, S; D'mello, A P

2001-03-14

Microencapsulated phenylalanine ammonia lyase (PAL) exhibits a marked reduction in activity compared to the activity of the free enzyme in pH 8.5 Tris buffer. The purpose of this investigation was to evaluate the contribution of incomplete entrapment, the internal environment of cellulose nitrate membrane microcapsules, the diffusional barrier of the membrane and the microcapsulation process to the low activity of encapsulated PAL. A solution of PAL and 10% w/v hemoglobin was incorporated into cellulose nitrate membrane microcapsules. Hemoglobin incorporation was used as a surrogate marker of PAL entrapment. Using 14C hemoglobin, the encapsulation efficiency was determined to be 70% and suggested that incomplete entrapment might partially account for the low activity of encapsulated PAL. The effect of the internal environment of the microcapsule (10% hemoglobin solution) on PAL activity was evaluated by comparing enzyme activity in 10% w/v hemoglobin solution and pH 8.5 Tris buffer. Similar K(M) and V(max) values of PAL in the two media indicated that the internal environment of the microcapsule did not contribute to the reduction in activity of the encapsulated enzyme. The contribution of a membrane diffusional barrier was determined by breaking the putative barrier and measuring PAL activity in intact and broken microcapsules. Similar activity of PAL in these two conditions is evidence for the lack of a diffusional barrier. The effect of the microencapsulation process on PAL activity was evaluated by comparing K(M) and V(max) of free and encapsulated PAL. Similar K(M) values in these two media suggested that the process did not affect the conformation of PAL. However, encapsulated PAL had a 50% lower V(max) value compared to free PAL, which showed that the microencapsulation process deactivated a substantial proportion of the enzyme.

Manufacture and Incorporation of Liposome-Entrapped Ethylenediaminetetraacetic Acid into Model Miniature Gouda-Type Cheese and Subsequent Effect on Starter Viability, pH, and Moisture Content.

PubMed

McAuliffe, Lisa N; Kilcawley, Kieran N; Sheehan, Jeremiah J; McSweeney, Paul L H

2016-10-25

Liposome-encapsulated ethylenediaminetetraacetic acid (EDTA) was incorporated into a model miniature Gouda-type cheese (20 g) in order to assess its effect on rennet gelation, starter viability, pH, and moisture content. EDTA was encapsulated within 2 different food-grade proliposome preparations, Pro-Lipo Duo and Pro-Lipo C (50% and 40% unsaturated soybean phospholipids and 50% and 60% aqueous medium, respectively), using the following high-shear technologies: Ultra-Turrax (5000 rpm), 2-stage homogenization (345 bar), or microfluidization (690 bar). Liposome size distribution was affected by the high-shear technology employed with the proportion of large vesicles (>100 nm) decreasing in the order microfluidization < 2-stage homogenization < Ultra-Turrax. All EDTA-containing liposomes were stable during 28 d refrigerated storage, with no significant (P ≤ 0.05) change in size distribution or EDTA entrapment efficiency (%EE). Liposome composition affected the entrapment of EDTA, with Pro-Lipo C having a significantly greater %EE than Pro-Lipo Duo, 63% and 54%, respectively. For this reason, Pro-Lipo C EDTA liposomes, with and without EDTA, were incorporated into model miniature Gouda-type cheese. Addition of liposome-encapsulated EDTA to milk during cheese making did not impact pH or rennet gel formation. No differences in composition or pH were evident in liposome-treated cheeses. The results of this study show that the incorporation of liposome-encapsulated EDTA into milk during cheese manufacture did not affect milk fermentation, moisture content, or pH, suggesting that this approach may be suitable for studying the effects of calcium equilibrium on the texture of brine-salted cheeses. © 2016 Institute of Food Technologists®.

Entrapment of Guide Wire in an Inferior Vena Cava Filter: A Technique for Removal

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

Abdel-Aal, Ahmed Kamel, E-mail: akamel@uabmc.edu; Saddekni, Souheil; Hamed, Maysoon Farouk

Entrapment of a central venous catheter (CVC) guide wire in an inferior vena cava (IVC) filter is a rare, but reported complication during CVC placement. With the increasing use of vena cava filters (VCFs), this number will most likely continue to grow. The consequences of this complication can be serious, as continued traction upon the guide wire may result in filter dislodgement and migration, filter fracture, or injury to the IVC. We describe a case in which a J-tipped guide wire introduced through a left subclavian access without fluoroscopic guidance during CVC placement was entrapped at the apex of anmore » IVC filter. We describe a technique that we used successfully in removing the entrapped wire through the left subclavian access site. We also present simple useful recommendations to prevent this complication.« less

Antioxidant activities and skin hydration effects of rice bran bioactive compounds entrapped in niosomes.

PubMed

Manosroi, Aranya; Chutoprapat, Romchat; Sato, Yuji; Miyamoto, Kukizo; Hsueh, Kesyin; Abe, Masahiko; Manosroi, Worapaka; Manosroi, Jiradej

2011-03-01

Bioactive compounds [ferulic acid (F), gamma-oryzanol (O) and phytic acid (P)] in rice bran have been widely used as antioxidants in skin care products. However, one of the major problems of antioxidants is the deterioration of their activities during long exposure to air and light. Niosomes have been used to entrap many degradable active agents not only for stability improvement, but also for increasing skin hydration. The objective of this study was to determine antioxidant activities [by in vitro ORAC (oxygen radical absorbance capacity) and ex vivo lipid peroxidation inhibition assay] and in vivo human skin hydration effects of gel and cream containing the rice bran extracts entrapped in niosomes. Gel and cream containing the rice bran extracts entrapped in niosomes showed higher antioxidant activity (ORAC value) at 20-28 micromol of Trolox equivalents (TE) per gram of the sample than the placebo gel and cream which gave 16-18 micromolTE/g. Human sebum treated with these formulations showed more lipid peroxidation inhibition activity than with no treatment of about 1.5 times. The three different independent techniques including corneometer, vapometer and confocal Raman microspectroscopy (CRM) indicated the same trend in human skin hydration enhancement of the gel or cream formulations containing the rice bran extracts entrapped in niosomes of about 20, 3 and 30%, respectively. This study has demonstrated the antioxidant activities and skin hydration enhancement of the rice bran bioactive compounds when entrapped in niosomes and incorporated in cream formulations.

A meta-analysis of perceptions of defeat and entrapment in depression, anxiety problems, posttraumatic stress disorder, and suicidality.

PubMed

Siddaway, Andy P; Taylor, Peter J; Wood, Alex M; Schulz, Joerg

2015-09-15

There is a burgeoning literature examining perceptions of being defeated or trapped in different psychiatric disorders. The disorders most frequently examined to date are depression, anxiety problems, posttraumatic stress disorder (PTSD), and suicidality. To quantify the size and consistency of perceptions of defeat and entrapment in depression, anxiety problems, PTSD and suicidality, test for differences across psychiatric disorders, and examine potential moderators and publication bias. Random-effects meta-analyses based on Pearson's correlation coefficient r. Forty studies were included in the meta-analysis (n = 10,072). Perceptions of defeat and entrapment were strong (around r = 0.60) and similar in size across all four psychiatric disorders. Perceptions of defeat were particularly strong in depression (r = 0.73). There was no between-study heterogeneity; therefore moderator analyses were conducted in an exploratory fashion. There was no evidence of publication bias. Analyses were cross-sectional, which precludes establishing temporal precedence or causality. Some of the meta-analyses were based on relatively small numbers of effect sizes, which may limit their generalisability. Perceptions of defeat and entrapment are clinically important in depression, anxiety problems, PTSD, and suicidality. Similar-sized, strong relationships across four different psychiatric disorders could suggest that perceptions of defeat and entrapment are transdiagnostic constructs. The results suggest that clinicians and researchers need to become more aware of perceptions of defeat and entrapment. Copyright © 2015 Elsevier B.V. All rights reserved.

Optimization and physicochemical characterization of a triamcinolone acetonide-loaded NLC for ocular antiangiogenic applications.

PubMed

Araújo, J; Gonzalez-Mira, E; Egea, M A; Garcia, M L; Souto, E B

2010-06-30

The purpose of this study was to develop a novel nanostructured lipid carrier (NLC) for the intravitreal-targeting delivery of triamcinolone acetonide (TA) by direct ocular instillation. A five-level central composite rotable design was used to study the influence of four different variables on the physicochemical characteristics of NLCs. The analysis of variance (ANOVA) statistical test was used to assess the optimization of NLC production parameters. The systems were produced by high pressure homogenization using Precirol ATO5 and squalene as solid and liquid lipids respectively, and Lutrol F68 as surfactant. Homogenization at 600 bar for 3 cycles of the optimized formulation resulted in the production of small NLC (mean diameter < 200 nm) with a homogeneous particle size distribution (polydispersity index (PI) approximately 0.1), of negatively charged surface (approximately |45| mV) and high entrapment efficiency (approximately 95%). Surface morphology was assessed by SEM which revealed fairly spherical shape. DSC, WAXS and FT-IR analyses confirmed that TA was mostly entrapped into the NLC, characterized by an amorphous matrix. In vivo Draize test showed no signs of ocular toxicity. 2010 Elsevier B.V. All rights reserved.

Zein Microneedles for Localized Delivery of Chemotherapeutic Agents to Treat Breast Cancer: Drug Loading, Release Behavior, and Skin Permeation Studies.

PubMed

Bhatnagar, Shubhmita; Kumari, Pooja; Pattarabhiran, Srijanaki Paravastu; Venuganti, Venkata Vamsi Krishna

2018-05-01

Localized delivery of chemotherapeutic agents to treat breast cancer could limit their adverse drug reactions. The aim of this study was to investigate the influence of physico-chemical properties of chemotherapeutic agents in their loading, release behavior, and skin permeation using microneedles. Zein microneedles were fabricated using the micromolding technique containing 36 microneedles in a 1-cm 2 area. These microneedles were loaded with two anti-breast cancer drugs, tamoxifen and gemcitabine, having different water solubilities. Entrapment or surface coating of chemotherapeutic agents in zein microneedles was optimized to achieve greater loading efficiency. The greatest loading achieved was 607 ± 21 and 1459 ± 74 μg for tamoxifen and gemcitabine using the entrapment approach, respectively. Skin permeation studies in excised porcine skin showed that the coating on microneedles approach results in greater skin deposition for tamoxifen; while the poke-and-patch approach would provide greater skin permeation for gemcitabine. Taken together, it can be concluded that different loading strategies and skin penetration approaches have to be studied for delivery of small molecules using polymeric microneedles.

cRGD-functionalized polymeric magnetic nanoparticles as a dual-drug delivery system for safe targeted cancer therapy.

PubMed

Shen, Jian-Min; Gao, Fei-Yun; Yin, Tao; Zhang, Hai-Xia; Ma, Ming; Yang, Yan-Jie; Yue, Feng

2013-04-01

In this paper we give a method of integrated treatment for cancer and drug-induced complications in the process of cancer therapy through dual-drug delivery system (DDDS). Two hydrophilic drugs, doxorubicin (an antitumor drug) and verapamil (an antiangiocardiopathy drug) combined preliminarily with chitosan shell coated on magnetic nanoparticles (MNPs), followed by entrapping into the PLGA nanoparticles. Further modification was conducted by conjugating tumor-targeting ligand, cyclo(Arg-Gly-Asp-D-Phe-Lys) (c(RGDfK)) peptide, onto the end carboxyl groups on the PLGA-NPs. The size of the resulting cRGD-DOX/VER-MNP-PLGA NPs was approximately 144nm under simulate physiological environment. Under present experiment condition, the entrapment efficiencies of DOX and VER were approximately 74.8 and 53.2wt% for cRGD-DOX/VER-MNP-PLGA NPs. This paper contains interesting pilot data such as NIR-triggered drug release, in vivo drug distribution studies and whole-mouse optical imaging. Histopathological examinations and electrocardiogram comparison demonstrated that the intelligent DDDS could markedly inhibit the growth of tumor and potentially offer an approach for safe cancer therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evaluation of Organogel Nanoparticles as Drug Delivery System for Lipophilic Compounds.

PubMed

Martin, Baptiste; Brouillet, Fabien; Franceschi, Sophie; Perez, Emile

2017-05-01

The purpose of the study was to evaluate organogel nanoparticles as a drug delivery system by investigating their stability, according to the formulation strategy, and their release profile. The gelled nanoparticles were prepared by hot emulsification (above the gelation temperature) of an organogel in water, and cooling at room temperature. In the first step, we used DLS and DSC to select the most suitable formulations by optimizing the proportion of ingredients (HSA, PVA, castor oil) to obtain particles of the smallest size and greatest stability. Then, two lipophilic drug models, indomethacin and ketoconazole were entrapped in the nanoparticles made of castor oil gelled by 12-hydroxystearic acid. Thermal studies (DSC) confirmed that there was no significant alteration of gelling due to the entrapped drugs, even at 3% w/w. Very stable dispersions were obtained (>3 months), with gelled oil nanoparticles presenting a mean diameter between 250 and 300 nm. High encapsulation efficiency (>98%) was measured for indomethacin and ketoconazole. The release profile determined by in vitro dialysis showed an immediate release of the drug from the organogel nanoparticles, due to rapid diffusion. The study demonstrates the interest of these gelled oil nanoparticles for the encapsulation and the delivery of lipophilic active compounds.

Inter-molecular β-sheet structure facilitates lung-targeting siRNA delivery

NASA Astrophysics Data System (ADS)

Zhou, Jihan; Li, Dong; Wen, Hao; Zheng, Shuquan; Su, Cuicui; Yi, Fan; Wang, Jue; Liang, Zicai; Tang, Tao; Zhou, Demin; Zhang, Li-He; Liang, Dehai; Du, Quan

2016-03-01

Size-dependent passive targeting based on the characteristics of tissues is a basic mechanism of drug delivery. While the nanometer-sized particles are efficiently captured by the liver and spleen, the micron-sized particles are most likely entrapped within the lung owing to its unique capillary structure and physiological features. To exploit this property in lung-targeting siRNA delivery, we designed and studied a multi-domain peptide named K-β, which was able to form inter-molecular β-sheet structures. Results showed that K-β peptides and siRNAs formed stable complex particles of 60 nm when mixed together. A critical property of such particles was that, after being intravenously injected into mice, they further associated into loose and micron-sized aggregates, and thus effectively entrapped within the capillaries of the lung, leading to a passive accumulation and gene-silencing. The large size aggregates can dissociate or break down by the shear stress generated by blood flow, alleviating the pulmonary embolism. Besides the lung, siRNA enrichment and targeted gene silencing were also observed in the liver. This drug delivery strategy, together with the low toxicity, biodegradability, and programmability of peptide carriers, show great potentials in vivo applications.

Enhanced antitumoral activity of doxorubicin against lung cancer cells using biodegradable poly(butylcyanoacrylate) nanoparticles

PubMed Central

Melguizo, Consolación; Cabeza, Laura; Prados, Jose; Ortiz, Raúl; Caba, Octavio; Rama, Ana R; Delgado, Ángel V; Arias, José L

2015-01-01

Doxorubicin (Dox) is widely used for the combined chemotherapy of solid tumors. However, the use of these drug associations in lung cancer has low antitumor efficacy. To improve its efficacious delivery and activity in lung adenocarcinoma cells, we developed a biodegradable and noncytotoxic nanoplatform based on biodegradable poly(butylcyanoacrylate) (PBCA). The reproducible formulation method was based on an anionic polymerization process of the PBCA monomer, with the antitumor drug being entrapped within the nanoparticle (NP) matrix during its formation. Improved drug-entrapment efficiencies and sustained (biphasic) drug-release properties were made possible by taking advantage of the synthesis conditions (drug, monomer, and surfactant-agent concentrations). Dox-loaded NPs significantly enhanced cellular uptake of the drug in the A549 and LL/2 lung cancer cell lines, leading to a significant improvement of the drug’s antitumoral activity. In vivo studies demonstrated that Dox-loaded NPs clearly reduced tumor volumes and increased mouse-survival rates compared to the free drug. These results demonstrated that PBCA NPs may be used to optimize the antitumor activity of Dox, thus exhibiting a potential application in chemotherapy against lung adenocarcinoma. PMID:26715840

Fabrication of granular activated carbons derived from spent coffee grounds by entrapment in calcium alginate beads for adsorption of acid orange 7 and methylene blue.

PubMed

Jung, Kyung-Won; Choi, Brian Hyun; Hwang, Min-Jin; Jeong, Tae-Un; Ahn, Kyu-Hong

2016-11-01

Biomass-based granular activated carbon was successfully prepared by entrapping activated carbon powder derived from spent coffee grounds into calcium-alginate beads (SCG-GAC) for the removal of acid orange 7 (AO7) and methylene blue (MB) from aqueous media. The dye adsorption process is highly pH-dependent and essentially independent of ionic effects. The adsorption kinetics was satisfactorily described by the pore diffusion model, which revealed that pore diffusion was the rate-limiting step during the adsorption process. The equilibrium isotherm and isosteric heat of adsorption indicate that SCG-GAC possesses an energetically heterogeneous surface and operates via endothermic process in nature. The maximum adsorption capacities of SCG-GAC for AO7 (pH 3.0) and MB (pH 11.0) adsorption were found to be 665.9 and 986.8mg/g at 30°C, respectively. Lastly, regeneration tests further confirmed that SCG-GAC has promising potential in its reusability, showing removal efficiency of more than 80% even after seven consecutive cycles. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhancing Endosomal Escape of Transduced Proteins by Photochemical Internalisation

PubMed Central

Mellert, Kevin; Lamla, Markus; Scheffzek, Klaus; Wittig, Rainer; Kaufmann, Dieter

2012-01-01

Induced internalisation of functional proteins into cultured cells has become an important aspect in a rising number of in vitro and in vivo assays. The endo-lysosomal entrapment of the transduced proteins remains the major problem in all transduction protocols. In this study we compared the efficiency, cytotoxicity and protein targeting of different commercially available transduction reagents by transducing a well-studied fluorescently labelled protein (Atto488-bovine serum albumin) into cultured human sarcoma cells. The amount of internalised protein and toxicity differed between the different reagents, but the percentage of transduced cells was consistently high. Furthermore, in all protocols the signals of the transduced Atto488-BSA were predominantly punctual consistent with an endosomal localisation. To overcome the endosomal entrapment, the transduction protocols were combined with a photochemical internalisation (PCI) treatment. Using this combination revealed that an endosomal disruption is highly effective in cell penetrating peptide (CPP) mediated transduction, whereas lipid-mediated transductions lead to a lower signal spreading throughout the cytosol. No change in the signal distribution could be achieved in treatments using non-lipid polymers as a transduction reagent. Therefore, the combination of protein transduction protocols based on CPPs with the endosomolytic treatment PCI can facilitate protein transduction experiments in vitro. PMID:23285056

Enhancing endosomal escape of transduced proteins by photochemical internalisation.

PubMed

Mellert, Kevin; Lamla, Markus; Scheffzek, Klaus; Wittig, Rainer; Kaufmann, Dieter

2012-01-01

Induced internalisation of functional proteins into cultured cells has become an important aspect in a rising number of in vitro and in vivo assays. The endo-lysosomal entrapment of the transduced proteins remains the major problem in all transduction protocols. In this study we compared the efficiency, cytotoxicity and protein targeting of different commercially available transduction reagents by transducing a well-studied fluorescently labelled protein (Atto488-bovine serum albumin) into cultured human sarcoma cells. The amount of internalised protein and toxicity differed between the different reagents, but the percentage of transduced cells was consistently high. Furthermore, in all protocols the signals of the transduced Atto488-BSA were predominantly punctual consistent with an endosomal localisation. To overcome the endosomal entrapment, the transduction protocols were combined with a photochemical internalisation (PCI) treatment. Using this combination revealed that an endosomal disruption is highly effective in cell penetrating peptide (CPP) mediated transduction, whereas lipid-mediated transductions lead to a lower signal spreading throughout the cytosol. No change in the signal distribution could be achieved in treatments using non-lipid polymers as a transduction reagent. Therefore, the combination of protein transduction protocols based on CPPs with the endosomolytic treatment PCI can facilitate protein transduction experiments in vitro.

Niosomes as a vesicular carrier for topical administration of minoxidil: formulation and in vitro assessment.

PubMed

Mali, Nitin; Darandale, Sharad; Vavia, Pradeep

2013-12-01

Niosomes are reported to increase the skin permeation and bioavailability of topically applied drug molecules. However, very few studies were reported for nanometer-sized niosome vesicles. The aim of the present study was to prepare minoxidil-loaded niosomal formulation using ethanol injection method. Surfactant screening showed that only Span 60, Span 20, and Tween 20 with cholesterol have capability of nano size vesicle formation. The formed niosomes were characterized for entrapment efficiency, vesicle size, scanning electron microscope, and physical stability. By modulation of surfactant and cholesterol ratio maximum entrapment up to 34.70 ± 1.1 % with size of 470 ± 27 nm was obtained (Span 60/cholesterol ratio of 1:2). The vesicle size obtained was between 150 and 800 nm that was depending on cholesterol ratio and type of nonionic surfactant employed. The in vitro skin permeation study showed that an increase in cholesterol concentration in niosome vesicles increases minoxidil skin retention. Niosome formulation prepared with 1:2 ratio of Span 60 and cholesterol showed 17.21 ± 3.2 % skin retention of minoxidil, which is more than eightfold as compared to control minoxidil gel.

Formulation and evaluation of gastroretentive microballoons containing baclofen for a floating oral controlled drug delivery system.

PubMed

Dube, T S; Ranpise, N S; Ranade, A N

2014-01-01

The objective of the present study was to fabricate and evaluate a multiparticulate oral gastroretentive dosage form of baclofen characterized by a central large cavity (hollow core) promoting unmitigated floatation with practical applications to alleviate the signs and symptoms of spasticity and muscular rigidity. Solvent diffusion and evaporation procedure were applied to prepare floating microspheres with a central large cavity using various combinations of ethylcellulose (release retardant) and HPMC K4M (release modifier) dissolved in a mixture of dichloromethane and methanol (2:1). The obtained microspheres (700-1000 µm) exhibit excellent floating ability (86 ± 2.00%) and release characteristics with entrapment efficiency of 95.2 ± 0.32%. Microspheres fabricated with ethylcellulose to HPMC K4M in the ratio 8.5:1.5 released 98.67% of the entrapped drug in 12 h. Muscle relaxation caused by baclofen microspheres impairs the rotarod performance for more than 12 h. Abdominal X-ray images showed that the gastroretention period of the floating barium sulfate- labeled microspheres was no less than 10 h. The buoyant baclofen microspheres provide a promising gastroretentive drug delivery system to deliver baclofen in spastic patients with a sustained release rate.

11β-Hydroxylation of Cortexolone (Reichstein Compound S) to Hydrocortisone by Curvularia lunata Entrapped in Photo-Cross-Linked Resin Gels

PubMed Central

Sonomoto, Kenji; Hoq, M. Mozammel; Tanaka, Atsuo; Fukui, Saburo

1983-01-01

Spores of Curvularia lunata were immobilized by entrapment with photo-cross-linkable resin prepolymers and incubated to form mycelium in potato dextrose broth containing cortexolone (Reichstein compound S) as an inducer of steroid 11β-hydroxylase. In a buffer system containing 2.5% dimethyl sulfoxide, this immobilized mycelium hydroxylated cortexolone to hydrocortisone. The activity of this mycelium was comparable to the activity of free mycelium. Dimethyl sulfoxide did not inhibit hydroxylase activity at the concentration used and was effective in dissolving the product. Of the various photo-cross-linkable resin prepolymers examined, use of ENT-4000, whose main chain was polyethylene glycol 4000 (chain length, approximately 40 nm), resulted in maximum hydroxylation activity of the entrapped mycelium. The chain length of prepolymers affected markedly mycelial growth in the gels and, subsequently, the activity of the entrapped mycelium. The immobilized hydroxylation system was more stable than the system in free mycelium and could be reactivated by incubation of the entrapped mycelium in potato dextrose broth containing cortexolone. The system was tested 50 times during 100 days of operation and was found to carry out the desired transformation with overall yields of 60%. Images PMID:16346194

16 CFR 1211.10 - Requirements for all entrapment protection devices.

Code of Federal Regulations, 2011 CFR

2011-01-01

... adjacent terminal. (c) Splash test. (1) An external entrapment protection device intended to be installed... such a manner most likely to cause water to splash the enclosure of electric components. However, the...

