Synthesis and characterization of emamectin-benzoate slow-release microspheres with different surfactants.

PubMed

Wang, Yan; Wang, Anqi; Wang, Chunxin; Cui, Bo; Sun, Changjiao; Zhao, Xiang; Zeng, Zhanghua; Shen, Yue; Gao, Fei; Liu, Guoqiang; Cui, Haixin

2017-10-06

Pesticide slow-release formulations provide a way to increase the efficiency of active components by reducing the amount of pesticide that needs to be applied. Slow-release formulations also increase the stability and prolong the control effect of photosensitive pesticides. Surfactants are an indispensable part of pesticide formulations, and the choice of surfactant can strongly affect formulation performance. In this study, emamectin-benzoate (EMB) slow-release microspheres were prepared by the microemulsion polymerization method. We explored the effect of different surfactants on the particle size and dispersity of EMB in slow-release microspheres. The results indicated that the samples had uniform spherical shapes with an average diameter of 320.5 ±5.24 nm and good dispersity in the optimal formulation with the polymeric stabilizer polyvinyl alcohol (PVA) and composite non-ionic surfactant polyoxyethylene castor oil (EL-40). The optimal EMB pesticide slow-release microspheres had excellent anti-photolysis performance, stability, controlled release properties, and good leaf distribution. These results demonstrated that EMB slow-release microspheres are an attractive candidate for improving pesticide efficacy and prolonging the control effect of EMB in the environment.

The development of injectable gelatin/silk fibroin microspheres for the dual delivery of curcumin and piperine.

PubMed

Ratanavaraporn, Juthamas; Kanokpanont, Sorada; Damrongsakkul, Siriporn

2014-02-01

The objective of this study was to develop the microspheres from gelatin (G) and silk fibroin (SF) aimed to be applied for the controlled release of curcumin and piperine. The glutaraldehyde-crosslinked G/SF microspheres at various weight blending ratios (100/0, 70/30, 50/50, and 30/70) were successfully fabricated by water in oil emulsion technique. The microspheres prepared from all compositions were in a round shape with homogeneous size distribution both in the dried (194-217 μm) and swollen states (297-367 μm). When subjected in collagenase solution at physiological condition, the G microspheres gradually degraded within 14 days while the blended G/SF microspheres, particularly at 50/50 and 30/70, were not degraded. For the release application, the microspheres were loaded with curcumin and/or piperine. It was found that the microspheres composed of SF tended to entrap curcumin and piperine with the high entrapment and loading efficiencies, possibly due to their hydrophobic interactions. The G/SF microspheres, particularly at the ratios of 50/50 and 30/70, released curcumin and piperine in a sustained manner both for the single and dual release systems. The controlled dual release of curcumin and piperine from the G/SF microspheres would prolong their half-life, provide the optimal concentrations for therapeutic effects at a target site, and improve the bioavailability of curcumin. These novel injectable microspheres dually releasing curcumin and piperine would be introduced for the treatment of diseases without the need of operation.

The development of non-toxic ionic-crosslinked chitosan-based microspheres as carriers for the controlled release of silk sericin.

PubMed

Aramwit, Pornanong; Ekasit, Sanong; Yamdech, Rungnapha

2015-10-01

Silk sericin is recently shown to possess various biological activities for biomedical applications. While various sericin carriers were developed for drug delivery system, very few researches considered sericin as a bioactive molecule itself. In this study, sericin incorporated in the chitosan-based microspheres was introduced as a bioactive molecule and bioactive carrier at the same time. The chitosan/sericin (CH/SS) microspheres at different composition (80/20, 70/30, 60/40, and 50/50) were successfully fabricated using anhydroustri-polyphosphate (TPP) as a polyanionic crosslinker. The microspheres with an average size of 1-4 μm and narrow size distribution were obtained. From FT-IR spectra, the presence of both chitosan and sericin in the microspheres confirmed the occurrence of ionic interaction that crosslink them within the microspheres. We also found that the CH/SS microspheres prepared at 50/50 could encapsulate sericin at the highest percentage (37.28%) and release sericin in the most sustained behavior, possibly due to the strong ionic interaction of the positively charged chitosan and the negatively charged sericin. On the other hand, the composition of CH/SS had no effect on the degradation rate of microspheres. All microspheres continuously degraded and remained around 20% after 14 days of enzymatic degradation. This explained that the ionic crosslinkings between chitosan and sericin could be demolished by the enzyme and hydrolysis. Furthermore, we have verified that all CH/SS microspheres at any concentrations showed non-toxicity to L929 mouse fibroblast cells. Therefore, we suggested that the non-toxic ionic-crosslinked CH/SS microspheres could be incorporated in wound dressing material to achieve the sustained release of sericin for accelerated wound healing.

Accelerated in vitro release testing method for naltrexone loaded PLGA microspheres.

PubMed

Andhariya, Janki V; Choi, Stephanie; Wang, Yan; Zou, Yuan; Burgess, Diane J; Shen, Jie

2017-03-30

The objective of the present study was to develop a discriminatory and reproducible accelerated release testing method for naltrexone loaded parenteral polymeric microspheres. The commercially available naltrexone microsphere product (Vivitrol ® ) was used as the testing formulation in the in vitro release method development, and both sample-and-separate and USP apparatus 4 methods were investigated. Following an in vitro drug stability study, frequent media replacement and addition of anti-oxidant in the release medium were used to prevent degradation of naltrexone during release testing at "real-time" (37°C) and "accelerated" (45°C), respectively. The USP apparatus 4 method was more reproducible than the sample-and-separate method. In addition, the accelerated release profile obtained using USP apparatus 4 had a shortened release duration (within seven days), and good correlation with the "real-time" release profile. Lastly, the discriminatory ability of the developed accelerated release method was assessed using compositionally equivalent naltrexone microspheres with different release characteristics. The developed accelerated USP apparatus 4 release method was able to detect differences in the release characteristics of the prepared naltrexone microspheres. Moreover, a linear correlation was observed between the "real-time" and accelerated release profiles of all the formulations investigated, suggesting that the release mechanism(s) may be similar under both conditions. These results indicate that the developed accelerated USP apparatus 4 method has the potential to be an appropriate fast quality control tool for long-acting naltrexone PLGA microspheres. Copyright © 2017 Elsevier B.V. All rights reserved.

Controlled Release of Chitosan and Sericin from the Microspheres-Embedded Wound Dressing for the Prolonged Anti-microbial and Wound Healing Efficacy.

PubMed

Aramwit, Pornanong; Yamdech, Rungnapha; Ampawong, Sumate

2016-05-01

One approach in wound dressing development is to incorporate active molecules or drugs in the dressing. In order to reduce the frequency of dressing changes as well as to prolong wound healing efficacy, wound dressings that can sustain the release of the active molecules should be developed. In our previous work, we developed chitosan/sericin (CH/SS) microspheres that released sericin in a controlled rate. However, the difficulty of applying the microspheres that easily diffuse and quickly degrade onto the wound was its limitations. In this study, we aimed to develop wound dressing materials which are easier to apply and to provide extended release of sericin. Different amounts of CH/SS microspheres were embedded into various compositions of polyvinyl alcohol/gelatin (PVA/G) scaffolds and fabricated using freeze-drying and glutaraldehyde crosslinking techniques. The obtained CH/SS microspheres-embedded scaffolds with appropriate design and formulation were introduced as a wound dressing material. Sericin was released from the microspheres and the scaffolds in a sustained manner. Furthermore, an optimized formation of the microspheres-embedded scaffolds (2PVA2G+2CHSS) was shown to possess an effective antimicrobial activity against both gram-positive and gram-negative bacteria. These microspheres-embedded scaffolds were not toxic to L929 mouse fibroblast cells, and they did not irritate the tissue when applied to the wound. Finally, probably by the sustained release of sericin, these microspheres-embedded scaffolds could promote wound healing as well as or slightly better than a clinically used wound dressing (Allevyn®) in a mouse model. The antimicrobial CH/SS microspheres-embedded PVA/G scaffolds with sustained release of sericin would appear to be a promising candidate for wound dressing application.

Thermal expansion of an epoxy-glass microsphere composite

NASA Technical Reports Server (NTRS)

Price, H. L.; Burks, H. D.

1977-01-01

The thermal expansion of a composite of epoxy (diglycidyl ether of bisphenol A) and solid glass microspheres was investigated. The microspheres had surfaces which were either untreated or treated with a silicone release agent, an epoxy coupling agent, or a general purpose silane coupling agent. Both room temperature (about 300 K) and elevated temperature (about 475 K) cures were used for the epoxy. Two microsphere size ranges were used, about 50 microns, which is applicable in filled moldings, and about 125 microns, which is applicable as bond line spacers. The thermal expansion of the composites was measured from 300 to 350 K or from 300 to 500 K, depending on the epoxy cure temperature. Measurements were made on composites containing up to .6 volume fraction microspheres. Two predictive models, which required only the values of thermal expansion of the polymer and glass and their specific gravities, were tested against the experimental data. A finite element analysis was made of the thermal strain of a composite cell containing a single microsphere surrounded by a finite-thickness interface.

Development of Poly Lactic/Glycolic Acid (PLGA) Microspheres for Controlled Release of Rho-Associated Kinase Inhibitor.

PubMed

Koda, Sho; Okumura, Naoki; Kitano, Junji; Koizumi, Noriko; Tabata, Yasuhiko

2017-01-01

The purpose of this study was to investigate the feasibility of poly lactic/glycolic acid (PLGA) as a drug delivery carrier of Rho kinase (ROCK) inhibitor for the treatment of corneal endothelial disease. ROCK inhibitor Y-27632 and PLGA were dissolved in water with or without gelatin (W1), and a double emulsion [(W1/O)/W2] was formed with dichloromethane (O) and polyvinyl alcohol (W2). Drug release curve was obtained by evaluating the released Y-27632 by using high performance liquid chromatography. PLGA was injected into the anterior chamber or subconjunctiva in rabbit eyes, and ocular complication was evaluated by slitlamp microscope and histological analysis. Y-27632 incorporated PLGA microspheres with different molecular weights, and different composition ratios of lactic acid and glycolic acid were fabricated. A high molecular weight and low content of glycolic acid produced a slower and longer release. The Y-27632 released from PLGA microspheres significantly promoted the cell proliferation of cultured corneal endothelial cells. The injection of PLGA did not induce any evident eye complication. ROCK inhibitor-incorporated PLGA microspheres were fabricated, and the microspheres achieved the sustained release of ROCK inhibitor over 7-10 days in vitro. Our data should encourage researchers to use PLGA microspheres for treating corneal endothelial diseases.

Formation of methotrexate-PLLA-PEG-PLLA composite microspheres by microencapsulation through a process of suspension-enhanced dispersion by supercritical CO2

PubMed Central

Chen, Ai-Zheng; Wang, Guang-Ya; Wang, Shi-Bin; Li, Li; Liu, Yuan-Gang; Zhao, Chen

2012-01-01

Background The aim of this study was to improve the drug loading, encapsulation efficiency, and sustained-release properties of supercritical CO2-based drug-loaded polymer carriers via a process of suspension-enhanced dispersion by supercritical CO2 (SpEDS), which is an advanced version of solution-enhanced dispersion by supercritical CO2 (SEDS). Methods Methotrexate nanoparticles were successfully microencapsulated into poly (L-lactide)-poly(ethylene glycol)-poly(L-lactide) (PLLA-PEG-PLLA) by SpEDS. Methotrexate nanoparticles were first prepared by SEDS, then suspended in PLLA-PEG-PLLA solution, and finally microencapsulated into PLLA-PEG-PLLA via SpEDS, where an “injector” was utilized in the suspension delivery system. Results After microencapsulation, the composite methotrexate (MTX)-PLLA-PEG-PLLA microspheres obtained had a mean particle size of 545 nm, drug loading of 13.7%, and an encapsulation efficiency of 39.2%. After an initial burst release, with around 65% of the total methotrexate being released in the first 3 hours, the MTX-PLLA-PEG-PLLA microspheres released methotrexate in a sustained manner, with 85% of the total methotrexate dose released within 23 hours and nearly 100% within 144 hours. Conclusion Compared with a parallel study of the coprecipitation process, microencapsulation using SpEDS offered greater potential to manufacture drug-loaded polymer microspheres for a drug delivery system. PMID:22787397

PLGA-Mesoporous Silicon Microspheres for the in Vivo Controlled Temporospatial Delivery of Proteins.

PubMed

Minardi, Silvia; Pandolfi, Laura; Taraballi, Francesca; De Rosa, Enrica; Yazdi, Iman K; Liu, Xeuwu; Ferrari, Mauro; Tasciotti, Ennio

2015-08-05

In regenerative medicine, the temporospatially controlled delivery of growth factors (GFs) is crucial to trigger the desired healing mechanisms in the target tissues. The uncontrolled release of GFs has been demonstrated to cause severe side effects in the surrounding tissues. The aim of this study was to optimize a translational approach for the fine temporal and spatial control over the release of proteins, in vivo. Hence, we proposed a newly developed multiscale composite microsphere based on a core consisting of the nanostructured silicon multistage vector (MSV) and a poly(dl-lactide-co-glycolide) acid (PLGA) outer shell. Both of the two components of the resulting composite microspheres (PLGA-MSV) can be independently tailored to achieve multiple release kinetics contributing to the control of the release profile of a reporter protein in vitro. The influence of MSV shape (hemispherical or discoidal) and size (1, 3, or 7 μm) on PLGA-MSV's morphology and size distribution was investigated. Second, the copolymer ratio of the PLGA used to fabricate the outer shell of PLGA-MSV was varied. The composites were fully characterized by optical microscopy, scanning electron microscopy, ζ potential, Fourier transform infrared spectroscopy, and thermogravimetric analysis-differential scanning calorimetry, and their release kinetics over 30 days. PLGA-MSV's biocompatibility was assessed in vitro with J774 macrophages. Finally, the formulation of PLGA-MSV was selected, which concurrently provided the most consistent microsphere size and allowed for a zero-order release kinetic. The selected PLGA-MSVs were injected in a subcutaneous model in mice, and the in vivo release of the reporter protein was followed over 2 weeks by intravital microscopy, to assess if the zero-order release was preserved. PLGA-MSV was able to retain the payload over 2 weeks, avoiding the initial burst release typical of most drug delivery systems. Finally, histological evaluation assessed the biocompatibility of the platform in vivo.

Enhanced encapsulation of metoprolol tartrate with carbon nanotubes as adsorbent

NASA Astrophysics Data System (ADS)

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

2011-12-01

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

[Prolonged-release drug formulations for parenteral administration. Part II. Microspheres and implants for injection].

PubMed

Płaczek, Margin; Jacyna, Julia; Sznitowska, Małgorzata

2014-01-01

Microspheres and implants are injectable drug forms, which by special design and selection of appropriate excipients, provide for a long time constant release rate of an active substance in the body. Development of both would not be possible without advances in polymer technology and invention of safe and biocompatible polymers such as: polyesters, vinyl acetate derivatives or silicones. Polymeric matrices provide retardation of drug release--for some implants up to a few years. In addition, this paper presents examples of all commercially available medicinal products containing microspheres and implants, currently registered in Poland, together with their characteristics: composition, time course and frequency of administration. Comments are also enclosed on frequently occurring inconsistent terminology in pharmaceutical forms.

pH-controlled drug release for dental applications

NASA Astrophysics Data System (ADS)

Wironen, John Francis

A large proportion of the dental fillings replaced at present are revised because of the perceived presence of a recurrent caries under or adjacent to the restoration. Many of these perceived caries may not exist, while others may go undetected. This work describes the preparation of drug loaded polymer microspheres that sense the presence of the bacteria that cause caries by the associated presence of acid by-products of digestion. These microspheres are designed to swell and release their antimicrobial drugs once the pH drops to a level that would normally cause caries. The preparation of the microspheres as well as their loading with potassium fluoride, chlorhexidine digluconate, chlorhexidine dihydrochloride, chlorhexidine diacetate, and tetracycline hydrochloride are described. A detailed study of the controlled release behavior of fluoride as a function of polymer composition and pH is presented first. A study of the release kinetics of potassium fluoride, chlorhexidine digluconate, diacetate, dihydrochloride, and tetracycline hydrochloride as a function of pH in the same polymer system is then presented. Additional studies of the swelling kinetics of chlorhexidine-loaded microspheres in various pH buffers are discussed with special reference to correlations with the controlled-release data. Finally, an experiment in which the microspheres are tested in an in vitro bacteria model that includes Streptococcus mutans is presented and discussed in detail.

Biocompatible magnetic and molecular dual-targeting polyelectrolyte hybrid hollow microspheres for controlled drug release.

PubMed

Du, Pengcheng; Zeng, Jin; Mu, Bin; Liu, Peng

2013-05-06

Well-defined biocompatible magnetic and molecular dual-targeting polyelectrolyte hybrid hollow microspheres have been accomplished via the layer-by-layer (LbL) self-assembly technique. The hybrid shell was fabricated by the electrostatic interaction between the polyelectrolyte cation, chitosan (CS), and the hybrid anion, citrate modified ferroferric oxide nanoparticles (Fe3O4-CA), onto the uniform polystyrene sulfonate microsphere templates. Then the magnetic hybrid core/shell composite particles were modified with a linear, functional poly(ethylene glycol) (PEG) monoterminated with a biotargeting molecule (folic acid (FA)). Afterward the dual targeting hybrid hollow microspheres were obtained after etching the templates by dialysis. The dual targeting hybrid hollow microspheres exhibit exciting pH response and stability in high salt-concentration media. Their pH-dependent controlled release of the drug molecule (anticancer drug, doxorubicin (DOX)) was also investigated in different human body fluids. As expected, the cell viability of the HepG2 cells which decreased more rapidly was treated by the FA modified hybrid hollow microspheres rather than the unmodified one in the in vitro study. The dual-targeting hybrid hollow microspheres demonstrate selective killing of the tumor cells. The precise magnetic and molecular targeting properties and pH-dependent controlled release offers promise for cancer treatment.

Controlled release microspheres loaded with BMP7 suppress primary tumors from human glioblastoma

PubMed Central

González-Gómez, P.; de la Fuente, M.; Hernández-Laín, Aurelio; Mira, H.; Sánchez-Gómez, P.; Garcia-Fuentes, M.

2015-01-01

Glioblastoma tumor initiating cells are believed to be the main drivers behind tumor recurrence, and therefore therapies that specifically manage this population are of great medical interest. In a previous work, we synthesized controlled release microspheres optimized for intracranial delivery of BMP7, and showed that these devices are able to stop the in vitro growth of a glioma cell line. Towards the translational development of this technology, we now explore these microspheres in further detail and characterize the mechanism of action and the in vivo therapeutic potential using tumor models relevant for the clinical setting: human primary glioblastoma cell lines. Our results show that BMP7 can stop the proliferation and block the self-renewal capacity of those primary cell lines that express the receptor BMPR1B. BMP7 was encapsulated in poly (lactic-co-glycolic acid) microspheres in the form of a complex with heparin and Tetronic, and the formulation provided effective release for several weeks, a process controlled by carrier degradation. Data from xenografts confirmed reduced and delayed tumor formation for animals treated with BMP7-loaded microspheres. This effect was coincident with the activation of the canonical BMP signaling pathway. Importantly, tumors treated with BMP7-loaded microspheres also showed downregulation of several markers that may be related to a malignant stem cell-like phenotype: CD133+, Olig2, and GFAPδ. We also observed that tumors treated with BMP7-loaded microspheres showed enhanced expression of cell cycle inhibitors and reduced expression of the proliferation marker PCNA. In summary, BMP7-loaded controlled release microspheres are able to inhibit GBM growth and reduce malignancy markers. We envisage that this kind of selective therapy for tumor initiating cells could have a synergistic effect in combination with conventional cytoreductive therapy (chemo-, radiotherapy) or with immunotherapy. PMID:25860932

Microencapsulated Dopamine (DA)-Induced Restitution of Function in 6-OHDA-Denervated Rat Striatum in vivo: Comparison Between Two Microsphere Excipients

PubMed Central

McRae, Amanda; Hjorth, Stephan; Mason, David W.; Dillon, Lynn; Tice, Thomas R.

1991-01-01

Biodegradable controlled-release microsphere systems made with the biocompatible biodegradable polyester excipient poly [DL lactide-co-glycolide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microspheres encapsulated within two different polymer excipients into denervated- striatal tissue assures a prolonged release of the transmitter in vivo. Moreover, in this regard, the results show that there were clear cut temporal differences in the effect of the two DA microsphere formulations compared in this study, probably reflecting variations in the actual composition (i.e., lactide to glycolide ratio) of the two copolymer excipients examined. This technology has considerable potential for basic research with possible clinical application. PMID:1782252

Collagen-cellulose nanocrystal scaffolds containing curcumin-loaded microspheres on infected full-thickness burns repair.

PubMed

Guo, Rui; Lan, Yong; Xue, Wei; Cheng, Biao; Zhang, Yuanming; Wang, Changyong; Ramakrishna, Seeram

2017-12-01

Burn infection is a serious problem that delays wound healing and leads to death. Curcumin (Cur) has been shown to exhibit antioxidant, anti-inflammatory, antimicrobial and anticarcinogenic activity. However, its instability, extremely low aqueous solubility and bioavailability in physiological fluids may make it difficult to maintain local Cur concentrations above the minimum inhibitory concentration for burn infection treatment. The objective of this study was to construct complexes of Cur/gelatin microspheres (GMs) and porous collagen (Coll)-cellulose nanocrystals (CNCs) composite scaffolds for full-thickness burn infection treatment. The Cur/GMs/Coll-CNCs scaffolds had high porosity, available pore size, and a long and sustained Cur release profile. Furthermore, the composite scaffold exhibited remarkably strong antibacterial activity. Hence, we evaluated the wound-healing effects and antibacterial properties of Cur/GMs/Coll-CNCs scaffolds in a rat full-thickness burn infection model. The Cur/GMs/Coll-CNCs scaffold was able to prevent not only local inflammation but also accelerated dermis regeneration. Thus, we conclude that Cur/GMs/Coll-CNCs scaffolds can act as an effective dermal regeneration template for full-thickness burn wound infection healing in rats models. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

An experimental design approach to the preparation of pegylated polylactide-co-glicolide gentamicin loaded microparticles for local antibiotic delivery.

PubMed

Dorati, Rossella; DeTrizio, Antonella; Genta, Ida; Grisoli, Pietro; Merelli, Alessia; Tomasi, Corrado; Conti, Bice

2016-01-01

The present paper takes into account the DOE application to the preparation process of biodegradable microspheres for osteomyelitis local therapy. With this goal gentamicin loaded polylactide-co-glycolide-copolyethyleneglycol (PLGA-PEG) microspheres were prepared and investigated. Two preparation protocols (o/w and w/o/w) with different process conditions, and three PLGA-PEG block copolymers with different compositions of lactic and glycolic acids and PEG, were tested. A Design Of Experiment (DOE) screening design was applied as an approach to scale up manufacturing step. The results of DOE screening design confirmed that w/o/w technique, the presence of salt and the 15%w/v polymer concentration positively affected the EE% (72.1-97.5%), and span values of particle size distribution (1.03-1.23), while salt addition alone negatively affected the yield process. Process scale up resulted in a decrease of gentamicin EE% that can be attributed to the high volume of water used to remove PVA and NaCl residues. The results of in vitro gentamicin release study show prolonged gentamicin release up to three months from the microspheres prepared with salt addition in the dispersing phase; the behavior being consistent with their highly compact structure highlighted by scanning electron microscopy analysis. The prolonged release of gentamicin is maintained even after embedding the biodegradable microspheres into a thermosetting composite gel made of chitosan and acellular bovine bone matrix (Orthoss® granules), and the microbiologic evaluation demonstrated the efficacy of the gentamicin loaded microspheres on Escherichia coli. The collected results confirm the feasibility of the scale up of microsphere manufacturing process and the high potential of the microparticulate drug delivery system to be used for the local antibiotic delivery to bone.

Effect of mean diameter and polydispersity of PLG microspheres on drug release: experiment and theory.

PubMed

Berchane, N S; Carson, K H; Rice-Ficht, A C; Andrews, M J

2007-06-07

The need to tailor release rate profiles from polymeric microspheres is a significant problem. Microsphere size, which has a significant effect on drug release rate, can potentially be varied to design a controlled drug delivery system with desired release profile. In this work the effects of microspheres mean diameter, polydispersity, and polymer degradation on drug release rate from poly(lactide-co-glycolide) (PLG) microspheres are described. Piroxicam containing PLG microspheres were fabricated at 20% loading, and at three different impeller speeds. A portion of the microspheres was then sieved giving five different size distributions. In vitro release kinetics were determined for each preparation. Based on these experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the microsphere size was increased. The mathematical model gave a good fit to the experimental release data. For highly polydisperse populations (polydispersity parameter b<3), incorporating the microsphere size distribution into the mathematical model gave a better fit to the experimental results than using the representative mean diameter. The validated mathematical model can be used to predict small-molecule drug release from PLG microsphere populations.

Preparation and release characteristics of polymer-coated and blended alginate microspheres.

PubMed

Lee, D W; Hwang, S J; Park, J B; Park, H J

2003-01-01

To prevent a rapid drug release from alginate microspheres in simulated intestinal media, alginate microspheres were coated or blended with polymers. Three polymers were selected and evaluated such as HPMC, Eudragit RS 30D and chitosan, as both coating materials and additive polymers for controlling the drug release. This study focused on the release characteristics of polymer-coated and blended alginate microspheres, varying the type of polymer and its concentration. The alginate microspheres were prepared by dropping the mixture of drug and sodium alginate into CaCl(2) solution using a spray-gun. Polymer-coated microspheres were prepared by adding alginate microspheres into polymer solution with mild stirring. Polymer-blended microspheres were prepared by dropping the mixture of drug, sodium alginate and additive polymer with plasticizer into CaCl(2) solution. In vitro release test was carried out to investigate the release profiles in 500 ml of phosphate buffered saline (PBS, pH 7.4). As the amount of polymer in sodium alginate or coating solution increase, the drug release generally decreased. HPMC-blended microspheres swelled but withstood the disintegration, showing an ideal linear release profiles. Chitosan-coated microspheres showed smooth and round surface and extended the release of drug. In comparison with chitosan-coated microspheres, HPMC-blended alginate microspheres can be easily made and used for controlled drug delivery systems due to convenient process and controlled drug release.

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.

Self-templated Synthesis of Nickel Silicate Hydroxide/Reduced Graphene Oxide Composite Hollow Microspheres as Highly Stable Supercapacitor Electrode Material

NASA Astrophysics Data System (ADS)

Zhang, Yanhua; Zhou, Wenjie; Yu, Hong; Feng, Tong; Pu, Yong; Liu, Hongdong; Xiao, Wei; Tian, Liangliang

2017-05-01

Nickel silicate hydroxide/reduced graphene oxide (Ni3Si2O5(OH)4/RGO) composite hollow microspheres were one-pot hydrothermally synthesized by employing graphene oxide (GO)-wrapped SiO2 microspheres as the template and silicon source, which were prepared through sonication-assisted interfacial self-assembly of tiny GO sheets on positively charged SiO2 substrate microspheres. The composition, morphology, structure, and phase of Ni3Si2O5(OH)4/RGO microspheres as well as their electrochemical properties were carefully studied. It was found that Ni3Si2O5(OH)4/RGO microspheres featured distinct hierarchical porous morphology with hollow architecture and a large specific surface area as high as 67.6 m2 g-1. When utilized as a supercapacitor electrode material, Ni3Si2O5(OH)4/RGO hollow microspheres released a maximum specific capacitance of 178.9 F g-1 at the current density of 1 A g-1, which was much higher than that of the contrastive bare Ni3Si2O5(OH)4 hollow microspheres and bare RGO material developed in this work, displaying enhanced supercapacitive behavior. Impressively, the Ni3Si2O5(OH)4/RGO microsphere electrode exhibited outstanding rate capability and long-term cycling stability and durability with 97.6% retention of the initial capacitance after continuous charging/discharging for up to 5000 cycles at the current density of 6 A g-1, which is superior or comparable to that of most of other reported nickel-based electrode materials, hence showing promising application potential in the energy storage area.

Self-templated Synthesis of Nickel Silicate Hydroxide/Reduced Graphene Oxide Composite Hollow Microspheres as Highly Stable Supercapacitor Electrode Material.

PubMed

Zhang, Yanhua; Zhou, Wenjie; Yu, Hong; Feng, Tong; Pu, Yong; Liu, Hongdong; Xiao, Wei; Tian, Liangliang

2017-12-01

Nickel silicate hydroxide/reduced graphene oxide (Ni 3 Si 2 O 5 (OH) 4 /RGO) composite hollow microspheres were one-pot hydrothermally synthesized by employing graphene oxide (GO)-wrapped SiO 2 microspheres as the template and silicon source, which were prepared through sonication-assisted interfacial self-assembly of tiny GO sheets on positively charged SiO 2 substrate microspheres. The composition, morphology, structure, and phase of Ni 3 Si 2 O 5 (OH) 4 /RGO microspheres as well as their electrochemical properties were carefully studied. It was found that Ni 3 Si 2 O 5 (OH) 4 /RGO microspheres featured distinct hierarchical porous morphology with hollow architecture and a large specific surface area as high as 67.6 m 2  g -1 . When utilized as a supercapacitor electrode material, Ni 3 Si 2 O 5 (OH) 4 /RGO hollow microspheres released a maximum specific capacitance of 178.9 F g -1 at the current density of 1 A g -1 , which was much higher than that of the contrastive bare Ni 3 Si 2 O 5 (OH) 4 hollow microspheres and bare RGO material developed in this work, displaying enhanced supercapacitive behavior. Impressively, the Ni 3 Si 2 O 5 (OH) 4 /RGO microsphere electrode exhibited outstanding rate capability and long-term cycling stability and durability with 97.6% retention of the initial capacitance after continuous charging/discharging for up to 5000 cycles at the current density of 6 A g -1 , which is superior or comparable to that of most of other reported nickel-based electrode materials, hence showing promising application potential in the energy storage area.

Composite microparticles of halloysite clay nanotubes bound by calcium carbonate.

PubMed

Jin, Yi; Yendluri, Raghuvara; Chen, Bin; Wang, Jingbo; Lvov, Yuri

2016-03-15

Natural halloysite clay nanotubes with 15 nm inner and 75 nm outer diameters have been used as vehicles for sustained release of drugs in composite hollow microparticles "glued" with CaCO3. We used a layer-by layer assembly accomplished alginate binding with Ca(2+) followed by CO2 bubbling to prepare the composite microspheres of CaCO3 and polyelectrolytes (PE) modified halloysite nanotubes (HNTs-PE2/CaCO3) with the diameter of about 5-10 μm. These microparticles have empty spherical structure and abundant pore distributions with maxima at 2.5, 3.9, 6.0 and 13.3 nm, and higher surface area of 82.3 m(2) g(-1) as characterized by SEM and BET test. We loaded drugs in these micro-nano carriers of tight piles of halloysite nanotube with end clogged with CaCO3. The sustained release of Nifedipine drug from HNTs-PE2/CaCO3 composite microspheres was slower than for pristine halloysite nanotubes. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of medium-chain triglycerides on the release behavior of Endostar encapsulated PLGA microspheres.

PubMed

Meng, Boyu; Li, Ling; Hua, Su; Wang, Qingsong; Liu, Chunhui; Xu, Xiangyang; Yin, Xiaojin

2010-09-15

The incomplete release of Endostar from PLGA microspheres was observed in our previous study. In the present study, we focused on the effect of medium-chain triglycerides (MCT) on the in vitro/in vivo release behavior of Endostar encapsulated PLGA microspheres, which were prepared by a water-in-oil-in-water (W/O/W) double-emulsion method with or without MCT. The in vitro accumulated release of Endostar from microspheres co-encapsulated with 30% MCT was found to be 79.04% after a 30-day incubation period in PBS (pH 7.4) at 37 degrees C. However, the accumulated release of Endostar from MCT-free microspheres was found to be only 32.22%. Pouches containing Endostar encapsulated PLGA microspheres were implanted subcutaneously in rats. The effect of MCT on the in vivo release showed a similar trend to the in vitro release. After 30 days, only 9.87% of the total encapsulated Endostar was retained in microspheres co-encapsulated with 30% MCT, while 42.25% of Endostar was retained in MCT-free microspheres. The co-encapsulation of MCT provided the microspheres with a porous surface, which significantly improved the in vitro/in vivo release of Endostar from PLGA microspheres. In addition, in vitro experiments showed that MCT co-encapsulated PLGA microspheres had more inter-connected pores, faster degradation of PLGA, and faster swelling of microspheres, which helped to explain the mechanism of the effect of MCT on improving the release of Endostar from PLGA microspheres. Copyright 2010 Elsevier B.V. All rights reserved.

In situ forming biodegradable poly(ε-caprolactone) microsphere systems: a challenge for transarterial embolization therapy. In vitro and preliminary ex vivo studies.

PubMed

Salis, Andrea; Porcu, Elena P; Gavini, Elisabetta; Fois, Giulia R; Icaro Cornaglia, Antonia; Rassu, Giovanna; Diana, Marco; Maestri, Marcello; Giunchedi, Paolo; Nikolakakis, Ioannis

2017-04-01

In situ forming biodegradable poly(ε-caprolactone) (PCL) microspheres (PCL-ISM) system was developed as a novel embolic agent for transarterial embolization (TAE) therapy of hepatocellular carcinoma (HCC). Ibuprofen sodium (Ibu-Na) was loaded on this platform to evaluate its potential for the treatment of post embolization syndrome. The influence of formulation parameters on the size/shape, encapsulation efficiency and drug release was investigated using mixture experimental design. Regression models were derived and used to optimize the formulation for particle size, encapsulation efficiency and drug release profile for TAE therapy. An ex vivo model using isolated rat livers was established to assess the in situ formation of microspheres. All PCL-ISM components affected the studied properties and fitting indices of the regression models were high (Radj 2  = 0.810 for size, 0.964 encapsulation efficiency, and 0.993 or 0.971 for drug release at 30 min or 48 h). The optimized composition was: PCL = 4%, NMP = 43.1%, oil = 48.9%, surfactant = 2% and drug = 2%. Ex vivo studies revealed that PCL-ISM was able to form microspheres in the hepatic arterial bed. PCL-ISM system provides a novel tool for the treatment of HCC and post-embolization syndrome. It is capable of forming microspheres with desirable size and Ibu-Na release profile after injection into blood vessels.

Microfluidic assembly of a nano-in-micro dual drug delivery platform composed of halloysite nanotubes and a pH-responsive polymer for colon cancer therapy.

PubMed

Li, Wei; Liu, Dongfei; Zhang, Hongbo; Correia, Alexandra; Mäkilä, Ermei; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

2017-01-15

Harsh conditions of the gastrointestinal tract hinder the oral delivery of many drugs. Developing oral drug delivery systems based on commercially available materials is becoming more challenging due to the demand for simultaneously delivering physicochemically different drugs for treating complex diseases. A novel architecture, namely nanotube-in-microsphere, was developed as a drug delivery platform by encapsulating halloysite nanotubes (HNTs) in a pH-responsive hydroxypropyl methylcellulose acetate succinate polymer using microfluidics. HNTs were selected as orally acceptable clay mineral and their lumen was enlarged by selective acid etching. Model drugs (atorvastatin and celecoxib) with different physicochemical properties and synergistic effect on colon cancer prevention and inhibition were simultaneously incorporated into the microspheres at a precise ratio, with atorvastatin and celecoxib being loaded in the HNTs and polymer matrix, respectively. The microspheres showed spherical shape, narrow particle size distribution and pH-responsive dissolution behavior. This nanotube/pH-responsive polymer composite protected the loaded drugs from premature release at pH⩽6.5, but allowed their fast release and enhanced the drug permeability, and the inhibition of colon cancer cell proliferation at pH 7.4. Overall, the nano-in-micro drug delivery composite fabricated by microfluidics is a promising and flexible platform for the delivery of multiple drugs for combination therapy. Halloysite nanotubes (HNTs) are attracting increasing attention for drug delivery applications. However, conventional HNTs-based oral drug delivery systems are lack of the capability to precisely control the drug release at a desired site in the gastrointestinal tract. In this study, a nanotube-in-microsphere drug delivery platform is developed by encapsulating HNTs in a pH-responsive polymer using microfluidics. Drugs with different physicochemical properties and synergistic effect on colon cancer therapy were simultaneously incorporated in the microspheres. The prepared microspheres prevented the premature release of the loaded drugs after exposure to the harsh conditions of the gastrointestinal tract, but allowed their simultaneously fast release, and enhanced the drug permeability and the inhibition of colon cancer cell proliferation in response to the colon pH. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

An Accelerated Release Method of Risperidone Loaded PLGA Microspheres with Good IVIVC.