16 CFR 1211.10 - Requirements for all entrapment protection devices.

Code of Federal Regulations, 2014 CFR

2014-01-01

... adjacent terminal. (c) Splash test. (1) An external entrapment protection device intended to be installed... such a manner most likely to cause water to splash the enclosure of electric components. However, the...

16 CFR 1211.10 - Requirements for all entrapment protection devices.

Code of Federal Regulations, 2012 CFR

2012-01-01

... adjacent terminal. (c) Splash test. (1) An external entrapment protection device intended to be installed... such a manner most likely to cause water to splash the enclosure of electric components. However, the...

16 CFR § 1211.10 - Requirements for all entrapment protection devices.

Code of Federal Regulations, 2013 CFR

2013-01-01

... adjacent terminal. (c) Splash test. (1) An external entrapment protection device intended to be installed... such a manner most likely to cause water to splash the enclosure of electric components. However, the...

Gas turbine engines with particle traps

DOEpatents

Boyd, Gary L.; Sumner, D. Warren; Sheoran, Yogendra; Judd, Z. Daniel

1992-01-01

A gas turbine engine (10) incorporates a particle trap (46) that forms an entrapment region (73) in a plenum (24) which extends from within the combustor (18) to the inlet (32) of a radial-inflow turbine (52, 54). The engine (10) is thereby adapted to entrap particles that originate downstream from the compressor (14) and are otherwise propelled by combustion gas (22) into the turbine (52, 54). Carbonaceous particles that are dislodged from the inner wall (50) of the combustor (18) are incinerated within the entrapment region (73) during operation of the engine (10).

Development of a glucose oxidase-based biocatalyst adopting both physical entrapment and crosslinking, and its use in biofuel cells

NASA Astrophysics Data System (ADS)

Chung, Yongjin; Ahn, Yeonjoo; Christwardana, Marcelinus; Kim, Hansung; Kwon, Yongchai

2016-04-01

New enzymatic catalysts prepared using physical entrapment and chemical bonding were used as anodic catalysts to enhance the performance of enzymatic biofuel cells (EBCs). For estimating the physical entrapment effect, the best glucose oxidase (GOx) concentration immobilized on polyethyleneimine (PEI) and carbon nanotube (CNT) (GOx/PEI/CNT) was determined, while for inspecting the chemical bonding effect, terephthalaldehyde (TPA) and glutaraldehyde (GA) crosslinkers were employed. According to the enzyme activity and XPS measurements, when the GOx concentration is 4 mg mL-1, they are most effectively immobilized (via the physical entrapment effect) and TPA-crosslinked GOx/PEI/CNT(TPA/[GOx/PEI/CNT]) forms π conjugated bonds via chemical bonding, inducing the promotion of electron transfer by delocalization of electrons. Due to the optimized GOx concentration and π conjugated bonds, TPA/[GOx/PEI/CNT], including 4 mg mL-1 GOx displays a high electron transfer rate, followed by excellent catalytic activity and EBC performance.New enzymatic catalysts prepared using physical entrapment and chemical bonding were used as anodic catalysts to enhance the performance of enzymatic biofuel cells (EBCs). For estimating the physical entrapment effect, the best glucose oxidase (GOx) concentration immobilized on polyethyleneimine (PEI) and carbon nanotube (CNT) (GOx/PEI/CNT) was determined, while for inspecting the chemical bonding effect, terephthalaldehyde (TPA) and glutaraldehyde (GA) crosslinkers were employed. According to the enzyme activity and XPS measurements, when the GOx concentration is 4 mg mL-1, they are most effectively immobilized (via the physical entrapment effect) and TPA-crosslinked GOx/PEI/CNT(TPA/[GOx/PEI/CNT]) forms π conjugated bonds via chemical bonding, inducing the promotion of electron transfer by delocalization of electrons. Due to the optimized GOx concentration and π conjugated bonds, TPA/[GOx/PEI/CNT], including 4 mg mL-1 GOx displays a high electron transfer rate, followed by excellent catalytic activity and EBC performance. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00902f

Cell-penetrating peptide-siRNA conjugate loaded YSA-modified nanobubbles for ultrasound triggered siRNA delivery.

PubMed

Xie, Xiangyang; Yang, Yanfang; Lin, Wen; Liu, Hui; Liu, Hong; Yang, Yang; Chen, Ying; Fu, Xudong; Deng, Jianping

2015-12-01

Due to the absence of effective in vivo delivery systems, the employment of small interference RNA (siRNA) in the clinic has been hindered. In this paper, a new siRNA targeting system for EphA2-positive tumors was developed, based on ultrasound-sensitive nanobubbles (NBs) and cell-permeable peptides (CPPs). Here, a CPP-siRNA conjugate (CPP-siRNA) was entrapped in an ephrin mimetic peptide (YSA peptide)-modified NB (CPP-siRNA/YSA-NB) and the penetration of the CPP-siRNA was temporally masked; local ultrasound stimulation triggered the release of CPP-siRNA from the NBs and activated its penetration. Subsequent research demonstrated that the CPP-siRNA/YSA-NBs had particle sizes of approximately 200 nm and a siRNA entrapment efficiency of more than 85%. The in vitro release results showed that over 90% of the encapsulated CPP-siRNA released from the NBs in the presence of ultrasound, while less than 1.5% of that (30 min) released without ultrasound. Cell experiments showed a the higher CPP-siRNA cellular uptake of CPP-siRNA/YSA-NB among the various formulations in human breast adenocarcinoma cells (MCF-7, EphA2 positive cells). Additionally, after systemic administration in mice, CPP-siRNA/YSA-NB accumulated in the tumor, augmented c-Myc silencing and delayed tumor progression. In conclusion, the application of CPP-siRNA/YSA-NB with ultrasound may provide a strategy for the selective and efficient delivery of siRNA. Copyright © 2015 Elsevier B.V. All rights reserved.

Efficient siRNA Delivery Using Novel Cell-Penetrating Peptide-siRNA Conjugate-Loaded Nanobubbles and Ultrasound.

PubMed

Xie, Xiangyang; Lin, Wen; Li, Mingyuan; Yang, Yang; Deng, Jianping; Liu, Hui; Chen, Ying; Fu, Xudong; Liu, Hong; Yang, Yanfang

2016-06-01

Because of the absence of tolerable and effective carriers for in vivo delivery, the applications of small interfering RNA (siRNA) in the clinic for therapeutic purposes have been limited. In this study, development of a novel siRNA delivery system based on ultrasound-sensitive nanobubbles (NBs, nano-sized echogenic liposomes) and cell-permeable peptides (CPPs) is described. A CPP-siRNA conjugate was entrapped in an NB, (CPP-siRNA)-NB, and the penetration of CPP-siRNA was temporally masked; local ultrasound stimulation triggered the release of CPP-siRNA from the NBs and activated its penetration. Subsequent research revealed that the (CPP-siRNA)-NBs had a mean particle size of 201 ± 2.05 nm and a siRNA entrapment efficiency >85%. In vitro release results indicated that >90% of the encapsulated CPP-siRNA was released from NBs in the presence of ultrasound, whereas <1.5% (30 min) was released in the absence of ultrasound. Cell experiments indicated higher cellular CPP-siRNA uptake of (CPP-siRNA)-NBs with ultrasound among the various formulations in human breast adenocarcinoma cells (HT-1080). Additionally, after systemic administration in mice, (CPP-siRNA)-NBs accumulated in the tumor, augmented c-myc silencing and delayed tumor progression. In conclusion, the application of (CPP-siRNA)-NBs with ultrasound may constitute an approach to selective targeted delivery of siRNA. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Resolution V fractional factorial design for screening of factors affecting weakly basic drugs liposomal systems.

PubMed

Nageeb El-Helaly, Sara; Habib, Basant A; Abd El-Rahman, Mohamed K

2018-07-01

This study aims to investigate factors affecting weakly basic drugs liposomal systems. Resolution V fractional factorial design (2 V 5-1 ) is used as an example of screening designs that would better be used as a wise step before proceeding with detailed factors effects or optimization studies. Five factors probable to affect liposomal systems of weakly basic drugs were investigated using Amisulpride as a model drug. Factors studied were; A: Preparation technique B: Phosphatidyl choline (PhC) amount (mg) C: Cholesterol: PhC molar ratio, D: Hydration volume (ml) and E: Sonication type. Levels investigated were; Ammonium sulphate-pH gradient technique or Transmembrane zinc chelation-pH gradient technique, 200 or 400 mg, 0 or 0.5, 10 or 20 ml and bath or probe sonication for A, B, C, D and E respectively. Responses measured were Particle size (PS) (nm), Zeta potential (ZP) (mV) and Entrapment efficiency percent (EE%). Ion selective electrode was used as a novel method for measuring unentrapped drug concentration and calculating entrapment efficiency without the need for liposomal separation. Factors mainly affecting the studied responses were Cholesterol: PhC ratio and hydration volume for PS, preparation technique for ZP and preparation technique and hydration volume for EE%. The applied 2 V 5-1 design enabled the use of only 16 trial combinations for screening the influence of five factors on weakly basic drugs liposomal systems. This clarifies the value of the use of screening experiments before extensive investigation of certain factors in detailed optimization studies. Copyright © 2018 Elsevier B.V. All rights reserved.

Polyphenoloxidases immobilized in organic gels: Properties and applications in the detoxification of aromatic compounds

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

Crecchio, C.; Ruggiero, P.; Pizzigallo, M.D.R.

1995-12-20

Gelatine gels originate from water in oil microemulsions in which the ternary system consists of isooctane/sulfosuccinic acid bis [2-ethyl hexyl] ester/water; the solubilization of gelatin in the water pool of these microemulsions transforms them into viscous gels in which it is possible to cosolubilize various reactive molecules. These gels were used to immobilize two phenoloxidases, a laccase from Trametes versicolor and a tyrosinase from mushroom. The best balance between gel retention and catalytic activity was reached at a gelatine concentration of 2.5% (w/v) in the case of tyrosinase, while laccase immobilization was independent of gelatine concentration. Both enzymes kept themore » same optimum pH as the corresponding soluble controls, while a partial loss of activity was observed when they were immobilized. Immobilized enzymes showed an increased stability when incubated for several days at 4 C with a very low release from the gels in the incubation solutions. The immobilization of tyrosinase and of laccase enhanced stability to thermal inactivation. Furthermore, gel-entrapped tyrosinase was almost completely preserved from proteolysis: more than 80% of the activity was maintained, while only 25% of the soluble control activity was detected after the same proteolytic treatments. A column packed with gel-immobilized tyrosinase was used to demonstrate that enzymes immobilized with this technique may be reused several times in the same reaction without loosing their efficiency. Finally, gel-entrapped tyrosinase and laccase were capable of removing naturally occurring and xenobiotic aromatic compounds from aqueous suspensions with different degrees of efficiency.« less

A novel transdermal nanoethosomal gel of betahistine dihydrochloride for weight gain control: in-vitro and in-vivo characterization

PubMed Central

El-Menshawe, Shahira F; Ali, Adel Ahmed; Halawa, Abdelkhalk Ali; Srag El-Din, Ahmed SG

2017-01-01

Background Betahistine dihydrochloride (BDH) is a histamine analog used to control weight gain, with short elimination half-life and gastric irritation as side effects. Objective The aim of the current investigation is to formulate and optimize a topical BDH ethosomal gel for weight gain control. Materials and methods Box–Behnken design was applied to study the effect of independent variables: phosphatidylcholine (PC), propylene glycol (PG), and ethanol on vesicle size; entrapment efficiency; % drug release; and flux. The morphology and zeta potential of the optimized formulation were evaluated. The % drug release, flux, and pharmacodynamics of the optimized formulation gel were studied. Results The size and entrapment efficiency percent had a direct positive relationship with the concentration of PC and negative relationship with ethanol and PG. The % drug release and flux decreased with increasing PC and PG, while ethanol enhanced both responses. Regression modeling indicated a good correlation between dependent and independent variables, where F16 was chosen as the optimized formulation. F16 showed well-defined spherical vesicles and zeta potential of −24 mV, and % release from the gel exceeded 99.5% over 16 h with the flux of 0.28 mg/cm2/h. Food intake and weight gain of rats were significantly decreased after transdermal application of the BDH ethosomal gel when compared with control, placebo, and BDH gel. The histopathological findings proved the absence of inflammation and decrease in adipose tissue. Conclusion Results obtained showed a significant, sustained transdermal absorption of BDH ethosomal gel and, consequently, a decrease in food intake and weight gain. PMID:29238164

Development and evaluation of intestinal targeted mucoadhesive microspheres of Bacillus coagulans.

PubMed

Alli, Sk Md Athar; Ali, Sk Md Ajhar; Samanta, Amalesh

2011-11-01

Intestinal targeted mucoadhesive microsphere of probiotics may provide numerous associated health benefits. To develop mucoadhesive microspheres that will deliver viable probiotic cells into gut protectively against harsh environmental conditions of stomach for extended period. Core mucoadhesive microspheres of Bacillus coagulans were prepared using hypromellose, following coacervation and phase separation technique and were then coated with hypromellose phthalate to achieve their site-specific release. Microspheres were evaluated for percent yield, entrapment efficiency, surface morphology, particle size and size distribution, flow property, swelling property, mucoadhesion property by the in vitro wash-off and the ex vivo mucoadhesive strength tests, in vitro release profile and release kinetic, in vivo probiotic activity, and stability. The values for kinetic constant and regression coefficient of model-dependent approaches and the difference factor, the similarity factor, and the Rescigno index of model-independent approaches were determined for accessing and comparing in vitro performance. Microsphere formulation batches have percent yield value between 56.26% and 69.13% and entrapment efficiency value between 66.95% and 77.89%. Microspheres were coarser with spherical shape having mean particle size from 28.03 to 48.31 μm. In vitro B. coagulans release profile follows zero-order kinetics and depends on the grade of hypromellose and the B. coagulans-to-hypromellose ratio. Experimental microspheres rendered adequate stability to B. coagulans at room temperature. Microspheres had delivered B. coagulans in simulated intestinal condition following zero-order kinetics, protectively in simulated gastric condition, exhibiting appreciable mucoadhesion in intestinal condition, which could be useful to achieve site-specific delivery for extended period.

Application of statistical experimental design to study the formulation variables influencing the coating process of lidocaine liposomes.

PubMed

González-Rodríguez, M L; Barros, L B; Palma, J; González-Rodríguez, P L; Rabasco, A M

2007-06-07

In this paper, we have used statistical experimental design to investigate the effect of several factors in coating process of lidocaine hydrochloride (LID) liposomes by a biodegradable polymer (chitosan, CH). These variables were the concentration of CH coating solution, the dripping rate of this solution on the liposome colloidal dispersion, the stirring rate, the time since the liposome production to the liposome coating and finally the amount of drug entrapped into liposomes. The selected response variables were drug encapsulation efficiency (EE, %), coating efficiency (CE, %) and zeta potential. Liposomes were obtained by thin-layer evaporation method. They were subsequently coated with CH according the experimental plan provided by a fractional factorial (2(5-1)) screening matrix. We have used spectroscopic methods to determine the zeta potential values. The EE (%) assay was carried out in dialysis bags and the brilliant red probe was used to determine CE (%) due to its property of forming molecular complexes with CH. The graphic analysis of the effects allowed the identification of the main formulation and technological factors by the analysis of the selected responses and permitted the determination of the proper level of these factors for the response improvement. Moreover, fractional design allowed quantifying the interactions between the factors, which will consider in next experiments. The results obtained pointed out that LID amount was the predominant factor that increased the drug entrapment capacity (EE). The CE (%) response was mainly affected by the concentration of the CH solution and the stirring rate, although all the interactions between the main factors have statistical significance.

Nanocomplexes of an insulinotropic drug: optimization, microparticle formation, and antidiabetic activity in rats

PubMed Central

Elmowafy, Enas; Osman, Rihab; El-Shamy, Abdel Hameed; Awad, Gehanne AS

2014-01-01

The aim of the present work was to test the ability of two non-diabetogenic carbohydrates to intranasally deliver the insulinotropic drug repaglinide (REP) for controlling blood glucose level. REP was loaded onto chitosan/alginate nanocomplexes (NCs) suitable for mucosal delivery and uptake. Improved stability and delivery characteristics were obtained by spray drying the selected NCs, yielding microparticles. A statistical experimental design was adopted to investigate the effects of the formulations’ variables on two critical responses: NC size and drug entrapment efficiency. Physicochemical characterizations of the network’s structures were done, and in vitro cytotoxicity and histopathological studies were conducted. The potential of the developed system to prolong the drug effect was tested on diabetic rats. The results showed that to attain particles suitable for nasal delivery, alginate should be used at its lowest level used in this study (0.6 mg/mL). A low level of chitosan (0.5 mg/mL) was needed when the drug was cation-loaded, while the high chitosan level (1 mg/mL) was more suitable when REP was anion-loaded. The best entrapment efficiency was achieved at a theoretical drug loading of 0.025 mg/mL. Discrete NCs could be rapidly recovered from the spray-dried microparticles. The cytotoxicity and histopathological studies indicated that such formulations were well tolerated. The antihyperglycemic activity of the nasally administered formulae was gradual but was significantly sustained over 24 hours, suggesting NC mucosal uptake. Nasal delivery of such dry powders achieved better glycemic control compared with the conventional oral tablets. PMID:25258534

Design, formulation and optimization of novel soft nano-carriers for transdermal olmesartan medoxomil delivery: In vitro characterization and in vivo pharmacokinetic assessment.

PubMed

Kamran, Mohd; Ahad, Abdul; Aqil, Mohd; Imam, Syed Sarim; Sultana, Yasmin; Ali, Asgar

2016-05-30

Olmesartan is a hydrophobic antihypertensive drug with a short biological half-life, and low bioavailability, presents a challenge with respect to its oral administration. The objective of the work was to formulate, optimize and evaluate the transdermal potential of novel vesicular nano-invasomes, containing above anti-hypertensive agent. To achieve the above purpose, soft carriers (viz. nano-invasomes) of olmesartan with β-citronellene as potential permeation enhancer were developed and optimized using Box-Behnken design. The physicochemical characteristics e.g., vesicle size, shape, entrapment efficiency and skin permeability of the nano-invasomes formulations were evaluated. The optimized formulation was further evaluated for in vitro drug release, confocal microscopy and in vivo pharmacokinetic study. The optimum nano-invasomes formulation showed vesicles size of 83.35±3.25nm, entrapment efficiency of 65.21±2.25% and transdermal flux of 32.78±0.703 (μg/cm(2)/h) which were found in agreement with the predicted value generated by Box-Behnken design. Confocal laser microscopy of rat skin showed that optimized formulation was eventually distributed and permeated deep into the skin. The pharmacokinetic study presented that transdermal nano-invasomes formulation showed 1.15 times improvement in bioavailability of olmesartan with respect to the control formulation in Wistar rats. It was concluded that the response surfaces estimated by Design Expert(®) illustrated obvious relationship between formulation factors and response variables and nano-invasomes were found to be a proficient carrier system for transdermal delivery of olmesartan. Copyright © 2016 Elsevier B.V. All rights reserved.

Electrosteric stealth Rivastigmine loaded liposomes for brain targeting: preparation, characterization, ex vivo, bio-distribution and in vivo pharmacokinetic studies.

PubMed

Nageeb El-Helaly, Sara; Abd Elbary, Ahmed; Kassem, Mohamed A; El-Nabarawi, Mohamed A

2017-11-01

Being one of the highly effective drugs in treatment of Alzheimer's disease, Rivastigmine brain targeting is highly demandable, therefore liposomal dispersion of Rivastigmine was prepared containing 2 mol% PEG-DSPE added to Lecithin, Didecyldimethyl ammonium bromide (DDAB), Tween 80 in 1:0.02:0.25 molar ratio. A major challenge during the preparation of liposomes is maintaining a stable formulation, therefore the aim of our study was to increase liposomal stability by addition of DDAB to give an electrostatic stability and PEG-DSPE to increase stability by steric hindrance, yielding what we called an electrosteric stealth (ESS) liposomes. A medium nano-sized liposome (478 ± 4.94 nm) with a nearly neutral zeta potential (ZP, -8 ± 0.2 mV) and an entrapment efficiency percentage of 48 ± 6.22 was prepared. Stability studies showed no major alteration after three months storage period concerning particle size, polydispersity index, ZP, entrapment efficiency and in vitro release study confirming the successful formation of a stable liposomes. No histopathological alteration was recorded for ESS liposomes of the sheep nasal mucosa. While ESS liposomes showed higher % of drug permeating through the sheep nasal mucosa (48.6%) than the drug solution (28.7%). On completing the in vivo pharmacokinetic studies of 36 rabbits showed 424.2% relative bioavailability of the mean plasma levels of the formula ESS compared to that of RHT intranasal solution and 486% relative bioavailability of the mean brain levels.

Formulation, Optimization, Characterization, and Pharmacokinetics of Progesterone Intravenous Lipid Emulsion for Traumatic Brain Injury Therapy.

PubMed

Zhao, Jin; Yuan, Quan; Cai, WeiHui; Sun, Pan; Ding, LiYan; Jin, Fang

2017-07-01

Traumatic brain injury (TBI) is a major cause of mortality and disability throughout the world. Progesterone (PROG) plays an important role in neurologic treatment. The aim of this study was to develop a progesterone formulation with good physical and chemical stability. Progesterone intravenous lipid emulsion (PILE) was prepared based on one-factor-at-a-time experiments and orthogonal design. The optimal PILE was evaluated for mean particle size, particle size distribution, zeta potential, morphology, pH, osmolarity, entrapment efficiency, storage stability, and pharmacokinetics in ICR mice compared with the commercial progesterone products. The droplets of PILE had the smallest possible diameters of 218.0 ± 1.8 nm and adequate zeta potential of -41.1 ± 0.9 mV. The volume percentage of droplets exceeding 5 μm (PFAT 5 ) of PILE was 0.003 ± 0.0015% and much less than the specified standard. The TEM imaging proved that emulsion droplets had a smooth spherical appearance. Chemically and physically stable PILE was obtained with excellent entrapment efficiency that was up to 95.23%, with suitable pH at 7.15 ± 0.01 and osmolarity at 301.3 ± 1.2 mOsmol/l. Storage stability tests indicated that the emulsion was stable long term under ambient temperature conditions. Animal studies demonstrated that the emulsion was more effective with the higher progesterone concentration in the brain compared with commercial products. Therefore, the optimized PILE would offer great promise as a means of progesterone delivery for TBI therapy.

The preparation and characterization of monomethoxypoly(ethylene glycol)-b-poly-DL-lactide microcapsules containing bovine hemoglobin.

PubMed

Meng, Fan-Tao; Zhang, Wan-Zhong; Ma, Guang-Hui; Su, Zhi-Guo

2003-08-01

Methoxypoly(ethylene glycol)-b-poly-DL-lactide (PELA) microcapsules containing bovine hemoglobin (bHb) were prepared by a W/O/W double emulsion-solvent diffusion process. bHb solution was used as the internal aqueous phase, PELA/organic solvent as the oil phase, and polyvinyl alcohol (PVA) solution as the external aqueous phase. This W/O/W double emulsion was added into a large volume of water (solidification solution) to allow organic solvent to diffuse into water. The optimum preparative condition for PELA microcapsules loaded with bovine hemoglobin was investigated. It was found that homogenization rate, type of organic solvent, and volume of the solidification solution influenced the activity of bovine hemoglobin encapsulated. When the homogenization rate was lower than 9000 rpm and ethyl acetate was used as the organic solvent, there was no significant influence on the activity of hemoglobin. High homogenization rate as 12 000 rpm decreased the P50 and Hill coefficient. Increasing the volume of solidification solution had an effect of improving the activity of microencapsulated hemoglobin. The composition of the PELA had the most important influence on the success of encapsulation. Microcapsules fabricated by PELA with MPEG2k block (molecular weight of MPEG block: 2000) achieved a high entrapment efficiency of 90%, better than PL A homopolymer and PELA with MPEG5k blocks. Hemoglobin microcapsules with native loading oxygen activity (P50 = 26.0 mmHg, Hill coefficient = 2.4), mean size of about 10 microm, and high entrapment efficiency (ca. 93%) were obtained at the optimum condition.

Development of ionic-complex-based nanostructured lipid carriers to improve the pharmacokinetic profiles of breviscapine

PubMed Central

Li, Mei; Zheng, Yong; Shan, Feng-ying; Zhou, Jing; Gong, Tao; Zhang, Zhi-rong

2013-01-01

Aim: Breviscapine isolated from the Chinese herb Erigeron breviscapus (Vant) Hand-Mazz is widely used to treat cardiovascular and cerebrovascular diseases. The aim of this study was to improve the pharmacokinetic profiles of breviscapine using nanostructured lipid carrier based on an ionic complex formation. Methods: Breviscapine nanostructured lipid carrier (Bre-NLC) was prepared using the thin film homogenization method. The morphology of Bre-NLCs was determined using transmission electron microscopy. The mean particle size, polydispersity index, zeta-potential analysis and entrapment efficiency were analized. In vitro release was studied using the dialysis method. In vitro stability was studied in fresh plasma and liver slurry of rats. In vivo pharmacokinetics was analyzed in rats after intravenous injection of a dose equivalent to breviscapine (10 mg/kg). Results: The Bre-NLCs were spherical with a mean particle size of ∼170 nm, a zeta potential of ∼20 mV and a high entrapment efficiency of ∼89%. Compared with a commercially available solution, a substantial decrease in the cumulative release of breviscapine was found for the Bre-NLCs. The NLC has a significantly protective effect against the liver enzyme degradation of breviscapine. After intravenous administration in rats, the Bre-NLCs exhibited a 32 times increase in the AUC0–t and a 12 times increase in T1/2 as compared to the commercially available breviscapine solution. Conclusion: The results demonstrate that the NLC has great potential to use as a novel sustained release system for breviscapine. PMID:23770990

Association of vasoactive intestinal peptide with polymer-grafted liposomes: structural aspects for pulmonary delivery.

PubMed

Stark, Brigitte; Debbage, Paul; Andreae, Fritz; Mosgoeller, Wilhelm; Prassl, Ruth

2007-03-01

A polymer-grafted liposomal formulation that has the potential to be developed for aerosolic pulmonary delivery of vasoactive intestinal peptide (VIP), a potent vasodilatory neuropeptide, is described. As VIP is prone to rapid proteolytic degradation in the microenvironment of the lung a proper delivery system is required to increase the half-life and bioavailability of the peptide. Here we investigate structural parameters of unilamellar liposomes composed of palmitoyl-oleoyl-phosphatidylcholine, lyso-stearyl-phosphatidylglycerol and distearyl-phosphatidyl-ethanolamine covalently linked to polyethylene glycol 2000, and report on VIP-lipid interaction mechanisms. We found that the cationic VIP is efficiently entrapped by the negatively charged spherical liposomes and becomes converted to an amphipathic alpha-helix. By fluorescence spectroscopy using single Trp-modified VIP we could show that VIP is closely associated to the membrane. Our data suggest that the N-terminal random-coiled domain is embedded in the interfacial headgroup region of the phospholipid bilayer. By doing so, neither the bilayer thickness of the lipid membrane nor the mobility of the phospholipid acyl chains are affected as shown by small angle X-ray scattering and electron spin resonance spectroscopy. Finally, in an ex vivo lung arterial model system we found that liposomal-associated VIP is recognized by its receptors to induce vasodilatory effects with comparable high relaxation efficiency as free VIP but with a significantly retarded dilatation kinetics. In conclusion, we have designed and characterized a liposomal formulation that is qualified to entrap biologically active VIP and displays structural features to be considered for delivery of VIP to the lung.

Preparation of curcumin nanoparticle by using reinforcement ionic gelation technique

NASA Astrophysics Data System (ADS)

Suryani, Halid, Nur Hatidjah Awaliyah; Akib, Nur Illiyyin; Rahmanpiu, Mutmainnah, Nina

2017-05-01

Curcumin, a polyphenolic compound present in curcuma longa has a wide range of activities including anti-inflammatory properties. The potency of curcumin is limited by its poor oral bioavailability because of its poor solubility in aqueous. Various methods have been tried to solve the problem including its encapsulation into nanoparticle. The aim of this study is to develop curcumin nanoparticle by using reinforcement ionic gelation technique and to evaluate the stability of curcumin nanoparticles in gastrointestinal fluid. Curcumin nanoparticles were prepared by using reinforcement ionic gelation technique with different concentrations of chitosan, trypolyphosphate, natrium alginate and calcium chloride. Curcumin nanoparticles were then characterized including particle size and zeta potential by using particle size analyzer and morphology using a transmission electron microscope, entrapment efficiency using UV-Vis Spectrophotometer and chemical structure analysis by Infra Red Spectrophotometer (FTIR). Furthermore, the stability of curcumin nanoparticles were evaluated on artificial gastric fluid and artificial intestinal fluids by measuring the amount of curcumin released in the medium at a time interval. The result revealed that curcumin nanoparticles can be prepared by reinforcement ionic gelation technique, the entrapment efficiency of curcumin nanoparticles were from 86.08 to 91.41%. The average of particle size was 272.9 nm and zeta potential was 12.05 mV. The morphology examination showed that the curcumin nanoparticles have spherical shape. The stability evaluation of curcumin nanoparticles showed that the nanoparticles were stable on artificial gastric fluid and artificial intestinal fluid. This result indicates that curcumin nanoparticles have the potential to be developed for oral delivery.

Topical vesicular formulations of Curcuma longa extract on recuperating the ultraviolet radiation-damaged skin.

PubMed

Kaur, Chanchal Deep; Saraf, Swarnlata

2011-12-01

  Ultraviolet radiations generate reactive oxygen species, leading to adverse effects on skin properties. Botanical extracts are multifunctional in nature having various properties like photoprotection, anti-aging, moisturizing, antioxidant, astringent, anti-irritant, and antimicrobial activity.   The aim of this study was to formulate creams having Curcuma longa extract loaded novel vesicular systems (liposomes, ethosomes, and transfersomes) and study their photoprotective effect by assessment of skin hydration (Cutometer) and sebum content (Sebumeter).   The alcoholic C. longa extract loaded liposomes, ethosomes, and transfersomes having 0.5-2.0% w/w extract were prepared, evaluated for size, entrapment efficiency, and incorporated into the cream. Their long-term interaction with skin (6 weeks) was compared in terms of their effects on skin hydration and sebum content.   Vesicular size obtained was in the range 167.3 ± 3.0 to 262.4 ± 2.4 nm with low polydispersity index (0.2-0.3) and high entrapment efficiency. The efficacy was in the order C. longa extract loaded transfersomal creams > C. longa extract loaded ethosomal creams > C. longa extract loaded liposomal creams > C. longa extract loaded creams > Empty transfersome loaded cream > Empty ethosome loaded cream > Empty liposome loaded cream > Base cream.   The photoprotective properties of the constituents of C. longa extract and hydrant, moisturizing lipid components of nano vesicles with better skin penetration resulted in improvement in skin properties like skin hydration and sebum content. The herbal extract loaded nano vesicles incorporated in cream could be used as photoprotective formulations. © 2011 Wiley Periodicals, Inc.

Formation and functional attributes of electrostatic complexes involving casein and anionic polysaccharides: An approach to enhance oral absorption of lycopene in rats in vivo.

PubMed

Jain, Ashay; Thakur, Deepika; Ghoshal, Gargi; Katare, O P; Singh, Bhupinder; Shivhare, U S

2016-12-01

The current work entails a novel strategy of formulating the microparticles of lycopene solely using rational blends of biopolymers without using equipment-intensive techniques. The study is intended to enhance oral bioavailability of lycopene by controlling its release from micro-formulation and facilitating its absorption though lymphatic pathways. Considering the minimum particle size, maximum entrapment efficiency and loading capacity, the amounts of casein (i.e., protein) and gum tragacanth (i.e., polysaccharide) were selected as the critical factors for formulation of microparticles. Complex formation and electrostatic interaction was confirmed by Fourier transform infra red (FTIR) spectra. Size and surface properties of microparticles were studied using scanning electron microscopy (SEM). The optimized formulation (mean particle size: ∼130μm; % entrapment efficiency: ∼67% and loading capacity: ∼71%) designated noticeable improvement in lycopene release profile (over 80% in 24h). Increment in the values of C max (2.22-fold) and AUC (1.97-fold) further indicated noteworthy augmentation in the rate and extent of bioavailability by the microparticles formulation compared to plain lycopene. The resulting formulation was found to be quite stable all through two months of study episode. The resultant microparticles formulation was evaluated for antioxidant activity and tested for their effectiveness in self life enhancement of vegetable oil by calculating peroxide value under temperature and storage condition. Encapsulation strongly increased the stability of micronutrients. The current investigations, therefore, report the successful development of biopolymeric microparticles with improved bioavailability potential of lycopene. Copyright © 2016. Published by Elsevier B.V.

16 CFR § 1211.6 - General entrapment protection requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... operator shall withstand 100,000 cycles of operation controlling a load no less severe (voltage, current...) described in paragraph (c) of this section results in loss of any entrapment protection required by §§ 1211...

16 CFR 1211.6 - General entrapment protection requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... shall withstand 100,000 cycles of operation controlling a load no less severe (voltage, current, power... paragraph (c) of this section results in loss of any entrapment protection required by §§ 1211.7(a), 1211.7...

16 CFR 1211.6 - General entrapment protection requirements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... shall withstand 100,000 cycles of operation controlling a load no less severe (voltage, current, power... paragraph (c) of this section results in loss of any entrapment protection required by §§ 1211.7(a), 1211.7...

16 CFR 1211.6 - General entrapment protection requirements.

Code of Federal Regulations, 2012 CFR

2012-01-01

... shall withstand 100,000 cycles of operation controlling a load no less severe (voltage, current, power... paragraph (c) of this section results in loss of any entrapment protection required by §§ 1211.7(a), 1211.7...

16 CFR 1211.6 - General entrapment protection requirements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... shall withstand 100,000 cycles of operation controlling a load no less severe (voltage, current, power... paragraph (c) of this section results in loss of any entrapment protection required by §§ 1211.7(a), 1211.7...

Closed cell metal foam method

DOEpatents

Patten, James W.

1978-01-01

Foamed metals and metal alloys which have a closed cellular structure are prepared by heating a metal body containing entrapped inert gas uniformly distributed throughout to a temperature above the melting point of the metal and maintaining the body at this temperature a period of time sufficient to permit the entrapped gas to expand, forming individual cells within the molten metal, thus expanding and foaming the molten metal. After cell formation has reached the desired amount, the foamed molten metal body is cooled to below the melting temperature of the metal. The void area or density of the foamed metal is controlled by predetermining the amount of inert gas entrapped in the metal body and by the period of time the metal body is maintained in the molten state. This method is useful for preparing foamed metals and metal alloys from any metal or other material of which a body containing entrapped inert gas can be prepared.

Bubble pinch-off and scaling during liquid drop impact on liquid pool

NASA Astrophysics Data System (ADS)

Ray, Bahni; Biswas, Gautam; Sharma, Ashutosh

2012-08-01

Simulations are performed to show entrapment of air bubble accompanied by high speed upward and downward water jets when a water drop impacts a pool of water surface. A new bubble entrapment zone characterised by small bubble pinch-off and long thick jet is found. Depending on the bubble and jet behaviour, the bubble entrapment zone is subdivided into three sub-regimes. The entrapped bubble size and jet height depends on the crater shape and its maximum depth. During the bubble formation, bubble neck develops an almost singular shape as it pinches off. The final pinch-off shape and the power law governing the pinching, rneck ∝ A(t0 - t)αvaries with the Weber number. Weber dependence of the function describing the radius of the bubble during the pinch-off only affects the coefficient A and not the power exponent α.

Response surface methodology as an approach to determine optimal activities of lipase entrapped in sol-gel matrix using different vegetable oils.

PubMed

Pinheiro, Rubiane C; Soares, Cleide M F; de Castro, Heizir F; Moraes, Flavio F; Zanin, Gisella M

2008-03-01

The conditions for maximization of the enzymatic activity of lipase entrapped in sol-gel matrix were determined for different vegetable oils using an experimental design. The effects of pH, temperature, and biocatalyst loading on lipase activity were verified using a central composite experimental design leading to a set of 13 assays and the surface response analysis. For canola oil and entrapped lipase, statistical analyses showed significant effects for pH and temperature and also the interactions between pH and temperature and temperature and biocatalyst loading. For the olive oil and entrapped lipase, it was verified that the pH was the only variable statistically significant. This study demonstrated that response surface analysis is a methodology appropriate for the maximization of the percentage of hydrolysis, as a function of pH, temperature, and lipase loading.

Water entrapment and structure ordering as protection mechanisms for protein structural preservation

NASA Astrophysics Data System (ADS)

Arsiccio, A.; Pisano, R.

2018-02-01

In this paper, molecular dynamics is used to further gain insight into the mechanisms by which typical pharmaceutical excipients preserve the protein structure. More specifically, the water entrapment scenario will be analyzed, which states that excipients form a cage around the protein, entrapping and slowing water molecules. Human growth hormone will be used as a model protein, but the results obtained are generally applicable. We will show that water entrapment, as well as the other mechanisms of protein stabilization in the dried state proposed so far, may be related to the formation of a dense hydrogen bonding network between excipient molecules. We will also present a simple phenomenological model capable of explaining the behavior and stabilizing effect provided by typical cryo- and lyo-protectants. This model uses, as input data, molecular properties which can be easily evaluated. We will finally show that the model predictions compare fairly well with experimental data.

Nerve Entrapment in Ankle and Foot: Ultrasound Imaging.

PubMed

Chari, Basavaraj; McNally, Eugene

2018-07-01

Peripheral nerve entrapment of the ankle and foot is relatively uncommon and often underdiagnosed because electrophysiologic studies may not contribute to the diagnosis. Anatomy of the peripheral nerves is variable and complex, and along with a comprehensive physical examination, a thorough understanding of the applied anatomy is essential. Several studies have helped identify specific areas in which nerves are commonly compressed. Identified secondary causes of nerve compression include previous trauma, osteophytes, ganglion cysts, edema, accessory muscles, tenosynovitis, vascular lesions, and a primary nerve tumor. Imaging plays a key role in identifying primary and secondary causes of nerve entrapment, specifically ultrasound (US) and magnetic resonance imaging. US is a dynamic imaging modality that is cost effective and offers excellent resolution. Symptoms of nerve entrapment may mimic other common foot and ankle conditions such as plantar fasciitis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Preparation of Oenothera biennis Oil Solid Lipid Nanoparticles Based on Microemulsion Technique].

PubMed

Piao, Lin-mei; Jin, Yong; Cui, Yan-lin; Yin, Shou-yu

2015-06-01

To study the preparation of Oenothera biennis oil solid lipid nanoparticles and its quality evaluation. The solid lipid nanoparticles were prepared by microemulsion technique. The optimum condition was performed based on the orthogonal design to examine the entrapment efficiency, the mean diameter of the particles and so on. The optimal preparation of Oenothera biennis oil solid lipid nanoparticles was as follows: Oenothera biennis dosage 300 mg, glycerol monostearate-Oenothera biennis (2: 3), Oenothera biennis -RH/40/PEG-400 (1: 2), RH-40/PEG-400 (1: 2). The resulting nanoparticles average encapsulation efficiency was (89.89 ± 0.71)%, the average particle size was 44.43 ± 0.08 nm, and the Zeta potential was 64.72 ± 1.24 mV. The preparation process is simple, stable and feasible.

Studies on paclitaxel-loaded glyceryl monostearate nanoparticles.

PubMed

Shenoy, Vikram Subraya; Rajyaguru, Tushar Himmatlal; Gude, Rajiv Phondu; Murthy, Rayasa S Ramchandra

2009-09-01

Solid lipid nanoparticles (SLNs) of Paclitaxel were prepared by modified Hot homogenization method using Glyceryl monostearate (GMS). The SLNs were characterized for its physicochemical characteristics such as mean particle size, percentage entrapment efficiency and zeta potential, which were found to be 226 nm, 92.43% and -29.4 mV, respectively. The Transmission Electron Microscopy (TEM) studies showed that prepared SLNs were of spherical shape. The drug retarding efficiency of the lipid (GMS) was better in pH 7.4 compared to pH 3.5. The release profile showed a tendency to follow Higuchi diffusion pattern at pH 7.4 and Peppas-Korsenmeyer model at pH 3.5. Chemosensitivity assay carried out using B16F10 cell lines showed that anti-proliferative activity of Paclitaxel was not hindered due to encapsulation.

Entrapment of alpha1-acid glycoprotein in high-performance affinity columns for drug-protein binding studies.

PubMed

Bi, Cong; Jackson, Abby; Vargas-Badilla, John; Li, Rong; Rada, Giana; Anguizola, Jeanethe; Pfaunmiller, Erika; Hage, David S

2016-05-15

A slurry-based method was developed for the entrapment of alpha1-acid glycoprotein (AGP) for use in high-performance affinity chromatography to study drug interactions with this serum protein. Entrapment was achieved based on the physical containment of AGP in hydrazide-activated porous silica supports and by using mildly oxidized glycogen as a capping agent. The conditions needed for this process were examined and optimized. When this type of AGP column was used in binding studies, the association equilibrium constant (Ka) measured by frontal analysis at pH 7.4 and 37°C for carbamazepine with AGP was found to be 1.0 (±0.5)×10(5)M(-1), which agreed with a previously reported value of 1.0 (±0.1)×10(5)M(-1). Binding studies based on zonal elution were conducted for several other drugs with such columns, giving equilibrium constants that were consistent with literature values. An entrapped AGP column was also used in combination with a column containing entrapped HSA in a screening assay format to compare the binding of various drugs to AGP and HSA. These results also agreed with previous data that have been reported in literature for both of these proteins. The same entrapment method could be extended to other proteins and to the investigation of additional types of drug-protein interactions. Potential applications include the rapid quantitative analysis of biological interactions and the high-throughput screening of drug candidates for their binding to a given protein. Copyright © 2015 Elsevier B.V. All rights reserved.

Entrapment of Alpha1-Acid Glycoprotein in High-Performance Affinity Columns for Drug-Protein Binding Studies

PubMed Central

Bi, Cong; Jackson, Abby; Vargas-Badilla, John; Li, Rong; Rada, Giana; Anguizola, Jeanethe; Pfaunmiller, Erika; Hage, David S.

2015-01-01

A slurry-based method was developed for the entrapment of alpha1-acid glycoprotein (AGP) for use in high-performance affinity chromatography to study drug interactions with this serum protein. Entrapment was achieved based on the physical containment of AGP in hydrazide-activated porous silica supports and by using mildly oxidized glycogen as a capping agent. The conditions needed for this process were examined and optimized. When this type of AGP column was used in binding studies, the association equilibrium constant (Ka) measured by frontal analysis at pH 7.4 and 37°C for carbamazepine with AGP was found to be 1.0 (± 0.5) × 105 M−1, which agreed with a previously reported value of 1.0 (± 0.1) × 105 M−1. Binding studies based on zonal elution were conducted for several other drugs with such columns, giving equilibrium constants that were consistent with literature values. An entrapped AGP column was also used in combination with a column containing entrapped HSA in a screening assay format to compare the binding of various drugs to AGP and HSA. These results also agreed with previous data that have been reported in literature for both of these proteins. The same entrapment method could be extended to other proteins and to the investigation of additional types of drug-protein interactions. Potential applications include the rapid quantitative analysis of biological interactions and the high-throughput screening of drug candidates for their binding to a given protein. PMID:26627938

Assessment of penetration potential of pH responsive double walled biodegradable nanogels coated with eucalyptus oil for the controlled delivery of 5-fluorouracil: In vitro and ex vivo studies.

PubMed

Sahu, Prashant; Kashaw, Sushil K; Jain, Sanyog; Sau, Samaresh; Iyer, Arun K

2017-05-10

Penetration enhancers coated biodegradable polymeric nanogels loaded with cytotoxic drugs applied via the topical route, can be a promising strategy for improving the chemotherapeutic efficiency of skin cancers. The major objective of proposed research was to investigate the in vitro and ex vivo chemotherapeutic potential of double walled PLGA-chitosan biodegradable nanogel entrapped with 5-fluororuacil (5-FU) coated with eucalyptus oil, topically applied onto the skin. 5-FU was first entrapped in PLGA core by solvent evaporation technique followed by coating with cationic chitosan for ionic interaction with anionic skin cancer cell membrane. A surface coating of eucalyptus oil (1%) was employed to improve the penetration efficacy of the nanogel into stratum corneum. The surface modified biodegradable double walled nanogel was characterized for particle size, charge and thermal properties followed by pH dependent in vitro analysis. Human keratinocyte (HaCaT) cell line was employed for the bio- and cyto-compatibility testing prior to the hemolysis assay and coagulation assessment. A porcine skin ex vivo screening was performed for assessing the penetration potential of the nanogels. DLS and TEM revealed a particle size about 170nm for the double walled nanogels. The nanogels also exhibited high thermal stability as analyzed by thermogravimetry (TG) and differential thermal analysis (DTA). The drug entrapment efficacy was about ~40%. The drug release showed sustained release pattern noted up to 24h. The low hemolysis of 2.39% with short prothrombin time (PT) and activated partial thromboplastin time (APTT) of 14.2 and 35.5s respectively, revealed high biocompatibility of the nanogels. The cellular uptake and localization was assessed by confocal microscopy. The cytotoxicity (MTT assay) on HaCaT cell line demonstrated high cytocompatibilty of the nanogels. An ex vivo evaluation using porcine skin displayed efficient and steady state flux of 5-FU from the biodegradable nanogles into the skin, while the histology of the porcine skin revealed enhanced penetration potential of eucalyptus oil coated PLGA-chitosan double walled nanogels. Taken together the in vivo and ex vivo results portend promising potential for the utility of the biodegradable nanogels for treating skin cancers. Copyright © 2017. Published by Elsevier B.V.

Physicochemical Characteristics and Slow Release Performances of Chlorpyrifos Encapsulated by Poly(butyl acrylate-co-styrene) with the Cross-Linker Ethylene Glycol Dimethacrylate.

PubMed

Wang, Yu; Gao, Zideng; Shen, Feng; Li, Yang; Zhang, Sainan; Ren, Xueqin; Hu, Shuwen

2015-06-03

Chlorpyrifos' application and delivery to the target substrate needs to be controlled to improve its use. Herein, poly(butyl acrylate-co-styrene) (poly(BA/St)) and poly(BA/St/ethylene glycol dimethacrylate (EGDMA)) microcapsules loaded with chlorpyrifos as a slow release formulation were prepared by emulsion polymerization. The effects of structural characteristics on the chlorpyrifos microcapsule particle size, entrapment rate (ER), pesticide loading (PL), and release behaviors in ethyl alcohol were investigated. Fourier transform infrared and thermogravimetric analysis confirmed the successful entrapment of chlorpyrifos. The ER and PL varied with the BA/St monomer ratio, chlorpyrifos/monomer core-to-shell ratio, and EGDMA cross-linker content with consequence that suitable PL was estimated to be smaller than 3.09% and the highest ER was observed as 96.74%. The microcapsule particle size (88.36-101.8 nm) remained mostly constant. The extent of sustainable release decreased with increasing content of BA, St, or chlorpyrifos in the oil phase. Specifically, an adequate degree of cross-linking with EGMDA (0.5-2.5%) increased the extent of sustainable release considerably. However, higher levels of cross-linking with EGDMA (5-10%) reduced the extent of sustainable release. Chlorpyrifos release from specific microcapsules (monomer ratio 1:2 with 0.5% EGDMA or 5 g chlopyrifos) tended to be a diffusion-controlled process, while for others, the kinetics probably indicated the initial rupture release.

Comparison of Airway Management Methods in Entrapped Patients: A Manikin Study.