PubMed

Hu, Xiaoqin; Zhang, Jianwei; Tang, Xuemei; Li, Mingyuan; Ma, Siyu; Liu, Cheng; Gao, Yue; Zhang, Yue; Liu, Yan; Yu, Fanglin; Yang, Yang; Guo, Jia; Li, Zhiping; Mei, Xingguo

2018-01-01

A long release period lasting several days or several weeks is always needed and thereby it is tedious and time consuming to screen formulations of such microspheres with so long release period and evaluate their release profiles in vitro with conventional long-term or "real-time" release method. So, an accelerated release testing of such system is necessary for formulation design as well as quality control purpose. The purpose of this study is to obtain an accelerated release method of risperidone loaded poly(lactic-co-glycolic acid) (PLGA) microspheres with good in vitro/in vivo correlation (IVIVC). Two formulations of risperidone loaded PLGA microspheres used for evaluating IVIVC were prepared by O/W method. The accelerated release condition was optimized by investigating the effect of pH, osmotic pressure, temperature and ethanol concentration on the release of risperidone from microspheres and the in vitro accelerated release profiles of risperidone from PLGA microspheres were obtained under this optimized accelerated release condition. The plasma concentration of risperidone were also detected after subcutaneous injection of risperidone loaded microspheres to rats. The in vivo cumulative absorption profiles were then calculated using Wagner-Nelson model, Loo- Riegelman model and numerical convolution model, respectively. The correlation between in vitro accelerated release and in vivo cumulative absorption were finally evaluated with Least Square Method. It was shown that temperature and ethanol concentration significantly affected the release of risperidone from the microspheres while pH and osmotic pressure of release media slightly affected the release behavior of risperidone. The in vitro release of risperidone from microspheres were finally undergone in PBS (pH7.0, 300mosm) with 20% (V/V) ethanol at 45°C. The sustained and complete release of risperidone was observed in both formulations under the accelerated release condition although these two release profiles were dissimilar. The correlation coefficients (R2) of IVIVC were all above 0.95 and the slopes were all between 0.9564 and 1.1868 in spite of fitted model and microsphere formulation. An in vitro accelerated release method of risperidone microspheres with good IVIVC was established in this paper and this accelerated release method was supposed to have great potential in both in vivo performance prediction and quality control for risperidone loaded PLGA microspheres. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Eudragit-coated dextran microspheres of 5-fluorouracil for site-specific delivery to colon.

PubMed

Rai, Gopal; Yadav, Awesh K; Jain, Narendra K; Agrawal, Govind P

2016-01-01

Objective of the present investigation was to prepare and evaluate the potential of enteric coated dextran microspheres for colon targeting of 5-fluorouracil (5-FU). Dextran microspheres were prepared by emulsification-crosslinking method and the formulation variables studied included different molecular weights of dextran, drug:polymer ratio, volume of crosslinking agent, stirring speed and time. Enteric coating (Eudragit S-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method using different coat:core ratios (4:1 or 8:1). Uncoated and coated dextran microspheres were characterized by particle size, surface morphology, entrapment efficiency, DSC, in vitro drug release in the presence of dextranase and 2% rat cecal contents. The release study of 5-FU from coated dextran microspheres was pH dependent. No release was observed at acidic pH; however, the drug was released quickly where Eudragit starts solublizing there was continuous release of drug from the microspheres. Organ distribution study was suggested that coated dextran microspheres retard the release of drug in gastric and intestinal pH environment and released of drug from microspheres in colon due to the degradation of dextran by colonic enzymes.

Preparation and evaluation of sustained release loxoprofen loaded microspheres.

PubMed

Venkatesan, P; Manavalan, R; Valliappan, K

2011-06-01

The aim of present study was to formulate and evaluate the loxoprofen loaded Sustained release microspheres by emulsion solvent evaporation technique. Ethylcellulose, a biocompatible polymer is used as the retardant material. The effects of process conditions such as drug loading, polymer type and solvent type on the characteristics of microspheres were investigated. The prepared microspheres were characterized for their particle size and drug loading and drug release. The in-vitro release studies were carried out in phosphate buffer at pH 7.4. The prepared microspheres were white, free flowing and spherical in shape. The drug-loaded microspheres showed 71.2% of entrapment and the in-vitro release studies showed that Loxoprofen microspheres of 1:3 ratios showed better sustained effect over a period of 8 hours.

Preparation and evaluation of sustained release loxoprofen loaded microspheres

PubMed Central

Venkatesan, P.; Manavalan, R.; Valliappan, K.

2011-01-01

The aim of present study was to formulate and evaluate the loxoprofen loaded Sustained release microspheres by emulsion solvent evaporation technique. Ethylcellulose, a biocompatible polymer is used as the retardant material. The effects of process conditions such as drug loading, polymer type and solvent type on the characteristics of microspheres were investigated. The prepared microspheres were characterized for their particle size and drug loading and drug release. The in-vitro release studies were carried out in phosphate buffer at pH 7.4. The prepared microspheres were white, free flowing and spherical in shape. The drug-loaded microspheres showed 71.2% of entrapment and the in-vitro release studies showed that Loxoprofen microspheres of 1:3 ratios showed better sustained effect over a period of 8 hours PMID:24826017

Polymer-coated albumin microspheres as carriers for intravascular tumour targeting of cisplatin.

PubMed

Verrijk, R; Smolders, I J; McVie, J G; Begg, A C

1991-01-01

We used a poly-lactide-co-glycolide polymer (PLAGA 50:50) to formulate cisplatin (cDDP) into microspheres designed for intravascular administration. Two systems were developed. PLAGA-coated albumin microspheres and microspheres consisting of PLAGA only. PLAGA-coated microspheres displayed a mean diameter of 31.8 +/- 0.9 microns and a payload of 7.5% cDDP (w/w). Solid PLAGA microspheres exhibited a mean diameter of 19.4 +/- 0.6 microns and a payload of 20% cDDP. Release characteristics and in vitro effects on L1210 leukemia and B16 melanoma cell lines were investigated. Both types of microsphere overcame the initial rapid release of cDDP (burst effect), and PLAGA-coated albumin microspheres also showed a lag phase of approximately 30 min before cDDP release began. PLAGA-coated albumin microspheres released most of their payload through diffusion, and the coating eventually cracked after 7 days' incubation in saline supplemented with 0.1% Tween at 37 degrees C, enabling the release of any cDDP remaining. Effects of platinum, pre-released from PLAGA-coated albumin microspheres on the in vitro growth of L1210 cells were comparable with those of standard formulations (dissolved) of cDDP. Material released from non-drug-loaded PLAGA microspheres had no effect on L1210 cell growth, suggesting the absence of cytotoxic compounds in the matrix. The colony-forming ability of B16 cells was also equally inhibited by standard cDDP and pre-released drug. These studies show that formulation of cDDP in PLAGA-based microspheres prevents the rapid burst effect of cDDP seen in previous preparations and offers an improved system of administration for hepatic artery infusion or adjuvant therapy, enabling better clinical handling and the promise of a higher ratio of tumour tissue to normal tissue.

Comparative assessment of in vitro release kinetics of calcitonin polypeptide from biodegradable microspheres.

PubMed

Prabhu, Sunil; Sullivan, Jennifer L; Betageri, Guru V

2002-01-01

The objective of our study was to compare the in vitro release kinetics of a sustained-release injectable microsphere formulation of the polypeptide drug, calcitonin (CT), to optimize the characteristics of drug release from poly-(lactide-co-glycolide) (PLGA) copolymer biodegradable microspheres. A modified solvent evaporation and double emulsion technique was used to prepare the microspheres. Release kinetic studies were carried out in silanized tubes and dialysis bags, whereby microspheres were suspended and incubated in phosphate buffered saline, sampled at fixed intervals, and analyzed for drug content using a modified Lowry protein assay procedure. An initial burst was observed whereby about 50% of the total dose of the drug was released from the microspheres within 24 hr and 75% within 3 days. This was followed by a period of slow release over a period of 3 weeks in which another 10-15% of drug was released. Drug release from the dialysis bags was more gradual, and 50% CT was released only after 4 days and 75% after 12 days of release. Scanning electron micrographs revealed spherical particles with channel-like structures and a porous surface after being suspended in an aqueous solution for 5 days. Differential scanning calorimetric studies revealed that CT was present as a mix of amorphous and crystalline forms within the microspheres. Overall, these studies demonstrated that sustained release of CT from PLGA microspheres over a 3-week period is feasible and that release of drug from dialysis bags was more predictable than from tubes.

Double walled POE/PLGA microspheres: encapsulation of water-soluble and water-insoluble proteins and their release properties.

PubMed

Shi, Meng; Yang, Yi-Yan; Chaw, Cheng-Shu; Goh, Suat-Hong; Moochhala, Shabbir M; Ng, Steve; Heller, Jorge

2003-04-29

The poly(orthoester) (POE)-poly(D,L-lactide-co-glycolide) (50:50) (PLGA) double-walled microspheres with 50% POE in weight were loaded with hydrophilic bovine serum albumin (BSA) and hydrophobic cyclosporin A (CyA). Most of the BSA and CyA was entrapped within the shell and core, respectively, because of the difference in their hydrophilicity. The morphologies and release mechanisms of proteins-loaded double-walled POE/PLGA microspheres were investigated. Scanning electron microscope studies revealed that the CyA-BSA-loaded double-walled POE/PLGA microspheres yielded a more porous surface and PLGA shell than those without BSA. The neat POE and PLGA yielded slow and incomplete CyA and BSA release. In contrast, nearly complete BSA and more than 95% CyA were released in a sustained manner from the double-walled POE/PLGA microspheres. Both the BSA- and CyA-BSA-loaded POE/PLGA microspheres yielded a sustained BSA release over 5 days. The CyA release pattern of the CyA-loaded double-walled POE/PLGA microspheres was biphasic, characterized by a slow release over 15 days followed by a sustained release over 27 days. However, the CyA-BSA-loaded double-walled POE/PLGA microspheres provided a more constant and faster CyA release due to their more porous shell. In the CyA-BSA-loaded double-walled POE/PLGA microspheres system, the PLGA layer acted as a carrier for BSA and mild reservoir for CyA. During the first 5 days, most BSA was released from the shell but only 14% CyA was left from the microspheres. Subsequently, more than 80% CyA were released in the next 25 days. The distinct structure of double-walled POE/PLGA microspheres would make an interesting device for controlled delivery of therapeutic agents.

Controlled release of anticancer drug methotrexate from biodegradable gelatin microspheres.

PubMed

Narayani, R; Rao, K P

1994-01-01

Biodegradable hydrophilic gelatin microspheres containing the anticancer drug methotrexate (MTX) of different mean particle sizes (1-5, 5-10, and 15-20 microns) were prepared by polymer dispersion technique and crosslinked with glutaraldehyde. The microspheres were uniform, smooth, solid and in the form of free-flowing powder. About 80 per cent of MTX was incorporated in gelatin microspheres of different sizes. The in vitro release of MTX was investigated in two different media, namely simulated gastric and intestinal fluids. The release profiles indicated that gelatin microspheres released MTX in a zero-order fashion for 4-6 days in simulated gastric fluid and for 5-8 days in simulated intestinal fluid. The rate of release of MTX decreased with increase in the particle size of the microspheres. MTX release was faster in gastric fluid when compared to intestinal fluid.

Enhanced gastric retention and drug release via development of novel floating microspheres based on Eudragit E100 and polycaprolactone: synthesis and in vitro evaluation

PubMed Central

Farooq, Umar; Khan, Samiullah; Nawaz, Shahid; Ranjha, Nazar Mohammad; Haider, Malik Salman; Khan, Muhammad Muzamil; Dar, Eshwa; Nawaz, Ahmad

2017-01-01

Abstract Eudragit E 100 and polycaprolactone (PCL) floating microspheres for enhanced gastric retention and drug release were successfully prepared by oil in water solvent evaporation method. Metronidazole benzoate, an anti-protozoal drug, was used as a model drug. Polyvinyl alcohol was used as an emulsifier. The prepared microspheres were observed for % recovery, % degree of hydration, % water uptake, % drug loading, % buoyancy and % drug release. The physico-chemical properties of the microspheres were studied by calculating encapsulation efficiency of microspheres and drug release kinetics. Drug release characteristics of microspheres were studied in simulated gastric fluid and simulated intestinal fluid i.e., at pH 1.2 and 7.4 respectively. Fourier transform infrared spectroscopy was used to reveal the chemical interaction between drug and polymers. Scanning electron microscopy was conducted to study the morphology of the synthesized microspheres. PMID:29491813

Controlling Release Kinetics of PLG Microspheres Using a Manufacturing Technique

NASA Astrophysics Data System (ADS)

Berchane, Nader

2005-11-01

Controlled drug delivery offers numerous advantages compared with conventional free dosage forms, in particular: improved efficacy and patient compliance. Emulsification is a widely used technique to entrap drugs in biodegradable microspheres for controlled drug delivery. The size of the formed microspheres has a significant influence on drug release kinetics. Despite the advantages of controlled drug delivery, previous attempts to achieve predetermined release rates have seen limited success. This study develops a tool to tailor desired release kinetics by combining microsphere batches of specified mean diameter and size distribution. A fluid mechanics based correlation that predicts the average size of Poly(Lactide-co-Glycolide) [PLG] microspheres from the manufacturing technique, is constructed and validated by comparison with experimental results. The microspheres produced are accurately represented by the Rosin-Rammler mathematical distribution function. A mathematical model is formulated that incorporates the microsphere distribution function to predict the release kinetics from mono-dispersed and poly-dispersed populations. Through this mathematical model, different release kinetics can be achieved by combining different sized populations in different ratios. The resulting design tool should prove useful for the pharmaceutical industry to achieve designer release kinetics.

Synthesis and characterisation of multifunctional alginate microspheres via the in situ formation of ZnO quantum dots and the graft of 4-(1-pyrenyl) butyric acid to sodium alginate.

PubMed

Luo, Guilin; Wang, Jianxin; Wang, Yingying; Feng, Bo; Weng, Jie

2015-01-01

Growth factor-loaded fluorescent alginate microspheres, which can realise sustained growth factor release and fluorescence imaging, were synthesised by in situ formation of ZnO quantum dots (QDs) and covalent graft of 4-(1-pyrenyl) butyric acid (PBA). BSA was chosen as a growth factor model protein to study the release kinetic of growth factors from alginate microspheres. The microsphere size and fluorescent properties were also investigated. Investigations of cell culture were used for evaluating biocompatibility of BSA-loaded fluorescent microspheres and fluorescence imaging property of ZnO QDs and PBA-grafted sodium alginate from the microspheres. The results show that they have good fluorescent property either to microspheres or to cells and fluorescent microspheres have good biocompatibility and property in sustained release of growth factors. The obtained microspheres will be expected to realise the imaging of cells and materials and also the release of growth factor in tissue engineering or in cell culture.

Preparation and characterisation of alendronate-loaded chitosan microparticles obtained through the spray drying technique.

PubMed

Ochiuz, Lacramioara; Peris, José-Esteban

2009-03-01

Microparticles of chitosan (CHT) containing alendronate sodium (AL) were prepared in four drug:polymer ratios (1:1, 1:2, 1:4, 1:6) using the spray drying technique. The efficiency of the method was evaluated by determining production yield (about 70 %) and microencapsulation efficiency, which was almost 100 % in the case of all four of the formulations studied. Particles had a mean size of between 3.6 and 4.6 microm, and a near-spherical shape. The formulations with the highest content of AL (drug:polymer ratio 1:1 and 1:2) showed an asymmetrical distribution of particles, which were larger in size, and had a higher proportion of irregular particles than the other formulations. FT-IR analysis revealed an ionic interaction between AL and CHT. Differential scanning calorimetry and thermogravimetric analysis confirmed the microencapsulation of AL and the increased thermal stability of encapsulated AL. The dissolution profiles of AL from CHT microspheres, at pH values of 1.2 and 6.8, showed a delayed release of AL from microspheres, and the dissolution rate was dependent on the pH and the drug:polymer ratio. It can be concluded that spray drying is a suitable technique for preparing AL-loaded CHT microspheres, and that the drug:polymer ratio can be used to control the rate of AL release from microspheres.

Enteric-coated epichlorohydrin crosslinked dextran microspheres for site-specific delivery to colon.

PubMed

Rai, Gopal; Yadav, Awesh K; Jain, Narendra K; Agrawal, Govind P

2015-01-01

Enteric-coated epichlorohydrin crosslinked dextran microspheres containing 5-Fluorouracil (5-FU) for colon drug delivery was prepared by emulsification-crosslinking method. The formulation variables studied includes different molecular weights of dextran, volume of crosslinking agent, stirring speed, time and temperature. Dextran microspheres showed mean entrapment efficiencies ranging between 77 and 87% and mean particle size ranging between 10 and 25 µm. About 90% of drug was released from uncoated dextran microspheres within 8 h, suggesting the fast release and indicated the drug loaded in uncoated microspheres, released before they reached colon. Enteric coating (Eudragit-S-100 and Eudragit-L-100) of dextran microspheres was performed by oil-in-oil solvent evaporation method. The release study of 5-FU from coated dextran microspheres was complete retardation in simulated gastric fluid (pH 1.2) and once the coating layer of enteric polymer was dissolved at higher pH (7.4 and 6.8), a controlled release of the drug from the microspheres was observed. Further, the release of drug was found to be higher in the presence of dextranase and rat caecal contents, indicating the susceptibility of dextran microspheres to colonic enzymes. Organ distribution and pharmacokinetic study in albino rats was performed to establish the targeting potential of optimized formulation in the colon.

Setting accelerated dissolution test for PLGA microspheres containing peptide, investigation of critical parameters affecting drug release rate and mechanism.

PubMed

Tomic, I; Vidis-Millward, A; Mueller-Zsigmondy, M; Cardot, J-M

2016-05-30

The objective of this study was development of accelerated in vitro release method for peptide loaded PLGA microspheres using flow-through apparatus and assessment of the effect of dissolution parameters (pH, temperature, medium composition) on drug release rate and mechanism. Accelerated release conditions were set as pH 2 and 45°C, in phosphate buffer saline (PBS) 0.02M. When the pH was changed from 2 to 4, diffusion controlled phases (burst and lag) were not affected, while release rate during erosion phase decreased two-fold due to slower ester bonds hydrolyses. Decreasing temperature from 45°C to 40°C, release rate showed three-fold deceleration without significant change in release mechanism. Effect of medium composition on drug release was tested in PBS 0.01M (200 mOsm/kg) and PBS 0.01M with glucose (380 mOsm/kg). Buffer concentration significantly affected drug release rate and mechanism due to the change in osmotic pressure, while ionic strength did not have any effect on peptide release. Furthermore, dialysis sac and sample-and-separate techniques were used, in order to evaluate significance of dissolution technique choice on the release process. After fitting obtained data to different mathematical models, flow-through method was confirmed as the most appropriate for accelerated in vitro dissolution testing for a given formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation of Tea Tree Oil/Poly(styrene-butyl methacrylate) Microspheres with Sustained Release and Anti-Bacterial Properties

PubMed Central

Lin, Guanquan; Chen, Huayao; Zhou, Hongjun; Zhou, Xinhua; Xu, Hua

2018-01-01

Using butyl methacrylate (BMA) and styrene (St) as monomers and divinylbenzene (DVB) as a crosslinking agent, P(St-BMA) microspheres were prepared by suspension polymerization. Tea tree oil (TTO) microspheres were prepared by adsorbing TTO on P(St-BMA) microspheres. The structure and surface morphology of P(St-BMA) microspheres and TTO microspheres were characterized by Fourier transformed infrared spectroscopy (FTIR), optical microscopy, and Thermogravimetric analysis (TGA). In doing so, the structural effect of P(St-BMA) microspheres on oil absorption and sustained release properties could be investigated. The results show that the surface of the P(St-BMA) microspheres in the process of TTO microsphere formation changed from initially concave to convex. The TTO microspheres significantly improved the stability of TTO, which was found to completely decompose as the temperature of the TTO increased from about 110 °C to 150 °C. The oil absorption behavior, which was up to 3.85 g/g, could be controlled by adjusting the monomer ratio and the amount of crosslinking agent. Based on Fickian diffusion, the sustained release behavior of TTO microspheres was consistent with the Korsmeyer-Pappas kinetic model. After 13 h of natural release, the anti-bacterial effect of the TTO microspheres was found to be significantly improved compared to TTO. PMID:29723967

Sustained release of simvastatin from hollow carbonated hydroxyapatite microspheres prepared by aspartic acid and sodium dodecyl sulfate.

PubMed

Wang, Ke; Wang, Yinjing; Zhao, Xu; Li, Yi; Yang, Tao; Zhang, Xue; Wu, Xiaoguang

2017-06-01

Hollow carbonated hydroxyapatite (HCHAp) microspheres as simvastatin (SV) sustained-release vehicles were fabricated through a novel and simple one-step biomimetic strategy. Firstly, hollow CaCO 3 microspheres were precipitated through the reaction of CaCl 2 with Na 2 CO 3 in the presence of aspartic acid and sodium dodecyl sulfate. Then, the as-prepared hollow CaCO 3 microspheres were transformed into HCHAp microspheres with a controlled anion-exchange method. The HCHAp microspheres were 3-5μm with a shell thickness of 0.5-1μm and were constructed of short needle nanoparticles. The HCHAp microspheres were then loaded with SV, exhibiting excellent drug-loading capacity and sustained release properties. These results present a new material synthesis strategy for HCHAp microspheres and suggest that the as-prepared HCHAp microspheres are promising for applications in drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Mesoporous metal oxide microsphere electrode compositions and their methods of making

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

Parans Paranthaman, Mariappan; Bi, Zhonghe; Bridges, Craig A.

Compositions and methods of making are provided for treated mesoporous metal oxide microspheres electrodes. The compositions include microspheres with an average diameter between about 200 nanometers and about 10 micrometers and mesopores on the surface and interior of the microspheres. The methods of making include forming a mesoporous metal oxide microsphere composition and treating the mesoporous metal oxide microspheres by at least annealing in a reducing atmosphere, doping with an aliovalent element, and coating with a coating composition.

Rational design on controlled release ion-exchange polymeric microspheres and polymer-lipid hybrid nanoparticles for the delivery of water-soluble drugs through a multidisciplinary approach

NASA Astrophysics Data System (ADS)

Li, Yongqiang

Sulfopropyl dextran sulfate (SP-DS) microspheres and polymer-lipid hybrid nanoparticles (PLN) for the delivery of water-soluble anticancer drugs and P-glycoprotein inhibitors were developed by our group recently and demonstrated effectiveness in local chemotherapy. To optimize the delivery performance of these particulate systems, particularly PLN, an integrated multidisciplinary approach was developed, based on an in-depth understanding of drug-excipient interactions, internal structure, drug loading and release mechanisms, and application of advanced modeling/optimization techniques. An artificial neural networks (ANN) simulator capable of formulation optimization and drug release prediction was developed. In vitro drug release kinetics of SP-DS microspheres, with various drug loading and in different release media, were predicted by ANN. The effects of independent variables on drug release were evaluated. Good modeling performance suggested that ANN is a useful tool to predict drug release from ion-exchange microspheres. To further improve the performance of PLN, drug-polymer-lipid interactions were characterized theoretically and experimentally using verapamil hydrochloride (VRP) as a model drug and dextran sulfate sodium (DS) as a counter-ion polymer. VRP-DS complexation followed a stoichiometric rule and solid-state transformation of VRP were observed. Dodecanoic acid (DA) was identified as the lead lipid carrier material. Based upon the optimized drug-polymer-lipid interactions, PLN with high drug loading capacity (36%, w/w) and sustained release without initial burst release were achieved. VRP remained amorphous and was molecularly dispersed within PLN. H-bonding contributed to the miscibility between the VRP-DS complex and DA. Drug release from PLN was mainly controlled by diffusion and ion-exchange processes. Drug loading capacity and particle size of PLN depend on the formulation factors of the weight ratio of drug to lipid and concentrations of surfactants applied. A three-factor spherical composite experimental design was used to map the cause-and-effect relationship. PLN with high drug loading efficiency (92%) and small particle size (100 nm) were predicted by ANN and confirmed by experiment. The roles of various factors on the properties of PLN were also investigated. In summary, this thesis demonstrates that an integrated multidisciplinary strategy ranging from preformulation to formulation to optimization is suitable for the rational design of SP-DS microspheres and PLN with desired properties.

Formation of nanoparticles of a hydrophilic drug using supercritical carbon dioxide and microencapsulation for sustained release.

PubMed

Thote, Amol J; Gupta, Ram B

2005-03-01

Our purpose was to produce nanoparticles of a hydrophilic drug with use of supercritical carbon dioxide (CO2), encapsulate the obtained nanoparticles into polymer microparticles with use of an anhydrous method and study their sustained in vitro drug release. The hydrophilic drug, dexamethasone phosphate, is dissolved in methanol and injected in supercritical CO2 with an ultrasonic field for enhanced molecular mixing (supercritical antisolvent technique with enhanced mass transfer [SAS-EM]). Supercritical CO2 rapidly extracts methanol leading to instantaneous precipitation of drug nanoparticles. The nanoparticles are then encapsulated in poly(lactide-co-glycolide) (PLGA) polymer by use of the anhydrous solid-oil-oil-oil technique. This results in a well-dispersed encapsulation of drug nanoparticles in polymer microspheres. In vitro drug release from these microparticles is studied. With supercritical CO2 used as an antisolvent, nanoparticles of dexamethasone phosphate were obtained in the range of 150 to 200 nm. On encapsulation in polylactide coglycolide, composite microspheres of approximately 70 microm were obtained. The in vitro drug release of these nanoparticles/microparticles composites shows sustained release of dexamethasone phosphate over a period of 700 hours with almost no initial burst release. Nanoparticles of dexamethasone phosphate can be produced with the SAS-EM technique. When microencapsulated, these particles can provide sustained drug release without initial burst release. Because the complete process is anhydrous, it can be easily extended to produce sustained release formulations of other hydrophilic drugs.

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.

FORMULATION AND EVALUATION OF MICROSPHERES CONTAINING LOSARTAN POTASSIUM BY SPRAY-DRYING TECHNIQUE.

PubMed

Balwierz, Radoslaw; Jankowski, Andrzej; Jasinska, Agata; Marciniak, Dominik; Pluta, Janusz

2016-09-01

Despite numerous applications of microspheres, few works devoted to the preparation of microspheres containing cardiac medications have been published. This study presents the potential of receiving microspheres containing losartan potassium, based on a matrix containing Eudragit L30D55. The study focuses on the possibilities of controlled release of losartan potassium from microspheres in order to reduce the dosage frequency, and also provides information on the effect of the addition of excipients to the quality of the microspheres. Microspheres are monolithic, porous or smooth microparticles ranging from 1 to 500 microns in size. For the preparation of microspheres containing losartan potassium, the spray-drying method was used. The performed study confirmed that the spray-drying technology used to obtain microspheres meets the criteria of size and morphology of the microparticles. The assessment of the kinetics of losartan potassium release from the examined microspheres demonstrated that the release profile followed the first- and/or zero-order kinetics. The use of spray-drying techniques as well as Eudragit L30D55 polymer matrix to obtain the microspheres containing losartan potassium makes it possible to obtain a product with the required particle morphology and particle size ensuring the release of the active substance up to 12 h.

Role of synbiotics in polysaccharide assisted colon targeted microspheres of mesalamine for the treatment of ulcerative colitis.

PubMed

Kaur, Rupinderjeet; Gulati, Monica; Singh, Sachin Kumar

2017-02-01

The present study explains the effect of concomitant administration of synbiotics with the polysaccharide based colon targeted delivery system. As the gut microflora get deranged on administration of mesalamine, drug release from such delivery systems is expected to be jeopardised because the release trigger is dependent solely on the colonic microbiota. To overcome this limitation, mesalamine was formulated as microspheres with guar gum and xanthan gum (prebiotics). These were combined with probiotics containing Lactobacillus acidophilus, L. rhamnosus, Bifidobacterium longumand Saccharomyces boulardi. Dissolution studies of the prepared formulation conducted in simulated colonic fluid clearly demonstrated its superiority over the marketed, delayed release dosage forms of mesalamine. The therapeutic benefit of the concomitant administration of synbiotic with mesalamine was evidenced by the comparative evaluation of faecal contents, weight gain trend and histopathological studies conducted in rats. The results suggest that co-administration of synbiotics with mesalamine can be used as a convenient methodology to achieve efficient and cost-effective targeting of the drug to colon. Copyright © 2016 Elsevier B.V. All rights reserved.

Kinetics of piroxicam release from low-methylated pectin/zein hydrogel microspheres

USDA-ARS?s Scientific Manuscript database

The kinetics of a model drug (piroxicam) release from pectin/zein hydrogel microspheres was studied under conditions simulating the gastrointestinal tract. It is established that the rate-limiting step in the release mechanism is drug diffusion out of the microspheres rather than its dissolution. ...

Evaluation of BSA protein release from hollow hydroxyapatite microspheres into PEG hydrogel

PubMed Central

Fu, Hailuo; Rahaman, Mohamed N.; Brown, Roger F.; Day, Delbert E.

2013-01-01

Implants that simultaneously function as an osteoconductive matrix and as a device for local drug or growth factor delivery could provide an attractive system for bone regeneration. In our previous work, we prepared hollow hydroxyapatite (abbreviated HA) microspheres with a high surface area, mesoporous shell wall and studied the release of a model protein, bovine serum albumin (BSA), from the microspheres into phosphate-buffered saline (PBS). The present work is an extension of our previous work to study the release of BSA from similar HA microspheres into a biocompatible hydrogel, poly(ethylene glycol) (PEG). BSA-loaded HA microspheres were placed in a PEG solution which was rapidly gelled using ultraviolet radiation. The BSA release rate into the PEG hydrogel, measured using a spectrophotometric method, was slower than into PBS, and it was dependent on the initial BSA loading and on the microstructure of the microsphere shell wall. A total of 35–40% of the BSA initially loaded into the microspheres was released into PEG over ~14 days. The results indicate that these hollow HA microspheres have promising potential as an osteoconductive device for local drug or growth factor delivery in bone regeneration and in the treatment of bone diseases. PMID:23498254

Core/shell PLGA microspheres with controllable in vivo release profile via rational core phase design.

PubMed

Yu, Meiling; Yao, Qing; Zhang, Yan; Chen, Huilin; He, Haibing; Zhang, Yu; Yin, Tian; Tang, Xing; Xu, Hui

2018-02-27

Highly soluble drugs tend to release from preparations at high speeds, which make them need to be taken at frequent intervals. Additionally, some drugs need to be controlled to release in vivo at certain periods, so as to achieve therapeutic effects. Thus, the objective of this study is to design injectable microparticulate systems with controllable in vivo release profile. Biodegradable PLGA was used as the matrix material to fabricate microspheres using the traditional double emulsification-solvent evaporation method as well as improved techniques, with gel (5% gelatine or 25% F127) or LP powders as the inner phases. Their physicochemical properties were systemically investigated. Microspheres prepared by modified methods had an increase in drug loading (15.50, 16.72, 15.66%, respectively) and encapsulation efficiencies (73.46, 79.42, 74.40%, respectively) when compared with traditional methods (12.01 and 57.06%). The morphology of the particles was characterized by optical microscope (OM) and scanning electron microscopy (SEM), and the amorphous nature of the encapsulated drug was confirmed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. To evaluate their release behaviour, the in vitro degradation, in vitro release and in vivo pharmacodynamics were subsequently studied. Traditional microspheres prepared in this study with water as the inner phase had a relatively short release period within 16 d when compared with modified microspheres with 5% gelatine as the inner phase, which resulted in a smooth release profile and appropriate plasma LP concentrations over 21 d. Thus this type of modified microspheres can be better used in drugs requiring sustained release. The other two formulations containing 25% F127 and LP micropowders presented two-stage release profiles, resulting in fluctuant plasma LP concentrations which may be suitable for drugs requiring controlled release. All the results suggested that drug release rates from the microspheres prepared by various methods were mainly controlled by either the porosity inside the microspheres or the degradation of materials, which could, therefore, lead to different release behaviours. This results indicated great potential of the PLGA microsphere formulation as an injectable depot for controllable in vivo release profile via rational core phase design. Core/shell microspheres fabricated by modified double emulsification-solvent evaporation methods, with various inner phases, to obtain high loading drugs system, as well as appropriate release behaviours. Accordingly, control in vivo release profile via rational core phase design.

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

Preparation of magnetic polylactic acid microspheres and investigation of its releasing property for loading curcumin

NASA Astrophysics Data System (ADS)

Li, Fengxia; Li, Xiaoli; Li, Bin

2011-11-01

In order to obtain a targeting drug carrier system, magnetic polylactic acid (PLA) microspheres loading curcumin were synthesized by the classical oil-in-water emulsion solvent-evaporation method. In the Fourier transform infrared spectra of microspheres, the present functional groups of PLA were all kept invariably. The morphology and size distribution of magnetic microspheres were observed with scanning electron microscopy and dynamic light scattering, respectively. The results showed that the microspheres were regularly spherical and the surface was smooth with a diameter of 0.55-0.75 μm. Magnetic Fe 3O 4 was loaded in PLA microspheres and the content of magnetic particles was 12 wt% through thermogravimetric analysis. The magnetic property of prepared microspheres was measured by vibrating sample magnetometer. The results showed that the magnetic microspheres exhibited typical superparamagnetic behavior and the saturated magnetization was 14.38 emu/g. Through analysis of differential scanning calorimetry, the curcumin was in an amorphous state in the magnetic microspheres. The drug loading, encapsulation efficiency and releasing properties of curcumin in vitro were also investigated by ultraviolet-visible spectrum analysis. The results showed that the drug loading and encapsulation efficiency were 8.0% and 24.2%, respectively. And curcumin was obviously slowly released because the cumulative release percentage of magnetic microspheres in the phosphate buffer (pH=7.4) solution was only 49.01% in 72 h, and the basic release of curcumin finished in 120 h.

Preparation and properties of BSA-loaded microspheres based on multi-(amino acid) copolymer for protein delivery

PubMed Central

Chen, Xingtao; Lv, Guoyu; Zhang, Jue; Tang, Songchao; Yan, Yonggang; Wu, Zhaoying; Su, Jiacan; Wei, Jie

2014-01-01

A multi-(amino acid) copolymer (MAC) based on ω-aminocaproic acid, γ-aminobutyric acid, L-alanine, L-lysine, L-glutamate, and hydroxyproline was synthetized, and MAC microspheres encapsulating bovine serum albumin (BSA) were prepared by a double-emulsion solvent extraction method. The experimental results show that various preparation parameters including surfactant ratio of Tween 80 to Span 80, surfactant concentration, benzyl alcohol in the external water phase, and polymer concentration had obvious effects on the particle size, morphology, and encapsulation efficiency of the BSA-loaded microspheres. The sizes of BSA-loaded microspheres ranged from 60.2 μm to 79.7 μm, showing different degrees of porous structure. The encapsulation efficiency of BSA-loaded microspheres also ranged from 38.8% to 50.8%. BSA release from microspheres showed the classic biphasic profile, which was governed by diffusion and polymer erosion. The initial burst release of BSA from microspheres at the first week followed by constant slow release for the next 7 weeks were observed. BSA-loaded microspheres could degrade gradually in phosphate buffered saline buffer with pH value maintained at around 7.1 during 8 weeks incubation, suggesting that microsphere degradation did not cause a dramatic pH drop in phosphate buffered saline buffer because no acidic degradation products were released from the microspheres. Therefore, the MAC microspheres might have great potential as carriers for protein delivery. PMID:24855351

[Optimization of calcium alginate floating microspheres loading aspirin by artificial neural networks and response surface methodology].