PubMed

Martin, Andrew B; Lingg, Jim; Lubin, Jeffrey S

2016-01-01

Endotracheal intubation remains one of the most challenging skills in prehospital care. There is a minimal amount of data on the optimal technique to use when managing the airway of an entrapped patient. We hypothesized that use of a blindly placed device would result in both the shortest time to airway management and highest success rate. A difficult airway manikin was placed in a cervical collar and secured upside down in an overturned vehicle. Experienced paramedics and prehospital registered nurses used four different methods to secure the airway: direct laryngoscopy, digital intubation, King LT-D, and CMAC video laryngoscopy. Each participant was given three opportunities to secure the airway using each technique in random order. A study investigator timed each attempt and confirmed successful placement, which was determined upon inflation of the manikin's lungs. Intubation success rates were analyzed using a general estimating equations model to account for repeated measures and a linear mixed effects model for average time. Twenty-two prehospital providers participated in the study. The one-pass success rate for the King LT-D was significantly higher than direct laryngoscopy (OR 0.048, CI 0.006-0.351, p < 0.01) and digital intubation (OR 0.040, CI 0.005-0.297, p < 0.01). However, there was no statistical difference between the one-pass success rate of the King LT-D and CMAC video laryngoscopy (OR 0.302, 95% CI 0.026-3.44, p = 0.33). The one-pass median placement time of the King LT-D (22 seconds, IQR 17-26) was significantly lower (p < 0.001) than direct laryngoscopy (60 seconds, IQR 42-75), digital intubation (38 seconds, IQR 26-74), and the CMAC (51 seconds, IQR 43-76). In this study, while the King LT-D offered the quickest airway placement, success rates were not significantly greater than intubation using the CMAC video laryngoscope. Intubation using direct laryngoscopy and digital intubation were less successful and took more time. Use of a blindly placed device or a video laryngoscope may provide the best avenues for airway management of entrapped patients.

Evaluation of consolidation problems in thicker Portland cement concrete pavements

DOT National Transportation Integrated Search

2003-08-01

Minimizing the amount of entrapped air in concrete is necessary to produce quality concrete with a longer pavement performance life, lower maintenance costs and fewer delays to the roadway users. Good quality concrete with low entrapped air content w...

POTENTIAL ENTRAPMENT OF OIL IN A TIDAL MARSH IN LONG ISLAND NEW YORK

EPA Science Inventory

This presentation describes hydraulic and biological characteristics of a tidal marsh located on the southern shore of Long Island, NY, coupled with transport simulations which indicated potential for entrapment of spilled oil in the marsh.

Role of entrapped vapor bubbles during microdroplet evaporation

NASA Astrophysics Data System (ADS)

Putnam, Shawn A.; Byrd, Larry W.; Briones, Alejandro M.; Hanchak, Michael S.; Ervin, Jamie S.; Jones, John G.

2012-08-01

On superheated surfaces, the air bubble trapped during impingement grows into a larger vapor bubble and oscillates at the frequency predicted for thermally induced capillary waves. In some cases, the entrapped vapor bubble penetrates the droplet interface, leaving a micron-sized coffee-ring pattern of pure fluid. Vapor bubble entrapment, however, does not influence the evaporation rate. This is also true on laser heated surfaces, where a laser can thermally excite capillary waves and induce bubble oscillations over a broad range of frequencies, suggesting that exciting perturbations in a pinned droplets interface is not an effective avenue for enhancing evaporative heat transfer.

Entrapment Neuropathies of the Foot and Ankle.

PubMed

Ferkel, Eric; Davis, William Hodges; Ellington, John Kent

2015-10-01

Posterior tarsal tunnel syndrome is the result of compression of the posterior tibial nerve. Anterior tarsal tunnel syndrome (entrapment of the deep peroneal nerve) typically presents with pain radiating to the first dorsal web space. Distal tarsal tunnel syndrome results from entrapment of the first branch of the lateral plantar nerve and is often misdiagnosed initially as plantar fasciitis. Medial plantar nerve compression is seen most often in running athletes, typically with pain radiating to the medial arch. Morton neuroma is often seen in athletes who place their metatarsal arches repetitively in excessive hyperextension. Copyright © 2015 Elsevier Inc. All rights reserved.

Atypical presentation of popliteal artery entrapment syndrome: involvement of the anterior tibial artery.

PubMed

Bou, Steven; Day, Carly

2014-11-01

Popliteal artery entrapment syndrome (PAES) is a rare condition that should be suspected in a young patient with exertional lower extremity pain. We report the case of an 18-year-old female volleyball player with bilateral exertional lower extremity pain who had been previously diagnosed with tendinitis and periostitis. Diagnostic studies showed entrapment of the left popliteal artery and the left anterior tibial artery. To our knowledge, there has only been 1 previous report of anterior tibial artery involvement in PAES. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Extrinsic mechanism obstructing the opening of a prosthetic mitral valve: an unusual case of suture entrapment.

PubMed

Ozkan, Mehmet; Astarcioglu, Mehmet Ali; Karakoyun, Suleyman; Balkanay, Mehmet

2012-02-01

Obstruction to a prosthetic cardiac valve is a well-recognized complication of cardiac valve replacement. Malfunction of the mobile component of a prosthetic valve to open or close correctly may occur in consequence of intrinsic or extrinsic causes (thrombus, vegetation, entrapment of left ventricular myocardium, suture entanglement, and pannus formation) that may result prosthetic valve stenosis and/or insufficiency. In the case we report a 48-year-old female with valve dysfunction occurred early after surgery, as one valve leaflet was only able to partially open due to suture entrapment. © 2011, Wiley Periodicals, Inc.

Psychological Processes and Repeat Suicidal Behavior: A Four-Year Prospective Study

PubMed Central

2013-01-01

Objective: Although suicidal behavior is a major public health concern, understanding of individually sensitive suicide risk mechanisms is limited. In this study, the authors investigated, for the first time, the utility of defeat and entrapment in predicting repeat suicidal behavior in a sample of suicide attempters. Method: Seventy patients hospitalized after a suicide attempt completed a range of clinical and psychological measures (depression, hopelessness, suicidal ideation, defeat, and entrapment) while in hospital. Four years later, a nationally linked database was used to determine who had been hospitalized again after a suicide attempt. Results: Over 4 years, 24.6% of linked participants were readmitted to hospital after a suicidal attempt. In univariate logistic regression analyses, defeat and entrapment as well as depression, hopelessness, past suicide attempts, and suicidal ideation all predicted suicidal behavior over this interval. However, in the multivariate analysis, entrapment and past frequency of suicide attempts were the only significant predictors of suicidal behavior. Conclusions: This longitudinal study supports the utility of a new theoretical model in the prediction of suicidal behavior. Individually sensitive suicide risk processes like entrapment could usefully be targeted in treatment interventions to reduce the risk of repeat suicidal behavior in those who have been previously hospitalized after a suicide attempt. PMID:23855989

Light-Addressed Electrodeposition of Enzyme-Entrapped Chitosan Membranes for Multiplexed Enzyme-Based Bioassays Using a Digital Micromirror Device

PubMed Central

Huang, Shih-Hao; Wei, Lu-Shiuan; Chu, Hsiao-Tzu; Jiang, Yeu-Long

2013-01-01

This paper describes a light-addressed electrolytic system used to perform an electrodeposition of enzyme-entrapped chitosan membranes for multiplexed enzyme-based bioassays using a digital micromirror device (DMD). In this system, a patterned light illumination is projected onto a photoconductive substrate serving as a photo-cathode to electrolytically produce hydroxide ions, which leads to an increased pH gradient. The high pH generated at the cathode can cause a local gelation of chitosan through sol-gel transition. By controlling the illumination pattern on the DMD, a light-addressed electrodeposition of chitosan membranes with different shapes and sizes, as well as multiplexed micropatterning, was performed. The effect of the illumination time of the light pattern on the dimensional resolution of chitosan membrane formation was examined experimentally. Moreover, multiplexed enzyme-based bioassay of enzyme-entrapped chitosan membranes was also successfully demonstrated through the electrodeposition of the chitosan membranes with various shapes/sizes and entrapping different enzymes. As a model experiment, glucose and ethanol were simultaneously detected in a single detection chamber without cross-talk using shape-coded chitosan membranes entrapped with glucose oxidase (GOX), peroxidase (POD), and Amplex Red (AmR) or alcohol oxidase (AOX), POD, and AmR by using same fluorescence indicator (AmR). PMID:23959236

Light-addressed electrodeposition of enzyme-entrapped chitosan membranes for multiplexed enzyme-based bioassays using a digital micromirror device.

PubMed

Huang, Shih-Hao; Wei, Lu-Shiuan; Chu, Hsiao-Tzu; Jiang, Yeu-Long

2013-08-16

This paper describes a light-addressed electrolytic system used to perform an electrodeposition of enzyme-entrapped chitosan membranes for multiplexed enzyme-based bioassays using a digital micromirror device (DMD). In this system, a patterned light illumination is projected onto a photoconductive substrate serving as a photo-cathode to electrolytically produce hydroxide ions, which leads to an increased pH gradient. The high pH generated at the cathode can cause a local gelation of chitosan through sol-gel transition. By controlling the illumination pattern on the DMD, a light-addressed electrodeposition of chitosan membranes with different shapes and sizes, as well as multiplexed micropatterning, was performed. The effect of the illumination time of the light pattern on the dimensional resolution of chitosan membrane formation was examined experimentally. Moreover, multiplexed enzyme-based bioassay of enzyme-entrapped chitosan membranes was also successfully demonstrated through the electrodeposition of the chitosan membranes with various shapes/sizes and entrapping different enzymes. As a model experiment, glucose and ethanol were simultaneously detected in a single detection chamber without cross-talk using shape-coded chitosan membranes entrapped with glucose oxidase (GOX), peroxidase (POD), and Amplex Red (AmR) or alcohol oxidase (AOX), POD, and AmR by using same fluorescence indicator (AmR).

Impact of co-incorporating laminin peptide dopants and neurotrophic growth factors on conducting polymer properties.

PubMed

Green, Rylie A; Lovell, Nigel H; Poole-Warren, Laura A

2010-01-01

Conductive neural interfaces tailored for cell interaction by incorporation of bioactive factors are hypothesized to produce superior neuroprostheses with improved charge transfer capabilities. This study examined the effect of entrapping nerve growth factor (NGF) within the conducting polymer poly(ethylene dioxythiophene) (PEDOT) during electrodeposition to create a polymer capable of stimulating neurite outgrowth from proximal neural tissue. NGF entrapment was performed on polymers doped with laminin peptides DEDEDYFQRYLI and DCDPGYIGSR and, additionally, a conventional dopant, paratoluene sulphonate (pTS). All polymer coatings were analysed for a range of physical, electrical and mechanical properties, with the biological activity of ligands examined using a PC12 neurite outgrowth assay. NGF was successfully entrapped in PEDOT during electrodeposition and was shown to produce a softer interface than conventional conducting polymers and films without the NGF modification. However, it was found that the use of a peptide dopant combined with NGF entrapment resulted in polymers with diminished electrical and mechanical stability. Entrapped NGF was determined to be biologically active, with PEDOT/pTS/NGF producing neurite outgrowth comparable with control films where NGF was supplied via the medium. Future studies will determine the effect of typical neural prosthetic stimulation regimes on the release of neurotrophins and subsequent cell response.

Remote-loading labeling of liposomes with (99m)Tc-BMEDA and its stability evaluation: effects of lipid formulation and pH/chemical gradient.

PubMed

Li, Shihong; Goins, Beth; Phillips, William T; Bao, Ande

2011-03-01

Efficient, convenient, and stable radiolabeling plays a critical role for the monitoring of liposome behavior via either blood sampling, organ distribution, or noninvasive nuclear imaging. The direct labeling of liposome-carrying drugs without any prior modification undoubtedly is convenient and optimal for liposomal drug testing. In this article, we investigated the effect of various lipid formulations and pH/chemical gradients on the radiolabeling efficiency and entrapment stability of technetium-99m ((99m)Tc) remotely loaded into liposomes, using (99m)Tc-N,N-bis(2-mercaptoethyl)-N',N'-diethyl-ethylenediamine ((99m)Tc-BMEDA) complex. The tested liposomes either contained unsaturated lipid or possessed various surface charges. (99m)Tc could be efficiently loaded into various premanufactured liposomes containing either an ammonium sulfate pH, citrate pH, or glutathione (GSH) chemical gradient. (99m)Tc-entrapment stabilities of these liposomes in phosphate-buffered saline (PBS; pH 7.4) buffer at 25°C were mainly dependent on the pH/chemical gradient, but not lipid formulation. Stability sequence was ammonium sulfate pH-gradient>citrate pH-gradient>GSH-gradient. Stabilities of (99m)Tc-liposomes in 50% fetal bovine serum (FBS)/PBS (pH 7.4) buffer at 37°C are dependent on both lipid formulation and pH/chemical gradient. Specifically, (99m)Tc labeling of the ammonium sulfate pH-gradient liposomes were less stable in 50% FBS/PBS than in PBS, whereas noncationic liposomes with citrate pH- or GSH-gradient displayed higher stability, except that anionic citrate pH-gradient liposomes showed no stability difference in these two media. Cationic liposomes aggregated in 50% FBS/PBS, forming a new discrete fraction with larger particle sizes. These in vitro characterization results have indicated the optimism of using (99m)Tc-BMEDA for labeling pH/GSH gradient liposomes without the requirement of modifying lipid formulation for liposomal therapeutic-agent development.

5-Aminolevulinic acid loaded ethosomal vesicles with high entrapment efficiency for in vitro topical transdermal delivery and photodynamic therapy of hypertrophic scars.

PubMed

Zhang, Zheng; Chen, Yunsheng; Xu, Heng; Wo, Yan; Zhang, Zhen; Liu, Ying; Su, Weijie; Cui, Daxiang; Zhang, Yixin

2016-11-24

Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an alternative therapy for hypertrophic scars (HS), which destroys human hypertrophic scar fibroblasts (HSF). However, the poor permeability of ALA both in HS tissue and HSF significantly restricts the PDT of HS. To overcome these barriers, ALA-loaded ethosomal vesicles (ALA-ES) were developed by a pH gradient active loading method and characterized by morphology, entrapment efficiency (EE) and stability. Results show that prepared ALA-ES are homogenous spherical lamellar vesicles, 53 ± 7 nm in size, 50.6 ± 2.3% in EE and have excellent stability. In vitro transdermal delivery studies through HS tissue were carried out by using Franz diffusion cells. Compared to the traditional ALA hydroalcoholic solution (ALA-HA), ALA-ES achieve higher drug retention in less administration time, and fluorescence microscopy showed that ALA-ES penetrate into the deeper dermis of HS in a shorter time, indicating that ALA-ES can enhance the penetration of ALA into HS. Additionally, ALA-ES was visualized in HS tissue for the first time by transmission electron microscopy (TEM). The irregular and collapsed ALA-ES suggest that they can squeeze through narrow spaces to the target area and release ALA into HS. Taking HSF as the target, the transcellular delivery of ALA-ES into HSF cells was investigated by intracellular protoporphyrin IX (PpIX) accumulation. The efficiency of PDT for HSF cells, including the formation of reactive oxygen species (ROS) and cell apoptosis, were also well investigated. Furthermore, the detailed changes of HSF were observed by TEM. The results strongly indicate that ALA-ES can facilitate ALA penetration into HSF cells, and can cause a higher level of cell apoptosis or necrosis than ALA-HA. ALA-ES with high EE is therefore a promising transdermal delivery system for topical ALA administration and has great potential in ALA-PDT of HS.

Peptide-substituted oligonucleotide synthesis and non-toxic, passive cell delivery

PubMed Central

Shang, Shiying; Monfregola, Luca; Caruthers, Marvin H

2016-01-01

Chemically modified oligodeoxynucleotides (ODNs) are known to modulate gene expression by interacting with RNA. An efficient approach for synthesizing amino acid- or peptide-substituted triazolylphosphonate analogs (TP ODNs) has been developed to provide improved stability and cell uptake. The chemistry is quite general, as peptides can be introduced throughout the TP ODN at any preselected internucleotide linkage. These synthetic TP ODNs enter cells through endocytosis in the absence of transfection reagents and localize into perinuclear organelles. The entrapped ODNs are released into the cytoplasm by treatment with endosomal-releasing agents and several are then active as microRNA inhibitors. PMID:29263901

Mobilization and biodegradation of 2-methylnaphthalene by amphiphilic polyurethane nano-particle.

PubMed

Kim, Young-Bum; Kim, Ju-Young; Kim, Eun-ki

2009-10-01

Amphiphilic polyurethane (APU) nano-particle enhanced the mobilization of 2-methylnaphthalene (2-MNPT) in soil. Significant increase in the solubility of 2-MNPT was achieved. The molar solubilization ratio was 0.4 (mole 2-MNPT/mole APU). Simple precipitation of APU particle by 2 N CaCl(2) recovered 95% of APU particle and 92% of 2-MNPT simultaneously. Also, 2-MNPT, which was entrapped inside the APU particle, was directly degraded by Acinetobacter sp. as same efficiency as without APU particle. These results showed the potentials of APU particle in the mobilization and biodegradation of hydrophobic compounds from soil.

Production of Bacteriophages by Listeria Cells Entrapped in Organic Polymers.

PubMed

Roy, Brigitte; Philippe, Cécile; Loessner, Martin J; Goulet, Jacques; Moineau, Sylvain

2018-06-13

Applications for bacteriophages as antimicrobial agents are increasing. The industrial use of these bacterial viruses requires the production of large amounts of suitable strictly lytic phages, particularly for food and agricultural applications. This work describes a new approach for phage production. Phages H387 ( Siphoviridae ) and A511 ( Myoviridae ) were propagated separately using Listeria ivanovii host cells immobilised in alginate beads. The same batch of alginate beads could be used for four successive and efficient phage productions. This technique enables the production of large volumes of high-titer phage lysates in continuous or semi-continuous (fed-batch) cultures.

Topical hydrogel matrix loaded with Simvastatin microparticles for enhanced wound healing activity.

PubMed

Yasasvini, S; Anusa, R S; VedhaHari, B N; Prabhu, P C; RamyaDevi, D

2017-03-01

A prolonged release drug delivery system was developed by loading Simvastatin-chitosan microparticles into poly vinyl alcohol (PVA) hydrogels for enhanced wound healing efficiency. The microparticles prepared by ionic gelation method with varying composition of chitosan and surfactants (Tween 80/Pluronic F-127) were optimized for entrapment efficiency, morphology and drug-polymer interactions. Microparticles prepared with 0.3% between 80 and 0.5:5 chitosan: drug ratio showed maximum entrapment efficiency of 82% with spherical morphology and mild interaction between drug and chitosan. 5% PVA solutions loaded with pure drug and drug loaded microparticles at three different doses (2.5mg, 5mg and 10mg equivalent of drug) were chemically cross linked using gluteraldehyde and HCl. The formulated hydrogels were optimized for swelling, in vitro release behavior and in vivo wound healing effect. Hydrogels containing 2.5mg equivalent dose of Simvastatin microparticles exhibited maximum cumulative percentage drug release of 92% (n=3) at the end of 7days. The in vitro drug release data was supported by the higher swelling index of the low dose hydrogels. The in vivo wound healing study was performed using Wistar rats (n=30, 5 groups with 6 animals in each group) for the formulated hydrogels (at 3 doses) and compared with the untreated animals and the positive control group treated with conventional topical Simvastatin ointment (1%). The wound healing effect was comparable to the in vitro results, wherein the animals treated with low dose hydrogels (replaced every 7days) exhibited considerable reduction in the wound area compared to medium and high dose hydrogels. Statistically significant difference (P<0.05) was observed in the wound area of the animals treated with low dose hydrogels compared to 1% ointment and untreated animals, as estimated by two-way ANOVA. The histopathology images of the different groups of animals also displayed the comparative changes in the wound healing process. Hence, the incorporation of Simvastatin-chitosan microparticles in PVA hydrogels has demonstrated significant wound healing efficiency at optimum dose. Copyright © 2016 Elsevier B.V. All rights reserved.

Single-Dose Electrospun Nanoparticles-in-Nanofibers Wound Dressings with Enhanced Epithelialization, Collagen Deposition, and Granulation Properties.

PubMed

Ali, Isra H; Khalil, Islam A; El-Sherbiny, Ibrahim M

2016-06-15

Phenytoin (Ph), an antiepileptic drug, was reported to exhibit high wound healing activity. However, its limited solubility, bioavailability, and inefficient distribution during topical administration limit its use. Therefore, this study aims to develop new single-dose electrospun nanoparticles-in-nanofibers (NPs-in-NFs) wound dressings that allow a well-controlled release of Ph. These NPs-in-NFs systems are based on enhanced chitosan (CS)/poly(ethylene oxide) (PEO) electrospun nanofibers (NFs) incorporating optimized Ph-loaded nanocarriers. First, a study was conducted to investigate Ph loading efficiency into polymeric nanocarriers of different types; pluronic nanomicelles and poly(lactic-co-glycolic) acids nanoparticles (PLGA NPs). The drug release profile from the nanocarriers was further optimized via lecithin coating. Second, different electrospinning parameters were manipulated to fabricate beads-free homogeneous NFs with optimized polymer ratios. Plain and Ph-loaded nanocarriers were characterized using Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), dynamic light scattering (DLS), and scanning electron microscopy (SEM). Both entrapment efficiency of Ph (EE%) and its release profile in phosphate buffer saline (PBS; pH 5.5), simulating the wound environment, were studied. Biodegradability, swelling, vapor permeability, and porosity of the developed Ph-loaded NPs-in-NFs wound dressings were investigated. Morphology of the NPs-in-NFs was also studied using SEM and confocal laser microscopy (CLSM). Besides, the release profiles of Ph from the optimized NPs-in-NFs were assessed. The newly developed wound dressings were evaluated in vitro for their cytotoxicity using human fibroblasts and in vivo using a wound healing mice model. Nanocarriers with particle size ranging from 100 to 180 nm were successfully prepared. All nanocarriers attained a high drug entrapment efficiency exceeding 94% and showed promising sustained release profiles compared to free Ph. Results also demonstrated that NFs incorporating the optimized lecithin-coated Ph-loaded PLGA NPs could be the most promising candidate for efficient wound healing. These NPs-in-NFs systems conferred a well-controlled and sustained release of Ph over 9 days. Moreover, they showed the best re-epithelization and healing quality during the in vivo study with minimal inflammatory and necrotic cells formation.

The War Crimes Act: Current Issues

DTIC Science & Technology

2006-10-02

divided into three overlapping categories: (1) defense of entrapment by estoppel , available when a defendant is informed by a government official that...defenses, the defense of entrapment by estoppel stems from the due process notions of fairness, rather than from common law concerning contract, equity

Synthesis and characterization of low-toxicity N-caprinoyl-N-trimethyl chitosan as self-assembled micelles carriers for osthole

PubMed Central

Hu, Xiao-juan; Liu, Yang; Zhou, Xiao-feng; Zhu, Qiao-ling; Bei, Yong-yan; You, Ben-gang; Zhang, Chun-ge; Chen, Wei-liang; Wang, Zhou-li; Zhu, Ai-jun; Zhang, Xue-nong; Fan, Yu-jiang

2013-01-01

Novel amphiphilic chitosan derivatives (N-caprinoyl-N-trimethyl chitosan [CA-TMC]) were synthesized by grafting the hydrophobic moiety caprinoyl (CA) and hydrophilic moiety trimethyl chitosan to prepare carriers with good compatibility for poorly soluble drugs. Based on self-assembly, CA-TMC can form micelles with sizes ranging from 136 nm to 212 nm. The critical aggregation concentration increased from 0.6 mg • L−1 to 88 mg • L−1 with decrease in the degree of CA substitution. Osthole (OST) could be easily encapsulated into the CA-TMC micelles. The highest entrapment efficiency and drug loading of OST-loaded CA-TMC micelles(OST/CA-TMC) were 79.1% and 19.1%, respectively. The antitumor efficacy results show that OST/CA-TMC micelles have significant antitumor activity on Hela and MCF-7 cells, with a 50% of cell growth inhibition (IC50) of 35.8 and 46.7 μg. mL−1, respectively. Cell apoptosis was the main effect on cell death of Hela and MCF-7 cells after OST administration. The blank micelles did not affect apoptosis or cell death of Hela and MCF-7 cells. The fluorescence imaging results indicated that OST/CA-TMC micelles could be easily uptaken by Hela and MCF-7 cells and could localize in the cell nuclei. These findings suggest that CA-TMC micelles are promising carriers for OST delivery in cancer therapy. PMID:24106424

Water-Soluble Combretastatin A4 Phosphate Orally Delivered via Composite Nanoparticles With Improved Inhibition Effect Toward S180 Tumors.

PubMed

Shen, Yurun; Wu, Liping; Qiu, Liyan

2017-10-01

Combretastatin A4 phosphate (CA4P) is a novel vascular disrupting agent for cancer therapy. However, frequent dosing and negative patient compliance have been encountered over CA4P by injection administration due to its quite short-term action and acute side effects. Therefore, it is significant to develop an oral formulation of CA4P. We established a novel method to prepare CA4P-loaded nanoparticles (CA4P-NPs) for oral administration by combining methoxy poly(ethylene glycol)-b-polylactide (PELA) and poly(d,l-lactic-co-glycolic acid) (PLGA) polymers. Transport study in vitro was evaluated on Madin-Darby canine kidney cell models, and antitumor effect evaluation in vivo was performed on S180 subcutaneous xenotransplanted tumor models in mice. The highest entrapment efficiency of CA4P-NPs was achieved when the weight ratio of PELA to PLGA was optimized to 1:1. The apparent permeability coefficient of CA4P-NPs was found to be 2.08-fold higher than that of free CA4P in transport study. CA4P-NPs reached an absolute bioavailability of 77.6% with the tumor inhibition ratio of 41.2% that was significantly superior to free CA4P. These results suggest a promising application of this composite nanoparticle for the oral delivery of water-soluble drugs. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Stable curcumin-loaded polymeric micellar formulation for enhancing cellular uptake and cytotoxicity to FLT3 overexpressing EoL-1 leukemic cells.

PubMed

Tima, Singkome; Anuchapreeda, Songyot; Ampasavate, Chadarat; Berkland, Cory; Okonogi, Siriporn

2017-05-01

The present study aims to develop a stable polymeric micellar formulation of curcumin (CM) with improved solubility and stability, and that is suitable for clinical applications in leukemia patients. CM-loaded polymeric micelles (CM-micelles) were prepared using poloxamers. The chemical structure of the polymers influenced micellar properties. The best formulation of CM-micelles, namely CM-P407, was obtained from poloxamer 407 at drug to polymer ratio of 1:30 and rehydrated with phosphate buffer solution pH 7.4. CM-P407 exhibited the smallest size of 30.3±1.3nm and highest entrapment efficiency of 88.4±4.1%. When stored at -80°C for 60days, CM-P407 retained high protection of CM and had no significant size change. In comparison with CM solution in dimethyl sulfoxide (CM-DMSO), CM kinetic degradation in both formulations followed a pseudo-first-order reaction, but the half-life of CM in CM-P407 was approx. 200 times longer than in CM-DMSO. Regarding the activity against FLT3 overexpressing EoL-1 leukemic cells, CM-P407 showed higher cytotoxicity than CM-DMSO. Moreover, intracellular uptake to leukemic cells of CM-P407 was 2-3 times greater than that of CM-DMSO. These promising results for CM-P407 will be further investigated in rodents and in clinical studies for leukemia treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

Professional driving and prolapsed lumbar intervertebral disc diagnosed by magnetic resonance imaging – a case–control study

PubMed Central

Palmer, Keith T; Griffin, Michael; Ntani, Georgia; Shambrook, James; McNee, Philip; Sampson, Madeleine; Harris, E Clare; Coggon, David

2012-01-01

Objectives The aim of this study was to investigate whether whole-body vibration (WBV) is associated with prolapsed lumbar intervertebral disc (PID) and nerve root entrapment among patients with low-back pain (LBP) undergoing magnetic resonance imaging (MRI). Methods A consecutive series of patients referred for lumbar MRI because of LBP were compared with controls X-rayed for other reasons. Subjects were questioned about occupational activities loading the spine, psychosocial factors, driving, personal characteristics, mental health, and certain beliefs about LBP. Exposure to WBV was assessed by six measures, including weekly duration of professional driving, hours driven at a spell, and current 8-hour daily equivalent root-mean-square acceleration A(8). Cases were sub-classified according to whether or not PID/nerve root entrapment was present. Associations with WBV were examined separately for cases with and without these MRI findings, with adjustment for age, sex, and other potential confounders. Results Altogether, 237 cases and 820 controls were studied, including 183 professional drivers and 176 cases with PID and/or nerve root entrapment. Risks associated with WBV tended to be lower for LBP with PID/nerve root entrapment but somewhat higher for risks of LBP without these abnormalities. However, associations with the six metrics of exposure were all weak and not statistically significant. Neither exposure–response relationships nor increased risk of PID/nerve root entrapment from professional driving or exposure at an A(8) above the European Union daily exposure action level were found. Conclusions WBV may be a cause of LBP but it was not associated with PID or nerve root entrapment in this study. PMID:22249859

Mixed germ cell-sex cord stromal tumor of the testis with an intratubular component: a problem in differential diagnosis.

PubMed

Roth, Lawrence M; Cheng, Liang

2016-05-01

The origin of mixed germ cell-sex cord stromal tumor (MGC-SCST) of the testis is uncertain, and a controversy exists as to whether the germ cells in these tumors are neoplastic. Although intratubular components of the common and several uncommon forms of testicular germ cell tumors have been described, to our knowledge, intratubular MGC-SCST has not previously been reported in detail. In a study of 13 cases of testicular MGC-SCST, we observed entrapped seminiferous tubules in 7 cases and an intratubular component in 2, both of which were associated with extensive entrapped tubules. Intratubular MGC-SCST is distinguished from entrapped tubules by the occurrence of germ cells resembling spermatogonia in the adluminal compartment and the absence of tubular lumens. By way of contrast, the adluminal compartment of entrapped tubules is composed entirely of immature Sertoli cells, and lumen formation is observed in favorably oriented tubules. Although the germ cells in our cases of MGC-SCST do not show histologic features of malignancy, the observation of spermatogonia-like cells in the adluminal compartment of the tubule, sometimes with concomitant germ cell proliferation, and the infiltrative pattern of the germ cells in the extratubular component support their neoplastic nature. The intratubular component tends to be more centrally located than the adjacent entrapped seminiferous tubules suggesting that it originates from the latter. The tubules of intratubular MGC-SCST are not expanded except in the advanced stage and are approximately the same size as entrapped seminiferous tubules but are considerably smaller than those of the uninvolved testis that shows active spermatogenesis. Copyright © 2015. Published by Elsevier Inc.

Use of entrapment and high-performance affinity chromatography to compare the binding of drugs and site-specific probes with normal and glycated human serum albumin

PubMed Central

Jackson, Abby J.; Anguizola, Jeanethe; Pfaunmiller, Erika L.; Hage, David S.

2013-01-01

Protein entrapment and high-performance affinity chromatography were used with zonal elution to examine the changes in binding that occurred for site-specific probes and various sulfonylurea drugs with normal and glycated forms of human serum albumin (HSA). Samples of this protein in a soluble form were physically entrapped within porous silica particles by using glycogen-capped hydrazide-activated silica; these supports were then placed into 1.0 cm × 2.1 mm inner diameter columns. Initial zonal elution studies were performed using (R)-warfarin and L-tryptophan as probes for Sudlow sites I and II (i.e., the major drug binding sites of HSA), giving quantitative measures of binding affinities in good agreement with literature values. It was also found for solutes with multisite binding to the same proteins, such as many sulfonylurea drugs, that this method could be used to estimate the global affinity of the solute for the entrapped protein. This entrapment and zonal approach provided retention information with precisions of ±0.1–3.3% (± one standard deviation) and elution within 0.50–3.00 min for solutes with binding affinities of 1 × 104–3 × 105 M−1. Each entrapped-protein column was used for many binding studies, which decreased the cost and amount of protein needed per injection (e.g., the equivalent of only 125–145 pmol of immobilized HSA or glycated HSA per injection over 60 sample application cycles). This method can be adapted for use with other proteins and solutes and should be valuable in high-throughput screening or quantitative studies of drug–protein binding or related biointeractions. PMID:23657448

The War Crimes Act: Current Issues

DTIC Science & Technology

2009-01-22

defense of entrapment by estoppel , available when a defendant is informed by a government official that certain conduct is legal, and thereafter...entrapment by estoppel stems from the due process notions of fairness, rather than from common law concerning contract, equity, or agency. United States v

Detection of entrapped moisture in honeycomb sandwich structures

NASA Technical Reports Server (NTRS)

Hallmark, W. B.

1967-01-01

Thermal neutron moisture detection system detects entrapped moisture in intercellular areas of bonded honeycomb sandwich structures. A radium/beryllium fast neutron source bombards a specimen. The emitted thermal neutrons from the target nucleus are detected and counted by a boron trifluoride thermal neutron detector.

Preliminary results from the hydrodynamic element of the 1994 entrapment zone study

USGS Publications Warehouse

Burau, J.R.; Stacey, M.; Gartner, J.W.

1995-01-01

This article discusses preliminary results from analyses of USGS hydrodynamic data collected as part of the 1994 Interagency Ecological Program entrapment zone study. The USGS took part in three 30-hour cruises and deployed instruments for measuring currents and salinity from April to June. This article primarily focuses on the analysis of data from five Acoustic Doppler Current ProUers (ADCPs) deployed in Carquinez Strait, Suisun Bay, and the Western Delta. From these analyses a revised conceptual model of the hydrodynamics of the entrapment/null zone has evolved. The ideas discussed in this newsletter article are essentially working hypotheses, which are presented here to stimulate discussion and further analyses. In this article we discuss the currently-held conceptual model of entrapment and present data that are inconsistent with this conceptual model. Finally, we suggest a revised conceptual model that is consistent with all of the hydrodynamic data collected to date and describe how the 1995 study incorporates our revised conceptual model into its design.

Enhancing total nitrogen removal from wastewater of a science and industrial park using entrapped biomass.

PubMed

Chao, Yeong-Nan; Ng, Kok-Kwang; Wu, Chung-Hsin; Hong, Pui-Kwan Andy; Lin, Cheng-Fang

2014-01-01

This study employed entrapped biomass technology to augment the conventional activated sludge process with anoxic-oxic (AO)/anaerobic-anoxic-oxic (A20) functions for the removal of total nitrogen (TN) from wastewater of a science and industrial park in Taiwan. The entrapped biomass unit was fabricated in the format of carrier plates on which microbial cells were entrapped. Due to mass transport limitations, anoxic and anaerobic conditions were created within the bioplates that enabled denitrification to occur. The treatment basin incorporated an equivalent amount of 1300-2400mg MLSS/L of activated sludge on the bioplates at packing ratios of 10-30% (volume ratio ofbioplates to basin) operating with the addition of sodium carbonate for alkalinity and methanol for the electron donor. The results showed nearly 90% of ammonia nitrogen being converted to nitrate and 63% of TN removal, in comparison with typically 10% of TN removal in traditional activated sludge process of domestic wastewater plants.

The scalene reflex: relationship between increased median or ulnar nerve pressure and scalene muscle activity.

PubMed

Monsivais, J J; Sun, Y; Rajashekhar, T P

1995-07-01

Neck pain, headaches, upper thoracic pain, and dystonic scalene muscles are common findings in patients who have severe entrapment neuropathies of the upper extremities. This problem was taken to the laboratory in an attempt to discover the correlation between distal entrapment neuropathies, brachial plexus entrapments, and prominent scalenus muscles. When increased pressure (over 40 mmHg) was applied to the median and ulnar nerves in the forelimbs of eight goats, increased electromyographic activity was noted in the ipsilateral scalenus muscle. Pressures ranging from 100 to 150 mmHg caused increased electromyographic activity on the contralateral scalene muscle, and the authors postulate that it is mediated by the gamma afferent and efferent system. This relationship may explain the commonly found neck pain and muscle spasm in patients with peripheral neuropathies, and it represents a link between the somatic efferent nerves and the gamma motor neuron system. At present, the same phenomenon has been documented in 30 humans with the diagnosis of brachial plexus entrapment.

Your money or your self-esteem: threatened egotism promotes costly entrapment in losing endeavors.

PubMed

Zhang, Liqing; Baumeister, Roy F

2006-07-01

The present research explored egotism-maintaining favorable views of the self-as a motivation underlying entrapment in losing endeavors. Four studies suggested that threatened selfesteem would cause decision makers to invest and lose more money in a previously chosen course of action. Ego-threatened participants consistently lost more money than nonthreatened participants across diverse entrapping situations regardless of whether the outcome was ostensibly determined by luck (Experiments 1 and 4), ability (Experiment 2), or interpersonal competition (Experiment 3). Thus, pursuing favorable views of the self could be costly to decision makers' financial well-being and may produce self-defeating behaviors.

ENTRAPMENT OF PROTEINS IN GLYCOGEN-CAPPED AND HYDRAZIDE-ACTIVATED SUPPORTS

PubMed Central

Jackson, Abby J.; Xuan, Hai; Hage, David S.

2010-01-01

A method is described for the entrapment of proteins in hydrazide-activated supports using oxidized glycogen as a capping agent. This approach is demonstrated using human serum albumin (HSA) as a model binding agent. After optimization of this method, a protein content of 43 (± 1) mg HSA/g support was obtained for porous silica. The entrapped HSA supports could retain a low mass drug (S-warfarin) and had activities and equilibrium constants comparable to those for soluble HSA. It was also found that this approach could be used with other proteins and binding agents that had masses between 5.8 and 150 kDa. PMID:20470745

The War Crimes Act: Current Issues

DTIC Science & Technology

2007-07-23

conduct was legal. These defenses can be divided into three overlapping categories: (1) defense of entrapment by estoppel , available when a defendant is...18 (11th Cir. 1994). Unlike the other defenses, the defense of entrapment by estoppel stems from the due process notions of fairness, rather than

The moderating effects of coping and self-esteem on the relationship between defeat, entrapment and suicidality in a sample of prisoners at high risk of suicide.

PubMed

Gooding, P; Tarrier, N; Dunn, G; Shaw, J; Awenat, Y; Ulph, F; Pratt, D

2015-11-01

Research is sparse which examines pathways to suicide, and resilience to suicide, in people who are particularly vulnerable to suicide, for example, prison inmates. The purpose of this study was to examine the ways in which perceptions of self-esteem and coping ability interacted with defeat and entrapment to both amplify suicidal thoughts and feelings, and to act as a buffer against suicidal thoughts and feelings. Participants were 65 male prisoners at high risk of suicide. A cross-sectional questionnaire design was used. Questionnaire measures of depression, defeat, entrapment, self-esteem, coping ability and suicidal probability were administered. For the hopelessness component of the suicide probability measure, high levels of coping ability together with low levels of defeat resulted in the lowest levels of suicidality indicative of a resilience factor. In contrast, low levels of coping skills together with high levels of entrapment were a high risk factor for this hopelessness component of suicide. This pattern of results pertained when controlling for depression levels. This is the first study to examine interactions between defeat, entrapment and appraisals of self-esteem and coping ability. Therapeutic interventions would benefit from boosting perceptions and appraisals of coping ability, in particular, in people who are at high risk for suicide. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

The moderating effects of coping and self-esteem on the relationship between defeat, entrapment and suicidality in a sample of prisoners at high risk of suicide

PubMed Central

Gooding, P.; Tarrier, N.; Dunn, G.; Shaw, J.; Awenat, Y.; Ulph, F.; Pratt, D.

2015-01-01

Background Research is sparse which examines pathways to suicide, and resilience to suicide, in people who are particularly vulnerable to suicide, for example, prison inmates. The purpose of this study was to examine the ways in which perceptions of self-esteem and coping ability interacted with defeat and entrapment to both amplify suicidal thoughts and feelings, and to act as a buffer against suicidal thoughts and feelings. Methods Participants were 65 male prisoners at high risk of suicide. A cross-sectional questionnaire design was used. Questionnaire measures of depression, defeat, entrapment, self-esteem, coping ability and suicidal probability were administered. Results For the hopelessness component of the suicide probability measure, high levels of coping ability together with low levels of defeat resulted in the lowest levels of suicidality indicative of a resilience factor. In contrast, low levels of coping skills together with high levels of entrapment were a high risk factor for this hopelessness component of suicide. This pattern of results pertained when controlling for depression levels. Conclusions This is the first study to examine interactions between defeat, entrapment and appraisals of self-esteem and coping ability. Therapeutic interventions would benefit from boosting perceptions and appraisals of coping ability, in particular, in people who are at high risk for suicide. PMID:26497469

Immunogenicity and protection in small-animal models with controlled-release tetanus toxoid microparticles as a single-dose vaccine.

PubMed Central

Singh, M; Li, X M; Wang, H; McGee, J P; Zamb, T; Koff, W; Wang, C Y; O'Hagan, D T

1997-01-01

Tetanus toxoid (TT) was encapsulated in microparticles prepared from polylactide-co-glycolide polymers by a solvent-evaporation technique. Combinations of small- and large-sized microparticles with controlled-release characteristics were used to immunize Sprague-Dawley rats, and the antibody responses were monitored for 1 year. For comparison, control groups of rats were immunized at 0, 1, and 2 months with TT adsorbed to alum. The antibody responses generated by the TT entrapped in microparticles were comparable to those generated by TT adsorbed to alum in control groups from 32 weeks onwards. Microparticles with a single entrapped antigen (TT) induced better antibody responses than microparticles with two antigens (TT and diphtheria toxoid) entrapped simultaneously. A combination vaccine consisting of TT adsorbed to alum and also entrapped in microparticles gave the best antibody responses. In an inhibition assay designed to determine the relative levels of binding of antisera to the antigens, the sera from the microparticle- and the alum-immunized animals showed comparable levels of binding. In addition, in a passive-challenge study with mice, TT adsorbed to alum and TT entrapped in microparticles provided equal levels of protection against a lethal challenge with tetanus toxin. An intradermal-challenge study was also performed with rabbits, which showed similar levels of protection in sera from alum- and microparticle-immunized animals at 4, 12, and 32 weeks after immunization. PMID:9125552

Optimization of Paclitaxel Containing pH-Sensitive Liposomes By 3 Factor, 3 Level Box-Behnken Design.

PubMed

Rane, Smita; Prabhakar, Bala

2013-07-01

The aim of this study was to investigate the combined influence of 3 independent variables in the preparation of paclitaxel containing pH-sensitive liposomes. A 3 factor, 3 levels Box-Behnken design was used to derive a second order polynomial equation and construct contour plots to predict responses. The independent variables selected were molar ratio phosphatidylcholine:diolylphosphatidylethanolamine (X1), molar concentration of cholesterylhemisuccinate (X2), and amount of drug (X3). Fifteen batches were prepared by thin film hydration method and evaluated for percent drug entrapment, vesicle size, and pH sensitivity. The transformed values of the independent variables and the percent drug entrapment were subjected to multiple regression to establish full model second order polynomial equation. F was calculated to confirm the omission of insignificant terms from the full model equation to derive a reduced model polynomial equation to predict the dependent variables. Contour plots were constructed to show the effects of X1, X2, and X3 on the percent drug entrapment. A model was validated for accurate prediction of the percent drug entrapment by performing checkpoint analysis. The computer optimization process and contour plots predicted the levels of independent variables X1, X2, and X3 (0.99, -0.06, 0, respectively), for maximized response of percent drug entrapment with constraints on vesicle size and pH sensitivity.

Development and in vitro evaluation of mucoadhesive patches of methotrexate for targeted delivery in oral cancer

PubMed Central

Jin, Bao-Zhong; Dong, Xiao-Qi; Xu, Xin; Zhang, Feng-He

2018-01-01

The present study focused on the development of a mucoadhesive patch of methotrexate (MTX) for targeted delivery in oral cancer. Initially, MTX-loaded liposomes were prepared using the thin film hydration method, and had a mean diameter of 105.7–137.4 nm and percentage entrapment efficiency of 54.6±3.5. These liposomes were cast in optimized mucoadhesive film. The film was characterized by its release pattern, thickness, weight and percentage swelling index and the sustained release profile of the optimized film was evaluated. The developed liposomes and liposomes cast in the film formulation were evaluated for cytotoxicity in HSC-3 cells using an MTT assay, and a significant decrease in the half maximal inhibitory concentration of MTX was identified with the MTX-entrapped liposomal film, M-LP-F7. The results of the mitochondria-dependent intrinsic pathway demonstrated that there was significant mitochondrial membrane potential disruption with M-LP-F7 compared with the plain drug. M-LP-F7 increased the rate of apoptosis in HSC-3 cells by almost 3-fold. Elevated levels of reactive oxygen species provided evidence that M-LP-F7 exerts a pro-oxidant effect in HSC-3 cells. PMID:29434971

Pirfenidone-loaded liposomes for lung targeting: preparation and in vitro/in vivo evaluation

PubMed Central

Meng, Hui; Xu, Yong

2015-01-01

Background The purpose of this study was to develop novel pirfenidone (PFD)-loaded liposomes for targeting to the lung. Methods The liposomes were prepared by the film hydration method, and their in vitro/vivo characteristics were evaluated. Results The PFD liposomes appeared visually as green to yellowish suspensions and were spherical in shape. The particle size was 582.3±21.6 nm and the entrapment efficiency was relatively high (87.2%±5.7%). The liposomes showed typical sustained and prolonged drug-release behavior in vitro and fitted well with the Weibull distribution equation. The relatively slower time taken to reach a minimal plasma PFD concentration in vivo suggests that PFD liposomes have a sustained-release profile, which is consistent with the results of the in vitro release study. The PFD liposomes showed the largest area under the curve for the lung. The high distribution of PFD achieved in the lungs using this liposomal formulation may be explained by physical entrapment of the liposomes in the vascular network of the lung. Histopathological results indicated that liposomal PFD could alleviate pathological injury in lung tissue. Conclusion This liposomal formulation can enable sustained release of PFD and increase targeting to the lung. PMID:26185416

PEG-lipid micelles as drug carriers: physiochemical attributes, formulation principles and biological implication.

PubMed

Gill, Kanwaldeep K; Kaddoumi, Amal; Nazzal, Sami

2015-04-01

PEG-lipid micelles, primarily conjugates of polyethylene glycol (PEG) and distearyl phosphatidylethanolamine (DSPE) or PEG-DSPE, have emerged as promising drug-delivery carriers to address the shortcomings associated with new molecular entities with suboptimal biopharmaceutical attributes. The flexibility in PEG-DSPE design coupled with the simplicity of physical drug entrapment have distinguished PEG-lipid micelles as versatile and effective drug carriers for cancer therapy. They were shown to overcome several limitations of poorly soluble drugs such as non-specific biodistribution and targeting, lack of water solubility and poor oral bioavailability. Therefore, considerable efforts have been made to exploit the full potential of these delivery systems; to entrap poorly soluble drugs and target pathological sites both passively through the enhanced permeability and retention (EPR) effect and actively by linking the terminal PEG groups with targeting ligands, which were shown to increase delivery efficiency and tissue specificity. This article reviews the current state of PEG-lipid micelles as delivery carriers for poorly soluble drugs, their biological implications and recent developments in exploring their active targeting potential. In addition, this review sheds light on the physical properties of PEG-lipid micelles and their relevance to the inherent advantages and applications of PEG-lipid micelles for drug delivery.

Operational Considerations for Oxygen Flammability Risks: Concentrated Oxygen Diffusion and Permeation Behaviors

NASA Technical Reports Server (NTRS)

Harper, Susana; Smith, Sarah; Juarez, Alfredo; Hirsch, David

2010-01-01

Increased human spaceflight operations utilize oxygen concentrations that are frequently varied with use of concentrations up to 100 percent oxygen. Even after exiting a higher percentage oxygen environment, high oxygen concentrations can still be maintained due to material saturation and oxygen entrapment between barrier materials. This paper examines the material flammability concerns that arise from changing oxygen environments during spaceflight operations. We examine the time required for common spacecraft and spacesuit materials exposed to oxygen to return to reduced ignitability and flammability once removed from the increased concentration. Various common spacecraft materials were considered: spacecraft cabin environment foams, Extra Vehicular Mobility Unit materials and foams, Advanced Crew Escape Suit materials, and other materials of interest such as Cotton, Nomex^ HT90-40, and Tiburon Surgical Drape. This paper presents calculated diffusion coefficients derived from experimentally obtained oxygen transmission rates for the tested materials and the analytically derived times necessary for reduced flammability to be achieved based on NASA flammability criteria. Oxygen material saturation and entrapment scenarios are examined. Experimental verification data on oxygen diffusion in saturation scenarios are also presented and discussed. We examine how to use obtained data to address flammability concerns during operational planning to reduce the likelihood of fires while improving efficiency for procedures.