PubMed

Zhang, An-yang; Fan, Tian-yuan

2010-04-18

To investigate the preparation and optimization of calcium alginate floating microspheres loading aspirin. A model was used to predict the in vitro release of aspirin and optimize the formulation by artificial neural networks (ANNs) and response surface methodology (RSM). The amounts of the material in the formulation were used as inputs, while the release and floating rate of the microspheres were used as outputs. The performances of ANNs and RSM were compared. ANNs were more accurate in prediction. There was no significant difference between ANNs and RSM in optimization. Approximately 90% of the optimized microspheres could float on the artificial gastric juice over 4 hours. 42.12% of aspirin was released in 60 min, 60.97% in 120 min and 78.56% in 240 min. The release of the drug from the microspheres complied with Higuchi equation. The aspirin floating microspheres with satisfying in vitro release were prepared successfully by the methods of ANNs and RSM.

Dynamic in vivo imaging of dual-triggered microspheres for sustained release applications: synthesis, characterization and cytotoxicity study.

PubMed

Efthimiadou, Eleni K; Tapeinos, Christos; Chatzipavlidis, Alexandros; Boukos, Nikos; Fragogeorgi, Eirini; Palamaris, Lazaros; Loudos, George; Kordas, George

2014-01-30

This paper deals with the synthesis, characterization and property evaluation of drug-loaded magnetic microspheres with pH-responsive cross-linked polymer shell. The synthetic procedure consists of 3 steps, of which the first two comprise the synthesis of a poly methyl methacrylate (PMMA) template and the synthesis of a shell by using acrylic acid (AA) and methyl methacrylate (MMA) as monomers, and divinyl benzene (DVB) as cross-linker. The third step of the procedure refers to the formation of magnetic nanoparticles on the microsphere's surface. AA that attaches pH-sensitivity in the microspheres and magnetic nanoparticles in the inner and the outer surface of the microspheres, enhance the efficacy of this intelligent drug delivery system (DDS), which constitutes a promising approach toward cancer therapy. A number of experimental techniques were used to characterize the resulting microspheres. In order to investigate the in vitro controlled release behavior of the synthesized microspheres, we studied the Dox release percentage under different pH conditions and under external magnetic field. Hyperthermia caused by an alternating magnetic field (AFM) is used in order to study the doxorubicin (Dox) release behavior from microspheres with pH functionality. The in vivo fate of these hybrid-microspheres was tracked by labeling them with the γ-emitting radioisotope (99m)Tc after being intravenously injected in normal mice. According to our results, microsphere present a pH depending and a magnetic heating, release behavior. As expected, labeled microspheres were mainly found in the mononuclear phagocyte system (MPS). The highlights of the current research are: (i) to illustrate the advantages of controlled release by combining hyperthermia and pH-sensitivity and (ii) to provide noninvasive, in vivo information on the spatiotemporal biodistribution of these microsphere by dynamic γ-imaging. Copyright © 2013 Elsevier B.V. All rights reserved.

5-Fluorouracil:carnauba wax microspheres for chemoembolization: an in vitro evaluation.

PubMed

Benita, S; Zouai, O; Benoit, J P

1986-09-01

5-Fluorouracil:carnauba wax microspheres were prepared using a meltable dispersion process with the aid of a surfactant as a wetting agent. It was noted that only hydrophilic surfactants were able to wet the 5-fluorouracil and substantially increased its content in the microspheres. No marked effect was observed in the particle size distribution of the solid microspheres as a function of the nature of the surfactant. Increasing the stirring rate in the preparation process decreased, first, the mean droplet size of the emulsified melted dispersion in the vehicle during the heating process, and, consequently, the mean particle size of the solidified microspheres during the cooling process. 5-Fluorouracil cumulative release from the microspheres followed first-order kinetics, as shown by nonlinear regression analysis. Although the kinetic results were not indicative of the true release mechanism from a single microsphere, it was believed that 5-fluorouracil release from the microspheres was probably governed by a dissolution process, rather than by a leaching process through the carnauba wax microspheres.

[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.

Study on encapsulation of chlorine dioxide in gelatin microsphere for reducing release rate

PubMed Central

Ci, Ying; Wang, Lin; Guo, Yanchuan; Sun, Ruixue; Wang, Xijie; Li, Jinyou

2015-01-01

Objective: This study aims to explore the effects of encapsulation of chlorine dioxide in a hydrophilic biodegradable polymer gelatin to reduce its release rate. Methods: An emulsification-coacervation method was adopted. The characterizations of chlorine dioxide-gelatin microspheres were described. Using UV-vis spectrophotometer the λmax of chlorine dioxide was observed at 358 nm. The particle size and distribution of chlorine oxide-gelatin microspheres was measured by a dynamic light scattering (DLS) method, the diameter was (1400~1900) nm. The entrapment of chlorine dioxide-gelatin microspheres was confirmed by IR. The surface morphology, size, and shape of chlorine dioxide-gelatin microspheres were analyzed using Scanning electron microscope (SEM). Results: It showed that the encapsulated microspheres size was around 2000 nm with uniform distribution. The percentage entrapment of chlorine dioxide in the encapsulated samples was about 80~85%. A slow release study of chlorine dioxide from the encapsulated biopolymer (gelatin) in air was also carried out, which showed continuous release up to ten days. Conclusions: It can be concluded that it is possible to make a slow release formulation of ClO2 by entrapped in a hydrophilic biodegradable polymer gelatin. ClO2-gelatin microspheres can stable release low concentration ClO2 gas over an extended period. PMID:26550151

Injectable hydrogels embedded with alginate microspheres for controlled delivery of bone morphogenetic protein-2.

PubMed

Zhu, Youjia; Wang, Jiulong; Wu, Jingjing; Zhang, Jun; Wan, Ying; Wu, Hua

2016-03-23

Some delivery carriers with injectable characteristics were built using the thermosensitive chitosan/dextran-polylactide/glycerophosphate hydrogel and selected alginate microspheres for the controllable release of bone morphogenetic protein-2 (BMP-2). BMP-2 was first loaded into the microspheres with an average size of around 20 μm and the resulting microspheres were then embedded into the gel in order to achieve well-controlled BMP-2 release. The microsphere-embedded gels show their incipient gelation temperature at around 32 °C and pH at about 7.1. Some gels had their elastic modulus close to 1400 Pa and the ratio of elastic modulus to viscous modulus at around 34, revealing that they behaved like mechanically strong gels. Optimized microsphere-embedded gels were found to be able to administer the BMP-2 release without significant initial burst release in an approximately linear manner over a period of time longer than four weeks. The release rate and the released amount of BMP-2 from these gels could be regulated individually or cooperatively by the initial BMP-2 load and the dextran-polylactide content in the gels. Measurements of the BMP-2 induced alkaline phosphatase activity in C2C12 cells confirmed that C2C12 cells responded to BMP-2 in a dose-dependent way and the released BMP-2 from the microsphere-embedded gels well retained their bioactivity. In vivo assessment of some gels revealed that the released BMP-2 maintained its osteogenesis functions.

Prolonged cytotoxic effect of colchicine released from biodegradable microspheres.

PubMed

Muvaffak, Asli; Gurhan, Ismet; Hasirci, Nesrin

2004-11-15

One the main problems of cancer chemotherapy is the unwanted damage to normal cells caused by the high toxicities of anticancer drugs. Any system of controlled drug delivery that would reduce the total amount of drug required, and thus reduce the side effects, would potentially help to improve chemotherapy. In this respect, biodegradable gelatin microspheres were prepared by water/oil emulsion polymerization and by crosslinking with glutaraldehyde (GTA) as the drug-carrier system. Microspheres were loaded with colchicine, a model antimitotic drug, which was frequently used as an antimitotic agent in cancer research involving cell cultures. Microsphere sizes, swelling and degradation properties, drug-release kinetics, and cytotoxities were studied. Swelling characteristics of microspheres changed upon changing GTA concentration. A decrease in swelling values was recorded as GTA crosslink density was increased. In vitro drug release in PBS (0.01M, pH 7.4) showed rapid colchicine release up to approximately 83% (at t = 92 h) for microspheres with low GTA (0.05% v/v), whereas a slower release profile (only approximately 39%) was obtained for microspheres with high GTA (0.50% v/v) content, for the same period. Cytotoxicity tests with MCF-7, HeLa and H-82 cancer cell lines showed that free colchicine was very toxic, showing an approximately 100% lethal effect in both HeLa and H-82 cell lines and more than 50% decrease in viability in MCF-7 cells in 4 days. Indeed, entrapped colchicine indicated similar initial high toxic effect on cell viability in MCF-7 cell line and this effect became more dominant as colchicine continued to be released from microspheres in the same period. In conclusion, the control of the release rate of colchicine from gelatin microspheres was achieved under in vitro conditions by gelatin through the alteration of crosslinking conditions. Indeed, the results suggested the potential application of gelatin microspheres crosslinked with GTA as a sustained drug-delivery system for anticancer drugs for local chemotherapy administrations. (c) 2004 Wiley Periodicals, Inc.

Preparation and in vitro evaluation of xanthan gum facilitated superabsorbent polymeric microspheres.

PubMed

Bhattacharya, Shiv Sankar; Mazahir, Farhan; Banerjee, Subham; Verma, Anurag; Ghosh, Amitava

2013-10-15

Interpenetrating polymer network (IPN) hydrogel microspheres of xanthan gum (XG) based superabsorbent polymer (SAP) and poly(vinyl alcohol) (PVA) were prepared by water-in-oil (w/o) emulsion crosslinking method for sustained release of ciprofloxacin hydrochloride (CIPRO). The microspheres were prepared with various ratios of hydrolyzed SAP to PVA and extent of crosslinking density. The prepared microspheres with loose and rigid surfaces were evidenced by scanning electron microscope (SEM). Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis confirmed the IPN formation. Differential scanning calorimetry (DSC) study was performed to understand the dispersion nature of drug after encapsulation. The in vitro drug release study was extensively evaluated depending on the process variables in both acidic and alkaline media. All the formulations exhibited satisfactory physicochemical and in vitro release characteristics. Release data indicated a non-Fickian trend of drug release from the formulations. Based on the results, this study suggest that CIPRO loaded IPN microspheres were suitable for sustained release application. Copyright © 2013 Elsevier Ltd. All rights reserved.

Development of implants composed of bioactive materials for bone repair

NASA Astrophysics Data System (ADS)

Xiao, Wei

The purpose of this Ph.D. research was to address the clinical need for synthetic bioactive materials to heal defects in non-loaded and loaded bone. Hollow hydroxyapatite (HA) microspheres created in a previous study were evaluated as a carrier for controlled release of bone morphogenetic protein-2 (BMP2) in bone regeneration. New bone formation in rat calvarial defects implanted with BMP2-loaded microspheres (43%) was significantly higher than microspheres without BMP2 (17%) at 6 weeks postimplantation. Then hollow HA microspheres with a carbonate-substituted composition were prepared to improve their resorption rate. Hollow HA microspheres with 12 wt. % of carbonate showed significantly higher new bone formation (73 +/- 8%) and lower residual HA (7 +/- 2%) than stoichiometric HA microspheres (59 +/- 2% new bone formation; 21 +/- 3% residual HA). The combination of carbonate-substituted hollow HA microspheres and clinically-safe doses of BMP2 could provide promising implants for healing non-loaded bone defects. Strong porous scaffolds of bioactive silicate (13-93) glass were designed with the aid of finite-element modeling, created by robocasting and evaluated for loaded bone repair. Scaffolds with a porosity gradient to mimic human cortical bone showed a compressive strength of 88 +/- 20 MPa, a flexural strength of 34 +/- 5 MPa and the ability to support bone infiltration in vivo. The addition of a biodegradable polylactic acid (PLA) layer to the external surface of these scaffolds increased their load-bearing capacity in four-point bending by 50% and dramatically enhanced their work of fracture, resulting in a "ductile" mechanical response. These bioactive glass-PLA composites, combining bioactivity, high strength, high work of fracture and an internal architecture conducive to bone infiltration, could provide optimal implants for structural bone repair.

Metronidazole loaded pectin microspheres for colon targeting.

PubMed

Vaidya, Ankur; Jain, Aviral; Khare, Piush; Agrawal, Ram K; Jain, Sanjay K

2009-11-01

A multiparticulate system having pH-sensitive property and specific enzyme biodegradability for colon-targeted delivery of metronidazole was developed. Pectin microspheres were prepared using emulsion-dehydration technique. These microspheres were coated with Eudragit(R) S-100 using oil-in-oil solvent evaporation method. The SEM was used to characterize the surface of these microspheres and a distinct coating over microspheres could be seen. The in vitro drug release studies exhibited no drug release at gastric pH, however continuous release of drug was observed from the formulation at colonic pH. Further, the release of drug from formulation was found to be higher in the presence of rat caecal contents, indicating the effect of colonic enzymes on the pectin microspheres. The in vivo studies were also performed by assessing the drug concentration in various parts of the GIT at different time intervals which exhibited the potentiality of formulation for colon targeting. Hence, it can be concluded that Eudragit coated pectin microspheres can be used for the colon specific delivery of drug. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association

Mesoporous metal oxide microsphere electrode compositions and their methods of making

DOEpatents

Paranthaman, Mariappan Parans; Liu, Hansan; Brown, Gilbert M.; Sun, Xiao-Guang; Bi, Zhonghe

2016-12-06

Compositions and methods of making are provided for mesoporous metal oxide microspheres electrodes. The mesoporous metal oxide microsphere compositions comprise (a) microspheres with an average diameter between 200 nanometers (nm) and 10 micrometers (.mu.m); (b) mesopores on the surface and interior of the microspheres, wherein the mesopores have an average diameter between 1 nm and 50 nm and the microspheres have a surface area between 50 m.sup.2/g and 500 m.sup.2/g. The methods of making comprise forming composite powders. The methods may also comprise refluxing the composite powders in a basic solution to form an etched powder, washing the etched powder with an acid to form a hydrated metal oxide, and heat-treating the hydrated metal oxide to form mesoporous metal oxide microspheres.

Design of a composite drug delivery system to prolong functionality of cell-based scaffolds.

PubMed

Murua, Ainhoa; Herran, Enara; Orive, Gorka; Igartua, Manoli; Blanco, Francisco Javier; Pedraz, José Luis; Hernández, Rosa M

2011-04-04

Cell encapsulation technology raises hopes in medicine and biotechnology. However, despite important advances in the field in the past three decades, several challenges associated with the biocompatibility are still remaining. In the present study, the effect of a temporary release of an anti-inflammatory agent on co-administered encapsulated allogeneic cells was investigated. The aim was to determine the biocompatibility and efficacy of the approach to prevent the inflammatory response. A composite delivery system comprised of alginate-poly-l-lysine-alginate (APA)-microencapsulated Epo-secreting myoblasts and dexamethasone (DXM)-releasing poly(lactic-co-glycolic acid) (PLGA) microspheres was implanted in the subcutaneous space of Balb/c mice for 45 days. The use of independently co-implanted DXM-loaded PLGA microspheres resulted in an improved functionality of the cell-based graft, evidenced by significantly higher hematocrit levels found in the cell-implanted groups by day 45, which was found to be more pronounced when higher cell-doses (100 μL) were employed. Moreover, no major host reaction was observed upon implantation of the systems, showing good biocompatibility and capability to partially avoid the inflammatory response, probably due to the immunosuppressive effects related to DXM. The findings of this study imply that DXM-loaded PLGA microspheres show promise as release systems to enhance biocompatibility and offer advantage in the development of long-lasting and effective implantable microencapsulated cells by generating a potential immunopriviledged local environment and an effective method to limit the structural ensheathing layer caused by inflammation. Copyright © 2010 Elsevier B.V. All rights reserved.

Magnetically stimulated ciprofloxacin release from polymeric microspheres entrapping iron oxide nanoparticles

PubMed Central

Sirivisoot, Sirinrath; Harrison, Benjamin S

2015-01-01

To extend the external control capability of drug release, iron oxide nanoparticles (NPs) encapsulated into polymeric microspheres were used as magnetic media to stimulate drug release using an alternating magnetic field. Chemically synthesized iron oxide NPs, maghemite or hematite, and the antibiotic ciprofloxacin were encapsulated together within polycaprolactone microspheres. The polycaprolactone microspheres entrapping ciprofloxacin and magnetic NPs could be triggered for immediate drug release by magnetic stimulation at a maximum value of 40%. Moreover, the microspheres were cytocompatible with fibroblasts in vitro with a cell viability percentage of more than 100% relative to a nontreated control after 24 hours of culture. Macrophage cell cultures showed no signs of increased inflammatory responses after in vitro incubation for 56 hours. Treatment of Staphylococcus aureus with the magnetic microspheres under an alternating (isolating) magnetic field increased bacterial inhibition further after 2 days and 5 days in a broth inhibition assay. The findings of the present study indicate that iron oxide NPs, maghemite and hematite, can be used as media for stimulation by an external magnetic energy to activate immediate drug release. PMID:26185446

A novel strategy for the preparation of porous microspheres and its application in peptide drug loading.

PubMed

Wei, Yi; Wang, Yuxia; Zhang, Huixia; Zhou, Weiqing; Ma, Guanghui

2016-09-15

A new strategy is developed to prepare porous microspheres with narrow size distribution for peptides controlled release, involving a fabrication of porous microspheres without any porogens followed by a pore closing process. Amphiphilic polymers with different hydrophobic segments (poly(monomethoxypolyethylene glycol-co-d,l-lactide) (mPEG-PLA), poly(monomethoxypolyethylene glycol-co-d,l-lactic-co-glycolic acid) (mPEG-PLGA)) are employed as microspheres matrix to prepare porous microspheres based on a double emulsion-premix membrane emulsification technique combined with a solvent evaporation method. Both microspheres possess narrow size distribution and porous surface, which are mainly caused by (a) hydrophilic polyethylene glycol (PEG) segments absorbing water molecules followed by a water evaporation process and (b) local explosion of microspheres due to fast evaporation of dichloromethane (MC). Importantly, mPEG-PLGA microspheres have a honeycomb like structure while mPEG-PLA microspheres have a solid structure internally, illustrating that the different hydrophobic segments could modulate the affinity between solvent and matrix polymer and influence the phase separation rate of microspheres matrix. Long term release patterns are demonstrated with pore-closed microspheres, which are prepared from mPEG-PLGA microspheres loading salmon calcitonin (SCT). These results suggest that it is potential to construct porous microspheres for drug sustained release using permanent geometric templates as new porogens. Copyright © 2016 Elsevier Inc. All rights reserved.

Mesoporous metal oxide microsphere electrode compositions and their methods of making

DOEpatents

Parans Paranthaman, Mariappan; Bi, Zhonghe; Bridges, Craig A; Brown, Gilbert M

2014-12-16

Compositions and methods of making are provided for treated mesoporous metal oxide microspheres electrodes. The compositions comprise (a) microspheres with an average diameter between 200 nanometers (nm) and 10 micrometers (.mu.m); (b) mesopores on the surface and interior of the microspheres, wherein the mesopores have an average diameter between 1 nm and 50 nm and the microspheres have a surface area between 50 m.sup.2/g and 500 m.sup.2/g, and wherein the composition has an electrical conductivity of at least 1.times.10.sup.-7 S/cm at 25.degree. C. and 60 MPa. The methods of making comprise forming a mesoporous metal oxide microsphere composition and treating the mesoporous metal oxide microspheres by at least one method selected from the group consisting of: (i) annealing in a reducing atmosphere, (ii) doping with an aliovalent element, and (iii) coating with a coating composition.

A quality by design (QbD) study on enoxaparin sodium loaded polymeric microspheres for colon-specific delivery.

PubMed

Hales, Dana; Vlase, Laurian; Porav, Sebastian Alin; Bodoki, Andreea; Barbu-Tudoran, Lucian; Achim, Marcela; Tomuță, Ioan

2017-03-30

The aim of this study was to apply quality by design (QbD) for pharmaceutical development of enoxaparin sodium microspheres for colon-specific delivery. The Process Parameters (CPPs) and Critical Quality Attributes (CQAs) were identified. A central composite experimental design was used in order to develop the design space of microspheres for colon-specific delivery that have the desired Quality Target Product Profile (QTPP). The CPPs studied were Eudragit® FS-30D/Eudragit® RS-PO ratio, poly(vinyl alcohol) (PVA) concentration and sodium chloride (NaCl) concentration. The encapsulation efficiency increased with NaCl concentration increase, the percentages of enoxaparin sodium reaching 94% for some formulations. Increasing the ratio Eudragit® FS-30D/Eudragit® RS-PO ensured a relatively complete release of enoxaparin sodium in the environment simulating the colonic pH. Based on these results, the optimum conditions were decided and the optimum formulation was prepared. The results obtained for the latter in terms of in vitro enoxaparin sodium release were good, the microparticles releasing only 9.42% enoxaparin sodium in acidic environment and 15.16% in the medium which simulated duodenal pH, but allowing the release of up to 89.24% in the medium which simulated colonic pH. The in vitro release profile of enoxaparin sodium was close to the ideal one, therefore the system was successfully designed using QbD approach. Copyright © 2017 Elsevier B.V. All rights reserved.

Release behavior and kinetic evaluation of berberine hydrochloride from ethyl cellulose/chitosan microspheres

NASA Astrophysics Data System (ADS)

Zhou, Hui-Yun; Cao, Pei-Pei; Zhao, Jie; Wang, Zhi-Ying; Li, Jun-Bo; Zhang, Fa-Liang

2014-12-01

Novel ethyl cellulose/chitosan microspheres (ECCMs) were prepared by the method of w/o/w emulsion and solvent evaporation. The microspheres were spherical, adhesive, and aggregated loosely with a size not bigger than 5 μm. The drug loading efficiency of berberine hydrochloride (BH) loaded in microspheres were affected by chitosan (CS) concentration, EC concentration and the volume ratio of V(CS)/ V(EC). ECCMs prepared had sustained release efficiency on BH which was changed with different preparation parameters. In addition, the pH value of release media had obvious effect on the release character of ECCMs. The release rate of BH from sample B was only a little more than 30% in diluted hydrochloric acid (dHCl) and that was almost 90% in PBS during 24 h. Furthermore, the drug release data were fitted to different kinetic models to analyze the release kinetics and the mechanism from the microspheres. The released results of BH indicated that ECCMs exhibited non-Fickian diffusion mechanism in dHCl and diffusion-controlled drug release based on Fickian diffusion in PBS. So the ECCMs might be an ideal sustained release system especially in dHCl and the drug release was governed by both diffusion of the drug and dissolution of the polymeric network.

A dual-application poly (dl-lactic-co-glycolic) acid (PLGA)-chitosan composite scaffold for potential use in bone tissue engineering.

PubMed

Boukari, Yamina; Qutachi, Omar; Scurr, David J; Morris, Andrew P; Doughty, Stephen W; Billa, Nashiru

2017-11-01

The development of patient-friendly alternatives to bone-graft procedures is the driving force for new frontiers in bone tissue engineering. Poly (dl-lactic-co-glycolic acid) (PLGA) and chitosan are well-studied and easy-to-process polymers from which scaffolds can be fabricated. In this study, a novel dual-application scaffold system was formulated from porous PLGA and protein-loaded PLGA/chitosan microspheres. Physicochemical and in vitro protein release attributes were established. The therapeutic relevance, cytocompatibility with primary human mesenchymal stem cells (hMSCs) and osteogenic properties were tested. There was a significant reduction in burst release from the composite PLGA/chitosan microspheres compared with PLGA alone. Scaffolds sintered from porous microspheres at 37 °C were significantly stronger than the PLGA control, with compressive strengths of 0.846 ± 0.272 MPa and 0.406 ± 0.265 MPa, respectively (p < 0.05). The formulation also sintered at 37 °C following injection through a needle, demonstrating its injectable potential. The scaffolds demonstrated cytocompatibility, with increased cell numbers observed over an 8-day study period. Von Kossa and immunostaining of the hMSC-scaffolds confirmed their osteogenic potential with the ability to sinter at 37 °C in situ.

A Novel Polymer-Synthesized Ceramic Composite Based System for Bone Repair: Osteoblast Growth on Scaffolds with Varied Calcium Phosphate Content

DTIC Science & Technology

2005-01-01

demongtrated the synthesis of degradable scaffolds from PLAGA /calcium phosphate composite microspheres in which an amorphous calcium phosphate is...EXPERIMENTAL DETAILS Scaffold Preparation Scaffolds were prepared as described in detail previously [3]. Briefly, PLAGA /calcium phosphate composite...culture polystyrene (TCPS) 2- pure PLAGA microspheres 64 3- composite microsphere matrices with a low polymer/ceramic ratio 4- composite microsphere

Use of Microsphere Technology for Targeted Delivery of Rifampin to Mycobacterium tuberculosis-Infected Macrophages

PubMed Central

Barrow, Esther L. W.; Winchester, Gary A.; Staas, Jay K.; Quenelle, Debra C.; Barrow, William W.

1998-01-01

Microsphere technology was used to develop formulations of rifampin for targeted delivery to host macrophages. These formulations were prepared by using biocompatible polymeric excipients of lactide and glycolide copolymers. Release characteristics were examined in vitro and also in two monocytic cell lines, the murine J774 and the human Mono Mac 6 cell lines. Bioassay assessment of cell culture supernatants from monocyte cell lines showed release of bioactive rifampin during a 7-day experimental period. Treatment of Mycobacterium tuberculosis H37Rv-infected monocyte cell lines with rifampin-loaded microspheres resulted in a significant decrease in numbers of CFU at 7 days following initial infection, even though only 8% of the microsphere-loaded rifampin was released. The levels of rifampin released from microsphere formulations within monocytes were more effective at reducing M. tuberculosis intracellular growth than equivalent doses of rifampin given as a free drug. These results demonstrate that rifampin-loaded microspheres can be formulated for effective sustained and targeted delivery to host macrophages. PMID:9756777

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

PubMed

Agrawal, Gauravkuma; Wakte, Pravin; Shelke, Santosh

2017-01-01

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

Investigation of triacetin effect on indomethacin release from poly(methyl methacrylate) microspheres: evaluation of interactions using FT-IR and NMR spectroscopies.

PubMed

Yuksel, Nilufer; Baykara, Meltem; Shirinzade, Hanif; Suzen, Sibel

2011-02-14

The purpose of this study was to form indomethacin (IND)-loaded poly(methyl methacrylate) (PMMA) microspheres having an extended drug release profile over a period of 24h. Microspheres were prepared by solvent evaporation method using sucrose stearate as a droplet stabilizer. When PMMA was used alone for the preparation of microspheres, only 44% of IND could be released at the end of 8h. Triacetin was added to PMMA, as a minor phase, and the obtained microspheres showed a high yield process with recovery of 89.82% and incorporation efficiency of 102.3%. A desired release profile lasting 24h was achieved. Differential scanning calorimetry (DSC) analysis showed that IND was found to be in an amorphous state in the microspheres. Fourier transform infrared (FT-IR) and nuclear magnetic resonance ((1)H NMR) spectra suggested that there might be a hydrogen bond present between the IND hydroxyl group and PMMA. No interaction between triacetin and IND or PMMA as the formation of secondary bonds was observed. The release enhancement of IND from microspheres was attributed to the physical plasticization effect of triacetin on PMMA and, to some extent, the amorphous state of the drug. Copyright © 2010 Elsevier B.V. All rights reserved.

Novel PLA modification of organic microcontainers based on ring opening polymerization: synthesis, characterization, biocompatibility and drug loading/release properties.

PubMed

Efthimiadou, E K; Tziveleka, L-A; Bilalis, P; Kordas, G

2012-05-30

In the current study, poly lactic acid (PLA) modified hollow crosslinked poly(hydroxyethyl methacrylate) (PHEMA) microspheres have been prepared, in order to obtain a stimulus-responsive, biocompatible carrier with sustained drug release properties. The synthetical process consisted of the preparation of poly(methacrylic acid)@poly(hydroxyethyl methacrylate-co-N,N'-methylene bis(acrylamide)) microspheres by a two stage distillation-precipitation polymerization technique using 2,2'-azobisisobutyronitrile as initiator. Following core removal, a PLA coating of the microspheres was formed, after ring opening polymerization of DL-lactide, attributing the initiator's role to the active hydroxyl groups of PHEMA. The anticancer drug daunorubicin (DNR) was selected for the study of loading and release behavior of the coated microspheres. The loading capacity of the PLA modified microspheres was found to be four times higher than that of the parent ones (16% compared to 4%). This coated microspherical carrier exhibited a moderate pH responsive drug release behavior due to the pH dependent water uptake of PHEMA, and PLA hydrolysis. The in vitro cytotoxicity of both the parent and the DNR-loaded or empty modified hollow microspheres has been also examined on MCF-7 breast cancer cells. The results showed that although the empty microspheres were moderately cytotoxic, the DNR-loaded microspheres had more potent anti-tumor effect than the free drug. Therefore, the prepared coated microspheres are interesting drug delivery systems. Copyright © 2012 Elsevier B.V. All rights reserved.

Influence of some formulation variables on the optimization of pH-dependent, colon-targeted, sustained-release mesalamine microspheres.

PubMed

El-Bary, Ahmed Abd; Aboelwafa, Ahmed A; Al Sharabi, Ibrahim M

2012-03-01

The aim of this work was to understand the influence of different formulation variables on the optimization of pH-dependent, colon-targeted, sustained-release mesalamine microspheres prepared by O/O emulsion solvent evaporation method, employing pH-dependent Eudragit S and hydrophobic pH-independent ethylcellulose polymers. Formulation variables studied included concentration of Eudragit S in the internal phase and the ratios between; internal to external phase, drug to Eudragit S and Eudragit S to ethylcellulose to mesalamine. Prepared microspheres were evaluated by carrying out in vitro release studies and determination of particle size, production yield, and encapsulation efficiency. In addition, morphology of microspheres was examined using optical and scanning electron microscopy. Emulsion solvent evaporation method was found to be sensitive to the studied formulation variables. Particle size and encapsulation efficiency increased by increasing Eudragit S concentration in the internal phase, ratio of internal to external phase, and ratio of Eudragit S to the drug. Employing Eudragit S alone in preparation of the microspheres is only successful in forming acid-resistant microspheres with pulsatile release pattern at high pH. Eudragit S and ethylcellulose blend microspheres were able to control release under acidic condition and to extend drug release at high pH. The stability studies carried out at 40°C/75% RH for 6 months proved the stability of the optimized formulation. From the results of this investigation, microencapsulation of mesalamine in microspheres using blend of Eudragit S and ethylcellulose could constitute a promising approach for site-specific and controlled delivery of drug in colon.

In Vitro-In Vivo Relationship of Amorphous Insoluble API (Progesterone) in PLGA Microspheres.

PubMed

Pu, Chenguang; Wang, Qiao; Zhang, Hongjuan; Gou, Jingxin; Guo, Yuting; Tan, Xinyi; Xie, Bin; Yin, Na; He, Haibing; Zhang, Yu; Wang, Yanjiao; Yin, Tian; Tang, Xing

2017-12-01

The mechanism of PRG release from PLGA microspheres was studied and the correlation of in vitro and in vivo analyses was assessed. PRG-loaded microspheres were prepared by the emulsion-evaporate method. The physical state of PRG and microstructure changings during the drug release period were evaluated by powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) respectively. Pharmacokinetic studies were performed in male Sprague-Dawley rats, and the in vivo-in vitro correlation (IVIVC) was established by linear fitting of the cumulative release (%) in vitro and fraction of absorption (%) in vivo. PXRD results indicated recrystallization of PRG during release. The changes of microstructure of PRG-loaded microspheres during the release period could be observed in SEM micrographs. Pharmacokinetics results performed low burst-release followed a steady-released manner. The IVIVC assessment exhibited a good correlation between vitro and in vivo. The burst release phase was caused by diffusion of amorphous PRG near the surface, while the second release stage was impacted by PRG-dissolution from crystal depots formed in microspheres. The IVIVC assessment suggests that the in vitro test method used in this study could predict the real situation in vivo and is helpful to study the release mechanism in vivo.

[Experimental study on loading naringin composite scaffolds for repairing rabbit osteochondral defects].

PubMed

Huang, Junbo; Wang, Shiyong; Zhang, Xiaomin; Li, Gen; Ji, Puzhong; Zhao, Hongbin

2017-04-01

To investigate the performance of loading naringin composite scaffolds and its effects on repair of osteochondral defects. The loading naringin and unloading naringin sustained release microspheres were prepared by W/O/W method; with the materials of the attpulgite and the collagen type I, the loading naringin, unloading naringin, and loading transforming growth factor β 1 (TGF-β 1 ) osteochondral composite scaffolds were constructed respectively by "3 layers sandwich method". The effect of sustained-release of loading naringin microspheres, the morphology of the composite scaffolds, and the biocompatibility were evaluated respectively by releasing in vitro , scanning electron microscope, and cell counting kit 8. Forty Japanese white rabbits were randomly divided into groups A, B, C, and D, 10 rabbits each group. After a osteochondral defect of 4.5 mm in diameter and 4 mm in depth was made in the intercondylar fossa of two femurs. Defect was not repaired in group A (blank control), and defect was repaired with unloading naringin composite scaffolds (negative control group), loading naringin composite scaffolds (experimental group), and loading TGF-β 1 composite scaffolds (positive control group) in groups B, C, and D respectively. At 3 and 6 months after repair, the intercondylar fossa was harvested for the general, HE staining, and toluidine blue staining to observe the repair effect. Western blot was used to detect the expression of collagen type II in the new cartilage. Loading naringin microspheres had good effect of sustained-release; the osteochondral composite scaffolds had good porosity; the cell proliferation rate on loading naringin composite scaffold was increased significantly when compared with unloading naringin scaffold ( P <0.05). General observation revealed that defect range of groups C and D was reduced significantly when compared with groups A and B at 3 months after repair; at 6 months after repair, defects of group C were covered by new cartilage, and new cartilage well integrated with the adjacent cartilage in group D. The results of histological staining revealed that defects were filled with a small amount of fibrous tissue in groups A and B, and a small amount of new cartilage in groups C and D at 3 months after repair; new cartilage of groups C and D was similar to normal cartilage, but defects were filled with a large amount of fibrous tissue in groups A and B at 6 months after repair. The expression of collagen type II in groups C and D was significantly higher than that in groups A and B ( P <0.05), but no significant difference was found between groups C and D ( P >0.05). Loading naringin composite scaffolds have good biocompatibility and effect in repair of rabbit articular osteochondral defects.

Recent advances in testing of microsphere drug delivery systems.

PubMed

Andhariya, Janki V; Burgess, Diane J

2016-01-01

This review discusses advances in the field of microsphere testing. In vitro release-testing methods such as sample and separate, dialysis membrane sacs and USP apparatus IV have been used for microspheres. Based on comparisons of these methods, USP apparatus IV is currently the method of choice. Accelerated in vitro release tests have been developed to shorten the testing time for quality control purposes. In vitro-in vivo correlations using real-time and accelerated release data have been developed, to minimize the need to conduct in vivo performance evaluation. Storage stability studies have been conducted to investigate the influence of various environmental factors on microsphere quality throughout the product shelf life. New tests such as the floating test and the in vitro wash-off test have been developed along with advancement in characterization techniques for other physico-chemical parameters such as particle size, drug content, and thermal properties. Although significant developments have been made in microsphere release testing, there is still a lack of guidance in this area. Microsphere storage stability studies should be extended to include microspheres containing large molecules. An agreement needs to be reached on the use of particle sizing techniques to avoid inconsistent data. An approach needs to be developed to determine total moisture content of microspheres.

Sustained-release microsphere formulation containing an agrochemical by polyurethane polymerization during an agitation granulation process.