"Liquid Crystalline Nanoparticles": Rationally Designed Vehicle To Improve Stability and Therapeutic Efficacy of Insulin Following Oral Administration.

PubMed

Agrawal, Ashish Kumar; Kumar, Kuldeep; Swarnakar, Nitin Kumar; Kushwah, Varun; Jain, Sanyog

2017-06-05

In the present article we investigate the feasibility of liquid crystalline nanoparticles (LCNPs) to improve the stability and therapeutic efficacy of insulin following oral administration. Compatibility studies of different formulation ingredients with insulin and extensive optimization of different process variables resulted into the formation of LCNPs with particle size of 245.50 ± 6.36 nm, PDI of 0.220 ± 0.042, and zeta potential of -18.30 ± 1.27 mV with an entrapment efficiency of 44.17 ± 1.47%. Mannitol (5% w/v) was identified as a suitable cryoprotectant to produce freeze-dried LCNPs without affecting their critical quality attributes. LCNPs demonstrated excellent stability in simulated biological fluids by simultaneously retaining the chemical and conformational stability of the insulin entrapped within the LCNPs. A sustained release of insulin was observed for up to 24 h in PBS (pH 7.4). Developed LCNPs demonstrated remarkably higher Caco-2 cell uptake in comparison with free insulin-FITC and more than double the cumulative hypoglycemia in comparison with subcutaneously administered insulin solution in diabetic rats. Data in hand suggest that the proposed formulation strategy can be exploited for improving the therapeutic efficacy of biomacromolecules like insulin.

DOE Optimization of Nano-based Carrier of Pregabalin as Hydrogel: New Therapeutic & Chemometric Approaches for Controlled Drug Delivery Systems

NASA Astrophysics Data System (ADS)

Arafa, Mona G.; Ayoub, Bassam M.

2017-01-01

Niosomes entrapping pregabalin (PG) were prepared using span 60 and cholesterol in different molar ratios by hydration method, the remaining PG from the hydrating solution was separated from vesicles by freeze centrifugation. Optimization of nano-based carrier of pregabalin (PG) was achieved. Quality by Design strategy was successfully employed to obtain PG-loaded niosomes with the desired properties. The optimal particle size, drug release and entrapment efficiency were attained by Minitab® program using design of experiment (DOE) that predicted the best parameters by investigating the combined effect of different factors simultaneously. Pareto chart was used in the screening step to exclude the insignificant variables while response surface methodology (RSM) was used in the optimization step to study the significant factors. Best formula was selected to prepare topical hydrogels loaded with niosomal PG using HPMC and Carbopol 934. It was verified, by means of mechanical and rheological tests, that addition of the vesicles to the gel matrix affected significantly gel network. In vitro release and ex vivo permeation experiments were carried out. Delivery of PG molecules followed a Higuchi, non Fickian diffusion. The present work will be of interest for pharmaceutical industry as a controlled transdermal alternative to the conventional oral route.

DOE Optimization of Nano-based Carrier of Pregabalin as Hydrogel: New Therapeutic & Chemometric Approaches for Controlled Drug Delivery Systems

PubMed Central

Arafa, Mona G.; Ayoub, Bassam M.

2017-01-01

Niosomes entrapping pregabalin (PG) were prepared using span 60 and cholesterol in different molar ratios by hydration method, the remaining PG from the hydrating solution was separated from vesicles by freeze centrifugation. Optimization of nano-based carrier of pregabalin (PG) was achieved. Quality by Design strategy was successfully employed to obtain PG-loaded niosomes with the desired properties. The optimal particle size, drug release and entrapment efficiency were attained by Minitab® program using design of experiment (DOE) that predicted the best parameters by investigating the combined effect of different factors simultaneously. Pareto chart was used in the screening step to exclude the insignificant variables while response surface methodology (RSM) was used in the optimization step to study the significant factors. Best formula was selected to prepare topical hydrogels loaded with niosomal PG using HPMC and Carbopol 934. It was verified, by means of mechanical and rheological tests, that addition of the vesicles to the gel matrix affected significantly gel network. In vitro release and ex vivo permeation experiments were carried out. Delivery of PG molecules followed a Higuchi, non Fickian diffusion. The present work will be of interest for pharmaceutical industry as a controlled transdermal alternative to the conventional oral route. PMID:28134262

Curcuminoids-loaded lipid nanoparticles: novel approach towards malaria treatment.

PubMed

Nayak, Aditya P; Tiyaboonchai, Waree; Patankar, Swati; Madhusudhan, Basavaraj; Souto, Eliana B

2010-11-01

In the present work, curcuminoids-loaded lipid nanoparticles for parenteral administration were successfully prepared by a nanoemulsion technique employing high-speed homogenizer and ultrasonic probe. For the production of nanoparticles, trimyristin, tristerin and glyceryl monostearate were selected as solid lipids and medium chain triglyceride (MCT) as liquid lipid. Scanning electron microscopy (SEM) revealed the spherical nature of the particles with sizes ranging between 120 and 250 nm measured by photon correlation spectroscopy (PCS). The zeta potential of the particles ranged between -28 and -45 mV depending on the nature of the lipid matrix produced, which also influenced the entrapment efficiency (EE) and drug loading capacity (LC) found to be in the range of 80-94% and 1.62-3.27%, respectively. The LC increased reciprocally on increasing the amount of MCT as confirmed by differential scanning calorimetry (DSC). DSC analyses revealed that increasing imperfections within the lipid matrix allowed for increasing encapsulation parameters. Nanoparticles were further sterilized by filtration process which was found to be superior over autoclaving in preventing thermal degradation of thermo-sensitive curcuminoids. The in vivo pharmacodynamic activity revealed 2-fold increase in antimalarial activity of curcuminoids entrapped in lipid nanoparticles when compared to free curcuminoids at the tested dosage level. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Solid lipid nanoparticles as vesicles for oral delivery of olmesartan medoxomil: formulation, optimization and in vivo evaluation.

PubMed

Nooli, Mounika; Chella, Naveen; Kulhari, Hitesh; Shastri, Nalini R; Sistla, Ramakrishna

2017-04-01

Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioavailability (28%) resulting from poor aqueous solubility, presystemic metabolism and P-glycoprotein mediated efflux. The present investigation studies the role of lipid nanocarriers in enhancing the OLM bioavailability through oral delivery. Solid lipid nanoparticles (SLN) were prepared by solvent emulsion-evaporation method. Statistical tools like regression analysis and Pareto charts were used to detect the important factors effecting the formulations. Formulation and process parameters were then optimized using mean effect plot and contour plots. The formulations were characterized for particle size, size distribution, surface charge, percentage of drug entrapped in nanoparticles, drug-excipients interactions, powder X-ray diffraction analysis and drug release in vitro. The optimized formulation comprised glyceryl monostearate, soya phosphatidylcholine and Tween 80 as lipid, co-emulsifier and surfactant, respectively, with an average particle size of 100 nm, PDI 0.291, zeta potential of -23.4 mV and 78% entrapment efficiency. Pharmacokinetic evaluation in male Sprague Dawley rats revealed 2.32-fold enhancement in relative bioavailability of drug from SLN when compared to that of OLM plain drug on oral administration. In conclusion, SLN show promising approaches as a vehicle for oral delivery of drugs like OLM.

Topical delivery of roxithromycin solid-state forms entrapped in vesicles.

PubMed

Csongradi, Candice; du Plessis, Jeanetta; Aucamp, Marique Elizabeth; Gerber, Minja

2017-05-01

Recently, considerable interest developed in using newer/improved antibiotics for the treatment of Acne vulgaris. During this study, different roxithromycin solid-state forms (i.e. crystalline and amorphous) were encapsulated into vesicle systems (niosomes, proniosomes, ufosomes and pro-ufosomes) for dermis targeted delivery. Characterization of the vesicles was done with transmission electron microscopy, light microscopy, droplet size, droplet size distribution, pH, zeta-potential and entrapment efficiency percentage. Finally, comparative release and topical diffusion studies were performed, to evaluate if targeted topical delivery was obtained and if the roxithromycin solid-state amorphous forms resulted in improved topical delivery. Vesicle systems containing different roxithromycin (2%) solid-state forms were successfully prepared and characterized. The vesicles showed optimal properties for topical delivery. All carrier systems had topical delivery to the epidermis-dermis, whilst no roxithromycin was found in the receptor compartment or stratum corneum-epidermis. The niosomes were the leading formulation and the two amorphous forms had better topical delivery than the crystalline form. Successful targeted delivery of roxithromycin was obtained in the dermis, where the activity against Propionibacterium acnes is needed. The amorphous forms seemed to have held their solid-state form during formulation and in the vesicles, showing improved topical delivery in comparison to the crystalline form. Copyright © 2017 Elsevier B.V. All rights reserved.

Ocular Sustained Release Nanoparticles Containing Stereoisomeric Dipeptide Prodrugs of Acyclovir

PubMed Central

Jwala, Jwala; Boddu, Sai H.S.; Shah, Sujay; Sirimulla, Suman; Pal, Dhananjay

2011-01-01

Abstract Purpose The objective of this study was to develop and characterize polymeric nanoparticles of appropriate stereoisomeric dipeptide prodrugs of acyclovir (L-valine-L-valine-ACV, L-valine-D-valine-ACV, D-valine-L-valine-ACV, and D-valine-D-valine-ACV) for the treatment of ocular herpes keratitis. Methods Stereoisomeric dipeptide prodrugs of acyclovir (ACV) were screened for bioreversion in various ocular tissues, cell proliferation, and uptake across the rabbit primary corneal epithelial cell line. Docking studies were carried out to examine the affinity of prodrugs to the peptide transporter protein. Prodrugs with optimum characteristics were selected for the preparation of nanoparticles using various grades of poly (lactic-co-glycolic acid) (PLGA). Nanoparticles were characterized for the entrapment efficiency, surface morphology, size distribution, and in vitro release. Further, the effect of thermosensitive gels on the release of prodrugs from nanoparticles was also studied. Results L-valine-L-valine-ACV and L-valine-D-valine-ACV were considered to be optimum in terms of enzymatic stability, uptake, and cytotoxicity. Docking results indicated that L-valine in the terminal position increases the affinity of the prodrugs to the peptide transporter protein. Entrapment efficiency values of L-valine-L-valine-ACV and L-valine-D-valine-ACV were found to be optimal with PLGA 75:25 and PLGA 65:35 polymers, respectively. In vitro release of prodrugs from nanoparticles exhibited a biphasic release behavior with initial burst phase followed by sustained release. Dispersion of nanoparticles in thermosensitive gels completely eliminated the burst release phase. Conclusion Novel nanoparticulate systems of dipeptide prodrugs of ACV suspended in thermosensitive gels may provide sustained delivery after topical administration. PMID:21500985

Development of Clotrimazole Multiple W/O/W Emulsions as Vehicles for Drug Delivery: Effects of Additives on Emulsion Stability.

PubMed

Suñer, Joaquim; Calpena, Ana C; Clares, Beatriz; Cañadas, Cristina; Halbaut, Lyda

2017-02-01

Multiple emulsions have attracted considerable attention in recent years for application as potential delivery systems for different drugs. The aim of the present work is to design a new formulation containing clotrimazole (CLT) loaded into multiple emulsions by two-step emulsification method for transdermal delivery. Different ingredients and quantities like primary and secondary co-emulsifiers and the nature of oily phase were assayed in order to optimize the best system for good. Resulting formulations were characterized in terms of droplet size, conductivity, pH, entrapment efficiency, rheological behavior, and stability under various storage conditions for 180 days. pH values of multiple emulsions containing CLT ranged from 7.04 ± 0.03 to 6.23 ± 0.04. Droplet size increased when increasing concentration of sorbitan stearate. The addition of polysorbate 80 resulted in significant decrease of oil droplet size comparing with those prepared without this. CLT entrapment efficiency ranged between 85.64% and 97.47%. All formulations exhibited non-Newtonian pseudoplastic flow with some apparent thixotropic behavior. Cross and Herschel-Bulkley equations were the models that best fitted experimental data. In general, the addition of 1% polysorbate 80 resulted in a decrease of viscosity values. No signals of optical instability were observed, and physicochemical properties remained almost constant when samples were stored at room temperature after 180 days. On the contrary, samples stored at 40°C exhibited pronounced increase in conductivity values 24 h after elaboration and some of them were unstable after 180 days of storage. JMLP01 was proposed as an innovative and stable system to incorporate CLT as active pharmaceutical ingredient.

Preparation, characterization and optimization of sildenafil citrate loaded PLGA nanoparticles by statistical factorial design

PubMed Central

2013-01-01

Background and the aim of the study The objective of the present study was to formulate and optimize nanoparticles (NPs) of sildenafil-loaded poly (lactic-co-glycolic acid) (PLGA) by double emulsion solvent evaporation (DESE) method. The relationship between design factors and experimental data was evaluated using response surface methodology. Method A Box-Behnken design was made considering the mass ratio of drug to polymer (D/P), the volumetric proportion of the water to oil phase (W/O) and the concentration of polyvinyl alcohol (PVA) as the independent agents. PLGA-NPs were successfully prepared and the size (nm), entrapment efficiency (EE), drug loading (DL) and cumulative release of drug from NPs post 1 and 8 hrs were assessed as the responses. Results The NPs were prepared in a spherical shape and the sizes range of 240 to 316 nm. The polydispersity index of size was lower than 0.5 and the EE (%) and DL (%) varied between 14-62% and 2-6%, respectively. The optimized formulation with a desirability factor of 0.9 was selected and characterized. This formulation demonstrated the particle size of 270 nm, EE of 55%, DL of 3.9% and cumulative drug release of 79% after 12 hrs. In vitro release studies showed a burst release at the initial stage followed by a sustained release of sildenafil from NPs up to 12 hrs. The release kinetic of the optimized formulation was fitted to Higuchi model. Conclusions Sildenafil citrate NPs with small particle size, lipophilic feature, high entrapment efficiency and good loading capacity is produced by this method. Characterization of optimum formulation, provided by an evaluation of experimental data, showed no significant difference between calculated and measured data. PMID:24355133

Solid lipid nanoparticles loaded with insulin by sodium cholate-phosphatidylcholine-based mixed micelles: preparation and characterization.

PubMed

Liu, Jie; Gong, Tao; Wang, Changguang; Zhong, Zhirong; Zhang, Zhirong

2007-08-01

Solid lipid nanoparticles (SLNs) loaded with insulin-mixed micelles (Ins-MMs) were prepared by a novel reverse micelle-double emulsion method, in which sodium cholate (SC) and soybean phosphatidylcholine (SPC) were employed to improve the liposolubility of insulin, and the mixture of stearic acid and palmitic acid were employed to prepare insulin loaded solid lipid nanoparticles (Ins-MM-SLNs). Some of the formulation parameters were optimized to obtain high quality nanoparticles. The particle size and zeta potential measured by photon correlation spectroscopy (PCS) were 114.7+/-4.68 nm and -51.36+/-2.04 mV, respectively. Nanospheres observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed extremely spherical shape. The entrapment efficiency (EE%) and drug loading capacity (DL%) determined with high performance liquid chromatogram (HPLC) by modified ultracentrifuge method were 97.78+/-0.37% and 18.92+/-0.07%, respectively. Differential scanning calorimetry (DSC) of Ins-MM-SLNs indicated no tendency of recrystallisation. The core-shell drug loading pattern of the SLNs was confirmed by fluorescence spectra and polyacrylamide gel electrophoresis (PAGE) which also proved the integrity of insulin after being incorporated into lipid carrier. The drug release behavior was studied by in situ and externally sink method and the release pattern of drug was found to follow Weibull and Higuchi equations. Results of stability evaluation showed a relatively long-term stability after storage at 4 degrees C for 6 months. In conclusion, SLNs with small particle size, excellent physical stability, high entrapment efficiency, good loading capacity for protein drug can be produced by this novel reverse micelle-double emulsion method in present study.

Herbal liposome for the topical delivery of ketoconazole for the effective treatment of seborrheic dermatitis

NASA Astrophysics Data System (ADS)

Dave, Vivek; Sharma, Swati; Yadav, Renu Bala; Agarwal, Udita

2017-11-01

The aim of the present study was to develop liposomal gel containing ketoconazole and neem extract for the treatment of seborrheic dermatitis in an effectual means. Azoles derivatives that are commonly used to prevent superficial fungal infections include triazole category like itraconazole. These drugs are available in the form of oral dosage that required a long period of time for treatment. Ketoconazole is available in the form of gel but is not used with any herbal extract. Neem ( Azadirachta indica) leaves show a good anti-bacterial and anti-fungal activity and have great potential as a bioactive compound. The thin film hydration method was used to design an herbal liposomal preparation. The formulation was further subjected to their characterization as particle size, zeta potential, entrapment efficiency, % cumulative drug release, and anti-fungal activity and it was also characterized by the mean of their physicochemical properties such as FTIR, SEM, DSC, TGA, and AFM. The results show that the formulation of liposomes with neem extract F12 were found to be optimum on the basis of entrapment efficiency in the range 88.9 ± 0.7%, with a desired mean particle size distribution of 141.6 nm and zeta potential - 45 mV. The anti-fungal activity of liposomal formulation F12 was carried out against Aspergillus niger and Candida tropicalis by measuring the inhibition zone 8.9 and 10.2 mm, respectively. Stability of optimized formulation was best seen at refrigerated condition. Overall, these results indicated that developed liposomal gel of ketoconazole with neem extract could have great potential for seborrheic dermatitis and showed synergetic effect for the treatment.

[Optimization and characterization of curcumin-piperine dual drug loaded self-microemulsifying drug delivery system by simplex lattice design].

PubMed

Li, Qiu-Ping; Dai, Jun-Dong; Zhai, Wen-Wen; Jiang, Qiao-Li

2014-10-01

The objective of the study was to prepare and evaluate the quality of curcumin-piperinedual drug loaded self-microemulsifying drug delivery system(Cur-PIP-SMEDDS). Simplex lattice design was constructed using optimal oil phase, surfactant and co-surfactant concentration as independent variables, and the curcumin and piperine were used as model drugs to optimize Cur-PIP-SMEDDS formulation. In the present study, the drug loadings of curcumin and piperine, mean particle size of Cur-PIP-SMEDDS were made as indicators, and the experiment design, model building and response surface analysis were established using Design Expert 8. 06 software to optimize and verify the composition of SMEDDS formulation. The quality of Cur-PIP-SMEDDS was evaluated by observing the appearance status, transmission electron microscope micrographs and determining particle diameter, electric potential, drug entrapment efficiency and drug loading of it. As a result, the optimal formulation of SMEDDS was CapryoL 90-Cremophor RH40-TranscutoL HP (10:60:30). The appearance of Cur-PIP-SMEDDS remained clarified and transparent, and the microemulsion droplets appeared spherical without aggregation with uniform particle size distribution. The mean size of microemulsion droplet formed from Cur-PIP-SMEDDS was 15.33 nm, the drug loading of SMEDDS for Cur and PIP were 40.90 mg · g(-1) and 0.97 mg · g(-1), respectively, the drug entrapment efficiency were 94.98% and 90.96%, respectively. The results show that Cur-PIP-SMEDDS can increase the solubility and stability of curcumin significantly, in the expectation of enhancing the bioavailability of it. Taken together, these findings can provide the reference to a preferable choice of the Cur formulation and contribute to therapeutic application in clinical research.

Terbinafine Hydrochloride Trans-ungual Delivery via Nanovesicular Systems: In Vitro Characterization and Ex Vivo Evaluation.

PubMed

Elsherif, Noha Ibrahim; Shamma, Rehab Nabil; Abdelbary, Ghada

2017-02-01

Treating a nail infection like onychomycosis is challenging as the human nail plate acts as a formidable barrier against all drug permeation. Available oral and topical treatments have several setbacks. Terbinafine hydrochloride (TBH), belonging to the allylamine class, is mainly used for treatment of onychomycosis. This study aims to formulate TBH in a nanobased spanlastic vesicular carrier that enables and enhances the drug delivery through the nail. The nanovesicles were formulated by ethanol injection method, using either Span® 60 or Span® 65, together with Tween 80 or sodium deoxycholate as an edge activator. A full factorial design was implemented to study the effect of different formulation and process variables on the prepared TBH-loaded spanlastic nanovesicles. TBH entrapment efficiency percentages, particle size diameter, percentage drug released after 2 h and 8 h were selected as dependent variables. Optimization was performed using Design-Expert® software to obtain an optimized formulation with high entrapment efficiency (62.35 ± 8.91%), average particle size of 438.45 ± 70.5 nm, and 29.57 ± 0.93 and 59.53 ± 1.73% TBH released after 2 and 8 h, respectively. The optimized formula was evaluated using differential scanning calorimetry and X-ray diffraction and was also morphologically examined using transmission electron microscopy. An ex vivo study was conducted to determine the permeation and retainment of the optimized formulation in a human cadaver nail plate, and confocal laser scanning microscope was used to show the extent of formulation permeation. In conclusion, the results confirmed that spanlastics exhibit promising results for the trans-ungual delivery of TBH.

Fabrication of a novel scaffold of clotrimazole-microemulsion-containing nanofibers using an electrospinning process for oral candidiasis applications.

PubMed

Tonglairoum, Prasopchai; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Kaomongkolgit, Ruchadaporn; Opanasopit, Praneet

2015-02-01

Clotrimazole (CZ)-loaded microemulsion-containing nanofiber mats were developed as an alternative for oral candidiasis applications. The microemulsion was composed of oleic acid (O), Tween 80 (T80), and a co-surfactant such as benzyl alcohol (BzOH), ethyl alcohol (EtOH) or isopropyl alcohol (IPA). The nanofiber mats were obtained by electrospinning a blended solution of a CZ-loaded microemulsion and a mixed polymer solution of 2% (w/v) chitosan (CS) and 10% (w/v) polyvinyl alcohol (PVA) at a weight ratio of 30:70. The nanofiber mats were characterized using various analytical techniques. The entrapment efficiency, drug release, antifungal activity and cytotoxicity were investigated. The average diameter of the nanofiber mats was in the range of 105.91-125.56 nm. The differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) results revealed the amorphous state of the CZ-loaded microemulsions incorporated into the nanofiber mats. The entrapment efficiency of CZ in the mats was approximately 72.58-98.10%, depended on the microemulsion formulation. The release experiment demonstrated different CZ release characteristics from nanofiber mats prepared using different CZ-loaded microemulsions. The extent of drug release from the fiber mats at 4h was approximately 64.81-74.15%. The release kinetics appeared to follow Higuchi's model. In comparison with CZ lozenges (10mg), the nanofiber mats exhibited more rapid killing activity. Moreover, the nanofiber mats demonstrated desirable mucoadhesive properties and were safe for 2h. Therefore, the nanofiber mats have the potential to be promising candidates for oral candidiasis applications. Copyright © 2014 Elsevier B.V. All rights reserved.