PubMed

Terada, Takatoshi; Tagami, Manabu; Ohtsubo, Toshiro; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

2016-07-25

In this report, a new solventless microencapsulation method by synthesizing polyurethane (PU) from polyol and isocyanate during an agglomeration process in a high-speed mixing apparatus was developed. Clothianidin (CTD), which is a neonicotinoid insecticide and highly effective against a wide variety of insect pests, was used as the model compound. The microencapsulated samples covered with PU (CTD microspheres) had a median diameter of <75μm and sustained-release properties. The CTD microspheres were analyzed by synchrotron X-ray computed tomography measurements. Multiple cores of CTD and other solid excipient were dispersed in PU. Although voids appeared in the CTD microspheres after CTD release, the spherical shape of the microspheres remained stable and no change in its framework was observed. The experimental release data were highly consistent with the Baker-Lonsdale model derived from drug release of spherical monolithic dispersions and consistent with the computed tomography measurements. Copyright © 2016 Elsevier B.V. All rights reserved.

Budesonide-Loaded Guar Gum Microspheres for Colon Delivery: Preparation, Characterization and in Vitro/in Vivo Evaluation

PubMed Central

Liu, Ye; Zhou, Hong

2015-01-01

A novel budesonide (BUD) colon delivery release system was developed by using a natural polysaccharide, guar gum. The rigidity of the microspheres was induced by a chemical cross-linking method utilizing glutaraldehyde as the cross-linker. The mean particle size of the microspheres prepared was found to be 15.21 ± 1.32 µm. The drug loading and entrapment efficiency of the formulation were 17.78% ± 2.31% and 81.6% ± 5.42%, respectively. The microspheres were spherical in shape with a smooth surface, and the size was uniform. The in vitro release profiles indicated that the release of BUD from the microspheres exhibited a sustained release behavior. The model that fitted best for BUD released from the microspheres was the Higuchi kinetic model with a correlation coefficient r = 0.9993. A similar phenomenon was also observed in a pharmacokinetic study. The prolongation of the half-life (t1/2), enhanced residence time (mean residence time, MRT) and decreased total clearance (CL) indicated that BUD microspheres could prolong the acting time of BUD in vivo. In addition, BUD guar gum microspheres are thought to have the potential to maintain BUD concentration within target ranges for a long time, decreasing the side effects caused by concentration fluctuation, ensuring the efficiency of treatment and improving patient compliance by reducing dosing frequency. None of the severe signs, like the appearance of epithelial necrosis and the sloughing of epithelial cells, were detected. PMID:25629228

pH-Sensitive Self-Assembled Microspheres Composed of Poly(Ethyleneimine) and Cinnamic Acid.

PubMed

Park, Danbi; Lee, Seung-Jun; Kim, Jin-Chul

2018-01-01

Microspheres which were sensitive to pH change were developed by utilizing cinnamic acid (CA) as a physical cross-linker for poly(ethyleneimine) (PEI). At pH 7.0, the microspheres were efficiently formed at the PEI/CA ratio of 1:3.4, 1:5.1, and 1:7.1 (w/w), which corresponded to the protonated amino group/deprotonated carboxyl group ratio of 5:5, 4:6, and 3:7. The mean diameter of wet microspheres was 3.2 ± 0.3 to 8.8 ± 0.5 μm and that of dry ones was 1.7 ± 0.2 to 2.7 ± 0.2 μm. The microspheres were disappeared upon the alkalification, possibly because the electrostatic interaction between PEI and CA was slackened down and the hydrophobic interaction among CA molecules was weakened. At pH 5.0 and 7.0, the microsphere released its content in a sustained manner and the release degree in 24 h was less than 40%. Whereas, at pH 8.0 and 9.0, the microsphere exhibited a burst release and the release degree in 24 h was greater than 80%. In the alkali condition, not only the electrostatic interaction between PEI and CA but also the hydrophobic interaction among CA molecules became weaker, leading to the disintegration of the microsphere and resulting in a burst and intensive release.

The Pharmacokinetics and Pharmacodynamics of Lidocaine-Loaded Biodegradable Poly(lactic-co-glycolic acid) Microspheres

PubMed Central

Liu, Jianming; Lv, Xin

2014-01-01

The purpose of this study was to develop novel lidocaine microspheres. Microspheres were prepared by the oil-in-water (o/w) emulsion technique using poly(d,l-lactide-co-glycolide acid) (PLGA) for the controlled delivery of lidocaine. The average diameter of lidocaine PLGA microspheres was 2.34 ± 0.3 μm. The poly disperse index was 0.21 ± 0.03, and the zeta potential was +0.34 ± 0.02 mV. The encapsulation efficiency and drug loading of the prepared microspheres were 90.5% ± 4.3% and 11.2% ± 1.4%. In vitro release indicated that the lidocaine microspheres had a well-sustained release efficacy, and in vivo studies showed that the area under the curve of lidocaine in microspheres was 2.02–2.06-fold that of lidocaine injection (p < 0.05). The pharmacodynamics results showed that lidocaine microspheres showed a significant release effect in rats, that the process to achieve efficacy was calm and lasting and that the analgesic effect had a significant dose-dependency. PMID:25268618

Effects of formulation variables and characterization of guaifenesin wax microspheres for controlled release.

PubMed

Mani, Narasimhan; Park, M O; Jun, H W

2005-01-01

Sustained-release wax microspheres of guaifenesin, a highly water-soluble drug, were prepared by the hydrophobic congealable disperse method using a salting-out procedure. The effects of formulation variables on the loading efficiency, particle properties, and in-vitro drug release from the microspheres were determined. The type of dispersant, the amount of wetting agent, and initial stirring time used affected the loading efficiency, while the volume of external phase and emulsification speed affected the particle size of the microspheres to a greater extent. The crystal properties of the drug in the wax matrix and the morphology of the microspheres were studied by differential scanning calorimetry (DSC), powder x-ray diffraction (XRD), and scanning electron microscopy (SEM). The DSC thermograms of the microspheres showed that the drug lost its crystallinity during the microencapsulation process, which was further confirmed by the XRD data. The electron micrographs of the drug-loaded microspheres showed well-formed spherical particles with a rough exterior.

Enhancement of Poly(orthoester) Microspheres for DNA Vaccine Delivery by Blending with Poly(ethylenimine)

PubMed Central

Nguyen, David N.; Raghavan, Shyam S.; Tashima, Lauren M.; Lin, Elizabeth C.; Fredette, Stephen J.; Langer, Robert S.; Wang, Chun

2008-01-01

Poly(ortho ester) (POE) microspheres have been previously shown to possess certain advantages for the in vivo delivery of DNA vaccines. In particular, timing of DNA release from POE microspheres in response to acidic phagosomal pH was shown to be an important factor in determining immunogenicity, which was hypothesized to be linked to the natural progression of antigen presenting cell uptake, transfection, maturation, and antigen presentation. Here we report in vitro characterization of the enhanced the efficacy of POE microspheres by blending poly(ethylenimine) (PEI), a well-characterized cationic transfection agent, into the POE matrix. Blending of a tiny amount of PEI (approximately 0.04 wt%) with POE caused large alterations in POE microsphere properties. PEI provided greater control over the rate of pH-triggered DNA release by doubling the total release time of plasmid DNA and enhanced gene transfection efficiency of the microspheres up to 50-fold without any significant cytotoxicity. Confocal microscopy with labeled PEI and DNA plasmids revealed that PEI caused a surface-localizing distribution of DNA and PEI within the POE microsphere as well as focal co-localization of PEI with DNA. We provide evidence that upon degradation, the microspheres of POE-PEI blends released electrostatic complexes of DNA and PEI, which are responsible for the enhanced gene transfection. Furthermore, blending PEI into the POE microsphere induced 50% to 60% greater phenotypic maturation and activation of bone marrow-derived dendritic cells in vitro, judged by up-regulation of co-stimulatory markers on the cell surface. Physically blending PEI with POE is a simple approach for modulating the properties of biodegradable microspheres in terms of gene transfection efficiency and DNA release kinetics. Combined with the ability to induce maturation of antigen-presenting cells, POE-PEI blended microspheres may be excellent carriers for DNA vaccines. PMID:18400294

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.

Preparation and drug controlled release of porous octyl-dextran microspheres.

PubMed

Hou, Xin; Liu, Yanfei

2015-01-01

In this work, porous octyl-dextran microspheres with excellent properties were prepared by two steps. Firstly, dextran microspheres were synthesized by reversed-phase suspension polymerization. Secondly, octyl-dextran microspheres were prepared by the reaction between dextran microspheres and ethylhexyl glycidyl ether and freezing-drying method. Porous structure of microspheres was formed through the interaction between octyl groups and organic solvents. The structure, morphology, dry density, porosity and equilibrium water content of porous octyl-dextran microspheres were systematically investigated. The octyl content affected the properties of microspheres. The results showed that the dry density of microspheres decreased from 2.35 to 1.21 g/ml, porosity increased from 80.68 to 95.05% with the octyl content increasing from 0.49 to 2.28 mmol/g. Meanwhile, the equilibrium water content presented a peak value (90.18%) when the octyl content was 2.25 mmol/g. Octyl-dextran microspheres showed high capacity. Naturally drug carriers play an important role in drug-delivery systems for their biodegradability, wide raw materials sources and nontoxicity. Doxorubicin (DOX) was used as a drug model to examine the drug-loading capacity of porous octyl-dextran microspheres. The drug-loading efficiency increased with the increase in microspheres/drug ratio, while the encapsulation efficiency decreased. When microspheres/drug mass ratio was 4/1, the drug-loading efficiency and encapsulation efficiency were 10.20 and 51.00%, respectively. The release rate of DOX increased as drug content and porosity increased. In conclusion, porous octyl-dextran microspheres were synthesized successfully and have the potential to serve as an effective delivery system in drug controlled release.

Biomimetic composite microspheres of collagen/chitosan/nano-hydroxyapatite: In-situ synthesis and characterization.

PubMed

Teng, Shu-Hua; Liang, Mian-Hui; Wang, Peng; Luo, Yong

2016-01-01

The collagen/chitosan/hydroxyapatite (COL/CS/HA) composite microspheres with a good spherical form and a high dispersity were successfully obtained using an in-situ synthesis method. The FT-IR and XRD results revealed that the inorganic phase in the microspheres was crystalline HA containing carbonate ions. The morphology of the composite microspheres was dependent on the HA content, and a more desirable morphology was achieved when 20 wt.% HA was contained. The composite microspheres exhibited a narrow particle distribution, most of which ranged from 5 to 10 μm. In addition, the needle-like HA nano-particles were uniformly distributed in the composite microspheres, and their crystallinity and crystal size decreased with the HA content. Copyright © 2015 Elsevier B.V. All rights reserved.

Oxaliplatin loaded PLAGA microspheres: design of specific release profiles.

PubMed

Lagarce, F; Cruaud, O; Deuschel, C; Bayssas, M; Griffon-Etienne, G; Benoit, J

2002-08-21

Oxaliplatin loaded PLAGA microspheres have been prepared by solvent extraction process. Parameters affecting the release kinetics in vitro have been studied in order to design specific release profiles suitable for direct intra-tumoral injection. By varying the nature and the relative proportions of different polymers we managed to prepare microspheres with good encapsulation efficiency (75-90%) and four different release profiles: zero order kinetics (type II) and the classical sigmoïd release profile with three different sizes of plateau and burst. These results, if correlated with in vivo activity, are promising to enhance effectiveness of local tumor treatment.

Potential differentiation ability of gingiva originated human mesenchymal stem cell in the presence of tacrolimus

PubMed Central

Ha, Dong-Ho; Pathak, Shiva; Yong, Chul Soon; Kim, Jong Oh; Jeong, Jee-Heon; Park, Jun-Beom

2016-01-01

The aim of the present study is to evaluate the potential differentiation ability of gingiva originated human mesenchymal stem cell in the presence of tacrolimus. Tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres were prepared using electrospraying technique. In vitro release study of tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres was performed in phosphate-buffered saline (pH 7.4). Gingiva-derived stem cells were isolated and incubated with tacrolimus or tacrolimus-loaded microspheres. Release study of the microspheres revealed prolonged release profiles of tacrolimus without any significant initial burst release. The microsphere itself did not affect the morphology of the mesenchymal stem cells, and cell morphology was retained after incubation with microspheres loaded with tacrolimus at 1 μg/mL to 10 μg/mL. Cultures grown in the presence of microspheres loaded with tacrolimus at 1 μg/mL showed the highest mineralization. Alkaline phosphatase activity increased with an increase in incubation time. The highest expression of pSmad1/5 was achieved in the group receiving tacrolimus 0.1 μg/mL every third day, and the highest expression of osteocalcin was achieved in the group receiving 1 μg/mL every third day. Biodegradable poly(lactic-co-glycolic acid)-based microspheres loaded with tacrolimus promoted mineralization. Microspheres loaded with tacrolimus may be applied for increased osteoblastic differentiation. PMID:27721434

Preclinical and clinical in vitro in vivo correlation of an hGH dextran microsphere formulation.

PubMed

Vlugt-Wensink, K D F; de Vrueh, R; Gresnigt, M G; Hoogerbrugge, C M; van Buul-Offers, S C; de Leede, L G J; Sterkman, L G W; Crommelin, D J A; Hennink, W E; Verrijk, R

2007-12-01

To investigate the in vitro in vivo correlation of a sustained release formulation for human growth hormone (hGH) based on hydroxyethyl methacrylated dextran (dex-HEMA) microspheres in Pit-1 deficient Snell dwarf mice and in healthy human volunteers. A hGH-loaded microsphere formulation was developed and tested in Snell dwarf mice (pharmacodynamic study) and in healthy human volunteers (pharmacokinetic study). Single subcutaneous administration of the microspheres in mice resulted in a good correlation between hGH released in vitro and in vivo effects for the hGH-loaded microsphere formulation similar to daily injected hGH indicating a retained bioactivity. Testing the microspheres in healthy volunteers showed an increase (over 7-8 days) in hGH serum concentrations (peak concentrations: 1-2.5 ng/ml). A good in vitro in vivo correlation was obtained between the measured and calculated (from in vitro release data) hGH serum concentrations. Moreover, an increased serum concentration of biomarkers (insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3) was found again indicating that bioactive hGH was released from the microspheres. Good in vitro in vivo correlations were obtained for hGH-loaded dex-HEMA microspheres, which is an important advantage in predicting the effect of the controlled drug delivery product in a clinical situations.

Preclinical and Clinical In Vitro In Vivo Correlation of an hGH Dextran Microsphere Formulation

PubMed Central

de Vrueh, R.; Gresnigt, M. G.; Hoogerbrugge, C. M.; van Buul-Offers, S. C.; de Leede, L. G. J.; Sterkman, L. G. W.; Crommelin, D. J. A.; Hennink, W. E.; Verrijk, R.

2007-01-01

Purpose To investigate the in vitro in vivo correlation of a sustained release formulation for human growth hormone (hGH) based on hydroxyethyl methacrylated dextran (dex-HEMA) microspheres in Pit-1 deficient Snell dwarf mice and in healthy human volunteers. Materials and Methods A hGH-loaded microsphere formulation was developed and tested in Snell dwarf mice (pharmacodynamic study) and in healthy human volunteers (pharmacokinetic study). Results Single subcutaneous administration of the microspheres in mice resulted in a good correlation between hGH released in vitro and in vivo effects for the hGH-loaded microsphere formulation similar to daily injected hGH indicating a retained bioactivity. Testing the microspheres in healthy volunteers showed an increase (over 7–8 days) in hGH serum concentrations (peak concentrations: 1–2.5 ng/ml). A good in vitro in vivo correlation was obtained between the measured and calculated (from in vitro release data) hGH serum concentrations. Moreover, an increased serum concentration of biomarkers (insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3) was found again indicating that bioactive hGH was released from the microspheres. Conclusions Good in vitro in vivo correlations were obtained for hGH-loaded dex-HEMA microspheres, which is an important advantage in predicting the effect of the controlled drug delivery product in a clinical situations. PMID:17929148

Polymer blends used to develop felodipine-loaded hollow microspheres for improved oral bioavailability.

PubMed

Pi, Chao; Feng, Ting; Liang, Jing; Liu, Hao; Huang, Dongmei; Zhan, Chenglin; Yuan, Jiyuan; Lee, Robert J; Zhao, Ling; Wei, Yumeng

2018-06-01

Felodipine (FD) has been widely used in anti-hypertensive treatment. However, it has extremely low aqueous solubility and poor bioavailability. To address these problems, FD hollow microspheres as multiple-unit dosage forms were synthesized by a solvent diffusion evaporation method. Particle size of the hollow microspheres, types of ethylcellulose (EC), amounts of EC, polyvinyl pyrrolidone (PVP) and FD were investigated based on an orthogonal experiment of three factors and three levels. In addition, the release kinetics in vitro and pharmacokinetics in beagle dogs of the optimized FD hollow microspheres was investigated and compared with Plendil (commercial FD sustained-release tablets) as a single-unit dosage form. Results showed that the optimal formulation was composed of EC 10 cp :PVP:FD (0.9:0.16:0.36, w/w). The FD hollow microspheres were globular with a hollow structure and have high drug loading (17.69±0.44%) and floating rate (93.82±4.05%) in simulated human gastric fluid after 24h. Pharmacokinetic data showed that FD hollow microspheres exhibited sustained-release behavior and significantly improved relative bioavailability of FD compared with the control. Pharmacodynamic study showed that the FD hollow microspheres could effectively lower blood pressure. Therefore, these findings demonstrated that the hollow microspheres were an effective sustained-release delivery system for FD. Copyright © 2018 Elsevier B.V. All rights reserved.

Validation of a cage implant system for assessing in vivo performance of long-acting release microspheres.

PubMed

Doty, Amy C; Hirota, Keiji; Olsen, Karl F; Sakamoto, Naoya; Ackermann, Rose; Feng, Meihua R; Wang, Yan; Choi, Stephanie; Qu, Wen; Schwendeman, Anna; Schwendeman, Steven P

2016-12-01

Here we describe development of a silicone rubber/stainless steel mesh cage implant system, much like that used to assess biocompatibility of biomaterials [1], for easy removal of injectable polymer microspheres in vivo. The sterile cage has a type 316 stainless steel mesh size (38 μm) large enough for cell penetration and free fluid flow in vivo but small enough for microsphere retention, and a silicone rubber shell for injection of the microspheres. Two model drugs, the poorly soluble steroid, triamcinolone acetonide, and the highly water-soluble luteinizing hormone-releasing hormone (LHRH) peptide superagonist, leuprolide, were encapsulated in PLGA microspheres large enough (63-90 μm) to be restrained by the cage implant in vivo. The in vitro release from both formulations was followed by ultra-performance liquid chromatography (UPLC) with and without the cage in a standard release media, PBS pH 7.4 + 0.02% Tween 80 + 0.05% sodium azide, at 37 °C. Pharmacokinetics (PK) in rats was assessed after SC injection or SC in-cage implantation of microspheres with plasma analysis by LC-MS/MS or EIA. Tr-A and leuprolide in vitro release was largely unaffected after the initial burst irrespective of the cage or test tube incubation vessel and release was much slower than observed in vivo for both drugs. Moreover, Tr-A and leuprolide pharmacokinetics with and without the cage were highly similar during the 2-3 week release duration before a significant inflammatory response was caused by the cage implant. Hence, the PK-validated cage implant provides a simple means to recover and evaluate the microsphere drug carriers in vivo during a time window of at least a few weeks in order to characterize the polymer microsphere release and erosion behavior in vivo. This approach may facilitate development of mechanism-based in vitro/in vivo correlations and enable development of more accurate and useful in vitro release tests. Copyright © 2016 Elsevier Ltd. All rights reserved.

Microcosmic mechanisms for protein incomplete release and stability of various amphiphilic mPEG-PLA microspheres.

PubMed

Wei, Yi; Wang, Yu Xia; Wang, Wei; Ho, Sa V; Qi, Feng; Ma, Guang Hui; Su, Zhi Guo

2012-10-02

The microcosmic mechanisms of protein (recombinant human growth hormone, rhGH) incomplete release and stability from amphiphilic poly(monomethoxypolyethylene glycol-co-D,L-lactide) (mPEG-PLA, PELA) microspheres were investigated. PELA with different hydrophilicities (PELA-1, PELA-2, and PELA-3) based on various ratios of mPEG to PLA were employed to prepare microspheres exhibiting a narrow size distribution using a combined double emulsion and premix membrane emulsification method. The morphology, rhGH encapsulation efficiency, in vitro release profile, and rhGH stability of PELA microspheres during the release were characterized and compared in detail. It was found that increasing amounts of PLA enhanced the encapsulation efficiency of PELA microspheres but reduced both the release rate of rhGH and its stability. Contact angle, atomic force microscope (AFM), and quartz crystal microbalance with dissipation (QCM-D) techniques were first combined to elucidate the microcosmic mechanism of incomplete release by measuring the hydrophilicity of the PELA film and its interaction with rhGH. In addition, the pH change within the microsphere microenvironment was monitored by confocal laser scanning microscopy (CLSM) employing a pH-sensitive dye, which clarified the stability of rhGH during the release. These results suggested that PELA hydrophilicity played an important role in rhGH incomplete release and stability. Thus, the selection of suitable hydrophilic polymers with adequate PEG lengths is critical in the preparation of optimum protein drug sustained release systems. This present work is a first report elucidating the microcosmic mechanisms responsible for rhGH stability and its interaction with the microspheres. Importantly, this research demonstrated the application of promising new experimental methods in investigating the interaction between biomaterials and biomacromolecules, thus opening up a range of exciting potential applications in the biomedical field including drug delivery and tissue regeneration.

Fabrication of Plasmonic Nanorod-Embedded Dipeptide Microspheres via the Freeze-Quenching Method for Near-Infrared Laser-Triggered Drug-Delivery Applications.

PubMed

Erdogan, Hakan; Yilmaz, Mehmet; Babur, Esra; Duman, Memed; Aydin, Halil M; Demirel, Gokhan

2016-05-09

Control of drug release by an external stimulus may provide remote controllability, low toxicity, and reduced side effects. In this context, varying physical external stimuli, including magnetic and electric fields, ultrasound, light, and pharmacological stimuli, have been employed to control the release rate of drug molecules in a diseased region. However, the design and development of alternative on-demand drug-delivery systems that permit control of the dosage of drug released via an external stimulus are still required. Here, we developed near-infrared laser-activatable microspheres based on Fmoc-diphenylalanine (Phe-Phe) dipeptides and plasmonic gold nanorods (AuNRs) via a simple freeze-quenching approach. These plasmonic nanoparticle-embedded microspheres were then employed as a smart drug-delivery platform for native, continuous, and pulsatile doxorubicin (DOX) release. Remarkable sustained, burst, and on-demand DOX release from the fabricated microspheres were achieved by manipulating the laser exposure time. Our results demonstrate that AuNR-embedded dipeptide microspheres have great potential for controlled drug-delivery systems.

Microsphere based improved sunscreen formulation of ethylhexyl methoxycinnamate.

PubMed

Gogna, Deepak; Jain, Sunil K; Yadav, Awesh K; Agrawal, G P

2007-04-01

Polymethylmethacrylate (PMMA) microspheres of ethylhexyl methoxycinnamate (EHM) were prepared by emulsion solvent evaporation method to improve its photostability and effectiveness as sunscreening agent. Process parameters like stirring speed and aqueous polyvinyl alcohol (PVA) concentration were analyzed in order to optimize the formulations. Shape and surface morphology of the microspheres were examined using scanning electron microscopy. Particle size of the microspheres was determined using laser diffraction particle size analyzer. The PMMA microspheres of EHM were incorporated in water-removable cream base. The in vitro drug release of EHM in pH 7.4 was performed using dialysis membrane. Thin layer chromatography was performed to determine photostability of EHM inside the microspheres. The formulations were evaluated for sun protection factor (SPF) and minimum erythema dose (MED) in albino rats. Cream base formulation containing microspheres prepared using EHM:PMMA in ratio of 1:3 (C(3)) showed slowest drug (EHM) release and those prepared with EHM: PMMA in ratio of 1:1 showed fastest release. The cream base formulations containing EHM loaded microspheres had shown better SPF (more than 16.0) as compared to formulation C(d) that contained 3% free EHM as sunscreen agent and showed SPF 4.66. These studies revealed that the incorporation of EHM loaded PMMA microspheres into cream base had greatly increased the efficacy of sunscreen formulation approximately four times. Further, photostability was also shown to be improved in PMMA microspheres.

Optimization of sustained release aceclofenac microspheres using response surface methodology.

PubMed

Deshmukh, Rameshwar K; Naik, Jitendra B

2015-03-01

Polymeric microspheres containing aceclofenac were prepared by single emulsion (oil-in-water) solvent evaporation method using response surface methodology (RSM). Microspheres were prepared by changing formulation variables such as the amount of Eudragit® RS100 and the amount of polyvinyl alcohol (PVA) by statistical experimental design in order to enhance the encapsulation efficiency (E.E.) of the microspheres. The resultant microspheres were evaluated for their size, morphology, E.E., and in vitro drug release. The amount of Eudragit® RS100 and the amount of PVA were found to be significant factors respectively for determining the E.E. of the microspheres. A linear mathematical model equation fitted to the data was used to predict the E.E. in the optimal region. Optimized formulation of microspheres was prepared using optimal process variables setting in order to evaluate the optimization capability of the models generated according to IV-optimal design. The microspheres showed high E.E. (74.14±0.015% to 85.34±0.011%) and suitably sustained drug release (minimum; 40% to 60%; maximum) over a period of 12h. The optimized microspheres formulation showed E.E. of 84.87±0.005 with small error value (1.39). The low magnitudes of error and the significant value of R(2) in the present investigation prove the high prognostic ability of the design. The absence of interactions between drug and polymers was confirmed by Fourier transform infrared (FTIR) spectroscopy. Differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRPD) revealed the dispersion of drug within microspheres formulation. The microspheres were found to be discrete, spherical with smooth surface. The results demonstrate that these microspheres could be promising delivery system to sustain the drug release and improve the E.E. thus prolong drug action and achieve the highest healing effect with minimal gastrointestinal side effects. Copyright © 2014 Elsevier B.V. All rights reserved.

Preparation and characterization of oxybenzone-loaded gelatin microspheres for enhancement of sunscreening efficacy.

PubMed

Patel, M; Jain, Sunil K; Yadav, Awesh K; Gogna, D; Agrawal, G P

2006-01-01

The objective of our present study was to prepare and evaluate gelatin microspheres of oxybenzone to enhance its sunscreening efficacy. The gelatin microspheres of oxybenzone were prepared by emulsion method. Process parameters were analyzed to optimize the formulation. The in vitro drug release study was performed in pH 7.4 using cellulose acetate membrane. Microspheres prepared using oxybenzone:gelatin ratio of 1:6 showed slowest drug release and those prepared with oxybenzone:gelatin ratio of 1:2 showed fastest drug release. The gelatin microspheres of oxybenzone were incorporated in aloe vera gel. Sun exposure method using sodium nitroprusside solution was used for in vitro sunscreen efficacy testing. The formulation C5 containing oxybenzone-bearing gelatin microspheres in aloe vera gel showed best sunscreen efficacy. The formulations were evaluated for skin irritation test in human volunteers, sun protection factor, and minimum erythema dose in albino rats. These studies revealed that the incorporation of sunscreening agent-loaded microspheres into aloe vera gel greatly increased the efficacy of sunscreen formulation more than four times.

Preparation of gastro-resistant pellets containing chitosan microspheres for improvement of oral didanosine bioavailability

PubMed Central

Severino, Patrícia; de Oliveira, George G.G.; Ferraz, Humberto G.; Souto, Eliana B.; Santana, Maria H.A.

2012-01-01

The purpose of this work was to introduce a new concept of coated pellets containing chitosan microspheres loaded with didadosine for oral administration, aiming at reducing the frequency of administration and improving the bioavailability by a suitable release profile. Chitosan microspheres were produced under fluidized bed, followed by extrusion and spheronization to obtain pellets with a mean diameter of about 1 mm. The pellets were then coated with Kollidon® VA64 and Kollicoat® MAE100P in water dispersion to depict a sustained release profile. Conventional hard gelatine capsules were loaded with these pellets and tested in vitro for their release profile of didadosine. Dissolution testing confirmed that chitosan microsphere pellets provides appropriate sustained release up to 2 h behavior for didanosine. PMID:29403741

Development of ligustrazine hydrochloride carboxymethyl chitosan and collagen microspheres: Formulation optimization, characterization, and vitro release

PubMed Central

Lin, Qiang; Huo, Qing; Qin, Yingzhe; Zhao, Zhuo; Tao, Fengyun

2017-01-01

ABSTRACT This study investigates the preparation of ligustrazine hydrochloride carboxymethyl chitosan and collagen microspheres. This experiment investigates effects of the ratio of carboxymethyl chitosan and collagen blend, water to oil ratio, stirring speed, and other factors on the microsphere properties. The experiment had the following conditions: a 1:2 proportion of carboxymethyl chitosan and collagen, a 1:2 proportion of drugs and materials, a 5:1 proportion of oil phase and water phase, 0.5% of span80, a 600r/min stirring speed, 3 ml of a cross-linking agent, 3 h of cross-linking curing, 1.25 ± 0.05 mm diameter LTH microcapsules, a 54.08% envelop rate, and a 14.16% carrier rate. The microspheres release rate reached 66% within 1 h, then steadily released within 5 h in vitro. The experimental results showed that the ligustrazine hydrochloride microsphere production process was stable and exhibited a good release effect compared with other ligustrazine hydrochloride tablets and pills. PMID:27689792

In-vitro evaluation of ion-exchange microspheres for the sustained release of liposomal-adenoviral conjugates.

PubMed

Steel, Jason C; Cavanagh, Heather M A; Burton, Mark A; Dingwall, Daniel; Kalle, Wouter H J

2004-03-24

This study looks at the development of a novel combination vector consisting of adenovirus conjugated to liposomes (AL complexes) bound to cation-exchanging microspheres (MAL complexes). With adenovirus having a net negative charge and the liposomes a net positive charge it was possible to modify the net charge of the AL complexes by varying the concentrations of adenovirus to liposomes. The modification of the net charge resulted in altered binding and release characteristics. Of the complexes tested, the 5:1 and 2:1 ratio AL complexes were able to be efficiently bound by the microspheres and exhibited sustained release over 24 h. The 1:1 and 1:2 AL complexes, however, bound poorly to the microspheres and were rapidly released. In addition the MAL complexes also were able to reduce the toxicity of the AL complexes, which was seen with the 10:1 ratio. The AL complexes showed considerably more toxicity alone than in combination with microspheres, highlighting a potential benefit of this vector.

Release and Degradation of Microencapsulated Spinosad and Emamectin Benzoate.

PubMed

Huang, Bin Bin; Zhang, Shao Fei; Chen, Peng Hao; Wu, Gang

2017-09-07

The dynamics of release and degradation of the microencapsulation formulation containing spinosad (SP) and emamectin benzoate (EM) were evaluated in the present study. SP and EM were microencapsulated using biodegradable poly-lactic acid (PLA) as the wall material. Their release from and degradation within the prepared SP and EM microspheres (SP-EM-microspheres) were studied. It was found that the encapsulation significantly prolonged the insecticide release. The release could be further extended if the external aqueous phase was pre-saturated with the insecticides and the microspheres were additionally coated with gelatin. On the other hand, increasing the water content of the emulsion or the hydrophilic polycaprolactone (PCL) content in the PLA/PCL mixture accelerated the release. Due to the photolysis and hydrolysis of SP and EM by sunlight, the toxicity of the non-encapsulated insecticides in water declined continuously from 0 through the 9 th day (d), and dissipated in 13 d. In contrast, an aqueous suspension containing 5% SP-EM-microspheres maintained a mostly constant toxicity to Plutella xylostella for 17 d. The biodegradable SP-EM-microspheres showed significantly higher long-term toxicity to P. xylostella due to lower release, reduced photolysis and hydrolysis of the encapsulated insecticides, which were affected by the varied preparation conditions.

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.

Polymeric microspheres

DOEpatents

Walt, David R.; Mandal, Tarun K.; Fleming, Michael S.

2004-04-13

The invention features core-shell microsphere compositions, hollow polymeric microspheres, and methods for making the microspheres. The microspheres are characterized as having a polymeric shell with consistent shell thickness.

Naltrexone-loaded poly[La-(Glc-Leu)] polymeric microspheres for the treatment of alcohol dependence: in vitro characterization and in vivo biocompatibility assessment.

PubMed

Pagar, Kunal P; Vavia, Pradeep R

2014-06-01

The poly[La-(Glc-Leu)] copolymer was applied in the present investigation as polymeric carrier to fabricate naltrexone (NTX)-loaded poly[La-(Glc-Leu)] microspheres in the single emulsion solvent evaporation technique for the long-term treatment of alcohol dependence. Newly synthesized poly[La-(Glc-Leu)] copolymer exhibited diminished crystallanity, good biocompatibility and favorable biodegradability to be explored for drug delivery application. Scanning Electron Microscopy study revealed smooth and spherical-shaped NTX-loaded polymeric microspheres with a mean size of 10-90 µm. Influence of various decisive formulation variables such as amount of polymer, stabilizer concentration, homogenization speed, homogenization time, drug loading and organic-to-aqueous phase ratio on particle size, and entrapment efficiency was studied. Differential scanning calorimeter and X-ray diffractometry study confirmed the drug entrapment within polymer matrix into the microsphere environment. In vitro drug release showed the sustained drug release of formulation for the period of 28 d giving biphasic release pattern. Histological examination of NTX-loaded poly[La-(Glc-Leu)] microspheres injected intramuscularly into the thigh muscle of Wistar rats showed minimal inflammatory reaction, demonstrating that NTX-loaded microspheres were biocompatible. Insignificant increase in the serum creatine phosphokinase level (p < 0.05) as compared with the normal value revealed good muscle compatibility of the poly[La-(Glc-Leu)] microsphere system. Biocompatible nature and sustained drug-release action of poly[La-(Glc-Leu)] microspheres may have potential application in depot therapy.

A facile method for preparing porous, optically active, magnetic Fe3 O4 @poly(N-acryloyl-leucine) inverse core/shell composite microspheres.

PubMed

Liu, Dong; Deng, Jianping; Yang, Wantai

2014-01-01

The first synthesis of porous, optically active, magnetic Fe3 O4 @poly(N-acryloyl-leucine) inverse core/shell composite microspheres is reported, in which the core is constructed of chiral polymer and the shell is constructed of Fe3 O4 NPs. The microspheres integrate three significant concepts, "porosity", "chirality", and "magneticity", in one single microspheric entity. The microspheres consist of Fe3 O4 nanoparticles and porous optically active microspheres, and thus combine the advantages of both magnetic nanoparticles and porous optically active microspheres. The pore size and specific surface area of the microspheres are characterized by N2 adsorption, from which it is found that the composite microspheres possess a desirable porous structure. Circular dichroism and UV-vis absorption spectroscopy measurements demonstrate that the microspheres exhibit the expected optical activity. The microspheres also have high saturation magnetization of 14.7 emu g(-1) and rapid magnetic responsivity. After further optimization, these novel microspheres may potentially find applications in areas such as asymmetric catalysis, chiral adsorption, etc. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Carbidopa/levodopa-loaded biodegradable microspheres: in vivo evaluation on experimental Parkinsonism in rats.

PubMed

Arica, Betül; Kaş, H Süheyla; Moghdam, Amir; Akalan, Nejat; Hincal, A Atilla

2005-02-16

The purpose of this study was to prepare and characterize injectable carbidopa (CD)/levodopa (LD)-loaded Poly(L-lactides) (L-PLA), Poly(D,L-lactides) (D,L-PLA) and Poly(D,L-lactide-co-glycolide) (PLAGA) microspheres for the intracerebral treatment of Parkinson's disease. The microspheres were prepared by solvent evaporation method. The polymers' (L-PLA, D,L-PLA and PLAGA) concentrations were 10% (w/w) in the organic phase; the emulsifiers [sodium carboxymethylcellulose (NaCMC):sodium oleate (SO) and Polyvinyl alcohol (PVA):SO mixture (4:1 w/v)] concentrations were 0.75% in the aqueous phase. Microspheres were analyzed for morphological characteristics, size distribution, drug loading and in vitro release. The release profile of CD/LD from microspheres was characterized in the range of 12-35% within the first hour of the in vitro release experiment. The efficiency of CD- and LD-encapsulated microspheres to striatal transplantation and the altering of apomorphine-induced rotational behavior in the 6-hydroxydopamine (6-OHDA) unilaterally lesioned rat model were also tested. 6-OHDA/CD-LD-loaded microsphere groups exhibited lower rotation scores than 6-OHDA/Blank microsphere groups as early as 1 week postlesion. These benefits continued throughout the entire experimental period and they were statistically significant during the 1, 2 and 8 weeks (p<0.05). CD/LD-loaded microspheres were specifically prepared to apply as an injectable dosage forms for brain implantation.

Dual Drug Loaded Biodegradable Nanofibrous Microsphere for Improving Anti-Colon Cancer Activity

PubMed Central

Fan, Rangrang; Li, Xiaoling; Deng, Jiaojiao; Gao, Xiang; Zhou, Liangxue; Zheng, Yu; Tong, Aiping; Zhang, Xiaoning; You, Chao; Guo, Gang

2016-01-01

One of the approaches being explored to increase antitumor activity of chemotherapeutics is to inject drug-loaded microspheres locally to specific anatomic sites, providing for a slow, long term release of a chemotherapeutic while minimizing systemic exposure. However, the used clinically drug carriers available at present have limitations, such as their low stability, renal clearance and residual surfactant. Here, we report docetaxel (DOC) and curcumin (CUR) loaded nanofibrous microspheres (DOC + CUR/nanofibrous microspheres), self-assembled from biodegradable PLA-PEO-PPO-PEO-PLA polymers as an injectable drug carrier without adding surfactant during the emulsification process. The obtained nanofibrous microspheres are composed entirely of nanofibers and have an open hole on the shell without the assistance of a template. It was shown that these DOC + CUR/nanofibrous microspheres could release curcumin and docetaxel slowly in vitro. The slow, sustained release of curcumin and docetaxel in vivo may help maintain local concentrations of active drug. The mechanism by which DOC + CUR/nanofibrous microspheres inhibit colorectal peritoneal carcinomatosis might involve increased induction of apoptosis in tumor cells and inhibition of tumor angiogenesis. In vitro and in vivo evaluations demonstrated efficacious synergistic antitumor effects against CT26 of curcumin and docetaxel combined nanofibrous microspheres. In conclusion, the dual drug loaded nanofibrous microspheres were considered potentially useful for treating abdominal metastases of colorectal cancer. PMID:27324595

Dual Drug Loaded Biodegradable Nanofibrous Microsphere for Improving Anti-Colon Cancer Activity

NASA Astrophysics Data System (ADS)

Fan, Rangrang; Li, Xiaoling; Deng, Jiaojiao; Gao, Xiang; Zhou, Liangxue; Zheng, Yu; Tong, Aiping; Zhang, Xiaoning; You, Chao; Guo, Gang

2016-06-01

One of the approaches being explored to increase antitumor activity of chemotherapeutics is to inject drug-loaded microspheres locally to specific anatomic sites, providing for a slow, long term release of a chemotherapeutic while minimizing systemic exposure. However, the used clinically drug carriers available at present have limitations, such as their low stability, renal clearance and residual surfactant. Here, we report docetaxel (DOC) and curcumin (CUR) loaded nanofibrous microspheres (DOC + CUR/nanofibrous microspheres), self-assembled from biodegradable PLA-PEO-PPO-PEO-PLA polymers as an injectable drug carrier without adding surfactant during the emulsification process. The obtained nanofibrous microspheres are composed entirely of nanofibers and have an open hole on the shell without the assistance of a template. It was shown that these DOC + CUR/nanofibrous microspheres could release curcumin and docetaxel slowly in vitro. The slow, sustained release of curcumin and docetaxel in vivo may help maintain local concentrations of active drug. The mechanism by which DOC + CUR/nanofibrous microspheres inhibit colorectal peritoneal carcinomatosis might involve increased induction of apoptosis in tumor cells and inhibition of tumor angiogenesis. In vitro and in vivo evaluations demonstrated efficacious synergistic antitumor effects against CT26 of curcumin and docetaxel combined nanofibrous microspheres. In conclusion, the dual drug loaded nanofibrous microspheres were considered potentially useful for treating abdominal metastases of colorectal cancer.

Development of Metronidazole-Loaded Colon-Targeted Microparticulate Drug Delivery System.

PubMed

Kumar, Manoj; Awasthi, Rajendra

2015-01-01

Crohn’s disease and ulcerative colitis are the main autoimmune inflammatory bowel diseases. Metronidazole is the most commonly used drug for the treatment of Crohn’s disease. However, the pharmacokinetic profile of this drug indicates that the largest amount of the drug is absorbed from the upper part of the intestines and very little concentration of the drugs reaches the colon.Objectives: The aim of this investigation was to formulate metronidazole loaded microspheres for the efficient therapy of inflammatory bowel diseases.Material and Methods: Microspheres were prepared using the emulsification-solvent evaporation method. The effect of Eudragit S100 concentration and the ratio of liquid paraffin (light: heavy) on percentage yield, particle size, morphology, drug encapsulation and in vitro drug release was examined. Drug-polymer interaction was investigated using Fourier Transformed Infrared Spectroscopy (FTIR). The results showed that the particle had good flow properties, encapsulation efficiency (56.11 ・} 1.51–81.02 ・} 2.14%)and cumulative drug release (64.14 ・} 0.83–79.69 ・} 2.45%) in a phosphate buffer (pH 6.8) after 10 h of the dissolution study.An increased particle size was observed with an increasing polymer concentration. It was observed that the Eudragit had a positive effect on the drug encapsulation and negative effect on drug release. Aggregation of drug-polymer droplets was observed at a lower level of magnesium stearate during microsphere preparation. The results of FTIR spectroscopy revealed the absence of any drug-polymer interactions. However, slight peak shifting and suppression in peak height was observed.This might be due to the minor ionic interactions. The microspheres were discrete, spherical and free-flowing. The spherical shape of the microspheres was confirmed from SEM photomicrographs. The developed microspheres showed a controlled drug release and were found to follow Higuchi’s model. The release mechanism of metronidazole from the microspheres was Fickian diffusion without swelling. The results suggest that the developed microspheres could enhance drug entrapment, and inflect the drug release.

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.

Biodegradable nano-micro carrier systems for sustained pulmonary drug delivery: (I) Self-assembled nanoparticles encapsulated in respirable/swellable semi-IPN microspheres

PubMed Central

El-Sherbiny, I. M.; Smyth, H. D. C.

2012-01-01

Design of appropriate inhaled carriers with adequate aerodynamic properties, drug release, biodegradation and evasion of macrophage uptake is a major challenge for controlled release pulmonary drug delivery. In this study, PEG graft copolymerized onto N-phthaloyl chitosan (NPHCs) was synthesized then characterized using FTIR, EA, DSC and 2D-XRD. The resulting PEG-g-NPHCs copolymers were self-assembled into drug loaded nanoparticles and encapsulated in respirable/swellable sodium alginate semi-IPN hydrogel microspheres as novel biodegradable carriers for controlled release pulmonary drug delivery. The developed nano-/microspheres carrier systems were formed via spray drying followed by ionotropic crosslinking in mild aqueous medium. The size of the developed self-assembled nanoparticles and the microspheres was measured using dynamic light scattering and laser diffraction, respectively. Morphology, moisture content, in-vitro biodegradation and dynamic swelling studies were also investigated for the developed carriers. A model protein was entrapped and the in-vitro release profiles were determined in PBS, pH 7.4 at 37°C. A dry powder aerosolization study was conducted using a Next Generation Impactor (NGI). The developed microspheres had suitable aerodynamic diameters (1.02–2.63 μm) and an excellent fine particle fraction, FPF of 31.52%. The microspheres showed also a very fast initial swelling within the first 2 min and started to enzymatically degrade within the first two hours. Moreover, the microspheres entrapped up 90% of the model drug and showed promising in-vitro sustained release profiles as compared to the control formulation. PMID:20580794

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.

Accelerated dissolution testing for controlled release microspheres using the flow-through dissolution apparatus.

PubMed

Collier, Jarrod W; Thakare, Mohan; Garner, Solomon T; Israel, Bridg'ette; Ahmed, Hisham; Granade, Saundra; Strong, Deborah L; Price, James C; Capomacchia, A C

2009-01-01

Theophylline controlled release capsules (THEO-24 CR) were used as a model system to evaluate accelerated dissolution tests for process and quality control and formulation development of controlled release formulations. Dissolution test acceleration was provided by increasing temperature, pH, flow rate, or adding surfactant. Electron microscope studies on the theophylline microspheres subsequent to each experiment showed that at pH values of 6.6 and 7.6 the microspheres remained intact, but at pH 8.6 they showed deterioration. As temperature was increased from 37-57 degrees C, no change in microsphere integrity was noted. Increased flow rate also showed no detrimental effect on integrity. The effect of increased temperature was determined to be the statistically significant variable.

Development of Yersinia pestis F1 antigen-loaded microspheres vaccine against plague

PubMed Central

Huang, Shih-shiung; Li, I-Hsun; Hong, Po-da; Yeh, Ming-kung

2014-01-01

Yersinia pestis F1 antigen-loaded poly(DL-lactide-co-glycolide)/polyethylene glycol (PEG) (PLGA/PEG) microspheres were produced using a water-in-oil-in-water emulsion/solvent extraction technique and assayed for their percent yield, entrapment efficiency, surface morphology, particle size, zeta potential, in vitro release properties, and in vivo animal protect efficacy. The Y. pestis F1 antigen-loaded microspheres (mean particle size 3.8 μm) exhibited a high loading capacity (4.5% w/w), yield (85.2%), and entrapment efficiency (38.1%), and presented a controlled in vitro release profile with a low initial burst (18.5%), then continued to release Y. pestis F1 antigen over 70 days. The distribution (%) of Y. pestis F1 on the microspheres surface, outer layer, and core was 3.1%, 28.9%, and 60.7%, respectively. A steady release rate was noticed to be 0.55 μg Y. pestis F1 antigen/mg microspheres/day of Y. pestis F1 antigen release maintained for 42 days. The cumulative release amount at the 1st, 28th, and 42nd days was 8.2, 26.7, and 31.0 μg Y. pestis F1 antigen/mg microspheres, respectively. The 100 times median lethal dose 50% (LD50) of Y. pestis Yokohama-R strain by intraperitoneal injection challenge in mice test, in which mice received one dose of 40 μg F1 antigen content of PLGA/PEG microspheres, F1 antigen in Al(OH)3, and in comparison with F1 antigen in Al(OH)3 vaccine in two doses, was evaluated after given by subcutaneous immunization of BALB/c mice. The study results show that the greatest survival was observed in the group of mice immunized with one dose of F1 antigen-loaded PLGA/PEG microspheres, and two doses of F1 antigen in Al(OH)3 vaccine (100%). In vivo vaccination studies also demonstrated that F1 vaccines microspheres had a protective ability; its steady-state IgG immune protection in mice plasma dramatic increased from 2 weeks (18,764±3,124) to 7 weeks (126,468±19,176) after vaccination. These findings strongly suggest that F1-antigen loaded microspheres vaccine offer a new therapeutic strategy in optimizing the vaccine incorporation and delivery properties of these potential vaccine targeting carriers. PMID:24550673

Comparative Investigation on Thermal Insulation of Polyurethane Composites Filled with Silica Aerogel and Hollow Silica Microsphere.

PubMed

Liu, Chunyuan; Kim, Jin Seuk; Kwon, Younghwan

2016-02-01

This paper presents a comparative study on thermal conductivity of PU composites containing open-cell nano-porous silica aerogel and closed-cell hollow silica microsphere, respectively. The thermal conductivity of PU composites is measured at 30 degrees C with transient hot bridge method. The insertion of polymer in pores of silica aerogel creates mixed interfaces, increasing the thermal conductivity of resulting composites. The measured thermal conductivity of PU composites filled with hollow silica microspheres is estimated using theoretical models, and is in good agreement with Felske model. It appears that the thermal conductivity of composites decreases with increasing the volume fraction (phi) when hollow silica microsphere (eta = 0.916) is used.

Biomechanical characterization of a low density silicone elastomer filled with hollow microspheres for maxillofacial prostheses.

PubMed

Liu, Q; Shao, L Q; Xiang, H F; Zhen, D; Zhao, N; Yang, S G; Zhang, X L; Xu, J

2013-01-01

An ideal material for maxillofacial prostheses has not been found. We created a novel material: silicone elastomer filled with hollow microspheres and characterized its biomechanical properties. Expancel hollow microspheres were mixed with MDX4-4210 silicone elastomer using Q7-9180 silicone fluid as diluent. The volume fractions of microspheres were 0, 5, 15, and 30% v/v (volume ratio to the total volume of MDX4-4210 and microspheres). The microspheres dispersed well in the matrix. The physical properties and biocompatibility of the composites were examined. Shock absorption was the greatest by the 5% v/v composite, and decreased with increasing concentrations of microspheres. The density, thermal conductivity, Shore A hardness, tear and tensile strength decreased with increasing concentrations of microspheres, while elongation at break increased. Importantly, the tear strength of all composites was markedly lower than that of pure silicone elastomer. Cell viability assays indicated that the composite was of good biocompatibility. The composite with a volume fraction of 5% exhibited the optimal properties for use as a maxillofacial prosthesis, though its tear strength was markedly lower than that of silicone elastomer. In conclusion, we developed a novel light and soft material with good flexibility and biocompatibility, which holds a promising prospect for clinical application as maxillofacial prosthesis.

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.

Preparation, characterization, and in vitro testing of poly(lactide-co-glycolide) and dextran magnetic microspheres for in vivo applications

NASA Astrophysics Data System (ADS)

Leamy, Patrick J.

Many research groups are investigating degradable magnetic particles for magnetic resonance imaging (MRI) contrast agents and as carriers for magnetic drug guidance. These particles are composite materials with a degradable polymer matrix and iron oxide nanoparticles for magnetic properties. The degradable polymer matrix acts to provide colloidal stability and, for drug delivery applications, provides a reservoir for the storage and release of drugs. Natural polymers, like albumin and dextran, which degrade by the action of enzymes; have been used for the polymer matrix. Iron oxide nanoparticles are used for magnetic properties since they can be digested in vivo and have low toxicities. Polylactic acid (PLA) and its copolymers with polyglycolic acid (PLGA) are versatile polymers that degrade by simple hydrolysis without the aid of enzymes. Microspheres are easily formed using the solvent extraction/evaporation method and a wide range of drugs can be encapsulated in them. Magnetic PLGA microspheres suitable for applications were synthesized for the first time in this dissertation. This was accomplished by coating iron oxide nanoparticles with oleic acid to make them dispersible in the organic solvents used in the extraction/evaporation microsphere preparation method. In addition to the magnetic PLGA microspheres, a novel all-aqueous method for preparing crosslinked dextran magnetic microspheres was developed in this dissertation. This method uses free radical polymerization for crosslinking and does not require the use of flammable and harmful solvents. For efficient MRI contrast and magnetic drug guidance, maximized iron oxide content of microspheres is desirable. The two different microsphere preparation methods were optimized for iron oxide content. The effect of iron oxide content on microsphere size and morphology was studied. In addition, an in vitro circulation model was used to evaluate the ability of magnetic microspheres to be guided at physiologic blood flow velocities. The MRI contrast effect was studied as a function of microsphere concentration.

Prolonged amelioration of experimental postoperative pain by bupivacaine released from microsphere-coated hernia mesh.

PubMed

Ohri, Rachit; Wang, Jeffery Chi-Fei; Pham, Lan; Blaskovich, Phillip D; Costa, Daniel; Nichols, Gary; Hildebrand, William; Scarborough, Nelson; Herman, Clifford; Strichartz, Gary R

2014-01-01

Postoperative pain alters physiological functions and delays discharge. Perioperative local anesthetics are effective analgesics in the immediate 1- to 2-day postoperative period, but acute pain often lasts longer. The goal of this work was to develop a local anesthetic formulation adhering to an intraoperative implanted device that reduces pain for at least 3 days after surgery. Six groups, each with 8 rats, were studied. In a control group (group I), one 1.2-cm-long incision of the skin was followed by blunt dissection to separate the skin away from the underlying tissues and closing with 2 sutures. In 3 of the treatment groups, the same surgical procedure was used, with the subcutaneous space formed by the blunt dissection lined with a 1-cm square patch of hernia mesh coated with poly lactide co-glycolic acid microspheres containing approximately 17 mg of bupivacaine (group II), no drug (placebo; group III), or bupivacaine free-base powder (group IV). Uncoated mesh implants (group V) served as a secondary control. A standard bupivacaine solution (0.4 mL, 0.5%; 2-mg dose) was infiltrated subcutaneously 30 minutes before the surgery and served as a standard control (group VI). Mechanosensitivity of the skin was tested by the local subcutaneous muscle responses to cutaneous tactile stimulation by von Frey hairs with forces of 4 g (for allodynia) and 15 g (for hyperalgesia) preoperatively and for 7 postoperative days. Control rats (group I) showed mechanohypersensitivity, indicative of postoperative allodynia and hyperalgesia, for all 7 postoperative days. Mechanohyperalgesia in rats that received mesh coated with bupivacaine-releasing microspheres (group II) was reduced during this period to 13% of control postoperative values (P < 0.001); mesh coated with bupivacaine base (group IV) reduced it by 50% (P = 0.034). The placebo mesh (group III) and uncoated mesh (group V) caused no significant reduction of mechanohypersensitivity, and bupivacaine solution infiltrated before the incision (group VI) reduced hypersensitivity for only approximately 2 hours, an overall insignificant effect. Bupivacaine slowly released for 72 hours from microspheres adsorbed to the hernia mesh significantly suppresses evoked postoperative hypersensitivity for at least 1 week and is more effective than a suspension of these microspheres or preoperative single-shot infiltration of bupivacaine.

Responsive copolymer–graphene oxide hybrid microspheres with enhanced drug release properties

DOE PAGES

Dong, Fuping; Firkowska-Boden, Izabela; Arras, Matthias M. L.; ...

2017-01-13

Here, the ability to integrate both high encapsulation efficiency and controlled release in a drug delivery system (DDS) is a highly sought solution to cure major diseases. However, creation of such a system is challenging. This study was aimed at constructing a new delivery system based on thermoresponsive poly(N-isopropylacrylamide-co-styrene) (PNIPAAm-co-PS) hollow microspheres prepared via two-step precipitation polymerization. To control the diffusion-driven drug release, the PNIPAAm-co-PS spheres were electrostatically coated with graphene oxide (GO) nanosheets. As a result of the coating the permeability of such copolymer-GO hybrid microspheres was reduced to the extent that suppressed the initial burst release and enabledmore » sustained drug release in in vitro testing. The hybrid microspheres showed improved drug encapsulation by 46.4% which was attributed to the diffusion barrier properties and -conjugated structure of GO. The system presented here is promising to advance, e.g., the anticancer drug delivery technologies by enabling sustained drug release and thus minimizing local and systemic side effects.« less

Responsive copolymer–graphene oxide hybrid microspheres with enhanced drug release properties

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

Dong, Fuping; Firkowska-Boden, Izabela; Arras, Matthias M. L.

Here, the ability to integrate both high encapsulation efficiency and controlled release in a drug delivery system (DDS) is a highly sought solution to cure major diseases. However, creation of such a system is challenging. This study was aimed at constructing a new delivery system based on thermoresponsive poly(N-isopropylacrylamide-co-styrene) (PNIPAAm-co-PS) hollow microspheres prepared via two-step precipitation polymerization. To control the diffusion-driven drug release, the PNIPAAm-co-PS spheres were electrostatically coated with graphene oxide (GO) nanosheets. As a result of the coating the permeability of such copolymer-GO hybrid microspheres was reduced to the extent that suppressed the initial burst release and enabledmore » sustained drug release in in vitro testing. The hybrid microspheres showed improved drug encapsulation by 46.4% which was attributed to the diffusion barrier properties and -conjugated structure of GO. The system presented here is promising to advance, e.g., the anticancer drug delivery technologies by enabling sustained drug release and thus minimizing local and systemic side effects.« less

A novel accelerated in vitro release method to evaluate the release of thymopentin from PLGA microspheres.

PubMed

Xie, Xiangyang; Li, Zhiping; Zhang, Ling; Chi, Qiang; Yang, Yanfang; Zhang, Hui; Yang, Yang; Mei, Xingguo

2015-01-01

A novel accelerated method of good correlations with "real-time" release to evaluate in vitro thymopentin release from poly (D, L-lactide-co-glycolide) (PLGA) microsphere was developed. Thymopentin-loaded microspheres were made from three types of PLGA, and peptide release was studied in various conditions. Incomplete release of peptide (<60%) from microspheres was found in accelerated testing with two typical release media. This problem was circumvented by adding organic solvents to the release media and varying the temperature in the media heating process. Release media containing three kinds of organic solvents at 50 °C were tested, respectively, and hydro-alcoholic solution was selected for further study. After the surfactant concentration (0.06%, W/V) and ethanol concentration (20%, V/V) were fixed, a gradient heating program, consisting of three stages and each stage with a different temperature, was introduced to enhance the correlations between the short- and long-term release. After adjusting the heating time of each stage, a good correlation (R(2) = 9896, formulation 8 K; R(2) = 0.9898, formulation 13 K; R(2) = 0.9886, formulation 28 K) between accelerated and "real-time" release was obtained. By optimizing the conditions as ethanol concentration and temperature gradients, this accelerated method may be appropriate for similar peptide formulations that not well correlate with "real-time" release.

Effect of sodium tripolyphosphate concentration and simulated gastrointestinal fluids on release profile of paracetamol from chitosan microsphere

NASA Astrophysics Data System (ADS)

Mulia, Kamarza; Andrie; Krisanti, Elsa A.

2018-03-01

The problem to overcome in oral drug administration is the significant pH changes present in the human digestive system. In this study, ionotropic gelation method employing 2-8% (w/v) tripolyphosphate solutions were used to crosslink chitosan microspheres for a controlled release of paracetamol as a model drug. The release profiles of paracetamol from chitosan microspheres were determined using simulated gastrointestinal fluids having pH values of 1.2, 6.8, and 7.4. The results showed that the paracetamol loading and the encapsulation efficiency values increased with increasing concentration of tripolyphosphate solutions used in the preparation step. Paracetamol released at pH 1.2 and 6.8 buffer solutions was significantly higher than that at pH 7.4; also, more paracetamol was released in the presence of α-amylase and β-glucosidase enzymes. The release profiles showed zero-order release behaviour up to 8 hours where the highest drug release was 39% of the paracetamol loaded in the chitosan microspheres, indicating a strong crosslinking between chitosan and TPP anions. The relatively low accumulated drug release could be compensated by employing suitable enzymes, lower TPP solution concentration, and addition of other biodegradable polymer to reduce the TPP crosslink.

Improvements in processing characteristics and engineering properties of wood flour-filled high density polyethylene composite sheeting in the presence of hollow glass microspheres

Treesearch

Baris Yalcin; Steve E Amos; Andrew S D Souza; Craig M Clemons; I Sedat Gunes; Troy K Ista

2012-01-01

Hollow glass microspheres were introduced into wood flour/high density polyethylene composites by melt compounding in a twin-screw extruder. The prepared composites were subsequently converted to extruded profiles in order to obtain composite sheeting. The presence of hollow glass microspheres highly reduced the density of the extruded sheets down to 0.9 g/cc, while...

PEG modulated release of etanidazole from implantable PLGA/PDLA discs.

PubMed

Wang, Fangjing; Lee, Timothy; Wang, Chi-Hwa

2002-09-01

In this work, etanidazole (one type of hypoxic radiosensitizer) is encapsulated into spray dried poly(D),L-lactide-co-glycolide) (PLGA) microspheres and then compressed into discs for controlled release applications. Etanidazole is characterized by intracellular glutathione depletion and glutathione transferases inhibition, thereby enhancing sensitivity to radiation. It is also cytotoxic to tumor cells and can chemosensitize some alkylating agents by activating their tumor cell killing capabilities. We observed the release characteristics of etanidazole in the dosage forms of microspheres and discs, subjected to different preparation conditions. The release characteristics, morphology changes, particle size, and encapsulation efficiency of microspheres are also investigated. The release rate of etanidazole from implantable discs (13 mm in diameter, 1 mm in thickness, fabricated by a press) is much lower than microspheres due to the reduced specific surface. After the initial burst of 1% release for the first day, the cumulative release within the first week is less than 2% until a secondary burst of release (caused by polymer degradation) occurs after one month. Some key preparation conditions such as drug loadings, disc thickness and diameter, and compression pressure can affect the initial burst of etanidazole from the discs. However, none of them can significantly make the release more uniform. In contrast, the incorporation of polyethylene glycol (PEG) can greatly enhance the release rate of discs and also reduces the secondary burst effect, thereby achieving a sustained release for about 2 months.

High-Q Microsphere Cavity for Laser Stabilization and Optoelectronic Microwave Oscillator

NASA Technical Reports Server (NTRS)

Ilchenko, Vladimir S.; Yao, X. Steve; Maleki, Lute

2000-01-01

With submillimeter size and optical Q up to approximately 10 (exp 10), microspheres with whispering-gallery (WG) modes are attractive new component for fiber-optics/photonics applications and a potential core in ultra-compact high-spectral-purity optical and microwave oscillators. In addition to earlier demonstrated optical locking of diode laser to WG mode in a microsphere, we report on microsphere application in the microwave optoelectronic oscillator, OEO. In OEO, a steady-state microwave modulation of optical carrier is obtained in a closed loop including electro-optical modulator, fiber-optic delay, detector and microwave amplifier. OEO demonstrates exceptionally low phase noise (-140 dBc/Hz at l0kHz from approximately 10GHz carrier) with a fiber length approximately 2km. Current technology allows to put all parts of the OEO, except the fiber, on the same chip. Microspheres, with their demonstrated Q equivalent to a kilometer fiber storage, can replace fiber delays in a truly integrated device. We have obtained microwave oscillation in microsphere-based OEO at 5 to 18 GHz, with 1310nm and 1550nm optical carrier, in two configurations: 1) with external DFB pump laser, and 2) with a ring laser including microsphere and a fiber optic amplifier. Also reported is a simple and efficient fiber coupler for microspheres facilitating their integration with existing fiber optics devices.

A novel sustained-release formulation of recombinant human growth hormone and its pharmacokinetic, pharmacodynamic and safety profiles.

PubMed

Wei, Yi; Wang, Yuxia; Kang, Aijun; Wang, Wei; Ho, Sa V; Gao, Junfeng; Ma, Guanghui; Su, Zhiguo

2012-07-02

An effective and safe formulation of sustained-release rhGH for two months using poly(monomethoxypolyethylene glycol-co-D,L-lactide) (mPEG-PLA, PELA) microspheres was developed to reduce the frequency of medication. The rhGH-loaded PELA microspheres with a narrow size distribution were successfully prepared by a double emulsion method combined with a premix membrane emulsification technique without any exogenous stabilizing excipients. The narrow size distribution of the microspheres would guarantee repeatable productivity and release behavior. Moreover, the amphiphilic PELA improved the bioactivity retention of protein drugs since it prevented protein contact with the oil/water interface and the hydrophobic network, and modulated diffusion of acidic degradation products from the carrier system. These PELA microspheres were compared in vivo with commercial rhGH solution, conventional poly(D,L-lactic acid) (PLA) and poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres. Administration of rhGH-PELA could extend the duration of rhGH release (for up to 56 days) and increase area under the curve (AUC) compared to rhGH solution, PLA or PLGA microspheres in Sprague-Dawley (SD) rats. In addition, rhGH-PELA microspheres induced a greater response in total insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) than other rhGH formulations. With a hypophysectomized SD rat model, the pharmacological efficacy of rhGH-PELA microspheres was shown to be better than that from daily administration of rhGH solutions over 6 days based on body weight gain and width of the tibial growth plate. Histological examination of the injection sites indicated a significantly milder inflammatory response than that observed after injection of PLA and PLGA microspheres. Neither anti-rhGH antibodies nor the toxic effects on heart, liver and kidney were detectable after administration of rhGH-PELA microspheres in SD rats. These results suggest that rhGH-PELA microspheres have the potential to be clinically effective and safe when administered only once every two months, a dose regimen for better patient acceptance and compliance.

Synergetic Effect of Yolk-Shell Structure and Uniform Mixing of SnS-MoS₂ Nanocrystals for Improved Na-Ion Storage Capabilities.

PubMed

Choi, Seung Ho; Kang, Yun Chan

2015-11-11

Mixed metal sulfide composite microspheres with a yolk-shell structure for sodium-ion batteries are studied. Tin-molybdenum oxide yolk-shell microspheres prepared by a one-pot spray pyrolysis process transform into yolk-shell SnS-MoS2 composite microspheres. The discharge capacities of the yolk-shell and dense-structured SnS-MoS2 composite microspheres for the 100th cycle are 396 and 207 mA h g(-1), and their capacity retentions measured from the second cycle are 89 and 47%, respectively. The yolk-shell SnS-MoS2 composite microspheres with high structural stability during repeated sodium insertion and desertion processes have low charge-transfer resistance even after long-term cycling. The synergetic effect of the yolk-shell structure and uniform mixing of the SnS and MoS2 nanocrystals result in the excellent sodium-ion storage properties of the yolk-shell SnS-MoS2 composite microspheres by improving their structural stability during cycling.

Degradation and protein release properties of microspheres prepared from biodegradable poly(lactide-co-glycolide) and ABA triblock copolymers: influence of buffer media on polymer erosion and bovine serum albumin release.

PubMed

Bittner, B; Witt, C; Mäder, K; Kissel, T

1999-08-05

The aim of the present study was to investigate the influence of the chemical insertion of poly(ethylene oxide), PEO, into a poly(lactide-co-glycolide), PLG, backbone on the mechanisms of in vitro degradation and erosion of the polymer. For this purpose microspheres prepared by a modified W/O/W double emulsion technique using ABA triblock copolymers, consisting of PLG A-blocks attached to central PEO B-blocks were compared with microspheres prepared from PLG. Due to their molecular architecture the ABA triblock copolymers differed in their erosion and degradation behavior from PLG. Degradation occurred faster in the ABA polymers by cleavage of ester bonds inside the polymer backbone. Even erosion was shown to start immediately after incubation in different buffer media. By varying pH and ionic strength of the buffer it was found that both mass loss and molecular weight decay were accelerated in alkaline and acidic pH in the case of the ABA triblock copolymers. Although the pH of the medium had a moderate influence on the degradation of PLG, the molecular weight decay was not accompanied by a mass loss during the observation time. In a second set of experiments we prepared bovine serum albumin, BSA, loaded microspheres from both polymers. The release of BSA from ABA microspheres under in vitro conditions parallels the faster swelling and erosion rates. This could be confirmed by electron paramagnetic resonance, EPR, measurements with spin labeled albumin where an influx of buffer medium into the ABA microspheres was already observed within a few minutes. In contrast, PLG microspheres revealed a burst release without any erosion. The current study shows that the environmental conditions affected the degradation and erosion of the pure polymer microspheres in the same way as the release of the model protein. This leads to the conclusion that the more favorable degradation profile of the ABA triblock copolymers was responsible for the improvement of the release profile.

Development of Recombinant Human Growth Hormone (rhGH) sustained-release microspheres by a low temperature aqueous phase/aqueous phase emulsion method.

PubMed

Kang, Jian; Wu, Fei; Cai, Yunpeng; Xu, Mingxin; He, Mu; Yuan, Weien

2014-10-01

A novel method has been developed to protect Recombinant Human Growth Hormone (rhGH) in poly (lactic-co-glycolic acid) (PLGA) microspheres using an aqueous phase/aqueous phase emulsion and S/O/W multi-emulsion method. This method develops a novel rhGH sustained-release system, which is based on the combination of rhGH-loaded dextran microparticles and PLGA microspheres. The process to fabricate rhGH-loaded dextran microparticles involves an aqueous phase/aqueous phase emulsion system formed at the reduced temperature. RhGH was first dissolved in water together with dextran and polyethylene glycol, followed by stirring at the speed of 2000 rpm for 20-30s at 0°C, and then a freezing process could enable the dextran phase to separate from the continuous PEG phase and rhGH could preferentially be loaded with dextran. The sample after freezing and phase separation was then lyophilized to powder and washed with dichloromethane to remove the PEG. Once loaded in the dextran microparticles (1-4 μm in diameter), rhGH gained resistance to interface tensions and was encapsulated into PLGA microspheres without aggregation thereafter. RhGH released from PLGA microspheres was in a sustained manner with minimal burst and maximally reduced incomplete release in vitro. Single subcutaneous injection of rhGH-loaded PLGA microspheres to rats resulted in a stable plasma concentration for 30 days avoiding the drug concentration fluctuations after multiple injections of protein solutions. In a hypophysectomized rat model, the IGF-1 and bodyweight results showed that there were higher than the levels obtained for the sustained release formulation by W/O/W for 40 days. These results suggest that the microsphere delivery system had the potential to be an injectable depot for sustained-release of the biocompatible protein of rhGH. Copyright © 2014 Elsevier B.V. All rights reserved.

Fabrication and evaluation of a sustained-release chitosan-based scaffold embedded with PLGA microspheres.

PubMed

Song, Kedong; Liu, Yingchao; Macedo, Hugo M; Jiang, Lili; Li, Chao; Mei, Guanyu; Liu, Tianqing

2013-04-01

Nutrient depletion within three-dimensional (3D) scaffolds is one of the major hurdles in the use of this technology to grow cells for applications in tissue engineering. In order to help in addressing it, we herein propose to use the controlled release of encapsulated nutrients within polymer microspheres into chitosan-based 3D scaffolds, wherein the microspheres are embedded. This method has allowed maintaining a stable concentration of nutrients within the scaffolds over the long term. The polymer microspheres were prepared using multiple emulsions (w/o/w), in which bovine serum albumin (BSA) and poly (lactic-co-glycolic) acid (PLGA) were regarded as the protein pattern and the exoperidium material, respectively. These were then mixed with a chitosan solution in order to form the scaffolds by cryo-desiccation. The release of BSA, entrapped within the embedded microspheres, was monitored with time using a BCA kit. The morphology and structure of the PLGA microspheres containing BSA before and after embedding within the scaffold were observed under a scanning electron microscope (SEM). These had a round shape with diameters in the range of 27-55 μm, whereas the chitosan-based scaffolds had a uniform porous structure with the microspheres uniformly dispersed within their 3D structure and without any morphological change. In addition, the porosity, water absorption and degradation rate at 37 °C in an aqueous environment of 1% chitosan-based scaffolds were (92.99±2.51) %, (89.66±0.66) % and (73.77±3.21) %, respectively. The studies of BSA release from the embedded microspheres have shown a sustained and cumulative tendency with little initial burst, with (20.24±0.83) % of the initial amount released after 168 h (an average rate of 0.12%/h). The protein concentration within the chitosan-based scaffolds after 168 h was found to be (11.44±1.81)×10(-2) mg/mL. This novel chitosan-based scaffold embedded with PLGA microspheres has proven to be a promising technique for the development of new and improved tissue engineering scaffolds. Copyright © 2012 Elsevier B.V. All rights reserved.