The comparison of protein-entrapped liposomes and lipoparticles: preparation, characterization, and efficacy of cellular uptake

PubMed Central

Chang, Wei-Kuo; Tai, Yu-Ju; Chiang, Chiao-Hsi; Hu, Chieh-Shen; Hong, Po-Da; Yeh, Ming-Kung

2011-01-01

Fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA)-loaded polyethylene glycol (PEG)-modified liposomes and lipoparticles with high protein entrapment were developed. The lipid formula of the liposomes contained PEGylated lipids and unsaturated fatty acids for enhancing membrane fluidity and effective delivery into cells. The preparation techniques, lipid content, and PEG-modified lipoparticle ratios were evaluated. The PEG-modified lipoparticles prepared by ethanol injection extrusion (100 nm pore size) achieve a population of blank liposomes with a mean size of 125 ± 2.3 nm and a zeta potential of −12.4 ± 1.5 mV. The average particle size of the PEG-modified lipoparticles was 133.7 ± 8.6 nm with a zeta potential of +13.3 mV. Lipoparticle conformation was determined using transmission electron microscopy and field-emission scanning electron microscopy. The FITC-BSA encapsulation efficiency was dramatically increased from 19.0% for liposomes to 59.7% for lipoparticles. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results confirmed the preparation process, and an 8-hour leaching test did not harm the protein structure. Once prepared, the physical and chemical stability of the PEG-modified lipoparticle formulations was satisfactory over 90 days. In vitro retention tests indicated that the 50% retention time for the protein-containing lipoparticles was 7.9 hours, substantially longer than the liposomes at 3.3 hours. A Caco-2 cell model was used for evaluating the cytotoxicity and cell uptake efficiency of the PEG-modified lipoparticles. At a lipid content below 0.25 mM, neither the liposomes nor the lipoparticles caused significant cellular cytotoxicity (P < 0.01) and FITC-BSA was significantly taken up into cells within 60 minutes (P < 0.01). PMID:22072876

Evaluation of Time-Temperature Integrators (TTIs) with Microorganism-Entrapped Microbeads Produced Using Homogenization and SPG Membrane Emulsification Techniques.

PubMed

Rahman, A T M Mijanur; Lee, Seung Ju; Jung, Seung Won

2015-12-28

A comparative study was conducted to evaluate precision and accuracy in controlling the temperature dependence of encapsulated microbial time-temperature integrators (TTIs) developed using two different emulsification techniques. Weissela cibaria CIFP 009 cells, immobilized within 2% Na-alginate gel microbeads using homogenization (5,000, 7,000, and 10,000 rpm) and Shirasu porous glass (SPG) membrane technologies (10 μm), were applied to microbial TTIs. The prepared micobeads were characterized with respect to their size, size distribution, shape and morphology, entrapment efficiency, and bead production yield. Additionally, fermentation process parameters including growth rate were investigated. The TTI responses (changes in pH and titratable acidity (TA)) were evaluated as a function of temperature (20°C, 25°C, and 30°C). In comparison with conventional methods, SPG membrane technology was able not only to produce highly uniform, small-sized beads with the narrowest size distribution, but also the bead production yield was found to be nearly 3.0 to 4.5 times higher. However, among the TTIs produced using the homogenization technique, poor linearity (R(2)) in terms of TA was observed for the 5,000 and 7,000 rpm treatments. Consequently, microbeads produced by the SPG membrane and by homogenization at 10,000 rpm were selected for adjusting the temperature dependence. The Ea values of TTIs containing 0.5, 1.0, and 1.5 g microbeads, prepared by SPG membrane and conventional methods, were estimated to be 86.0, 83.5, and 76.6 kJ/mol, and 85.5, 73.5, and 62.2 kJ/mol, respectively. Therefore, microbial TTIs developed using SPG membrane technology are much more efficient in controlling temperature dependence.

Novel Solid Lipid Nanocarrier Of Glibenclamide: A Factorial Design Approach With Response Surface Methodology.

PubMed

Pandey, Sonia; Patel, Payal; Gupta, Arti

2018-05-21

In the present investigation a factorial design approach attempt was applied to develop the solid lipid nanoparticles (SLN) of Glibenclamide (GLB) a poorly water-soluble drug (BCS -II) used in the treatment of type 2 diabetes. Prime objectives of this experiment are to optimize the SLN formulation of Glibenclamide and improve the therapeutic effectiveness of the developed formulation. Glibenclamide loaded SLNs (GLB-SLN) were fabricated by High speed homogenization technique. A 32-factorial design approach has been employed to assess the influence of two independent variables, namely amount of Poloxamer 188 and Glyceryl Monostearate on entrapment efficiency (% EE) (Y1), Particle Size (nm) (Y2), % drug release at 8hr Q8 (Y3) and 24 hr Q24 (Y4) of prepared SLNs. Differential scanning calorimetry analysis revealed the compatibility of the drug into lipid matrix with surfactant, while Transmission electron and Scanning electron microscopy studies indicated the size and shape of SLN. The entrapment efficiency, particle size, Q8 and Q24 of the optimized SLNs were 88.93%, 125 nm, 31.12±0.951% and 86.07±1.291% respectively. Optimized GLB-SLN formula was derived from an overlay plot. Three dimensional response surface plots and regression equations confirmed the corresponding influence of selected independent variables on measured responses. In vivo testing of the GLB-SLN in diabetic albino rats demonstrated significant antidiabetic effect of GLB-SLN. The hypoglycemic effect obtained by GLB-SLN remained significantly higher than that given by drug alone and marketed formulation, further confirming the higher therapeutic effectiveness of the GLB-SLN formulation. Our findings suggested the feasibility of investigated system for oral administration of Glibenclamide. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Preparation and Evaluation of Montelukast Sodium Loaded Solid Lipid Nanoparticles

PubMed Central

Priyanka, K; Sathali, A Abdul Hasan

2012-01-01

Solid lipid nanoparticles (SLNs) are an alternative carrier system used to load the drug for targeting, to improve the bioavailability by increasing its solubility, and protecting the drug from presystemic metabolism. The avoidance of presystemic metabolism is due to the nano-metric size range, so that the liver cannot uptake the drug from the delivery system and is not metabolized by the liver. Montelukast sodium is an anti-asthmatic drug, because of its poor oral bioavailability, presystemic metabolism, and decreased half-life; it was chosen to formulate as the solid lipid nanoparticle (SLN) system by hot homogenization followed by an ultrasonication method, to overcome the above. Compritol ATO 888, stearic acid, and glyceryl monostearate were used as a lipid matrix and polyvinyl alcohol as a surfactant. The prepared formulations have been evaluated for entrapment efficiency, drug content, in vitro drug release, particle size analysis, scanning electron microscopy, Fourier transform-infrared studies (FT-IR), differential scanning calorimetry (DSC), and stability. Particle size analysis revealed that the SLN prepared from the higher melting point lipid showed a larger particle size and with increased carbon chain length of the fatty acids. Entrapment efficiency (EE) was ranging from 42% to 92%. In vitro release studies showed maximum cumulative drug release was obtained for F 1 (59.1%) containing stearic acid, and the lowest was observed for F 18 (28.1%) containing compritol ATO 888 after 12 h and all the formulations followed first-order release kinetics. FT-IR and DSC studies revealed no interaction between drug and lipids. Studies showed that increase in lipid concentration, increased particle size, EE, and maintained the sustained release of drug. Among all, compritol ATO 888 was chosen as the best lipid for formulating SLN because it had high EE and sustained the drug release. PMID:23112531

Optimization and development of antidiabetic phytosomes by the Box-Behnken design.

PubMed

Rathee, Sushila; Kamboj, Anjoo

2018-06-01

Researchers have extensively reviewed on herbs and natural products for their marked clinical efficacy in some recent years, however, maximum of the newly discovered bioactive constituents offer poor bioavailability due to their large size molecules or to their poor miscibility with oils and lipids, thereby limiting their ability to pass across the lipid-rich outer membranes of the enterocytes of the small intestine. Phytosomes are more bioavailable as compared to herbal extracts owing to their enhanced capacity to cross the bio-membranes and thus reaching the systemic circulation. This study was aimed to investigate the development and optimization of antidiabetic phytosomes using a three-factor, three-level the Box-Behnken design (17 batches). The fruits of Citrullus colocynthis (L.) Momordica balsamina and Momordica dioica were extracted using Soxhlet's apparatus. The phytochemical fingerprint profile of the combined methanolic extracts was done by using high-performance thin layer chromatography (HPTLC). The polynomial quadratic equation analysis was designed to study the response (entrapment efficiency (EE), % yield) of independent significant factors at different levels. Phytosomes were characterized in terms of drug content, particle size, EE, zeta potential and in vitro dissolution. TEM analysis revealed good stability and a spherical, self-closed structure of phytosomes in complex formulations. Average particle size was found to 450 nm. Total flavonoid content was found to be 10.0 ± 0.002 μg/g. Optimized formulation was selected and was prepared using A (1:3), B (60 °C) and C (2.5 h) to give maximum yield and entrapment efficiencies (72% and 92.1 ± 5.1%). Phytosomes were found to have antidiabetic activity comparable to metformin in low dose. HPTLC showed the presence of the phyto-constituent quercetin.

In-situ single pass intestinal permeability and pharmacokinetic study of developed Lumefantrine loaded solid lipid nanoparticles.

PubMed

Garg, Anuj; Bhalala, Kripal; Tomar, Devendra Singh; Wahajuddin

2017-01-10

The present investigation aims to develop lumefantrine loaded binary solid lipid nanoparticles (LF-SLNs) to improve its poor and variable oral bioavailability. The oral bioavailability of LF is poor and variable due to its limited aqueous solubility and P-gp mediated efflux occurring in small intestine. LF-SLNs were prepared using binary lipid mixture of stearic acid and caprylic acid stabilized with TPGS (D-alpha tocopheryl polyethylene glycol 1000 succinate) and Poloxamer 188. Developed LF-SLNs were characterized for particle size distribution, zeta potential, entrapment efficiency, solid state properties and biopharmaceutical properties including in situ intestinal permeability and oral bioavailability. The particle size distribution, zeta potential and entrapment efficiency of optimized batch (LF-SLN7) was found to be 357.7±43.27nm, 25.29±1.15mV and 97.35±0.30%, respectively. DSC thermographs showed loss of crystalline nature of lumefantrine in LF-SLNs. In situ single pass intestinal permeability study (SPIP) study indicated significant enhancement in the effective intestinal permeability of LF from LF-SLN7 as compared to that of control. Pharmacokinetic study also showed significant increase in Cmax and area under curve (AUC0- ∞ ) from LF-SLN7 (3860±521ng/mL and 43181±2557h×ng/mL, respectively) as compared to that of LF-control suspension (1425±563ng/mL and 19586±1537h×ng/mL, respectively). Thus, developed LF-SLNs can be promising to overcome P-gp efflux pump and enhance the oral bioavailability of lumefantrine. Copyright © 2016 Elsevier B.V. All rights reserved.

Applicability of electrospun polypropylene carbonate polymers as a drug carrier for sirolimus.

PubMed

Sun, Hourong; Gu, Xinghua; Liu, Kai; Fang, Changcun; Tang, Mengmeng

2017-06-01

Polypropylene carbonate (PPC), a biodegradable aliphatic polyester, exhibits one particular advantage over other polyesters, which is that following degradation in vivo, it primarily produces H2O and CO2, causing minimal side effects. Although PPC exhibits limited mechanical strength, and is therefore not able to serve as a scaffold to support tissue regeneration, it may be suitable for drug delivery; however, this requires further investigation. In the present study, electrospinning was applied to generate PPC polymers containing sirolimus, a cell growth‑inhibiting drug which is used to treat restenosis. The properties of PPC‑sirolimus polymers were examined using scanning electron microscopy, differential scanning calorimetry and in vitro degradation assays. Drug loading and entrapment efficiency were determined, and in vitro sirolimus‑release from the polymer was assessed. Furthermore, the effect of PPC‑sirolimus polymers on cell growth was measured using an MTT assay in vitro. The results of the present study demonstrated that electrospun PPC polymers formed a uniform three‑dimensional, grid‑intertwined, net‑like structure; the surface of the polymers was smooth and the diameter was ~3 µm. Differential scanning calorimetry analysis demonstrated that sirolimus existed in an amorphous state in the polymer. Following soaking in PBS for 4 weeks, the polymer swelled and the net‑like structure broke down and fragmented. Sirolimus loading and entrapment efficiency were 10.3±3.2 and 95.1±10.6%, respectively. Sirolimus‑release from PPC‑sirolimus polymers continued for 28 days in PBS. PPC‑sirolimus markedly inhibited the growth of rat aortic adventitial fibroblast cells, an effect which was not observed with PPC alone. The results of the present study suggest that PPC polymers are a promising alternative drug carrier for sirolimus.

Fabrication of novel GMO/Eudragit E100 nanostructures for enhancing oral bioavailability of carvedilol.

PubMed

Patil, Sharvil S; Roy, Krishtey; Choudhary, Bhavana; Mahadik, Kakasaheb R

2016-08-01

In the present work, novel nanostructures comprising of glyceryl monooleate (GMO) and Eudragit E100 were prepared using high intensity ultrasonic homogenization. 3(2) Factorial design approach was used for optimization of nanostructures. Results of regression analysis revealed that the amount of GMO and Eudragit E100 had a drastic effect on particle size and percent entrapment efficiency. Optimized carvedilol-loaded nanostructures (Car-NS) were characterized by FTIR, TEM, DSC, in vitro drug release study. Pharmacokinetic parameters such as Cmax, Tmax, Ke, Ka, Vd and AUC were estimated for Car-NS upon its oral administration in Sprague-Dawley rats. Particle size of Car-NS was found to be 183 ± 2.43 nm with an entrapment efficiency of 81.4 ± 0.512%. FTIR studies revealed loading and chemical compatibility of carvedilol with the components of nanostructures. DSC thermograms did not show endothermic peak for melting of carvedilol which could be attributed to solubilization of carvedilol in molten GMO during DSC run. The prepared Car-NS released carvedilol in sustained manner over a period of 10 h as suggested by in vitro drug release study. The pharmacokinetic study of Car-NS showed significant improvement in Cmax (two fold, p < 0.001) and AUC (four folds, p < 0.001) of carvedilol when compared to carvedilol suspension. Car-NS were found to be stable for a period of 3 months. Thus, a stable, floating, multiparticulate GMO/Eudragit E100 nanostructures having ability to release the drug in sustained manner with enhanced oral bioavailability can prove to be a promising carrier system for poorly water soluble drugs.

Strategy for chemotherapeutic delivery using a nanosized porous metal-organic framework with a central composite design

PubMed Central

Li, Yingpeng; Li, Xiuyan; Guan, Qingxia; Zhang, Chunjing; Xu, Ting; Dong, Yujing; Bai, Xinyu; Zhang, Weiping

2017-01-01

Background Enhancing drug delivery is an ongoing endeavor in pharmaceutics, especially when the efficacy of chemotherapy for cancer is concerned. In this study, we prepared and evaluated nanosized HKUST-1 (nanoHKUST-1), nanosized metal-organic drug delivery framework, loaded with 5-fluorouracil (5-FU) for potential use in cancer treatment. Materials and methods NanoHKUST-1 was prepared by reacting copper (II) acetate [Cu(OAc)2] and benzene-1,3,5-tricarboxylic acid (H3BTC) with benzoic acid (C6H5COOH) at room temperature (23.7°C±2.4°C). A central composite design was used to optimize 5-FU-loaded nanoHKUST-1. Contact time, ethanol concentration, and 5-FU:material ratios were the independent variables, and the entrapment efficiency of 5-FU was the response parameter measured. Powder X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nitrogen adsorption were used to determine the morphology of nanoHKUST-1. In addition, 5-FU release studies were conducted, and the in vitro cytotoxicity was evaluated. Results Entrapment efficiency and drug loading were 9.96% and 40.22%, respectively, while the small-angle X-ray diffraction patterns confirmed a regular porous structure. The SEM and TEM images of the nanoHKUST-1 confirmed the presence of round particles (diameter: approximately 100 nm) and regular polygon arrays of mesoporous channels of approximately 2–5 nm. The half-maximal lethal concentration (LC50) of the 5-FU-loaded nanoHKUST-1 was approximately 10 µg/mL. Conclusion The results indicated that nanoHKUST-1 is a potential vector worth developing as a cancer chemotherapeutic drug delivery system. PMID:28260892

Strategy for chemotherapeutic delivery using a nanosized porous metal-organic framework with a central composite design.

PubMed

Li, Yingpeng; Li, Xiuyan; Guan, Qingxia; Zhang, Chunjing; Xu, Ting; Dong, Yujing; Bai, Xinyu; Zhang, Weiping

2017-01-01

Enhancing drug delivery is an ongoing endeavor in pharmaceutics, especially when the efficacy of chemotherapy for cancer is concerned. In this study, we prepared and evaluated nanosized HKUST-1 (nanoHKUST-1), nanosized metal-organic drug delivery framework, loaded with 5-fluorouracil (5-FU) for potential use in cancer treatment. NanoHKUST-1 was prepared by reacting copper (II) acetate [Cu(OAc) 2 ] and benzene-1,3,5-tricarboxylic acid (H 3 BTC) with benzoic acid (C 6 H 5 COOH) at room temperature (23.7°C±2.4°C). A central composite design was used to optimize 5-FU-loaded nanoHKUST-1. Contact time, ethanol concentration, and 5-FU:material ratios were the independent variables, and the entrapment efficiency of 5-FU was the response parameter measured. Powder X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and nitrogen adsorption were used to determine the morphology of nanoHKUST-1. In addition, 5-FU release studies were conducted, and the in vitro cytotoxicity was evaluated. Entrapment efficiency and drug loading were 9.96% and 40.22%, respectively, while the small-angle X-ray diffraction patterns confirmed a regular porous structure. The SEM and TEM images of the nanoHKUST-1 confirmed the presence of round particles (diameter: approximately 100 nm) and regular polygon arrays of mesoporous channels of approximately 2-5 nm. The half-maximal lethal concentration (LC 50 ) of the 5-FU-loaded nanoHKUST-1 was approximately 10 µg/mL. The results indicated that nanoHKUST-1 is a potential vector worth developing as a cancer chemotherapeutic drug delivery system.

Metal-inorganic-organic matrices as efficient sorbents for hydrogen storage.

PubMed

Azzouz, Abdelkrim; Nousir, Saadia; Bouazizi, Nabil; Roy, René

2015-03-01

Stabilization of metal nanoparticles (MNPs) without re-aggregation is a major challenge. An unprecedented strategy is developed for achieving high dispersion of copper(0) or palladium(0) on montmorillonite-supported diethanolamine or thioglycerol. This results in novel metal-inorganic-organic matrices (MIOM) that readily capture hydrogen at ambient conditions, with easy release under air stream. Hydrogen retention appears to involve mainly physical interactions, slightly stronger on thioglycerol-based MIOM (S-MIOM). Thermal enhancement of desorption suggests also a contribution of chemical interactions. The increase of hydrogen uptake with prolonged contact times arises from diffusion hindrance, which appears to be beneficial by favoring hydrogen entrapment. Even with compact structures, MIOMs act as efficient sorbents with much higher efficiency factor (1.14-1.17 mmol H 2 m(-2)) than many other sophisticated adsorbents reported in the literature. This opens new prospects for hydrogen storage and potential applications in microfluidic hydrogenation reactions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dual properties of a hydrogen oxidation Ni-catalyst entrapped within a polymer promote self-defense against oxygen.

PubMed

Oughli, Alaa A; Ruff, Adrian; Boralugodage, Nilusha Priyadarshani; Rodríguez-Maciá, Patricia; Plumeré, Nicolas; Lubitz, Wolfgang; Shaw, Wendy J; Schuhmann, Wolfgang; Rüdiger, Olaf

2018-02-28

The Ni(P 2 N 2 ) 2 catalysts are among the most efficient non-noble-metal based molecular catalysts for H 2 cycling. However, these catalysts are O 2 sensitive and lack long term stability under operating conditions. Here, we show that in a redox silent polymer matrix the catalyst is dispersed into two functionally different reaction layers. Close to the electrode surface is the "active" layer where the catalyst oxidizes H 2 and exchanges electrons with the electrode generating a current. At the outer film boundary, insulation of the catalyst from the electrode forms a "protection" layer in which H 2 is used by the catalyst to convert O 2 to H 2 O, thereby providing the "active" layer with a barrier against O 2 . This simple but efficient polymer-based electrode design solves one of the biggest limitations of these otherwise very efficient catalysts enhancing its stability for catalytic H 2 oxidation as well as O 2 tolerance.

The War Crimes Act: Current Issues

DTIC Science & Technology

2006-09-25

entrapment by estoppel , available when a defendant is informed by a government official that certain conduct is legal, and thereafter commits what...United States v. Baptista-Rodriguez, 17 F.3d 1354, 1368 n. 18 (11th Cir. 1994). Unlike the other defenses, the defense of entrapment by estoppel stems

Defeat and entrapment as predictors of depression and suicidal ideation versus hopelessness and helplessness.

PubMed

Lester, David

2012-10-01

In a sample of 140 undergraduate students, measures of defeat and entrapment and of haplessness, helplessness, and hopelessness were similar in their ability to predict depression and suicidality. It was concluded that the two sets of measures may tap the same cognitive mind set.

Entrapment of viral capsids in nuclear PML cages is an intrinsic antiviral host defense against varicella-zoster virus.

PubMed

Reichelt, Mike; Wang, Li; Sommer, Marvin; Perrino, John; Nour, Adel M; Sen, Nandini; Baiker, Armin; Zerboni, Leigh; Arvin, Ann M

2011-02-03

The herpesviruses, like most other DNA viruses, replicate in the host cell nucleus. Subnuclear domains known as promyelocytic leukemia protein nuclear bodies (PML-NBs), or ND10 bodies, have been implicated in restricting early herpesviral gene expression. These viruses have evolved countermeasures to disperse PML-NBs, as shown in cells infected in vitro, but information about the fate of PML-NBs and their functions in herpesvirus infected cells in vivo is limited. Varicella-zoster virus (VZV) is an alphaherpesvirus with tropism for skin, lymphocytes and sensory ganglia, where it establishes latency. Here, we identify large PML-NBs that sequester newly assembled nucleocapsids (NC) in neurons and satellite cells of human dorsal root ganglia (DRG) and skin cells infected with VZV in vivo. Quantitative immuno-electron microscopy revealed that these distinctive nuclear bodies consisted of PML fibers forming spherical cages that enclosed mature and immature VZV NCs. Of six PML isoforms, only PML IV promoted the sequestration of NCs. PML IV significantly inhibited viral infection and interacted with the ORF23 capsid surface protein, which was identified as a target for PML-mediated NC sequestration. The unique PML IV C-terminal domain was required for both capsid entrapment and antiviral activity. Similar large PML-NBs, termed clastosomes, sequester aberrant polyglutamine (polyQ) proteins, such as Huntingtin (Htt), in several neurodegenerative disorders. We found that PML IV cages co-sequester HttQ72 and ORF23 protein in VZV infected cells. Our data show that PML cages contribute to the intrinsic antiviral defense by sensing and entrapping VZV nucleocapsids, thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The efficient sequestration of virion capsids in PML cages appears to be the outcome of a basic cytoprotective function of this distinctive category of PML-NBs in sensing and safely containing nuclear aggregates of aberrant proteins.

Biochemical, hydrological and mechanical behaviors of high food waste content MSW landfill: Liquid-gas interactions observed from a large-scale experiment.

PubMed

Zhan, Liang-Tong; Xu, Hui; Chen, Yun-Min; Lan, Ji-Wu; Lin, Wei-An; Xu, Xiao-Bing; He, Pin-Jing

2017-10-01

The high food waste content (HFWC) MSW at a landfill has the characteristics of rapid hydrolysis process, large leachate production rate and fast gas generation. The liquid-gas interactions at HFWC-MSW landfills are prominent and complex, and still remain significant challenges. This paper focuses on the liquid-gas interactions of HFWC-MSW observed from a large-scale bioreactor landfill experiment (5m×5m×7.5m). Based on the connected and quantitative analyses on the experimental observations, the following findings were obtained: (1) The high leachate level observed at Chinese landfills was attributed to the combined contribution from the great quantity of self-released leachate, waste compression and gas entrapped underwater. The contribution from gas entrapped underwater was estimated to be 21-28% of the total leachate level. (2) The gas entrapped underwater resulted in a reduction of hydraulic conductivity, decreasing by one order with an increase in gas content from 13% to 21%. (3) The "breakthrough value" in the gas accumulation zone was up to 11kPa greater than the pore liquid pressure. The increase of the breakthrough value was associated with the decrease of void porosity induced by surcharge loading. (4) The self-released leachate from HFWC-MSW was estimated to contribute to over 30% of the leachate production at landfills in Southern China. The drainage of leachate with a high organic loading in the rapid hydrolysis stage would lead to a loss of landfill gas (LFG) potential of 13%. Based on the above findings, an improved method considering the quantity of self-released leachate was proposed for the prediction of leachate production at HFWC-MSW landfills. In addition, a three-dimensional drainage system was proposed to drawdown the high leachate level and hence to improve the slope stability of a landfill, reduce the hydraulic head on a bottom liner and increase the collection efficiency for LFG. Copyright © 2017. Published by Elsevier Ltd.

Influence of α-amylase template concentration on systematic entrapment of highly stable and monodispersed colloidal gold nanoparticles

NASA Astrophysics Data System (ADS)

Ananth, A. Nitthin; Ananth, A. Nimrodh; Jose, Sujin P.; Umapathy, S.; Mathavan, T.

2016-01-01

Nano gold / α-amylase colloidal dispersions of profound stability were made using simple procedure with a conventional reducing agent. The surface plasmon resonance of the gold nanocrystals was used to quantify the extent of the dispersion stability and functionalization. It is found that the reduced gold nanoparticles were trapped into the protein network without denaturation the structure of α-amylase protein. This kind of entrapment of particles into the protein network prevents clustering of individual gold nanoparticles (6.42 nm ± 0.92 nm) by acting as a natural spacer. Systematic entrapment was facilitated by the affinity of gold to the sulfur moieties (Au-S) in the protein structure.

Anterior Cutaneous Nerve Entrapment Syndrome in a Pediatric Patient Previously Diagnosed With Functional Abdominal Pain: A Case Report.

PubMed

DiGiusto, Matthew; Suleman, M-Irfan

2018-03-23

Chronic abdominal pain is common in children and adolescents but challenging to diagnose, because practitioners may be concerned about missing serious occult disease. Abdominal wall pain is an often ignored etiology for chronic abdominal pain. Anterior cutaneous nerve entrapment syndrome causes abdominal wall pain but is frequently overlooked. Correctly diagnosing patients with anterior cutaneous nerve entrapment syndrome is important because nerve block interventions are highly successful in the remittance of pain. Here, we present the case of a pediatric patient who received a diagnosis of functional abdominal pain but experienced pain remittance after receiving a trigger-point injection and transverse abdominis plane block.

Prospective Predictors of Suicidality: Defeat and Entrapment Lead to Changes in Suicidal Ideation over Time

ERIC Educational Resources Information Center

Taylor, Peter James; Gooding, Patricia A.; Wood, Alex M.; Johnson, Judith; Tarrier, Nicholas

2011-01-01

Theoretical perspectives into suicidality have suggested that heightened perceptions of defeat and entrapment lead to suicidality. However, all previous empirical work has been cross-sectional. We provide the first longitudinal test of the theoretical predictions, in a sample of 79 students who reported suicidality. Participants completed…

The Role of Defeat and Entrapment in Depression, Anxiety, and Suicide

ERIC Educational Resources Information Center

Taylor, Peter James; Gooding, Patricia; Wood, Alex M.; Tarrier, Nicholas

2011-01-01

Defeat and entrapment are psychological constructs that have played a central role in evolutionary accounts of depression. These concepts have since been implicated in theoretical accounts of anxiety disorders and suicidality. The current article reports on a systematic review of the existing research investigating the links among defeat,…

Association between Computer Use and Entrapment Neuropathies in the Wrist Region

ERIC Educational Resources Information Center

Colak, S.; Bamac, B.; Colak, T.; Ozbek, A.

2013-01-01

There is general consensus in the literature that computer use is often associated with an increased prevalence of hand and wrist disorders. Symptoms may be associated with specific clinical entities such as peripheral nerve entrapment. Motor and sensory nerve conduction velocity and vibration threshold in the hand of computer users have been…

Entrapment and Escape: Inventional Metaphors in Ronald Reagan's Economic Rhetoric.

ERIC Educational Resources Information Center

Aden, Roger C.

1989-01-01

Examines Ronald Reagan's use of inventional metaphors of entrapment and escape, language meshing with the American public's perception of the economy in the early 1980s. Notes that Reagan's reliance on inventional metaphors produced a rigidity in his approach to new situations, ultimately damaging his ability to lead the nation. (MM)

Reappraising entrapment neuropathies--mechanisms, diagnosis and management.

PubMed

Schmid, Annina B; Nee, Robert J; Coppieters, Michel W

2013-12-01

The diagnosis of entrapment neuropathies can be difficult because symptoms and signs often do not follow textbook descriptions and vary significantly between patients with the same diagnosis. Signs and symptoms which spread outside of the innervation territory of the affected nerve or nerve root are common. This Masterclass provides insight into relevant mechanisms that may account for this extraterritorial spread in patients with entrapment neuropathies, with an emphasis on neuroinflammation at the level of the dorsal root ganglia and spinal cord, as well as changes in subcortical and cortical regions. Furthermore, we describe how clinical tests and technical investigations may identify these mechanisms if interpreted in the context of gain or loss of function. The management of neuropathies also remains challenging. Common treatment strategies such as joint mobilisation, neurodynamic exercises, education, and medications are discussed in terms of their potential to influence certain mechanisms at the site of nerve injury or in the central nervous system. The mechanism-oriented approach for this Masterclass seems warranted given the limitations in the current evidence for the diagnosis and management of entrapment neuropathies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Labile conjugation of a hydrophilic drug to PLA oligomers to modify a drug delivery system: cephradin in a PLAGA matrix.

PubMed

Ustariz-Peyret, C; Coudane, J; Vert, M; Kaltsatos, V; Boisramené, B

2000-01-01

The physical entrapment of a hydrophilic drug within degradable microspheres is generally difficult because of poor entrapment yield and/or fast release, depending on the microsphere fabrication method. In order to counter the effects of drug hydrophilicity, it is proposed to covalently attach the drug to lactic acid oligomers, with the aim of achieving temporary hydrophobization and slower release controlled by the separation of the drug from the degradable link within the polymer matrix. This strategy was tested on microspheres of the antibiotic cephradin. As the prodrug form, the entrapment of the drug was almost quantitative. The prodrug did degrade in an aqueous medium, modelling body fluids, but cleavage did not occur at the drug-oligomer junction and drug molecules bearing two lactyl residual units were released. When the prodrug is entrapped within a PLAGA matrix, no release was observed within the experimental time period. However, data suggest that conjugation via a bond more sensitive to hydrolysis than the main chain PLA ester bonds should make the system work as desired.

Air entrapment under an impacting drop

NASA Astrophysics Data System (ADS)

Thoroddsen, S. T.; Etoh, T. G.; Takehara, K.

2003-03-01

When a drop impacts on a liquid surface it entraps a small amount of air under its centre as the two liquid surfaces meet. The contact occurs along a ring enclosing a thin disk of air. We use the next-generation ultra-high-speed video camera, capable of 1 million f.p.s. (Etoh et al. 2002), to study the dynamics of this air sheet as it contracts due to surface tension, to form a bubble or, more frequently, splits into two bubbles. During the contraction of the air disk an azimuthal undulation, resembling a pearl necklace, develops along its edge. The contraction speed of the sheet is accurately described by a balance between inertia and surface tension. The average initial thickness of the air sheet decreases with higher impact Reynolds numbers, becoming less than one micron. The total volume of air entrapped depends strongly on the bottom curvature of the drop at impact. A sheet of micro-bubbles is often observed along the original interface. Oguz Prosperetti bubble rings are also observed. For low Weber numbers (We<20) a variety of other entrapment phenomena appear.

Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids

PubMed Central

Lee, Chun-Ting; Huang, Yen-Wei; Yang, Chih-Hui; Huang, Keng-Shiang

2015-01-01

Developing new methods for chemotherapy drug delivery has become a topic of great concern. Vinca alkaloids are among the most widely used chemotherapy reagents for tumor therapy; however, their side effects are particularly problematic for many medical doctors. To reduce the toxicity and enhance the therapeutic efficiency of vinca alkaloids, many researchers have developed strategies such as using liposome-entrapped drugs, chemical- or peptide-modified drugs, polymeric packaging drugs, and chemotherapy drug combinations. This review mainly focuses on the development of a vinca alkaloid drug delivery system and the combination therapy. Five vinca alkaloids (eg, vincristine, vinblastine, vinorelbine, vindesine, and vinflunine) are reviewed. PMID:25877096

Production of α-keto acids Part I. Immobilized cells ofTrigonopsis variabilis containing D-amino acid oxidase.

PubMed

Brodelius, P; Nilsson, K; Mosbach, K

1981-12-01

Whole cells ofTrigonopsis variabilis were immobilized by entrapment in Ca(2+)-alginate and used for the production of α-keto acids from the corresponding D-amino acids. The D-amino acid oxidase within the immobilized cells has a broad substrate specificity. Hydrogen peroxide formed in the enzymatic reaction was efficiently hydrolyzed by manganese oxide co-immobilized with the cells. The amino acid oxidase activity was assayed with a new method based on reversed-phase HPLC. Oxygen requirements, bead size, concentration of cells in the beads, flow rate, and other factors were investigated in a " trickle-bed " reactor.

Method of regulating the amount of underfire air for combustion of wood fuels in spreader-stroke boilers

DOEpatents

Tuttle, Kenneth L.

1980-01-01

A method of metering underfire air for increasing efficiency and reducing particulate emissions from wood-fire, spreader-stoker boilers is disclosed. A portion of the combustion air, approximately one pound of air per pound of wood, is fed through the grate into the fuel bed, while the remainder of the combustion air is distributed above the fuel in the furnace, and the fuel bed is maintained at a depth sufficient to consume all oxygen admitted under fire and to insure a continuous layer of fresh fuel thereover to entrap charred particles inside the fuel bed.

Vacuum Powder Injector

NASA Technical Reports Server (NTRS)

Working, Dennis C.

1991-01-01

Method developed to provide uniform impregnation of bundles of carbon-fiber tow with low-solubility, high-melt-flow polymer powder materials to produce composite prepregs. Vacuum powder injector expands bundle of fiber tow, applies polymer to it, then compresses bundle to hold powder. System provides for control of amount of polymer on bundle. Crystallinity of polymer maintained by controlled melt on takeup system. All powder entrapped, and most collected for reuse. Process provides inexpensive and efficient method for making composite materials. Allows for coating of any bundle of fine fibers with powders. Shows high potential for making prepregs of improved materials and for preparation of high-temperature, high-modulus, reinforced thermoplastics.

Silica/quercetin sol–gel hybrids as antioxidant dental implant materials

PubMed Central

Catauro, Michelina; Papale, Ferdinando; Bollino, Flavia; Piccolella, Simona; Marciano, Sabina; Nocera, Paola; Pacifico, Severina

2015-01-01

The development of biomaterials with intrinsic antioxidant properties could represent a valuable strategy for preventing the onset of peri-implant diseases. In this context, quercetin, a naturally occurring flavonoid, has been entrapped at different weight percentages in a silica-based inorganic material by a sol–gel route. The establishment of hydrogen bond interactions between the flavonol and the solid matrix was ascertained by Fourier transform infrared spectroscopy. This technique also evidenced changes in the stretching frequencies of the quercetin dienonic moiety, suggesting that the formation of a secondary product occurs. Scanning electron microscopy was applied to detect the morphology of the synthesized materials. Their bioactivity was shown by the formation of a hydroxyapatite layer on sample surface soaked in a fluid that simulates the composition of human blood plasma. When the potential release of flavonol was determined by liquid chromatography coupled with ultraviolet and electrospray ionization tandem mass spectrometry techniques, the eluates displayed a retention time that was 0.5 min less than quercetin. Collision-activated dissociation mass spectrometry and untraviolet-visible spectroscopy were in accordance with the release of a quercetin derivative. The antiradical properties of the investigated systems were evaluated by DPPH and ABTS methods, whereas the 2,7-dichlorofluorescein diacetate assay highlighted their ability to inhibit the H2O2-induced intracellular production of reactive oxygen species in NIH-3T3 mouse fibroblast cells. Data obtained, along with data gathered from the MTT cytotoxicity test, revealed that the materials that entrapped the highest amount of quercetin showed notable antioxidant effectiveness. PMID:27877802

High fluorescent water soluble CdTe quantum dots—a promising system for light harvesting applications

NASA Astrophysics Data System (ADS)

de Sa, Arsenio; Moura, Isabel; Abreu, Ana S.; Oliveira, Manuel; Ferreira, Miguel F.; Machado, Ana V.

2017-05-01

The entrapment of quantum dots (QDs) in the inner part of micelles formed by surfactant polymers is a powerful methodology to prepare stable and photoluminescent core nanoparticles with enhanced optical properties. These features are crucial for the application of QDs in the design of hybrid assemblies for light harvesting applications, where energy transfer processes are required. The present work was focused on the synthesis of a surfactant homopolymer, poly (acrylic acid) (PAA) macroRAFT, to be used as a stabilizer of hydrophobic cadmium telluride (CdTe) QDs in aqueous solution. PAA macroRAFT was synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization in a single chemical reaction. Its micelles were used to entangle and entrap hydrophobic CdTe QDs, with different molar ratio of polymer and QDs. The morphology and optical properties of the entrapped QDs were determined. The results showed that PAA macroRAFT is able to form micelles with a critical micelle concentration of 2.08 mg/mL. It was also noticed that the molar ratio of polymer and QDs have high influence on the QDs' morphology and their optical properties. The QDs' photoluminescence quantum yield was enhanced approximately 23% upon their entrapment in PAA macroRAFT micelles, using 60 equivalents of polymer. Moreover, while in solution, QDs are well-dispersed, having a 3.5 nm diameter, upon being entrapped in the micelles, tend to form clusters with a size around 100 nm.

Characterization of voids formed during liquid impregnation of nonwoven multifilament glass networks as related to composite processing

NASA Technical Reports Server (NTRS)

Mahale, Anant D.; Prudhomme, Robert K.; Rebenfeld, Ludwig

1993-01-01

A technique based on matching the refractive index of an invading liquid to that of a fiber mat was used to study entrapment of air ('voids') that occurs during forced in-plane radial flow into nonwoven multifilament glass networks. The usefulness of this technique is demonstrated in quantifying and mapping the air pockets. Experiments with a series of fluids with surface tensions varying from 28 x 10(exp -3) to 36 x 10(exp -3) N/m, viscosities from 45 x 10(exp -3) to 290 x 10(exp -3) Pa.s, and inlet flow rates from 0.15 x 10(exp -6) to 0.75 x 10(exp -6) m(exp 3)/s, showed that void content is a function of the capillary number characterizing the flow process. A critical value of capillary number, Ca = 2.5 x 10(exp -3), identifies a zone below which void content increases exponentially with decreasing capillary number. Above this critical value, negligible entrapment of voids is observed. Similar experiments carried out on surface treated nonwoven mats spanning a range of equilibrium contact angles from 20 deg to 78 deg showed that there is a critical contact angle above which negligible entrapment is observed. Below this value, there is no apparent effect of contact angle on the void fraction - capillary number relationship described earlier. Studies on the effect of filament wettability, and fluid velocity and viscosity on the size of the entrapment (voids) were also carried out. These indicate that larger sized entrapments which envelop more than one pore are favored by a low capillary number in comparison to smaller, pore level bubbles. Experiments were carried out on deformed mats - imposing high permeability spots at regular intervals on a background of low permeability. The effect of these spatial fluctuations in heterogeneity of the mat on entrapment is currently being studied.

GE11-modified liposomes for non-small cell lung cancer targeting: preparation, ex vitro and in vivo evaluation.

PubMed

Cheng, Liang; Huang, Fa-Zhen; Cheng, Li-Fang; Zhu, Ya-Qin; Hu, Qing; Li, Ling; Wei, Lin; Chen, Da-Wei

2014-01-01

Non-small cell lung cancer (NSCLC) is a serious threat to human health, and 40%-80% of NSCLCs express high levels of epidermal growth factor receptor (EGFR). GE11 is a novel peptide and exhibits high affinity for EGFR binding. The aim of this study was to construct and evaluate GE11-modified liposomes for targeted drug delivery to EGFR-positive NSCLC. Doxorubicin, a broad-spectrum antitumor agent, was chosen as the payload. GE11 was conjugated to the distal end of DSPE-PEG2000-Mal by an addition reaction with a conjugation efficiency above 90%. Doxorubicin-loaded liposomes containing GE11 (GE11-LP/DOX) at densities ranging from 0% to 15% were prepared by combination of a thin film hydration method and a post insertion method. Irrespective of GE11 density, the physicochemical properties of these targeted liposomes, including particle size, zeta potential, and drug entrapment efficiency, were nearly identical. Interestingly, the cytotoxic effect of the liposomes on A549 tumor cells was closely related to GE11 density, and liposomes with 10% GE11 had the highest tumor cell killing activity and a 2.6-fold lower half maximal inhibitory concentration than that of the nontargeted counterpart (PEG-LP/DOX). Fluorescence microscopy and flow cytometry analysis revealed that GE11 significantly increased cellular uptake of the liposomes, which could be ascribed to specific EGFR-mediated endocytosis. It was found that multiple endocytic pathways were involved in entry of GE11-LP/DOX into cells, but GE11 assisted in cellular internalization mainly via the clathrin-mediated endocytosis pathway. Importantly, the GE11-modified liposomes showed enhanced accumulation and prolonged retention in tumor tissue, as evidenced by a 2.2-fold stronger mean fluorescence intensity in tumor tissue than the unmodified liposomes at 24 hours. In summary, GE11-modified liposomes may be a promising platform for targeted delivery of chemotherapeutic drugs in NSCLC.

The influence of magma degassing on entrapment pressures recorded in olivine-hosted melt inclusions

NASA Astrophysics Data System (ADS)

Gaetani, G. A.

2013-12-01

The concentrations of H2O and CO2 in olivine-hosted melt inclusions provide estimates for the pressures at which they were entrapped, and represent an important source of information on the depths at which basaltic magmas crystallize [1]. Results from recent dehydration experiments demonstrate that diffusive loss of H2O from melt inclusions, driven by degassing of the external magma, leads to significant decreases to pressure within the inclusion [2, 3]. This, in turn, lowers the solubility of CO2 in the included melt causing a vapor to exsolve and form a bubble. This process has the potential to significantly modify estimates of entrapment pressures derived from volatile concentrations in olivine hosted melt inclusions. I have developed a quantitative model that describes this process, allowing the influence of degassing on entrapment pressures to be rigorously evaluated. Diffusive loss of H2O from the inclusions was determined using the model of [3]. An equation of state (EOS) for the silicate melt was taken from the results of [4] and [5], while the EOS for H2O-CO2 vapor was taken from [6]. The solubilities of H2O and CO2 in the silicate melt were derived from VolatileCalc [7]. Modeling results demonstrate that degassing of H2O-rich magma produces significant pressure drops, so that entrapment pressures never exceed crustal values and always represent a minimum. Conversely, degassing of H2O-poor magma does not significantly perturb the H2O content of olivine-hosted melt inclusions. Therefore, these inclusions preserve reliable records of the pressures at which they were entrapped. These results are consistent with a global compilation of olivine-hosted melt inclusion entrapment pressures presented by [3]. References: [1] Wanless, VD, and Shaw, AM, Nature Geosci, 5, 651-655 (2012); [2] Gaetani, GA, et al., Geology, 40, 915-918 (2012); [3] Bucholz, CE, et al., Earth Planet Sci Lett, 374, 145-155 (2013); [4] Lange, R. A., and Carmichael, ISE, Geochim Cosmochim Acta, 51, 2931-2946, (1987); [5] Kress, VC, and Carmichael, ISE, Contrib Mineral Petrol, 108, 82-92 (1991); [6] Duan, Z, and Zhang, Z, Geochim Cosmochim Acta, 70, 2311-2324 (2006); [7] Newman, S, and Lowenstern, JB, Comput Geosci, 28, 597-604 (2002).

Constraining magma ascent and degassing paths with olivine- and clinopyroxene-hosted melt inclusions: Evidence for multiple depths of crystallization and boundary-layer entrapment

NASA Astrophysics Data System (ADS)

Lloyd, A. S.; Newcombe, M. E.; Plank, T. A.

2016-12-01

Although olivine-hosted melt inclusions (MIs) remain the gold standard for recovering volatile concentrations of primitive magmas, later-fractionating minerals may be more appropriate for assessing magma storage conditions immediately prior to eruption. We present volatile analyses of MIs entrapped in early (Mg# 81-83) olivine and later (Mg# 70-80) clinopyroxene (Cpx) from the 1977 eruption of Seguam volcano, to assess the ascent history prior to this violent strombolian eruption. The olivine-hosted MIs contain average volatile concentrations (n=16) of 3.79 wt% H2O, 167 ppm CO2, 592 ppm Cl, and 133 ppm F, consistent with an entrapment pressure of 200 to 300 MPa ( 10-13 km depth) if the CO2 contained in the bubble is taken into account (Moore et al., 2015). Cpx phenocrysts contain two distinct MI assemblages; the inner assemblage consists of randomly distributed, rounded MIs which never contain a vapor bubble. Average volatile concentrations of the inner assemblage MIs (n=11) are 0.96 wt% H2O, 98 ppm CO2, 798 ppm Cl, and 280 ppm F, consistent with an entrapment at much shallower depth, 2 km. The outer assemblage contains inclusions too small for routine volatile analysis. Inner assemblage Cpx-hosted MIs preserve average enrichments of 1.3x and 2x for Cl and F respectively, and are similarly enriched in incompatible minor and trace elements (up to a factor of 5x). Two potential scenarios can explain these observations. The enrichments may represent the entrapment of an unrelated highly-fractionated, shallow magma (which is unsupported by the whole rock record at Seguam). A second possibility is enrichment through boundary layer entrapment during a period of rapid crystal growth during ascent through the upper crust. Boundary layer entrapment during MI formation is further supported by a negative correlation between the degree of enrichment and the diffusivity of individual elements, which is consistent with growth rates 10-8 m/s. Although the olivine-hosted MIs record a volatile-rich storage region, the later-fractionating Cpx indicate a phase of rapid crystallization, likely driven by water loss from the melt at shallow depths. This work highlights the information added by analyzing multiple phases in order to reconstruct the degassing path of magma prior to eruption.

A new technique for surface and shallow subsurface paleobarometry using fluid inclusions: An example from the Upper Ordovician Viola Formation, Kansas, USA

USGS Publications Warehouse

Newell, K.D.; Goldstein, R.H.

1999-01-01

This research illustrates a new approach for paleobarometry employing heterogeneously entrapped fluid inclusions to determine timing and depth of diagenesis. Heterogeneously entrapped fluid inclusions (gas + water) in vug-filling quartz from the Upper Ordovician Viola Formation in the Midcontinent of the United States were analyzed for their internal pressure with a fluid-inclusion crushing stage. The free gas in fluid inclusions was entrapped at near-surface temperature, as indicated by the presence of all-liquid fluid inclusions and fluid inclusions with low homogenization temperatures ( <40??C). Crushing the crystal and measuring the change in bubble size determines the pressure of entrapment directly. Heterogeneous trapping is indicated by widely varying L:V ratios, from all-liquid to vapor-rich. Gas bubbles in most fluid inclusions analyzed expanded upon release to atmospheric pressure, but some collapsed. A mode of 1.5 to 2.0 atm internal pressure was indicated by the crushing runs, but pressures up to 42.9 atm were recorded. Quartz precipitation and associated fluid-inclusion entrapment therefore occurred over a wide depth-range, but principally at depths of approximately 10 m. Crushing runs done in kerosene confirmed the presence of hydrocarbon gases in most of these inclusions, and bulk analyses of gases in the quartz by quadrupole mass spectrometer revealed methane, ethane, and atmospheric gases. The hydrocarbon gases may have originated in deeper thermogenically mature sedimentary strata, and then leaked to the near-surface where they were entrapped in the precipitating quartz cement. Freezing data indicate an event of quartz precipitation from fluids of marine-fresh water intermediate salinity and other events of precipitation from more saline fluids. Considering the determined pressures, the precipitating fluids probably originated at surfaces of subaerial exposure (unconformities) and surfaces of evaporite precipitation in the overlying Silurian strata. Thus, saline inclusions most likely originated from sinking of saline surface waters during Silurian time. Lower-salinity fluids record fluxes of meteoric water during development of unconformities in the Silurian. This type of paleobarometric study may have application in many other sedimentary systems, provided low-temperature and heterogeneous entrapment of an immiscible gas phase can be demonstrated for the fluid-inclusion assemblages studied.