In situ growth of copper nanocrystals from carbonaceous microspheres with electrochemical glucose sensing properties

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

Zhou, Xiaoliang; Yan, Zhengguang, E-mail: yanzg2004@gmail.com; Han, Xiaodong, E-mail: xdhan@bjut.edu.cn

2014-02-01

Graphical abstract: In situ growth of copper nanoparticles from hydrothermal copper-containing carbonaceous microspheres was induced by annealing or electron beam irradiation. Obtained micro-nano carbon/copper composite microspheres show electrochemical glucose sensing properties. - Highlights: • We synthesized carbonaceous microspheres containing non-nanoparicle copper species through a hydrothermal route. • By annealing or electron beam irradiation, copper nanoparticles would form from the carbonaceous microspheres in situ. • By controlling the annealing temperature, particle size of copper could be controlled in the range of 50–500 nm. • The annealed carbon/copper hierarchical composite microspheres were used to fabricate an electrochemical glucose sensor. - Abstract: Inmore » situ growth of copper nanocrystals from carbon/copper microspheres was observed in a well-controlled annealing or an electron beam irradiation process. Carbonaceous microspheres containing copper species with a smooth appearance were yielded by a hydrothermal synthesis using copper nitrate and ascorbic acid as reactants. When annealing the carbonaceous microspheres under inert atmosphere, copper nanoparticles were formed on carbon microspheres and the copper particle sizes can be increased to a range of 50–500 nm by altering the heating temperature. Similarly, in situ formation of copper nanocrystals from these carbonaceous microspheres was observed on the hydrothermal product carbonaceous microspheres with electron beam irradiation in a vacuum transmission electron microscopy chamber. The carbon/copper composite microspheres obtained through annealing were used to modify a glassy carbon electrode and tested as an electrochemical glucose sensor.« less

Chitosan microspheres as candidate plasmid vaccine carrier for oral immunisation of Japanese flounder (Paralichthys olivaceus).

PubMed

Tian, Jiyuan; Yu, Juan; Sun, Xiuqin

2008-12-15

Oral DNA-based immunotherapy is a new treatment option for fish immunisation in intensive culture. However, because of the existence of the nucleases and severe gastrointestinal conditions, DNA-based vaccines can be hydrolyzed or denatured. In our laboratory, a plasmid DNA (pDNA) containing major capsid protein (MCP) gene of lymphocystis disease virus (LCDV) was prepared, and then pDNA was encapsulated in chitosan microspheres through an emulsion-based methodology. The yield, loading percent and encapsulation efficiency of microspheres were 93.6%, 0.3% and 94.5%, respectively. Scanning electron microscopy (SEM) showed that pDNA-loaded microspheres yielded a spherical shape with smooth surfaces. The disproportion of super-coiled to open circle and linear pDNA suggested that high transfection efficiencies of pDNA in microspheres were retained. The cumulative release of pDNA showed that chitosan microspheres were resistant to degradation in simulated gastrointestinal tract environment. The release profile at PBS buffer (pH 7.4) displayed that pDNA-loaded chitosan microspheres had a release up to 42 days after intestinal imbibition. RT-PCR showed that RNA containing information of MCP gene existed in various tissues 10-90 days post-vaccination. SDS-PAGE and immunofluorescent images indicated that pDNA expressed MCP in tissues of fish 10-90 days after oral administration. In addition, indirect ELISA displayed that the immune responses of sera were positive (O.D.> or =0.3) from week 1 to week 16 for fish vaccinated with microspheres, in comparison with fish vaccinated with naked pDNA. Data obtained suggested that chitosan microspheres were promising carriers for oral pDNA vaccine. Because this encapsulation technique was easy to operate and immunisation efficacy of microspheres loaded with pDNA was significant, it had potential to be used in drug delivery applications.

Statistical optimization of controlled release microspheres containing cetirizine hydrochloride as a model for water soluble drugs.

PubMed

El-Say, Khalid M; El-Helw, Abdel-Rahim M; Ahmed, Osama A A; Hosny, Khaled M; Ahmed, Tarek A; Kharshoum, Rasha M; Fahmy, Usama A; Alsawahli, Majed

2015-01-01

The purpose was to improve the encapsulation efficiency of cetirizine hydrochloride (CTZ) microspheres as a model for water soluble drugs and control its release by applying response surface methodology. A 3(3) Box-Behnken design was used to determine the effect of drug/polymer ratio (X1), surfactant concentration (X2) and stirring speed (X3), on the mean particle size (Y1), percentage encapsulation efficiency (Y2) and cumulative percent drug released for 12 h (Y3). Emulsion solvent evaporation (ESE) technique was applied utilizing Eudragit RS100 as coating polymer and span 80 as surfactant. All formulations were evaluated for micromeritic properties and morphologically characterized by scanning electron microscopy (SEM). The relative bioavailability of the optimized microspheres was compared with CTZ marketed product after oral administration on healthy human volunteers using a double blind, randomized, cross-over design. The results revealed that the mean particle sizes of the microspheres ranged from 62 to 348 µm and the efficiency of entrapment ranged from 36.3% to 70.1%. The optimized CTZ microspheres exhibited a slow and controlled release over 12 h. The pharmacokinetic data of optimized CTZ microspheres showed prolonged tmax, decreased Cmax and AUC0-∞ value of 3309 ± 211 ng h/ml indicating improved relative bioavailability by 169.4% compared with marketed tablets.

Effects of VEGF-ANG-1-PLA nano-sustained release microspheres on proliferation and differentiation of ADSCs.

PubMed

He, Yucang; Li, Zihao; Chen, Zhuojie; Yu, Xiaofang; Ji, Ziwan; Wang, Jingping; Qian, Yao; Li, Liqun

2018-05-10

The improvement of fat graft viability might depend on the presence of multipotent resident adipose derived stem cells (ADSCs) which is the important component of stromal vascular fraction (SVF). Vascular endothelial growth factor (VEGF) and angiogenin-1 (Ang-1) are responsible for neovascularization. However, their half-life is too short to produce a biological effect. We thus investigated whether VEGF-ANG-1-polylactic acid (PLA) microspheres could enhance the angiogenic properties of ADSCs. PLA microspheres containing VEGF and ANG-1 were prepared by in vitro ultrasonic emulsification and characterized according to their encapsulation efficiency (EE), drug-loading rate (DL), particle size and drug release. The systemic toxicity of empty loaded nanospheres (NPs) and the ability of these microspheres to promote the proliferation and differentiation of ADSCs were evaluated. The EE and DL were above 86% and 2.8%, respectively. The drug release was completed after 20 days. Systemic toxicity was verified in ADSCs that received the unloaded NPs. It was observed that ADSCs treated with VEGF-ANG-1-PLA microspheres had an increase in the proliferation and the number of CD31 positive cells. ADSCs proliferation and differentiation toward endothelial cells (ECs) could be enhanced by the addition of VEGF-ANG-1-PLA nano-sustained release microspheres. This article is protected by copyright. All rights reserved.

N-(furfural) chitosan hydrogels based on Diels-Alder cycloadditions and application as microspheres for controlled drug release.

PubMed

Montiel-Herrera, Marcelino; Gandini, Alessandro; Goycoolea, Francisco M; Jacobsen, Neil E; Lizardi-Mendoza, Jaime; Recillas-Mota, Maricarmen; Argüelles-Monal, Waldo M

2015-09-05

In this study, chitosan was chemically modified by reductive amination in a two-step process. The synthesis of N-(furfural) chitosan (FC) was confirmed by FT-IR and (1)H NMR analysis, and the degrees of substitution were estimated as 8.3 and 23.8%. The cross-linkable system of bismaleimide (BM) and FC shows that FC shared properties of furan-maleimide chemistry. This system produced non-reversible hydrogel networks by Diels-Alder cycloadditions at 85 °C. The system composed of BM and FC (23.8% substitution) generated stronger hydrogel networks than those of FC with an 8.3% degree of substitution. Moreover, the FC-BM system was able to produce hydrogel microspheres. Environmental scanning electron microscopy revealed the surface of the microspheres to be non-porous with small protuberances. In water, the microspheres swelled, increasing their volume by 30%. Finally, microspheres loaded with methylene blue were able to release the dye gradually, obeying second-order kinetics for times less than 600 min. This behavior suggests that diffusion is governed by the relaxation of polymer chains in the swelled state, thus facilitating drug release outside the microspheres. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prednisolone Delivery Platforms: Capsules and Beads Combination for a Right Timing Therapy

PubMed Central

Cerciello, Andrea; Auriemma, Giulia; Morello, Silvana; Aquino, Rita P.; Del Gaudio, Pasquale

2016-01-01

In this work, a platform of alginate beads loaded with Prednisolone in hypromellose/gellan gum capsules (F6/Cps) able to delay steroidal anti-inflammatory drug (SAID) release as needed for chronotherapy of rheumatoid arthritis is proposed. Rheumatoid arthritis, showing a worsening in symptoms in the morning upon waking, is a pathology that can benefit from chronotherapy. With the aim to maximize prednisolone therapeutic action allowing the right timing of glucocorticoid therapy, different engineered microparticles (gel-beads) were manufactured using prilling (laminar jet break-up) as micro-encapsulation technique and Zn-alginate as gastroresistant carrier. Starting from various feed solutions and process parameters, the effect of the variables on particles size, morphology, solid state properties and drug release was studied. The optimization of operative and prilling/ionotropic gelation variables led to microspheres with almost spherical shape and a narrow dimensional range. The feed solution with the highest alginate (2.5% w/v) amount and drug/polymer ratio (1:5 w/w) gave rise to the highest encapsulation efficiency (78.5%) as in F6 formulation. As to drug release, F6 exhibited an interesting dissolution profile, releasing about 24% of the drug in simulated gastric fluid followed by a more sustained profile in simulated intestinal fluid. #F6, acting as a gastro-resistant and delayed release formulation, was selected for in vivo studies on male Wistar rats by means of a carrageenan-induced oedema model. Finally, this efficacious formulation was used as core material for the development of a final dosage form: F6/Cps allowed to significantly reduce prednisolone release in simulated gastric fluid (12.6%) and delayed drug release up to about 390 minutes. PMID:27472446

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

Chen, Limiao, E-mail: chenlimiao@csu.edu.cn; College of Chemistry and Chemical Engineering, Central South University, Changsha 410083; Wu, Min

The semiconductor nanostructures decorated with noble metals have attracted increasing attention due to their interesting physical and chemical properties. In this work, urchin-like monoclinic (m-) LaVO{sub 4} microspheres were prepared by a hydrothermal method and used as a template to fabricate Ag nanoparticle-decorated m-LaVO{sub 4} composites. The morphology and structure were characterized by transmission electron microscope, high-resolution transmission electron microscope, scanning electron microscope, and energy-dispersive X-ray. It was found that Ag nanoparticles with narrow size distribution were uniformly loaded on urchin-like m-LaVO{sub 4} microspheres, and the resulted composite microspheres showed distinct surface plasmon absorption band compared to pure m-LaVO{sub 4}more » microspheres. Photocatalytic activities of as-prepared samples were examined by studying the degradation of methyl orange solutions under visible-light irradiation (> 400 nm). Results clearly showed that urchin-like m-LaVO{sub 4}/Ag microspheres possess much higher photocatalytic activity than pure m-LaVO{sub 4} microspheres and P25. - Highlights: • m-LaVO{sub 4}/Ag composites microspheres were fabricated by a hydrothermal method. • m-LaVO{sub 4} microspheres show higher photocatalytic activity than m-LaVO{sub 4} microspheres. • m-LaVO{sub 4}/Ag microspheres exhibit a good stability.« less

Alginate microspheres obtained by the spray drying technique as mucoadhesive carriers of ranitidine.

PubMed

Szekalska, Marta; Amelian, Aleksandra; Winnicka, Katarzyna

2015-03-01

The present study is aimed at formulation of alginate (ALG) microspheres with ranitidine (RNT) by the spray drying method. Obtained microspheres were characterized for particle size, surface morphology, entrapment efficiency, drug loading, in vitro drug release and zeta potential. Mucoadhesive properties were examined by a texture analyser and three types of adhesive layers--gelatine discs, mucin gel and porcine stomach mucosa. Microspheres showed a smooth surface with narrow particle size distribution and RNT loading of up to 70.9%. All formulations possessed mucoadhesive properties and exhibited prolonged drug release according to the first-order kinetics. DSC reports showed that there was no interaction between RNT and ALG. Designed microspheres can be considered potential carriers of ranitidine with prolonged residence time in the stomach.

A short term quality control tool for biodegradable microspheres.

PubMed

D'Souza, Susan; Faraj, Jabar A; Dorati, Rossella; DeLuca, Patrick P

2014-06-01

Accelerated in vitro release testing methodology has been developed as an indicator of product performance to be used as a discriminatory quality control (QC) technique for the release of clinical and commercial batches of biodegradable microspheres. While product performance of biodegradable microspheres can be verified by in vivo and/or in vitro experiments, such evaluation can be particularly challenging because of slow polymer degradation, resulting in extended study times, labor, and expense. Three batches of Leuprolide poly(lactic-co-glycolic acid) (PLGA) microspheres having varying morphology (process variants having different particle size and specific surface area) were manufactured by the solvent extraction/evaporation technique. Tests involving in vitro release, polymer degradation and hydration of the microspheres were performed on the three batches at 55°C. In vitro peptide release at 55°C was analyzed using a previously derived modification of the Weibull function termed the modified Weibull equation (MWE). Experimental observations and data analysis confirm excellent reproducibility studies within and between batches of the microsphere formulations demonstrating the predictability of the accelerated experiments at 55°C. The accelerated test method was also successfully able to distinguish the in vitro product performance between the three batches having varying morphology (process variants), indicating that it is a suitable QC tool to discriminate product or process variants in clinical or commercial batches of microspheres. Additionally, data analysis utilized the MWE to further quantify the differences obtained from the accelerated in vitro product performance test between process variants, thereby enhancing the discriminatory power of the accelerated methodology at 55°C.

In vitro evaluation of suspoemulsions for in situ-forming polymeric microspheres and controlled release of progesterone.

PubMed

Turino, Ludmila N; Mariano, Rodolfo N; Mengatto, Luciano N; Luna, Julio A

2015-01-01

One possibility to obtain a higher dose of drug in a lower formulation volume can be by using of saturated quantity of drug in one of the phases of an emulsion. These formulations are called suspoemulsions (S/O/W). When a hydrophobic polymer is added to the organic phase of suspoemulsions, these formulations can be used to entrap the drug inside microspheres after in situ precipitation of the polymer-drug-excipients mix. In this work, performance and stability of progesterone suspensions in triacetin as organic phase of suspoemulsions were evaluated. These formulations were compared with O/W emulsions. Mathematical models were used to study in vitro release profiles. The results confirmed that S/O/W systems could be an attractive alternative to O/W formulations for the entrapment of progesterone inside poly(d,l-lactide-co-glycolide) microspheres. Diffusive-based models fit the in vitro release of progesterone from in situ-formed microspheres. For longer release periods, a time-dependent diffusion coefficient was successfully estimated.

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

PubMed

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

2018-01-01

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

Porous-wall hollow glass microspheres as carriers for biomolecules

DOEpatents

Li, Shuyi; Dynan, William S; Wicks, George; Serkiz, Steven

2013-09-17

The present invention includes compositions of porous-wall hollow glass microspheres and one or more biomolecules, wherein the one or more biomolecules are positioned within a void location within the hollow glass microsphere, and the use of such compositions for the diagnostic and/or therapeutic delivery of biomolecules.

Nanocarrier-Integrated Microspheres: Nanogel Tectonic Engineering for Advanced Drug-Delivery Systems.

PubMed

Tahara, Yoshiro; Mukai, Sada-Atsu; Sawada, Shin-Ichi; Sasaki, Yoshihiro; Akiyoshi, Kazunari

2015-09-09

A nanocarrier-integrated bottom-up method is a promising strategy for advanced drug-release systems. Self-assembled nanogels, which are one of the most beneficial nanocarriers for drug-delivery systems, are tectonically integrated to prepare nanogel-crosslinked (NanoClik) microspheres. NanoClik microspheres consisting of nanogel-derived structures (observed by STED microscopy) release "drug-loaded nanogels" after hydrolysis, resulting in successful sustained drug delivery in vivo. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Collagen I derived recombinant protein microspheres as novel delivery vehicles for bone morphogenetic protein-2.

PubMed

Mumcuoglu, Didem; de Miguel, Laura; Jekhmane, Shehrazade; Siverino, Claudia; Nickel, Joachim; Mueller, Thomas D; van Leeuwen, Johannes P; van Osch, Gerjo J; Kluijtmans, Sebastiaan G

2018-03-01

Bone morphogenetic protein-2 (BMP-2) is a powerful osteoinductive protein; however, there is a need for the development of a safe and efficient BMP-2 release system for bone regeneration therapies. Recombinant extracellular matrix proteins are promising next generation biomaterials since the proteins are well-defined, reproducible and can be tailored for specific applications. In this study, we have developed a novel and versatile BMP-2 delivery system using microspheres from a recombinant protein based on human collagen I (RCP). In general, a two-phase release pattern was observed while the majority of BMP-2 was retained in the microspheres for at least two weeks. Among different parameters studied, the crosslinking and the size of the RCP microspheres changed the in vitro BMP-2 release kinetics significantly. Increasing the chemical crosslinking (hexamethylene diisocyanide) degree decreased the amount of initial burst release (24h) from 23% to 17%. Crosslinking by dehydrothermal treatment further decreased the burst release to 11%. Interestingly, the 50 and 72μm-sized spheres showed a significant decrease in the burst release compared to 207-μm sized spheres. Very importantly, using a reporter cell line, the released BMP-2 was shown to be bioactive. SPR data showed that N-terminal sequence of BMP-2 was important for the binding and retention of BMP-2 and suggested the presence of a specific binding epitope on RCP (K D : 1.2nM). This study demonstrated that the presented RCP microspheres are promising versatile BMP-2 delivery vehicles. Copyright © 2017 Elsevier B.V. All rights reserved.

Gellan gum microspheres crosslinked with trivalent ion: effect of polymer and crosslinker concentrations on drug release and mucoadhesive properties.

PubMed

Boni, Fernanda Isadora; Prezotti, Fabíola Garavello; Cury, Beatriz Stringhetti Ferreira

2016-08-01

Gellan gum microspheres were obtained by ionotropic gelation technique, using the trivalent ion Al(3+). The percentage of entrapment efficiency ranged from 48.76 to 87.52% and 2(2) randomized full factorial design demonstrated that both the increase of polymer concentration and the decrease of crosslinker concentration presented a positive effect in the amount of encapsulated drug. Microspheres size and circularity ranged from 700.17 to 938.32 μm and from 0.641 to 0.796 μm, respectively. The increase of polymer concentration (1-2%) and crosslinker concentration (3-5%) led to the enlargement of particle size and circularity. However, the association of increased crosslinker concentration and reduced polymer content made the particles more irregular. In vitro and ex vivo tests evidenced the high mucoadhesiveness of microspheres. The high liquid uptake ability of the microspheres was demonstrated and the pH variation did not affect this parameter. Drug release was pH dependent, with low release rates in acid pH (42.40% and 44.93%) and a burst effect in phosphate buffer pH (7.4). The Weibull model had the best correlation with the drug release data, demonstrating that the release process was driven by a complex mechanism involving the erosion and swelling of the matrix or by non-Fickian diffusion.

Fast synthesis, formation mechanism, and control of shell thickness of CuS–polystyrene core–shell microspheres

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

Zhao, Li-min, E-mail: zhaolimin@lcu.ecu.cn; Shao, Xin; Yin, Yi-bin

2012-09-15

Graphical abstract: Core–shell structure PSt/CuS were prepared using polystyrene which were modified by 3-methacryloxypropyltrimethoxysilane as template. The coating thickness of CuS can be controlled by the amount of 3-methacryloxypropyltrimethoxysilane and the UV–vis absorption intensity of PSt/CuS composite also changed with the coating thickness of CuS. Highlights: ► Core–shell structure PSt/CuS were prepared using silanol-modified polystyrene microspheres as template. ► The coating thickness of core–shell structure PSt/CuS can be controlled by a simple method. ► The UV–vis absorption intensity of PSt/CuS composite also changed with the coating thickness of CuS. -- Abstract: The silanol-modified polystyrene microspheres were prepared through dispersion polymerization.more » Then copper sulfide particles were grown on silanol-modified polystyrene through sonochemical deposition in an aqueous bath containing copper acetate and sulfide, released through the hydrolysis of thioacetamide. The resulting particles were continuous and uniform as characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Fourier transform infrared, thermogravimetric analysis and UV–vis absorption spectroscopy were used to characterize the structure and properties of core–shell particles. The results showed the coating thickness of CuS shell can be controlled by the amount of silanol and the UV–vis absorption intensity of PSt/CuS composite also changed with the coating thickness of CuS.« less

Preparation of hollow magnetite microspheres and their applications as drugs carriers

PubMed Central

2012-01-01

Hollow magnetite microspheres have been synthesized by a simple process through a template-free hydrothermal approach. Hollow microspheres were surface modified by coating with a silica nanolayer. Pristine and modified hollow microparticles were characterized by field-emission electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, FT-IR and Raman spectroscopy, and VSM magnetometry. The potential application of the modified hollow magnetite microspheres as a drug carrier was evaluated by using Rhodamine B and methotrexate as model drugs. The loading and release kinetics of both molecules showed a clear pH and temperature dependent profile. Graphical abstract Hollow magnetite microspheres have been synthesized. Load-release experiments with Rhodamine-B as a model drug and with Methotrexate (chemotherapy drug used in treating certain types of cancer) demonstrated the potential applications of these nanostructures in biomedical applications. PMID:22490731

Design of tablets for the delayed and complete release of poorly water-soluble weak base drugs using SBE7M-β-CD as a solubilizing agent.

PubMed

Rao, Venkatramana M; Zannou, Erika A; Stella, Valentino J

2011-04-01

The challenge of designing a delayed-release oral dosage form is significantly increased when the drug substance is poorly water soluble. This manuscript describes the design and characterization of a novel controlled-release film-coated tablet for the pH-triggered delayed and complete release of poorly water-soluble weak base drugs. Delivery of weak bases is specifically highlighted with the use of dipyridamole and prazosin as model compounds. Tailored delayed release is achieved with a combination of an insoluble but semipermeable polymer and an enteric polymer, such as cellulose acetate and hydroxypropyl cellulose phthalate, respectively, as coatings. The extent of the time lag prior to complete release depends on the film-coating composition and thickness. Complete release is achieved by the addition of a cyclodextrin, namely SBE7M-β-CD with or without a pH modifier added to the tablet core to ensure complete solubilization and release of the drug substance. The film-coating properties allow the complex formation/solubilization to occur in situ. Additionally, the drug release rate can be modulated on the basis of the cyclodextrin to drug molar ratio. This approach offers a platform technology for delayed release of potent but poorly soluble drugs and the release can be modulated by adjusting the film-coating composition and thickness and/or the cyclodextrin and pH modifier, if necessary. Copyright © 2010 Wiley-Liss, Inc.

Injectable alginate/hydroxyapatite gel scaffold combined with gelatin microspheres for drug delivery and bone tissue engineering.

PubMed

Yan, Jingxuan; Miao, Yuting; Tan, Huaping; Zhou, Tianle; Ling, Zhonghua; Chen, Yong; Xing, Xiaodong; Hu, Xiaohong

2016-06-01

Injectable and biodegradable alginate-based composite gel scaffolds doubly integrated with hydroxyapatite (HAp) and gelatin microspheres (GMs) were cross-linked via in situ release of calcium cations. As triggers of calcium cations, CaCO3 and glucono-D-lactone (GDL) were fixed as a mass ratio of 1:1 to control pH value ranging from 6.8 to 7.2 during gelation. Synchronously, tetracycline hydrochloride (TH) was encapsulated into GMs to enhance bioactivity of composite gel scaffolds. The effects of HAp and GMs on characteristics of gel scaffolds, including pH value, gelation time, mechanical properties, swelling ratio, degradation behavior and drug release, were investigated. The results showed that HAp and GMs successfully improved mechanical properties of gel scaffolds at strain from 0.1 to 0.5, which stabilized the gel network and decreased weight loss, as well as swelling ratio and gelation time. TH could be released from this composite gel scaffold into the local microenvironment in a controlled fashion by the organic/inorganic hybrid of hydrogel network. Our results demonstrate that the HAp and GMs doubly integrated alginate-based gel scaffolds, especially the one with 6% (w/v) HAp and 5% (w/v) GMs, have suitable physical performance and bioactive properties, thus provide a potential opportunity to be used for bone tissue engineering. The potential application of this gel scaffold in bone tissue engineering was confirmed by encapsulation behavior of osteoblasts. In combination with TH, the gel scaffold exhibited beneficial effects on osteoblast activity, which suggested a promising future for local treatment of pathologies involving bone loss. Copyright © 2016 Elsevier B.V. All rights reserved.

POE/PLGA composite microspheres: formation and in vitro behavior of double walled microspheres.

PubMed

Yang, Yi-Yan; Shi, Meng; Goh, Suat-Hong; Moochhala, Shabbir M; Ng, Steve; Heller, Jorge

2003-03-07

The poly(ortho ester) (POE) and poly(D,L-lactide-co-glycolide) 50:50 (PLGA) composite microspheres were fabricated by a water-in-oil-in-water (w/o/w) double emulsion process. The morphology of the composite microspheres varied depending on POE content. When the POE content was 50, 60 or 70% in weight, the double walled microspheres with a dense core of POE and a porous shell of PLGA were formed. The formation of the double walled POE/PLGA microspheres was analysed. Their in vitro degradation behavior was characterized by scanning electron microscopy, gel permeation chromatography, Fourier-transform infrared microscopy and nuclear magnetic resonance spectroscopy (NMR). It was found that compared to the neat POE or PLGA microspheres, distinct degradation mechanism was achieved in the double walled POE/PLGA microspheres system. The degradation of the POE core was accelerated due to the acidic microenvironment produced by the hydrolysis of the outer PLGA layer. The formation of hollow microspheres became pronounced after the first week in vitro. 1H NMR spectra showed that the POE core was completely degraded after 4 weeks. On the other hand, the outer PLGA layer experienced slightly retarded degradation after the POE core disappeared. PLGA in the double walled microspheres kept more than 32% of its initial molecular weight over a period of 7 weeks.

Preparation and Characterization of Thermoresponsive Poly(N-isopropylacrylamide-co-acrylic acid)-Grafted Hollow Fe3O4/SiO2 Microspheres with Surface Holes for BSA Release

PubMed Central

Zhao, Jing; Zeng, Ming; Zheng, Kaiqiang; He, Xinhua; Xie, Minqiang; Fu, Xiaoyi

2017-01-01

Thermoresponsive P(NIPAM-AA)/Fe3O4/SiO2 microspheres with surface holes serving as carriers were prepared using p-Fe3O4/SiO2 microspheres with a thermoresponsive copolymer. The p-Fe3O4/SiO2 microspheres was obtained using a modified Pickering method and chemical etching. The surface pore size of p-Fe3O4/SiO2 microspheres was in the range of 18.3 nm~37.2 nm and the cavity size was approximately 60 nm, which are suitable for loading and transporting biological macromolecules. P(NIPAM-AA) was synthesized inside and outside of the p-Fe3O4/SiO2 microspheres via atom transfer radical polymerization of NIPAM, MBA and AA. The volume phase transition temperature (VPTT) of the specifically designed P(NIPAM-AA)/Fe3O4/SiO2 microspheres was 42.5 °C. The saturation magnetization of P(NIPAM-AA)/Fe3O4/SiO2 microspheres was 72.7 emu/g. The P(NIPAM-AA)/Fe3O4/SiO2 microspheres were used as carriers to study the loading and release behavior of BSA. This microsphere system shows potential for the loading of proteins as a drug delivery platform. PMID:28772770

Magnetic alginate microspheres: system for the position controlled delivery of nerve growth factor.

PubMed

Ciofani, Gianni; Raffa, Vittoria; Menciassi, Arianna; Cuschieri, Alfred; Micera, Silvestro

2009-04-01

The use of polymeric carriers containing dispersed magnetic nanocrystalline particles for targeted delivery of drugs in clinical practice has attracted the interest of the scientific community. In this paper a system comprised of alginate microparticles with a core of magnetite and carrying nerve growth factor (NGF) is described. The magnetic properties of these microspheres, typical of superparamagnetic materials, allow precise and controlled delivery to the intended tissue environment. Experiments carried out on PC12 cells with magnetic alginate microspheres loaded with NGF have confirmed the induction of cell differentiation which is strongly dependent on the distance from the microsphere cluster. In addition, finite element modelling (FEM) of the release profile from the microspheres in culture, indicated the possibility of creating defined and predictable NGF gradients from the loaded microspheres. These observations on the carriage and release of growth factors by the proposed microparticles open new therapeutic options for both neuronal regeneration and of the development of effective neuronal interfaces.

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.

SPIO-labeled Yttrium Microspheres for MR Imaging Quantification of Transcatheter Intrahepatic Delivery in a Rodent Model

PubMed Central

Li, Weiguo; Zhang, Zhuoli; Gordon, Andrew C.; Chen, Jeane; Nicolai, Jodi; Lewandowski, Robert J.; Omary, Reed A.

2016-01-01

Purpose To investigate the qualitative and quantitative impacts of labeling yttrium microspheres with increasing amounts of superparamagnetic iron oxide (SPIO) material for magnetic resonance (MR) imaging in phantom and rodent models. Materials and Methods Animal model studies were approved by the institutional Animal Care and Use Committee. The r2* relaxivity for each of four microsphere SPIO compositions was determined from 32 phantoms constructed with agarose gel and in eight concentrations from each of the four compositions. Intrahepatic transcatheter infusion procedures were performed in rats by using each of the four compositions before MR imaging to visualize distributions within the liver. For quantitative studies, doses of 5, 10, 15, or 20 mg 2% SPIO-labeled yttrium microspheres were infused into 24 rats (six rats per group). MR imaging R2* measurements were used to quantify the dose delivered to each liver. Pearson correlation, analysis of variance, and intraclass correlation analyses were performed to compare MR imaging measurements in phantoms and animal models. Results Increased r2* relaxivity was observed with incremental increases of SPIO microsphere content. R2* measurements of the 2% SPIO–labeled yttrium microsphere concentration were well correlated with known phantom concentrations (R2 = 1.00, P < .001) over a broader linear range than observed for the other three compositions. Microspheres were heterogeneously distributed within each liver; increasing microsphere SPIO content produced marked signal voids. R2*-based measurements of 2% SPIO–labeled yttrium microsphere delivery were well correlated with infused dose (intraclass correlation coefficient, 0.98; P < .001). Conclusion MR imaging R2* measurements of yttrium microspheres labeled with 2% SPIO can quantitatively depict in vivo intrahepatic biodistribution in a rat model. © RSNA, 2015 Online supplemental material is available for this article. PMID:26313619

Diclofenac salts, part 6: release from lipid microspheres.

PubMed

Fini, Adamo; Cavallari, Cristina; Rabasco Alvarez, Antonio M; Rodriguez, Marisa Gonzalez

2011-08-01

The release of diclofenac (20%, w/w) was studied from lipidic solid dispersions using three different chemical forms (acid, sodium salt, and pyrrolidine ethanol salt) and two different lipid carriers (Compritol 888 ATO or Carnauba wax) either free or together with varying amounts (10%-30%, w/w) of stearic acid. Microspheres were prepared by ultrasound-assisted atomization of the molten dispersions and analyzed by scanning electron microscopy, differential scanning calorimetry, and hot stage microscopy. The effects of different formulations on the resulting drug release profiles as a function of pH were studied and the results were discussed. The formulation of the 18 systems and the chemical form of the drug were found to strongly affect the mode of the drug release. The solubility of the chemical forms in the lipid mixture is in the following order: pyrrolidine ethanol salt ≫ acid > sodium salt (according to the solubility parameters), and the nature of the systems thus obtained ranges from a matrix, for mutually soluble drug/carrier pairs, to a microcapsule, for pairs wherein mutual solubility is poor. Drug release from microspheres prepared by pure lipids was primarily controlled by diffusion, whereas the release from microspheres containing stearic acid was diffusion/erosion controlled at pH 7.4. Copyright © 2011 Wiley-Liss, Inc.

Development of near zero-order release PLGA-based microspheres of a novel antipsychotic.

PubMed

Zhao, Jinlong; Wang, Lexi; Fan, Chunyu; Yu, Kongtong; Liu, Ximing; Zhao, Xiaolei; Wang, Dan; Liu, Wenhua; Su, Zhengxing; Sun, Fengying; Li, Youxin

2017-01-10

The novel antipsychotic isoperidone, a prodrug of paliperidone, was designed to improve liposolubility for the development of poly(D,L-lactide-co-glycolide) (PLGA)-based microspheres to achieve near zero-order release behaviour in vivo. Microspheres with a smooth surface were obtained using the oil-in-water emulsion solvent evaporation method and yielded a high encapsulation efficiency of 92%. Pharmacokinetic studies in beagle dogs showed a one-week plateau phase followed by a two-week quasi-zero-order release with no burst release. The in vitro release method with a good in vitro-in vivo correlation was also established. Pharmacodynamic evaluation was performed using the MK-801-induced schizophrenic behavioural mouse model, and the sustained suppressive effect lasted two weeks. The pharmacokinetic-pharmacodynamic (PK-PD) relationship of isoperidone microspheres was compared to that of oral administration of free drug. The results revealed a strong correlation between the plasma drug level and the antipsychotic effect. A stable drug plasma concentration was detected in mice both intraday and interday from 8 to 22 d after a single injection of isoperidone microspheres, and a sustained suppressive effect on the schizophrenic model was also observed. In comparison, the mouse group receiving oral daily administration exhibited more dose-dependent effects, and the pharmacological effect diminished rapidly in conjunction with a reduction of the plasma drug levels 8h after the last administration of isoperidone on day 3. The above results confirm the superiority of long-acting release over oral administration and indicate a valuable alternative for the clinical treatment of schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Bone regeneration in osteoporosis by delivery BMP-2 and PRGF from tetronic-alginate composite thermogel.

PubMed

Segredo-Morales, Elisabet; García-García, Patricia; Reyes, Ricardo; Pérez-Herrero, Edgar; Delgado, Araceli; Évora, Carmen

2018-05-30

As the life expectancy of the world population increases, osteoporotic (OP) fracture risk increase. Therefore in the present study a novel injectable thermo-responsive hydrogel loaded with microspheres of 17β-estradiol, microspheres of bone morphogenetic protein-2 (BMP-2) and plasma rich in growth factors (PRGF) was applied locally to regenerate a calvaria critical bone defect in OP female rats. Three systems were characterized: Tetronic® 1307 (T-1307) reinforced with alginate (T-A), T-A with PRGF and T-A-PRGF with microspheres. The addition of the microspheres increased the viscosity but the temperature for the maximum viscosity did not change (22-24 °C). The drugs were released during 6 weeks in one fast phase (three days) followed by a long slow phase. In vivo evaluation was made in non-OP and OP rats treated with T-A, T-A with microspheres of 17β-estradiol (T-A-βE), T-A-βE prepared with PRGF (T-A-PRGF-βE), T-A-βE with microspheres of BMP-2 (T-A-βE-BMP-2) and the combination of the three (T-A-PRGF-βE-BMP). After 12 weeks, histological and histomorphometric analyzes showed a synergic effect due to the addition of BMP-2 to the T-A-βE formulation. The PRGF did not increased the bone repair. The new bone filling the OP defect was less mineralized than in the non-OP groups. Copyright © 2018 Elsevier B.V. All rights reserved.

Physical Stability Studies of Semi-Solid Formulations from Natural Compounds Loaded with Chitosan Microspheres

PubMed Central

Acosta, Niuris; Sánchez, Elisa; Calderón, Laura; Cordoba-Diaz, Manuel; Cordoba-Diaz, Damián; Dom, Senne; Heras, Ángeles

2015-01-01

A chitosan-based hydrophilic system containing an olive leaf extract was designed and its antioxidant capacity was evaluated. Encapsulation of olive leaf extract in chitosan microspheres was carried out by a spray-drying process. The particles obtained with this technique were found to be spherical and had a positive surface charge, which is an indicator of mucoadhesiveness. FTIR and X-ray diffraction results showed that there are not specific interactions of polyphenolic compounds in olive leaf extract with the chitosan matrix. Stability and release studies of chitosan microspheres loaded with olive leaf extract before and after the incorporation into a moisturizer base were performed. The resulting data showed that the developed formulations were stable up to three months. The encapsulation efficiency was around 44% and the release properties of polyphenols from the microspheres were found to be pH dependent. At pH 7.4, polyphenols release was complete after 6 h; whereas the amount of polyphenols released was 40% after the same time at pH 5.5. PMID:26389926

Effect of a freeze-dried CMC/PLGA microsphere matrix of rhBMP-2 on bone healing.

PubMed

Schrier, J A; Fink, B F; Rodgers, J B; Vasconez, H C; DeLuca, P P

2001-10-07

The hypothesis of this research was that implants of poly(lactide-co-glycolide) (PLGA) microspheres loaded with bone morphogenetic protein-2 (rhBMP-2) and distributed in a freeze-dried carboxymethylcellulose (CMC) matrix would produce more new bone than would matrix implants of non-protein-loaded microspheres or matrix implants of only CMC. To test this hypothesis it was necessary to fashion microsphere-loaded CMC implants that were simple to insert, fit precisely into a defect, and would not elicit swelling. Microspheres were produced via a water-in-oil-in-water double-emulsion system and were loaded with rhBMP-2 by soaking them in a buffered solution of the protein at a concentration of 5.4 mg protein per gram of PLGA. Following recovery of the loaded microspheres by lyophilization, matrices for implantation were prepared by lyophilizing a suspension of the microspheres in 2% CMC in flat-bottom tissue culture plates. Similar matrices were made with 2% CMC and with 2% CMC containing blank microspheres. A full-thickness calvarial defect model in New Zealand white rabbits was used to assess bone growth. Implants fit the defect well, allowing for direct application. Six weeks postsurgery, defects were collected and processed for undecalcified histology. In vitro, 60% of the loaded rhBMP-2 released from devices or microspheres in 5 to 7 days, with the unembedded microspheres releasing faster than those embedded in CMC. In vivo, the rhBMP-2 microspheres greatly enhanced bone healing, whereas nonloaded PLGA microspheres in the CMC implants had little effect. The results showed that a lyophilized device of rhBMP-2/PLGA microspheres in CMC was an effective implantable protein-delivery system for use in bone repair.

Microstructural investigation using synchrotron radiation X-ray microtomography reveals taste-masking mechanism of acetaminophen microspheres.

PubMed

Guo, Zhen; Yin, Xianzhen; Liu, Congbiao; Wu, Li; Zhu, Weifeng; Shao, Qun; York, Peter; Patterson, Laurence; Zhang, Jiwen

2016-02-29

The structure of solid drug delivery systems has considerable influence on drug release behaviors from particles and granules and also impacts other properties relevant to release characteristics such as taste. In this study, lipid-based microspheres of acetaminophen were prepared to mask the undesirable taste of drug and therefore to identify the optimal formulation for drug release. Synchrotron radiation X-ray computed microtomography (SR-μCT) was used to investigate the fine structural architectures of microspheres non-destructively at different sampling times during drug release test, which were simultaneously determined to quantitatively correlate the structural data with drug release behaviors. The results demonstrated that the polymeric formulation component, namely, cationic polymethacrylate (Eudragit E100), was the key factor to mask the bitter taste of acetaminophen by inhibiting immediate drug release thereby reducing the interaction intensity of the bitter material with the oral cavity taste buds. The structure and morphology of the microspheres were found to be influenced by the shape and particle size of the drug, which was also an important factor for taste-masking performance. The quantitative analysis generated detailed structural information which was correlated well with drug release behaviors. Thus, SR-μCT has been proved as a powerful tool to investigate the fine microstructure of particles and provides a new approach in the design of particles for taste masking. Copyright © 2015 Elsevier B.V. All rights reserved.

In-vitro studies of enteric coated diclofenac sodium-carboxymethylcellulose microspheres.

PubMed

Arica, B; Arica, M Y; Kaş, H S; Hincal, A A; Hasirci, V

1996-01-01

MIcrospheres containing diclofenac sodium (DS) were prepared using carboxymethylcellulose (CMC) as the main support material (1.0, 2.0, 3.0% (w/v)) and aluminum chloride as the crosslinker. Drug to polymer ratios of 1:1, 1:2 and 1:4 were used to obtain a range of microspheres. The microspheres were then coated with an enteric coating material, Eudragit S-100, efficiency, % yield value, particle sizes an in-vitro dissolution behaviour were investigated. The surface of the enteric coated microspheres seemed to be all covered with Eudragit S-100 from scanning electron microscopy observation. It was also observed that increasing the CMC concentration led to an increase in the encapsulation efficiency, % yield value and particle size and decreased the release rate. Eudragit S-100 coating did not significantly alter the size but the release rate was significantly lower even when the lower concentration solution was used.

Controlled delivery of a hydrophilic drug from a biodegradable microsphere system by supercritical anti-solvent precipitation technique.

PubMed

Lee, S; Kim, M S; Kim, J S; Park, H J; Woo, J S; Lee, B C; Hwang, S J

2006-11-01

The purpose of this study was to prepare microspheres loaded with hydrophilic drug, bupivacaine HCl using poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(L-lactic acid) (PLLA). Microspheres were prepared with varying the PLGA/PLLA ratio with two different levels of bupivacaine HCl (5 and 10%) using a supercritical anti-solvent (SAS) technique. Microspheres ranging from 4-10 microm in geometric mean diameter could be prepared, with high loading efficiency. Powder X-ray diffraction (PXRD) revealed that bupivacaine HCl retained its crystalline state within the polymer and was present as a dispersion within the polymer phase after SAS processing. The release of bupivacaine HCl from biodegradable polymer microspheres was rapid up to 4 h, thereafter bupivacaine HCl was continuously and slowly released for at least 7 days according to the PLGA/PLLA ratio and the molecular weight of PLLA.

A facile in-situ hydrothermal synthesis of SrTiO3/TiO2 microsphere composite

NASA Astrophysics Data System (ADS)

Wang, Hongxing; Zhao, Wei; Zhang, Yubo; Zhang, Shimeng; Wang, Zihao; Zhao, Dan

2016-06-01

TiO2 was successfully used as sacrificed template to synthesise SrTiO3/TiO2 microsphere composite via an in-situ hydrothermal process. The diameter of SrTiO3/TiO2 microsphere was about 700 nm with the same size of the template, and all of the microspheres were in good dispersity. The optimized reaction parameters for the phase and morphology of the as-synthesized samples were investigated. The results showed the SrTiO3/TiO2 microsphere can be synthesized at 170 °C when the concentration of sodium hydroxide was 0.1 M. Lower hydrothermal temperature hampered the formation of the SrTiO3/TiO2 composite, the higher alkali concentration, however, will destroy the morphology of products. The formation mechanism of SrTiO3/TiO2 microsphere composite was proposed and the photocatalytic properties of the samples were characterized using methylene blue solution as the pollutant under the UV light irradiation. The results indicated the proper OH- concentration will provide a channel for Sr2+ to react with Ti4+ located in the template and form the SrTiO3/TiO2 composite, and those with micro-scaled spherical morphology exhibited good photocatalytic activities.

Polyphosphazene/Nano-Hydroxyapatite Composite Microsphere Scaffolds for Bone Tissue Engineering

PubMed Central

Nukavarapu, Syam P.; Kumbar, Sangamesh G.; Brown, Justin L.; Krogman, Nicholas R.; Weikel, Arlin L.; Hindenlang, Mark D.; Nair, Lakshmi S.; Allcock, Harry R; Laurencin, Cato T.

2009-01-01

The non-toxic, neutral degradation products of amino acid ester polyphosphazenes make them ideal candidates for in vivo orthopaedic applications. The quest for new osteocompatible materials for load bearing tissue engineering applications has led us to investigate mechanically competent amino acid ester substituted polyphosphazenes. In this study, we have synthesized three biodegradable polyphosphazenes substituted with side groups namely leucine, valine and phenylalanine ethyl esters. Of these polymers, the phenylalanine ethyl ester substituted polyphosphazene showed the highest glass transition temperature (41.6 °C) and hence was chosen as a candidate material for forming composite microspheres with 100 nm sized hydroxyapatite (nHAp). The fabricated composite microspheres were sintered into a three-dimensional (3-D) porous scaffold by adopting a dynamic solvent sintering approach. The composite microsphere scaffolds showed compressive moduli of 46–81 MPa with mean pore diameters in the range of 86–145 µm. The three-dimensional polyphosphazene-nHAp composite microsphere scaffolds showed good osteoblast cell adhesion, proliferation and alkaline phosphatase expression, and are potential suitors for bone tissue engineering applications. PMID:18517248

PELA microspheres with encapsulated arginine-chitosan/pBMP-2 nanoparticles induce pBMP-2 controlled-release, transfected osteoblastic progenitor cells, and promoted osteogenic differentiation.

PubMed

Xu, Xiaolong; Qiu, Sujun; Zhang, Yuxian; Yin, Jie; Min, Shaoxiong

2017-03-01

Repair of the bone injury remains a challenge in clinical practices. Recent progress in tissue engineering and therapeutic gene delivery systems have led to promising new strategies for successful acceleration of bone repair process. The aim of this study was to create a controlled-release system to slowly release the arginine-chitosan/plasmid DNA nanoparticles encoding BMP-2 gene (Arg-CS/pBMP-2 NPs), efficiently transfect osteoblastic progenitor cells, secrete functional BMP-2 protein, and promote osteogenic differentiation. In this study, chitosan was conjugated with arginine to generate arginine-chitosan polymer (Arg-CS) for gene delivery. Mix the Arg-CS with pBMP-2 to condense pBMP-2 into nano-sized particles. In vitro transfection assays demonstrated that the transfection efficiency of Arg-CS/pBMP-2 nanoparticles and the expression level of BMP-2 was obviously exceed control groups. Further, PELA microspheres as the controlled-release carrier for the nanoparticles were used to encapsulate Arg-CS/pBMP-2 NPs. We demonstrated that the Arg-CS/pBMP-2 NPs could slowly release from the PELA microspheres at least for 42 d. During the co-culture with the PELA microspheres, the content of BMP-2 protein secreted by MC3T3-E1 reached the peak at 7 d. After 21d, the secretion of BMP-2 protein still maintain a higher level. The alkaline phosphatase activity, alizarin red staining, and osteogenesis-related gene expression by real-time quantitative PCR analysis all showed the PELA microspheres entrapping with Arg-CS/pBMP-2 NPs can obviously induce the osteogenic differentiation. The results indicated that the Arg-CS is a suitable gene vector which can promote the gene transfection. And the novel PELA microspheres-nanoparticle controlled-release system has potential clinical application in the future after further research.

Simple Synthesis of Molybdenum Disulfide/Reduced Graphene Oxide Composite Hollow Microspheres as Supercapacitor Electrode Material.

PubMed

Xiao, Wei; Zhou, Wenjie; Feng, Tong; Zhang, Yanhua; Liu, Hongdong; Tian, Liangliang

2016-09-20

MoS₂/RGO composite hollow microspheres were hydrothermally synthesized by using SiO₂/GO microspheres as a template, which were obtained via the sonication-assisted interfacial self-assembly of tiny GO sheets on positively charged SiO₂ microspheres. The structure, morphology, phase, and chemical composition of MoS₂/RGO hollow microspheres were systematically investigated by a series of techniques such as FE-SEM, TEM, XRD, TGA, BET, and Raman characterizations, meanwhile, their electrochemical properties were carefully evaluated by CV, GCD, and EIS measurements. It was found that MoS₂/RGO hollow microspheres possessed unique porous hollow architecture with high-level hierarchy and large specific surface area up to 63.7 m²·g -1 . When used as supercapacitor electrode material, MoS₂/RGO hollow microspheres delivered a maximum specific capacitance of 218.1 F·g -1 at the current density of 1 A·g -1 , which was much higher than that of contrastive bare MoS₂ microspheres developed in the present work and most of other reported MoS₂-based materials. The enhancement of supercapacitive behaviors of MoS₂/RGO hollow microspheres was likely due to the improved conductivity together with their distinct structure and morphology, which not only promoted the charge transport but also facilitated the electrolyte diffusion. Moreover, MoS₂/RGO hollow microsphere electrode displayed satisfactory long-term stability with 91.8% retention of the initial capacitance after 1000 charge/discharge cycles at the current density of 3 A·g -1 , showing excellent application potential.

DNA hydrogel microspheres and their potential applications for protein delivery and live cell monitoring

PubMed Central

Kim, Taeyoung; Park, Seongmin; Baek, Solhee; Lee, Jong Bum; Park, Nokyoung

2016-01-01

Microfluidic devices have been extensively developed as methods for microscale materials fabrication. It has also been adopted for polymeric microsphere fabrication and in situ drug encapsulation. Here, we employed multi-inlet microfluidic channels for DNA hydrogel microsphere formation and in situ protein encapsulation. The release of encapsulated proteins from DNA hydrogels showed different profiles accordingly with the size of microspheres. PMID:27279936

Controlled, sustained release of proteins via an injectable, mineral-coated microsphere delivery vehicle

NASA Astrophysics Data System (ADS)

Franklin-Ford, Travelle

Hydroxyapatite interfaces have demonstrated strong protein binding and protein selection from a passing solution and can serve as a biocompatible carrier for controlled protein delivery. Hydroxyapatite is a major component of long bones and tooth enamel and is the most stable of all calcium phosphate isoforms in aqueous solutions at physiologic pH, providing a sensitive chromatographic mechanism for separating proteins. Here we describe an approach to create a synthetic hydroxyapatite coating through a biomimetic, heterogeneous nucleation from a modified simulated body fluid--supersaturated with calcium and phosphate ions on the surface of injectable polymer microspheres. We are able to bind and release bioactive growth factors into a variety of in vitro and in vivo conditions, demonstrating the functionality and advantage of the biomaterial. Creating a hydroxyapatite layer on the Poly(D,L-lactide-co-glycolide) (PLG) microsphere surface, avails the microsphere interior for another application that will not compete with protein binding and release. Encapsulating an imaging agent within the aqueous phase of the emulsion provides a visual reference for the injectable therapy upon microsphere fabrication. Another advantage of this system is that the mineral coating and subsequent protein binding is not compromised by the encapsulated imaging agent. This dual function delivery vehicle is not only advantageous for spatial tracking therapeutic applications, but also determining the longevity of the delivery vehicle once injected. In the broader sense, providing a mechanism to image and track our temporally controlled, sustained delivery system gives more evidence to support the effects of released protein on in vivo responses (bioactivity) and locate microspheres within different biological systems.

In vitro and in vivo dissolution behavior of a dysprosium lithium borate glass designed for the radiation synovectomy treatment of rheumatoid arthritis.

PubMed

Conzone, Samuel D; Brown, Roger F; Day, Delbert E; Ehrhardt, Gary J

2002-05-01

Dysprosium lithium borate (DyLB) glass microspheres were investigated for use in the radiation synovectomy treatment of rheumatoid arthritis. In vitro testing focused on weight loss and cation dissolution from glass microspheres immersed in simulated synovial fluid (SSF) at 37 degrees C for up to 64 days. In vivo testing was performed by injecting glass microspheres into the stifle joints of Sprague-Dawley rats and monitoring the biodegradability of the microspheres and the tissue response within the joints. The DyLB microspheres reacted nonuniformly in SSF with the majority of lithium and boron being dissolved, whereas nearly all of the dysprosium (>99.7%) remained in the reacted microspheres. Because the DyLB glasses released negligible amounts of dysprosium while reacting with SSF, they are considered safe for radiation synovectomy from the standpoint of unwanted radiation release from the joint capsule. Furthermore, the DyLB microspheres fragmented, degraded, and reacted with body fluids while in the joints of rats without histologic evidence of joint damage. Copyright 2002 Wiley Periodicals, Inc. J Biomed Mater Res 60: 260--268, 2002; DOI 10.1002/jbm.10047

Pluronic F127/chitosan blend microspheres for mucoadhesive drug delivery

NASA Astrophysics Data System (ADS)

Gu, W. Z.; Hu, X. F.

2017-01-01

Pluronic F127/chitosan blend microspheres were prepared via emulsification and cross-linking process using glutaraldehyde as a cross-linker. Compared with chitosan microspheres fabricated under the same experimental conditions, blend microspheres exhibited better physical stability and higher swelling capacity. Puerarin, a traditional Chinese medicine, was incorporated into microparticlesas the model drug. The in vitro release of puerarin from blend microspheres was reduced because of the improved compatibility of the drug with the matrices. According to the results from in vitro adhesion experiments, mucoadhesive behavior of blend microspheres on a mucosa-like surface was similar to that of chitosan microspheres, despite their good ability of anti-protein absorption in solution.

Development of starch-gelatin complex microspheres as sustained release delivery system

PubMed Central

Hari, B. N. Vedha; Praneetha, T.; Prathyusha, T.; Mounika, K.; Devi, D. Ramya

2012-01-01

The starch was isolated from jackfruit seeds and evaluated for its preformulation properties, like tapped density, bulk density, and particle size. The fourier transform infrared (FTIR) analysis was done and compared with that of the commercially available starch which confirmed the properties. Using the various concentrations of jackfruit seed starch, the microspheres were prepared, combining with gelatin by ionotropic gelation technique. The developed microspheres were subjected to analysis of particle size, drug content, entrapment efficiency, and percentage yield. The spectral analysis confirmed the presence of drug and absence of interactions. Scanning electron microscope image showed that the particles were in spherical shape with a rough surface. The in vitro drug release in water for 12 hours proved to be in the range of 89 to 100%. The various kinetic models were applied using release data to confirm the mechanism of drug. It was concluded that the jackfruit starch-gelatin microspheres gave satisfactory results and met pharmacopieal limits. PMID:23057005

Hydrogel-PLGA delivery system prolongs 2-methoxyestradiol-mediated anti-tumor effects in osteosarcoma cells.

PubMed

Maran, Avudaiappan; Dadsetan, Mahrokh; Buenz, Colleen M; Shogren, Kristen L; Lu, Lichun; Yaszemski, Michael J

2013-09-01

Osteosarcoma is a bone tumor that affects children and young adults. 2-Methoxyestradiol (2-ME), a naturally occurring estrogen metabolite, kills osteosarcoma cells, but does not affect normal osteoblasts. In order to effectively target osteosarcoma and improve the therapeutic index of the drug 2-ME, we have encapsulated 2-ME in a composite of oligo-(polyethylene glycol) fumarate (OPF) hydrogel and poly (lactic-co-glycolic acid) (PLGA) microspheres and investigated the effect of polymer composition on 2-ME release kinetics and osteosarcoma cell survival. The in vitro study shows that 2-ME can be released in a controlled manner over 21-days. The initial burst releases observed on day 1 were 50% and 32% for OPF and OPF/PLGA composites, respectively. The extended release kinetics show that 100% of the encapsulated 2-ME is released by day 12 from OPF, whereas the OPF/PLGA composites showed a release of 85% on day 21. 2-ME released from the polymers was biologically active and blocked osteosarcoma cell proliferation in vitro. Also, comparison of 2-ME delivery in osteosarcoma cells in culture, shows that direct treatment has no effect after 3 days, whereas polymer-mediated delivery produces anti-tumor effects that could be sustained for 21 days. These findings show that the OPF and PLGA polymeric system may prove to be useful in controlled and sustained delivery of 2-ME and could be further explored in the treatment of osteosarcoma. Copyright © 2012 Wiley Periodicals, Inc.

Albumin/gentamicin microspheres produced by supercritical assisted atomization: optimization of size, drug loading and release.

PubMed

Della Porta, G; Adami, R; Del Gaudio, P; Prota, L; Aquino, R; Reverchon, E

2010-11-01

In this work, the supercritical assisted atomization (SAA) is proposed, for the first time, not only as a micronization technology but also as a thermal coagulation process for the production of bovine serum albumin (BSA) microspheres charged with Gentamicin sulfate (GS). Particularly, different water solutions of BSA/GS were processed by SAA to produce protein microspheres with different size and antibiotic content. SAA precipitation temperature was selected in the range 100-130 °C to generate protein coagulation and to recover micronized BSA in form of hydrophobic aggregates; GS loading was varied between 10% and 50% (w/w) with an encapsulation efficiency which often reached 100%. In all cases, spherical and noncoalescing particles were successfully produced with a mean particle size of 2 µm and with a standard deviation of about ±1 µm. The microspheres also showed a good stability and constant water content after 60 days of storage. The release profiles of the entrapped drug were monitored using Franz cells to evaluate the possible application of the produced microspheres in wound dressing formulations. Particularly, the microspheres with a BSA/GS ratio of 4:1 after the first burst effect (of 40% of GS loaded) were able to release the GS continuously over 10 days. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

Adsorptive removal of an anionic dye Congo red by flower-like hierarchical magnesium oxide (MgO)-graphene oxide composite microspheres

NASA Astrophysics Data System (ADS)

Xu, Jing; Xu, Difa; Zhu, Bicheng; Cheng, Bei; Jiang, Chuanjia

2018-03-01

Flower-like magnesium oxide (MgO) microspheres and MgO-graphene oxide (GO) composites with an average diameter of 500 nm and hierarchical structure were synthesized through an ethylene glycol-mediated self-assembly process. The adsorption of Congo red (CR) by the prepared samples was evaluated in water under ambient conditions. The equilibrium adsorption isotherms of CR on the as-prepared samples could be described by the Langmuir model. The MgO-GO microspheres prepared with 0.5 wt% GO showed higher adsorption capacity (237.0 mg/g) than the MgO microspheres (227.7 mg/g). Adsorption kinetics results of CR indicated that pseudo-second-order kinetic equation could well explain the adsorption kinetics behaviors of CR. These findings indicate that the MgO-GO composite microspheres are potential adsorbents for effective removal of Congo red from wastewater.

Release of a wound-healing agent from PLGA microspheres in a thermosensitive gel.

PubMed

Machado, H A; Abercrombie, J J; You, T; Deluca, P P; Leung, K P

2013-01-01

The purpose of this research was to develop a topical microsphere delivery system in a thermosensitive 20% poloxamer 407 gel (Pluronic F127) to control release of KSL-W, a cationic antimicrobial decapeptide, for a period of 4-7 days for potential application in combat related injuries. KSL-W loaded microsphere formulations were prepared by a solvent extraction-evaporation method (water-oil-water), with poly (D,L-lactic-co-glycolic acid) (PLGA) (50 : 50, low-weight, and hydrophilic end) as the polymeric system. After optimization of the process, three formulations (A, B, and C) were prepared with different organic to water ratio of the primary emulsion while maintaining other components and manufacturing parameters constant. Formulations were characterized for surface morphology, porous nature, drug loading, in vitro drug release, and antimicrobial activity. Microspheres containing 20% peptide with porous surfaces and internal structure were prepared in satisfactory yields and in sizes varying from 25 to 50 μm. Gels of 20% Pluronic F127, which were liquid at or below 24.6°C and formed transparent films at body temperature, were used as carriers for the microspheres. Rheological studies showed a gelation temperature of 24.6°C for the 20% Pluronic F127 gel alone. Gelation temperature and viscosity of formulations A, B, and C as a function of temperature were very close to those of the carrier. A Franz diffusion cell system was used to study the release of peptide from the microspheres suspended in both, phosphate-buffered saline (PBS) and a 20% Pluronic F127 gel. In vitro release of greater than 50% peptide was found in all formulations in both PBS and the gel, and in one formulation there was a release of 75% in both PBS and the gel. Fractions collected from the release process were also tested for bactericidal activity against Staphylococcus epidermidis using the broth microdilution method and found to provide effective antimicrobial activity to warrant consideration and testing in animal wound models for treating combat-related injuries.

Preparation and characterization of injectable Mitoxantrone poly (lactic acid)/fullerene implants for in vivo chemo-photodynamic therapy.

PubMed

Li, Zhi; Zhang, Fei-long; Pan, Li-li; Zhu, Xia-li; Zhang, Zhen-zhong

2015-08-01

Fullerene (C60) L-phenylalanine derivative attached with poly (lactic acid) (C60-phe-PLA) was developed to prepare injectable Mitoxantrone (MTX) multifunctional implants. C60-phe-PLA was self-assembled to form microspheres consisting of a hydrophilic antitumor drug (MTX) and a hydrophobic block (C60) by dispersion-solvent diffusion method. The self-assembled microspheres showed sustained release pattern almost 15days in vitro release experiments. According to the tissue distribution of C57BL mice after intratumoral administration of the microspheres, the MTX mainly distributed in tumors, and rarely in heart, liver, spleen, lung, and kidney. Photodynamic antitumor efficacy of blank microsphere was realized. Microspheres afforded high antitumor efficacy without obvious toxic effects to normal organs, owing to its significantly increased MTX tumor retention time, low MTX levels in normal organs and strong photodynamic activity of PLA-phe-C60. These C60-phe-PLA microspheres may be promising for the efficacy with minimal side effects in future treatment of solid tumors. Copyright © 2015 Elsevier B.V. All rights reserved.

Programmed cell delivery from biodegradable microcapsules for tissue repair.

PubMed

Draghi, L; Brunelli, D; Farè, S; Tanzi, M C

2015-01-01

Injectable and resorbable hydrogels are an extremely attractive class of biomaterials. They make it possible to fill tissue defects accurately with an undoubtedly minimally invasive approach and to locally deliver cells that support repair or regeneration processes. However, their use as a cell carrier is often hindered by inadequate diffusion in bulk. A possible strategy for overcoming this transport limitation might be represented by injection of rapidly degradable cell-loaded microcapsules, so that maximum material thickness is limited by sphere radius. Here, the possibility of achieving programmable release of viable cells from alginate-based microcapsules was explored in vitro, by evaluating variations in material stability resulting from changes in hydrogel composition and assessing cell viability after encapsulation and in vitro release from microcapsules. Degradation of pure alginate microspheres was varied from a few days to several weeks by varying sodium alginate and calcium chloride concentrations. The addition of poloxamer was also found to accelerate degradation significantly, with capsule breakdown almost complete by two weeks, while chitosan was confirmed to strengthen alginate cross-linking. The presence of viable cells inside microspheres was revealed after encapsulation, and released cells were observed for all the formulations tested after a time interval dependent on bead degradation speed. These findings suggest that it may be possible to fine tune capsule breakdown by means of simple changes in material formulation and regulate, and eventually optimize, cell release for tissue repair.

Novel pH- and temperature-responsive blend hydrogel microspheres of sodium alginate and PNIPAAm-g-GG for controlled release of isoniazid.

PubMed

Kajjari, Praveen B; Manjeshwar, Lata S; Aminabhavi, Tejraj M

2012-12-01

This paper reports the preparation and characterization of novel pH- and thermo-responsive blend hydrogel microspheres of sodium alginate (NaAlg) and poly(N-isopropylacrylamide)(PNIPAAm)-grafted-guar gum (GG) i.e., PNIPAAm-g-GG by emulsion cross-linking method using glutaraldehyde (GA) as a cross-linker. Isoniazid (INZ) was chosen as the model antituberculosis drug to achieve encapsulation up to 62%. INZ has a plasma half-life of 1.5 h, whose release was extended up to 12 h. Fourier transform infrared spectroscopy was used to confirm the grafting reaction and chemical stability of INZ during the encapsulation. Differential scanning calorimetry was used to investigate the drug's physical state, while powder X-ray diffraction confirmed the molecular level dispersion of INZ in the matrix. Scanning electron microscopy confirmed varying surface morphologies of the drug-loaded microspheres. Temperature- and pH-responsive nature of the blend hydrogel microspheres were investigated by equilibrium swelling, and in vitro release experiments were performed in pH 1.2 and pH 7.4 buffer media at 37°C as well as at 25°C. Kinetics of INZ release was analyzed by Ritger-Peppas empirical equation to compute the diffusional exponent parameter (n), whose value ranged between 0.27 and 0.58, indicating the release of INZ follows a diffusion swelling controlled release mechanism.

21 CFR 522.1451 - Moxidectin microspheres for injection.

Code of Federal Regulations, 2014 CFR

2014-04-01

... constitution of the moxidectin microspheres. Each milliliter of constituted, sustained-release suspension... Uncinaria stenocephala infections. (3) Limitations. Federal law restricts this drug to use by or on the...

Hierarchical Polyphosphazene@Molybdenum Disulfide Hybrid Structure for Enhancing the Flame Retardancy and Mechanical Property of Epoxy Resins.

PubMed

Zhou, Xia; Qiu, Shuilai; Xing, Weiyi; Gangireddy, Chandra Sekhar Reddy; Gui, Zhou; Hu, Yuan

2017-08-30

A novel polyphosphazene (PZS) microsphere@molybdenum disulfide nanoflower (MoS 2 ) hierarchical hybrid architecture was first synthesized and applied for enhancing the mechanical performance and flame retardancy of epoxy (EP) resin via a cooperative effect. Herein, using PZS microsphere as the template, a layer of MoS 2 nanoflowers were anchored to PZS spheres via a hydrothermal strategy. The well-designed PZS@MoS 2 exhibits excellent fire retardancy and a reinforcing effect. The obtained PZS@MoS 2 significantly enhanced the flame-retardant performance of EP composites, which can be proved by thermogravimetric and cone calorimeter results. For instance, the incorporation of 3 wt % PZS@MoS 2 brought about a 41.3% maximum reduction in the peak heat-release rate and decreased by 30.3% maximum in the total heat release, accompanying the higher graphitized char layer. With regard to mechanical property, the storage modulus of EP/PZS@MoS 2 3.0 in the glassy state was dramatically increased to 22.4 GPa in comparison with that of pure EP (11.15 GPa). It is sensible to know that the improved flame-retardant performance for EP composites is primarily assigned to a physical barrier effect of the MoS 2 nanoflowers and the polyphosphazene structure has an positive impact on promoting char formation in the condensed phase.

Protective effects of alginate–chitosan microspheres loaded with alkaloids from Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. (Zuojin Pill) against ethanol-induced acute gastric mucosal injury in rats

PubMed Central

Wang, Qiang-Song; Zhu, Xiao-Ning; Jiang, Heng-Li; Wang, Gui-Fang; Cui, Yuan-Lu

2015-01-01

Zuojin Pill (ZJP), a traditional Chinese medicine formula, consists of Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. in a ratio of 6:1 (w/w) and was first recorded in “Danxi’s experiential therapy” for treating gastrointestinal disorders in the 15th century. However, the poor solubility of alkaloids from ZJP restricted the protective effect in treating gastritis and gastric ulcer. The aim of the study was to investigate the protective mechanism of mucoadhesive microspheres loaded with alkaloids from C. chinensis Franch. and E. rutaecarpa (Juss.) Benth. on ethanol-induced acute gastric mucosal injury in rats. Surface morphology, particle size, drug loading, encapsulation efficiency, in vitro drug release, mucoadhesiveness, and fluorescent imaging of the microspheres in gastrointestinal tract were studied. The results showed that the mucoadhesive microspheres loaded with alkaloids could sustain the release of drugs beyond 12 hours and had gastric mucoadhesive property with 82.63% retention rate in vitro. The fluorescence tracer indicated high retention of mucoadhesive microspheres within 12 hours in vivo. The mucoadhesive microspheres loaded with alkaloids could reduce the gastric injury by decreasing the mucosal lesion index, increasing the percentage of inhibition and increasing the amount of mucus in the gastric mucosa in an ethanol-induced gastric mucosal injury rat model. Moreover, the mucoadhesive microspheres loaded with alkaloids reduce the inflammatory response by decreasing the levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), downregulating the mRNA expression of inducible nitric oxide synthase, TNF-α, and IL-1β in gastric mucosa. All the results indicate that mucoadhesive microspheres loaded with alkaloids could not only increase the residence time of alkaloids in rat stomach, but also exert gastroprotective effects through reducing the inflammatory response on ethanol-induced gastric mucosal damage. Thus, these microspheres could be developed as a potential controlled release drug for treatment of gastric ulcer. PMID:26640368

Controlled release of sulfasalazine release from "smart" pectin gel microspheres under physiological simulated fluids.

PubMed

Costas, Luciana; Pera, Licia M; López, Azucena Gómez; Mechetti, Magdalena; Castro, Guillermo R

2012-07-01

Sulfasalazine (SLZ) is a synthetic nonsteroidal anti-inflammatory drug used mainly for the treatment of an inflammatory bowel and other diseases. Two pectins with different methylation degrees were blended to synthesized gel microspheres by ionotropic gelation for SLZ encapsulation. The encapsulation efficiency was found to be around of 99% in all formulations tested. However, different SLZ release profiles related to the methylation degrees of pectin were observed. Mixture of low methylated (LM) and high methylated (HM) pectins in the presence of calcium(II) displayed the best microsphere morphologies among the formulations tested determined by optical and electronic microscopies. The percentage of drug release using a mixture of LM and HM pectins after 255 min in simulated gastric fluid (pH = 1.2), simulated intestinal fluid (pH = 6.8), and phosphate buffer (pH = 7.4) were 15.0%, 47.0%, and 52.2%, respectively.

Sustained release of nerve growth factor from biodegradable polymer microspheres.

PubMed

Camarata, P J; Suryanarayanan, R; Turner, D A; Parker, R G; Ebner, T J

1992-03-01

Although grafted adrenal medullary tissue to the striatum has been used both experimentally and clinically in parkinsonism, there is a definite need to augment long-term survival. Infusion of nerve growth factor (NGF) or implantation of NGF-rich tissue into the area of the graft prolongs survival and induces differentiation into neural-like cells. To provide for prolonged, site-specific delivery of this growth factor to the grafted tissue in a convenient manner, we fabricated biodegradable polymer microspheres of poly(L-lactide)co-glycolide (70:30) containing NGF. Biologically active NGF was released from the microspheres, as assayed by neurite outgrowth in a dorsal root ganglion tissue culture system. Anti-NGF could block this outgrowth. An enzyme-linked immunosorbent assay detected NGF still being released in vitro for longer than 5 weeks. In vivo immunohistochemical studies showed release over a 4.5-week period. This technique should prove useful for incorporating NGF and other growth factors into polymers and delivering proteins and other macromolecules intracerebrally over a prolonged time period. These growth factor-containing polymer microspheres can be used in work aimed at prolonging graft survival, treating experimental Alzheimer's disease, and augmenting peripheral nerve regeneration.

Nanocomposite strategies for limiting medical and marine biofouling

NASA Astrophysics Data System (ADS)

Cooper, Scott Patrick

Microorganisms affect many aspects of human life. When microorganisms colonize a surface, the resulting microbial community is called a biofilm. Biofilms can negatively affect human health and productivity. Osteomyelitis is caused by biofilms of bacteria attached to the bone. These biofilms pose a threat to human life and lead to the loss of healthy tissue. Biofilms attached to marine vessels decrease the fuel economy of ships, resulting in a significant economic cost. There is a need to develop new materials which eradicate and prevent biofouling. Nanocomposites and mixed-phase organic/inorganic materials are presented in various embodiments as a means to limit biofouling. Antibiotic-filled microspheres are created to improve the treatment of osteomyelitis. These microspheres consist of bioactive glass and poly(n-vinylpyrrolidone) (PVP) or gelatin. Bioactive glasses have historically been shown to promote the regeneration of bone. Sol-gel chemistry is used to make the bioactive glass component, in this case a calcium silicate. The low temperature of the reaction allows organic molecules such as drugs and polymers to be blended with the glass. The catalyst used during the sol-gel reaction affects the structure and composition of the microspheres. Base catalysis leads to microspheres that exhibit behavior indicative of a nanocomposite structure. Acid catalysis produces microspheres that appear to exist as more as a mixed phase between silica and PVP. These structures directly affect the stability of the microspheres in simulated body fluid (SBF): base-catalyzed microspheres degrade within the first day in SBF, while acid-catalyzed microspheres are stable for at least one week. The morphology of acid-catalyzed microspheres is directly affected by the following compositional parameters: molecular weight of PVP, concentration of PVP, and concentration of calcium. Solid, hollow, and core/shell morphologies are produced by adjusting these parameters. These morphologies are likely caused by various rates of silicate hydrolysis, condensation, and hydrogen bonding to PVP. Viscosity of the sol plays little role in determining the diameter of the dried microspheres. An antibiotic, vancomycin, is successfully incorporated into these hybrid microspheres. Vancomycin is released for 5-7 days as measured by UV absorption. An in vitro assay against cultures of Staphylococcus aureus demonstrates that the drug remains effective for 4 days. Marine biofouling is addressed by imparting topography onto silica-reinforced poly(dimethylsiloxane) elastomeric (PDMSe) films. Swimming zoospores from the green alga Ulva are used as a model fouling organism. A bio-inspired topography deterred attachment of the zoospores by 70-80% over a 4-hr assay. Image analysis of the zoospores suggests that the topography may inhibit biofilm formation by disrupting the early-stage aggregation of spores on the surface. The attachment kinetics fit, with high correlation, equations used to describe that adsorption of bacteria to surfaces. This suggests the same physical phenomena drives the attachment of bacteria and swimming algal zoospores to solid surfaces.

Effect of pH on polyethylene glycol (PEG)-induced silk microsphere formation for drug delivery.

PubMed

Wu, Jianbing; Xie, Xusheng; Zheng, Zhaozhu; Li, Gang; Wang, Xiaoqin; Wang, Yansong

2017-11-01

The effects of changing solution pH in the range of 3.6-10.0 during a one-step silk microsphere preparation process, by mixing silk and polyethylene glycol (PEG), was assessed. The microspheres prepared at low pH (3.6) showed a more homogeneous size (1-3μm) and less porous texture than those prepared at neutral pH. High pH (10.0) inhibited microsphere formation, yielding small and inhomogeneous microspheres. Compared to neutral pH, low pH also increased the content of silk crystalline β-sheet structure from approx. 30% to above 40%. As a result, the microspheres produced at low pH were more thermally stable as well as resistant to chemical (8M urea) and enzymatic (protease XIV) degradation when compared to microspheres prepared at neutral pH. Doxorubicin hydrochloride (DOX) and curcumin (CUR) were successfully loaded in silk microspheres via control of solution pH. The loading efficiency of DOX was approx. 95% at pH7.0 and approx. 60% for CUR at pH3.6, attributed to charge-charge interactions and hydrophobic interactions between the silk and drug molecules, respectively. When PBS, pH7.4, was used as a medium for release studies, the pH3.6 microspheres released both drugs more slowly than the pH7.0 microspheres, likely due to the high content of crystalline β-sheet structure that enhanced drug-silk interactions as well as restricted drug molecule diffusion. Copyright © 2017. Published by Elsevier B.V.

Formulation and evaluation of microsphere based oro dispersible tablets of itopride hcl

PubMed Central

2012-01-01

Background The purpose of the present work is to mask the intensely bitter taste of Itopride HCl and to formulate an Oro dispersible tablet (ODT) of the taste-masked drug by incorporation of microspheres in the tablets for use in specific populations viz. pediatrics, geriatrics and patients experiencing difficulty in swallowing. Methods With this objective in mind, microspheres loaded with Itopride HCl were prepared by solvent evaporation method using acetone as solvent for pH-sensitive polymer, Eudragit EPO and light liquid paraffin as the encapsulating medium. The prepared microspheres were characterized with regard to yield, drug content, flow properties, particle size and size distribution, surface features, in vitro drug release and taste. The ODTs so prepared from these microspheres were evaluated for hardness, thickness, weight variation, friability, disintegration time, drug content, wetting time, water absorption ratio, moisture uptake, in vitro dispersion, in vitro disintegration, in vitro drug release and stability. Results The average size of microspheres was found to be satisfactory in terms of the size and size distribution. Microspheres prepared were of a regular spherical shape. Comparison of the dissolution profiles of microspheres in different pH media showed that microspheres having drug: polymer ratio of 1:2 produced a retarding effect in simulated salivary fluid (pH 6.8) and were further used for formulation into ODTs after addition of suitable amounts of excipients such as superdisintegrant, diluent, sweetener and flavor of directly compressible grade. Conclusions Effective taste-masking was achieved for Itopride HCl by way of preparation of microspheres and ODTs of acceptable characteristics. PMID:23351176

Formulation and evaluation of microsphere based oro dispersible tablets of itopride hcl.

PubMed

Shah, Sanjay; Madan, Sarika; Agrawal, Ss

2012-09-03

The purpose of the present work is to mask the intensely bitter taste of Itopride HCl and to formulate an Oro dispersible tablet (ODT) of the taste-masked drug by incorporation of microspheres in the tablets for use in specific populations viz. pediatrics, geriatrics and patients experiencing difficulty in swallowing. With this objective in mind, microspheres loaded with Itopride HCl were prepared by solvent evaporation method using acetone as solvent for pH-sensitive polymer, Eudragit EPO and light liquid paraffin as the encapsulating medium. The prepared microspheres were characterized with regard to yield, drug content, flow properties, particle size and size distribution, surface features, in vitro drug release and taste. The ODTs so prepared from these microspheres were evaluated for hardness, thickness, weight variation, friability, disintegration time, drug content, wetting time, water absorption ratio, moisture uptake, in vitro dispersion, in vitro disintegration, in vitro drug release and stability. The average size of microspheres was found to be satisfactory in terms of the size and size distribution. Microspheres prepared were of a regular spherical shape. Comparison of the dissolution profiles of microspheres in different pH media showed that microspheres having drug: polymer ratio of 1:2 produced a retarding effect in simulated salivary fluid (pH 6.8) and were further used for formulation into ODTs after addition of suitable amounts of excipients such as superdisintegrant, diluent, sweetener and flavor of directly compressible grade. Effective taste-masking was achieved for Itopride HCl by way of preparation of microspheres and ODTs of acceptable characteristics.

Starch-entrapped biopolymer microspheres as a novel approach to vary blood glucose profiles.

PubMed

Venkatachalam, Mahesh; Kushnick, Michael R; Zhang, Genyi; Hamaker, Bruce R

2009-10-01

With emerging knowledge of the impact of the metabolic quality of glycemic carbohydrates on human health, there is a need for novel carbohydrate ingredients that can be custom-made to deliver controlled amounts of glucose to the body and to test hypotheses on the postprandial metabolic consequences of carbohydrates. The goal of the present study was to demonstrate the applicability and action of starch-entrapped biopolymer microspheres as customized, novel, slowly digestible carbohydrates to obtain desired glycemic responses. Starch-entrapped microspheres were developed; and starch digestion and glucose release, subsequent to their cooking (100 degrees C, 20 min) in water, were initially monitored by measuring the rapidly digestible, slowly digestible, and resistant starch fractions using the in vitro Englyst assay. Glycemic and insulinemic responses after consumption of glucose and two different slowly digestible starch microsphere diets were compared using a crossover study in 10 healthy individuals. The mechanism of starch digestion in the microspheres was elucidated from scanning electron microscopic images of the in vitro digested microspheres. Factors such as biopolymer type and concentration, microsphere size, and starch type were manipulated to obtain starch materials with defined amounts of slowly digestible starch based on in vitro studies. Scanning electron microscopy showed that cooked starch entrapped in the dense biopolymer matrix is digested layer by layer from the outside to the inside of the microsphere. Glycemic and insulinemic responses to microsphere test diets were moderate as compared to a glucose diet, but more important, they showed extended glucose release. Starch-entrapped microspheres provide a useful tool to study the postprandial metabolic consequences of slowly digestible carbohydrates.

Cephradin-plaga microspheres for sustained delivery to cattle.

PubMed

Ustariz-Peyret, C; Coudane, J; Vert, M; Kaltsatos, V; Boisramé, B

1999-01-01

In the field of controlled drug delivery, most of the reported work is aimed at introducing new systems, or at providing basic information on the critical parameters which affect release profiles in vitro and occasionally in vivo. The situation is totally different when one wants to fulfil the specific requirements imposed by the marketing of a sustained release device to be used in humans or in animals eaten by human beings. The control of the release characteristics is then a difficult challenge. In this work, attempts were made to combine cephradin, a hydrophilic beta-lactam antibiotic, and bioresorbable polymeric matrices of a poly(alpha-hydroxy acid) in the form of microspheres with the aim of delivering the antibiotic to cattle at a dose rate of 4-5 mg/kg/day over a 3-4 days period after i.m. injection. PLAGA aliphatic polyesters were selected because they are already FDA approved as matrices. The solvent evaporation technique using PVA as the emulsion stabilizer was selected because it is efficient and can be extended to an industrial scale. Various experimental conditions were used in order to obtain the highest encapsulation yields compatible with the desired specifications. Decreasing the volume of the aqueous phase and adding a water-miscible organic solvent/non-solvent of cephradin failed. In contrast, microspheres containing up to 30% cephradin were prepared after addition of sodium chloride to the aqueous dispersing phase. The amount of entrapped drug was raised to 40% by decreasing the temperature and the pressure. Preliminary investigations using dogs showed that 20% cephradin microspheres prepared under these conditions extended the presence of cephradin in the blood circulation up to 48 h. Increasing the load led to higher blood concentrations but shorter sustained release. The fact that the microspheres were for cattle limited the volume of the injection and thus the amount of microspheres to be administered. The other limiting factors were related to microsphere morphology.

Novel Fabrication of Biodegradable Superabsorbent Microspheres with Diffusion Barrier through Thermo-Chemical Modification and Their Potential Agriculture Applications for Water Holding and Sustained Release of Fertilizer.

PubMed

Feng, Diejing; Bai, Bo; Wang, Honglun; Suo, Yourui

2017-07-26

Synergistic utilization of water and fertilizer has vital contribution to the modern production of agriculture. This work reports on a simple and facile strategy to prepare biodegradable yeast/sodium alginate/poly(vinyl alcohol) superabsorbent microspheres with a diffusion barrier merit by thermo-chemical modification route. The integrated performances, including water absorbency, water retention, water evaporation ratio, leaching loss control, sustained-release behaviors, and degradation in soil, were systematically investigated. The results revealed that the modified microspheres were a triumphant water and fertilizer manager to effectively hold water and control the unexpected leakage of fertilizer for sustained release. Therefore, this work provides a promising approach to ameliorate the utilization efficiency of water and fertilizer in potential agriculture applications.

Eudragit® S100 coated calcium pectinate microspheres of curcumin for colon targeting.

PubMed

Zhang, Lin; Cao, Fengliang; Ding, Buyun; Li, Qilu; Xi, Yanwei; Zhai, Guangxi

2011-01-01

Currently, colon-specific drug delivery systems have been investigated for drugs that can exert their bioactivities in the colon. In this study, Eudragit® S100 coated calcium pectinate microsphere, a pH-dependent and enzyme-dependent system, as colon-specific delivery carrier for curcumin was investigated. Curcumin-loaded calcium pectinate microspheres were prepared by emulsification-linkage method, and the preparation technology was optimised by uniform experimental design. The morphology of microspheres was observed under scanning electron microscopy. Interactions between drug and polymers were investigated with differential scanning calorimetry (DSC) and X-ray diffraction. In vitro drug release studies were performed in simulated colonic fluid in the presence of Pectinex Ultra SP-L or 1% (w/v) rat caecal content, and the results indicated that the release of curcumin was significantly increased in the presence of 1% (w/v) rat caecal contents. It could be concluded that Eudragit® S100 coated calcium pectinate microsphere was a potential carrier for colon delivery of curcumin.

High pressure-resistant nonincendive emulsion explosive

DOEpatents

Ruhe, Thomas C.; Rao, Pilaka P.

1994-01-01

An improved emulsion explosive composition including hollow microspheres/bulking agents having high density and high strength. The hollow microspheres/bulking agents have true particle densities of about 0.2 grams per cubic centimeter or greater and include glass, siliceous, ceramic and synthetic resin microspheres, expanded minerals, and mixtures thereof. The preferred weight percentage of hollow microspheres/bulking agents in the composition ranges from 3.0 to 10.0 A chlorinated paraffin oil, also present in the improved emulsion explosive composition, imparts a higher film strength to the oil phase in the emulsion. The emulsion is rendered nonincendive by the production of sodium chloride in situ via the decomposition of sodium nitrate, a chlorinated paraffin oil, and sodium perchlorate. The air-gap sensitivity is improved by the in situ formation of monomethylamine perchlorate from dissolved monomethylamine nitrate and sodium perchlorate. The emulsion explosive composition can withstand static pressures to 139 bars and dynamic pressure loads on the order of 567 bars.

Graphene Aerogel Templated Fabrication of Phase Change Microspheres as Thermal Buffers in Microelectronic Devices.

PubMed

Wang, Xuchun; Li, Guangyong; Hong, Guo; Guo, Qiang; Zhang, Xuetong

2017-11-29

Phase change materials, changing from solid to liquid and vice versa, are capable of storing and releasing a large amount of thermal energy during the phase change, and thus hold promise for numerous applications including thermal protection of electronic devices. Shaping these materials into microspheres for additional fascinating properties is efficient but challenging. In this regard, a novel phase change microsphere with the design for electrical-regulation and thermal storage/release properties was fabricated via the combination of monodispersed graphene aerogel microsphere (GAM) and phase change paraffin. A programmable method, i.e., coupling ink jetting-liquid marbling-supercritical drying (ILS) techniques, was demonstrated to produce monodispersed graphene aerogel microspheres (GAMs) with precise size-control. The resulting GAMs showed ultralow density, low electrical resistance, and high specific surface area with only ca. 5% diameter variation coefficient, and exhibited promising performance in smart switches. The phase change microspheres were obtained by capillary filling of phase change paraffin inside the GAMs and exhibited excellent properties, such as low electrical resistance, high latent heat, well sphericity, and thermal buffering. Assembling the phase change microsphere into the microcircuit, we found that this tiny device was quite sensitive and could respond to heat as low as 0.027 J.

Development and evaluation of a novel biodegradable sustained release microsphere formulation of paclitaxel intended to treat breast cancer

PubMed Central

Shiny, Jacob; Ramchander, Thadkapally; Goverdhan, Puchchakayala; Habibuddin, Mohammad; Aukunuru, Jithan Venkata

2013-01-01

Objective: The objective of this study was to develop a novel 1 month depot paclitaxel (PTX) microspheres that give a sustained and complete drug release. Materials and Methods: PTX loaded microspheres were prepared by o/w emulsion solvent evaporation technique using the blends of poly(lactic-co-glycolic acid) (PLGA) 75/25, polycaprolactone 14,000 and polycaprolactone 80,000. Fourier transform infrared spectroscopy was used to investigate drug excipient compatibility. Compatible blends were used to prepare F1-F6 microspheres, the process was characterised and the optimum formulation was selected based on the release. Optimised formulation was characterised for solid state of the drug using the differential scanning calorimetry (DSC) studies, surface morphology using the scanning electron microscopy (SEM), in vivo drug release, in vitro in vivo correlation (IVIVC) and anticancer activity. Anticancer activity of release medium was determined using the cell viability assay in Michigan Cancer Foundation (MCF-7) cell line. Results: Blend of PLGA with polycaprolactone (Mwt 14,000) at a ratio of 1:1 (F5) resulted in complete release of the drug in a time frame of 30 days. F5 was considered as the optimised formulation. Incomplete release of the drug resulted from other formulations. The surface of the optimised formulation was smooth and the drug changed its solid state upon fabrication. The formulation also resulted in 1-month drug release in vivo. The released drug from F5 demonstrated anticancer activity for 1-month. Cell viability was reduced drastically with the release medium from F5 formulation. A 100% IVIVC was obtained with F5 formulation suggesting the authenticity of in vitro release, in vivo release and the use of the formulation in breast cancer. Conclusions: From our study, it was concluded that with careful selection of different polymers and their combinations, PTX 1 month depot formulation with 100% drug release and that can be used in breast cancer was developed. PMID:24167783

Three-dimensional Macroscopic Scaffolds With a Gradient in Stiffness for Functional Regeneration of Interfacial Tissues

PubMed Central

Singh, Milind; Dormer, Nathan; Salash, Jean R.; Christian, Jordan M.; Moore, David S.; Berkland, Cory; Detamore, Michael S.

2010-01-01

A novel approach has been demonstrated to construct biocompatible, macroporous 3-D tissue engineering scaffolds containing a continuous macroscopic gradient in composition that yields a stiffness gradient along the axis of the scaffold. Polymeric microspheres, made of poly(d,l-lactic-co-glycolic acid) (PLGA), and composite microspheres encapsulating a higher stiffness nano-phase material (PLGA encapsulating CaCO3 or TiO2 nanoparticles) were used for the construction of microsphere-based scaffolds. Using controlled infusion of polymeric and composite microspheres, gradient scaffolds displaying an anisotropic macroscopic distribution of CaCO3/TiO2 were fabricated via an ethanol sintering technique. The controllable mechanical characteristics and biocompatible nature of these scaffolds warrants further investigation for interfacial tissue engineering applications. PMID:20336753

Nanoporous TiNb2O7/C Composite Microspheres with Three-Dimensional Conductive Network for Long-Cycle-Life and High-Rate-Capability Anode Materials for Lithium-Ion Batteries.

PubMed

Zhu, Guozhen; Li, Qing; Zhao, Yunhao; Che, Renchao

2017-11-29

On the basis of the advantages of ideal cycling stability, high discharge voltage (1.65 V), and excellent reversibility, more and more attention has been focused on TiNb 2 O 7 (marked as TNO) as an anode material candidate for lithium-ion batteries. However, the poor electronic conductivity and low ionic diffusion rate intrinsically restrict its practical use. Herein, we first synthesize the TNO/C composite microspheres with three-dimensionally (marked as 3D) electro-conductive carbon network and abundant nanoporous structure by a simple spray-drying method. The microspheres are constructed by irregularly primary cubic nanoparticle units with size of 100-200 nm. The nanopores throughout the microspheres range from 1 to 50 nm. As an anode material, the prepared TNO/C composite microspheres demonstrate a prominent charge/discharge capacity of 323.2/326 mA h g -1 after 300 cycles at 0.25 C (1 C = 388 mA g -1 ) and 259.9/262.5 mA h g -1 after 1000 long cycles at a high current density of 5 C, revealing the ideal reversible capacity and long cycling life. Meanwhile, the TNO/C composite microspheres present ideal rate performance, showing the discharge capacity of 120 mA h g -1 at 30 C after 10 cycles. The super electrochemical performance could be attributed to the 3D electro-conductive carbon network and nanoporous structure. The nanopores facilitate the permeation of electrolyte into the intercontacting regions of the anode materials. Carbon layers disperse uniformly throughout the 3D microspheres, effectively improving the electrical conductivity of the electrode. Hence, the prepared TNO/C composite microspheres have great potential to be used as an anode material for lithium-ion batteries.

Chitosan conduits combined with nerve growth factor microspheres repair facial nerve defects

PubMed Central

Liu, Huawei; Wen, Weisheng; Hu, Min; Bi, Wenting; Chen, Lijie; Liu, Sanxia; Chen, Peng; Tan, Xinying

2013-01-01

Microspheres containing nerve growth factor for sustained release were prepared by a compound method, and implanted into chitosan conduits to repair 10-mm defects on the right buccal branches of the facial nerve in rabbits. In addition, chitosan conduits combined with nerve growth factor or normal saline, as well as autologous nerve, were used as controls. At 90 days post-surgery, the muscular atrophy on the right upper lip was more evident in the nerve growth factor and normal sa-line groups than in the nerve growth factor-microspheres and autologous nerve groups. physiological analysis revealed that the nerve conduction velocity and amplitude were significantly higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. Moreover, histological observation illustrated that the di-ameter, number, alignment and myelin sheath thickness of myelinated nerves derived from rabbits were higher in the nerve growth factor-microspheres and autologous nerve groups than in the nerve growth factor and normal saline groups. These findings indicate that chitosan nerve conduits bined with microspheres for sustained release of nerve growth factor can significantly improve facial nerve defect repair in rabbits. PMID:25206635

Yolk-Shell Porous Microspheres of Calcium Phosphate Prepared by Using Calcium L-Lactate and Adenosine 5'-Triphosphate Disodium Salt: Application in Protein/Drug Delivery.

PubMed

Ding, Guan-Jun; Zhu, Ying-Jie; Qi, Chao; Sun, Tuan-Wei; Wu, Jin; Chen, Feng

2015-06-26

A facile and environmentally friendly approach has been developed to prepare yolk-shell porous microspheres of calcium phosphate by using calcium L-lactate pentahydrate (CL) as the calcium source and adenosine 5'-triphosphate disodium salt (ATP) as the phosphate source through the microwave-assisted hydrothermal method. The effects of the concentration of CL, the microwave hydrothermal temperature, and the time on the morphology and crystal phase of the product are investigated. The possible formation mechanism of yolk-shell porous microspheres of calcium phosphate is proposed. Hemoglobin from bovine red cells (Hb) and ibuprofen (IBU) are used to explore the application potential of yolk-shell porous microspheres of calcium phosphate in protein/drug loading and delivery. The experimental results indicate that the as-prepared yolk-shell porous microspheres of calcium phosphate have relatively high protein/drug loading capacity, sustained protein/drug release, favorable pH-responsive release behavior, and a high biocompatibility in the cytotoxicity test. Therefore, the yolk-shell porous microspheres of calcium phosphate have promising applications in various biomedical fields such as protein/drug delivery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Controlled dexamethasone delivery via double-walled microspheres to enhance long-term adipose tissue retention

PubMed Central

Kelmendi-Doko, Arta; Rubin, J Peter; Klett, Katarina; Mahoney, Christopher; Wang, Sheri; Marra, Kacey G

2017-01-01

Current materials used for adipose tissue reconstruction have critical shortcomings such as suboptimal volume retention, donor-site morbidity, and poor biocompatibility. The aim of this study was to examine a controlled delivery system of dexamethasone to generate stable adipose tissue when mixed with disaggregated human fat in an athymic mouse model for 6 months. The hypothesis that the continued release of dexamethasone from polymeric microspheres would enhance both adipogenesis and angiogenesis more significantly when compared to the single-walled microsphere model, resulting in long-term adipose volume retention, was tested. Dexamethasone was encapsulated within single-walled poly(lactic-co-glycolic acid) microspheres (Dex SW MS) and compared to dexamethasone encapsulated in a poly(lactic-co-glycolic acid) core surrounded by a shell of poly-l-lactide. The double-walled polymer microsphere system in the second model was developed to create a more sustainable drug delivery process. Dexamethasone-loaded poly(lactic-co-glycolic acid) microspheres (Dex SW MS) and dexamethasone-loaded poly(lactic-co-glycolic acid)/poly-l-lactide double-walled microspheres (Dex DW MS) were prepared using single and double emulsion/solvent techniques. In vitro release kinetics were determined. Two doses of each type of microsphere were examined; 50 and 27 mg of Dex MS and Dex DW MS were mixed with 0.3 mL of human lipoaspirate. Additionally, 50 mg of empty MS and lipoaspirate-only controls were examined. Samples were analyzed grossly and histologically after 6 months in vivo. Mass and volume were measured; dexamethasone microsphere-containing samples demonstrated greater adipose tissue retention compared to the control group. Histological analysis, including hematoxylin and eosin and CD31 staining, indicated increased vascularization (p < 0.05) within the Dex MS-containing samples. Controlled delivery of adipogenic factors, such as dexamethasone via polymer microspheres, significantly affects adipose tissue retention by maintaining healthy tissue formation and vascularization. Dex DW MS provide an improved model to former Dex SW MS, resulting in notably longer release time and, consequently, larger volumes of adipose retained in vivo. The use of microspheres, specifically double-walled, as vehicles for controlled drug delivery of adipogenic factors therefore present a clinically relevant model of adipose retention that has the potential to greatly improve soft tissue repair. PMID:29051810

Sequential delivery of TAT-HSP27 and VEGF using microsphere/hydrogel hybrid systems for therapeutic angiogenesis.

PubMed

Shin, Seung-Hwa; Lee, Jangwook; Lim, Kwang Suk; Rhim, Taiyoun; Lee, Sang Kyung; Kim, Yong-Hee; Lee, Kuen Yong

2013-02-28

Ischemic disease is associated with high mortality and morbidity rates, and therapeutic angiogenesis via systemic or local delivery of protein drugs is one potential approach to treat the disease. In this study, we hypothesized that combined delivery of TAT-HSP27 (HSP27 fused with transcriptional activator) and VEGF could enhance the therapeutic efficacy in an ischemic mouse model, and that sequential release could be critical in therapeutic angiogenesis. Alginate hydrogels containing TAT-HSP27 as an anti-apoptotic agent were prepared, and porous PLGA microspheres loaded with VEGF as an angiogenic agent were incorporated into the hydrogels to prepare microsphere/hydrogel hybrid delivery systems. Sequential in vitro release of TAT-HSP27 and VEGF was achieved by the hybrid systems. TAT-HSP27 was depleted from alginate gels in 7 days, while VEGF was continually released for 28 days. The release rate of VEGF was attenuated by varying the porous structures of PLGA microspheres. Sequential delivery of TAT-HSP27 and VEGF was critical to protect against muscle degeneration and fibrosis, as well as to promote new blood vessel formation in the ischemic site of a mouse model. This approach to controlling the sequential release behaviors of multiple drugs could be useful in the design of novel drug delivery systems for therapeutic angiogenesis. Copyright © 2012 Elsevier B.V. All rights reserved.

Self-Assembly of pH-Responsive Microspheres for Intestinal Delivery of Diverse Lipophilic Therapeutics.

PubMed

Zhou, Xing; Zhao, Yang; Chen, Siyu; Han, Songling; Xu, Xiaoqiu; Guo, Jiawei; Liu, Mengyu; Che, Ling; Li, Xiaohui; Zhang, Jianxiang

2016-08-08

Targeted delivery of therapeutics to the intestine is preferred for the management of many diseases due to its diverse advantages. Currently, there are still challenges in creating cost-effective and translational pH-responsive microspheres for intestinal delivery of various hydrophobic drugs. Herein we report a multiple noncovalent interactions-mediated assembly strategy in which carboxyl-bearing compounds (CBCs) are guest molecules, while poly(N-isopropylacrylamide) (PNIPAm) serves as a host polymer. Formation of microparticles and therapeutic packaging can be achieved simultaneously by this assembly approach, leading to well-shaped microspheres with extremely higher drug loading capacity as compared to microspheres based on two FDA-approved materials of poly(d,l-lactide-co-glycolide) (PLGA) and an enteric coating polymer EudragitS 100 (S100). Also, carboxyl-deficient hydrophobic drugs can be effectively entrapped. These assembled microspheres, with excellent reconstitution capability as well as desirable scalability, could selectively release drug molecules under intestinal conditions. By significantly enhancing drug dissolution/release in the intestine, these pH-responsive assemblies may notably improve the oral bioavailability of loaded therapeutics. Moreover, the assembled microspheres possessed superior therapeutic performance in rodent models of inflammation and tumor over the control microspheres derived from PLGA and S100. Therapy with newly developed microspheres did not cause undesirable side effects. Furthermore, in vivo evaluation in mice revealed the carrier material PNIPAm was safe for oral delivery at doses as high as 10 g/kg. Collectively, our findings demonstrated that this type of pH-responsive microsphere may function as superior and translational intestine-directed delivery systems for a diverse array of therapeutics.

Preparation and in vitro/in vivo evaluation of PLGA microspheres containing norquetiapine for long-acting injection.

PubMed

Park, Chun-Woong; Lee, Hyo-Jung; Oh, Dong-Won; Kang, Ji-Hyun; Han, Chang-Soo; Kim, Dong-Wook

2018-01-01

Norquetiapine ( N -desalkyl quetiapine, NQ) is an active metabolite of quetiapine with stable pharmacokinetic and pharmacological properties. However, its short half-life is a drawback for clinical applications, and long-acting formulations are required. The objectives of this study were to prepare improved entrapment efficiency NQ freebase microspheres by the solvent evaporation method with poly(d,l-lactic-co-glycolic acid) (PLGA) as a release modulator and to evaluate their physicochemical and in vitro/in vivo release properties. NQ freebase PLGA (1:5 w/w) formulations were prepared by the oil-in-water (o/w) emulsion-solvent evaporation method. A solution of the drug and PLGA in 9:1 v/v dichloromethane:ethanol was mixed with 0.2% polyvinyl alcohol and homogenized at 2,800 rpm. The emulsion was stirred for 3 h to dilute and evaporate the solvent. After that, the resulting product was freeze-dried. Drug-loading capacity was measured by the validated RP-HPLC method. The surface morphology of the microspheres was observed by scanning electron microscopy (SEM), and the physicochemical properties were evaluated by differential scanning calorimetry, powder X-ray diffraction, and Fourier-transform infrared spectroscopy particle size distribution. The in vitro dissolution test was performed using a rotary shaking bath at 37°C, with constant shaking at 50 rpm in sink condition. The NQ freebase microspheres prepared by o/w emulsion-solvent evaporation showed over 30% efficiency. NQ was confirmed to be amorphous in the microspheres by powder X-ray diffraction and differential scanning calorimetry. Special chemical interaction in the microspheres was not observed by FT-IR. The in vitro dissolution test demonstrated that the prepared microspheres' release properties were maintained for more than 20 days. The in vivo test also confirmed that the particles' long acting properties were maintained. Therefore, good in vitro-in vivo correlation was established. In this study, NQ freebase-PLGA microspheres showed potential for the treatment of schizophrenia for long-periods.

Apatite nano-crystalline surface modification of poly(lactide-co-glycolide) sintered microsphere scaffolds for bone tissue engineering: implications for protein adsorption.

PubMed

Jabbarzadeh, Ehsan; Nair, Lakshmi S; Khan, Yusuf M; Deng, Meng; Laurencin, Cato T

2007-01-01

A number of bone tissue engineering approaches are aimed at (i) increasing the osteconductivity and osteoinductivity of matrices, and (ii) incorporating bioactive molecules within the scaffolds. In this study we examined the growth of a nano-crystalline mineral layer on poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds for tissue engineering. In addition, the influence of the mineral precipitate layer on protein adsorption on the scaffolds was studied. Scaffolds were mineralized by incubation in simulated body fluid (SBF). Scanning electron microscopy (SEM) analysis revealed that mineralized scaffolds possess a rough surface with a plate-like nanostructure covering the surface of microspheres. The results of protein adsorption and release studies showed that while the protein release pattern was similar for PLAGA and mineralized PLAGA scaffolds, precipitation of the mineral layer on PLAGA led to enhanced protein adsorption and slower protein release. Mineralization of tissue-engineered surfaces provides a method for both imparting bioactivity and controlling levels of protein adsorption and release.

Effect of formulation and processing variables on the characteristics of microspheres for water-soluble drugs prepared by w/o/o double emulsion solvent diffusion method.

PubMed

Lee, J; Park, T G; Choi, H

2000-02-25

80% except for acetaminophen, due to its lower solubility in water and higher solubility in corn oil. The release profile of the drug was pH dependent. In acidic medium, the release rate was much slower, however, the drug was released quickly at pH 7.4. Tacrine showed unexpected release profiles, probably due to ionic interaction with polymer matrix and the shell structure and the highest release rate was obtained at pH 2.0. The prepared microspheres had a sponge-like inner structure with or without central hollow core and the surface was dense with no apparent pores.

Fire hazard reduction of hollow glass microspheres in thermoplastic polyurethane composites.

PubMed

Jiao, Chuanmei; Wang, Hongzhi; Li, Shaoxiang; Chen, Xilei

2017-06-15

Nowadays, reducing the fire hazard of thermoplastic polyurethane (TPU) is an important research direction in the fields of fire safety materials. In this article, hollow glass microsphere (HGM) was used to reduce the fire hazard of TPU in combustion process. The fire characteristics including smoke and heat production of TPU composites were evaluated using smoke density test (SDT) and cone calorimeter test (CCT). And the thermal decomposition and flammable properties were further studied using thermogravimetric analysis/infrared spectrometry (TG-IR) and limiting oxygen index (LOI), etc. The SDT results showed that the luminous flux (LF) of TPU4 containing 2.00wt% HGM was up to 24% at the end of test without flame, which is much higher than that of TPU0 (5%). And, the CCT results indicated that 2.00wt% HGM could make the total smoke release (TSR) decrease from 1019m 2 /m 2 (TPU0) to 757m 2 /m 2 (TPU4), reduced by 26%. The TG-IR results confirmed that HGM could improve the thermal stability of composites and reduce the production of some toxic gases. The above results illustrated HGM had a good prospect in reducing the fire hazard for TPU. Copyright © 2017 Elsevier B.V. All rights reserved.

Composition and structure of calcium aluminosilicate microspheres

NASA Astrophysics Data System (ADS)

Sharonova, O. M.; Oreshkina, N. A.; Zhizhaev, A. M.

2017-06-01

The composition was studied of calcium aluminosilicate microspheres of three morphological types in high-calcium fly ash from combustion of brown coal from the Kansk-Achinsk basin in slag-tap boilers at temperatures from 1400 to 1500°C and sampled in the first field of electrostatic precipitators at the Krasnoyarsk Cogeneration Power Station no. 2 (TETs-2). Gross compositions and the composition of local areas were determined using a scanning electron microscopy technique and an energy-dispersive analysis with full mapping of globules. With a high content of basic oxides O ox (68 to 79 wt %) and a low content of acid oxides K ox (21 to 31 wt %), type 1 microspheres are formed. They consist of heterogeneous areas having a porous structure and crystalline components in which the content of CaO, SiO2, or Al2O3 differs by two to three times and the content of MgO differs by seven times. With a lower content of O ox (55 to 63 wt %) and an elevated content of K ox (37 to 45 wt %), type 2 microspheres are formed. They are more homogeneous in the composition and structure and consist of similar crystalline components. Having a close content of O ox (46 to 53 wt %) and K ox (47 to 54 wt %), type 3 microspheres, which are a dense matter consisting of amorphous substance with submicron- and nanostructure of crystalline components, are formed. The basic precursor in formation of high-calcium aluminosilicate microspheres is calcium from the organomineral matter of coals with various contribution of Mg, Fe, S, or Na from the coal organic matter and Al, Fe, S, or Si in the form of single mineral inclusions in a coal particle. On the basis of the available data, the effect was analyzed of the composition of a CaO-MgO-Al2O3-SiO2-FeO system on the melting and viscous properties of the matter in microspheres and formation of globules of different morphology. The results of this analysis will help to find a correlation with properties of microspheres in their use as functional microaggregates in cement or polymeric composite materials, or in the production of ceramic membranes or zeolite sorbents.

Compression molding of aerogel microspheres

DOEpatents

Pekala, R.W.; Hrubesh, L.W.

1998-03-24

An aerogel composite material produced by compression molding of aerogel microspheres (powders) mixed together with a small percentage of polymer binder to form monolithic shapes in a cost-effective manner is disclosed. The aerogel composites are formed by mixing aerogel microspheres with a polymer binder, placing the mixture in a mold and heating under pressure, which results in a composite with a density of 50--800 kg/m{sup 3} (0.05--0.80 g/cc). The thermal conductivity of the thus formed aerogel composite is below that of air, but higher than the thermal conductivity of monolithic aerogels. The resulting aerogel composites are attractive for applications such as thermal insulation since fabrication thereof does not require large and expensive processing equipment. In addition to thermal insulation, the aerogel composites may be utilized for filtration, ICF target, double layer capacitors, and capacitive deionization. 4 figs.

Compression molding of aerogel microspheres

DOEpatents

Pekala, Richard W.; Hrubesh, Lawrence W.

1998-03-24

An aerogel composite material produced by compression molding of aerogel microspheres (powders) mixed together with a small percentage of polymer binder to form monolithic shapes in a cost-effective manner. The aerogel composites are formed by mixing aerogel microspheres with a polymer binder, placing the mixture in a mold and heating under pressure, which results in a composite with a density of 50-800 kg/m.sup.3 (0.05-0.80 g/cc). The thermal conductivity of the thus formed aerogel composite is below that of air, but higher than the thermal conductivity of monolithic aerogels. The resulting aerogel composites are attractive for applications such as thermal insulation since fabrication thereof does not require large and expensive processing equipment. In addition to thermal insulation, the aerogel composites may be utilized for filtration, ICF target, double layer capacitors, and capacitive deionization.

A new approach for the one-step synthesis of bioactive PS vs. PMMA silica hybrid microspheres as potential drug delivery systems.

PubMed

Angelopoulou, A; Efthimiadou, E K; Boukos, N; Kordas, G

2014-05-01

In this work, hybrid microspheres were prepared in a two-step process combining the emulsifier free-emulsion polymerization and the sol-gel coating method. In the first step, polystyrene (St) and poly(methyl methacrylate) (PMMA) microspheres were prepared as sacrificial template and in the second step a silanol shell was fabricated. The functionalized surface of the hybrid microspheres by silane analogs (APTES, TEOS) resulted in enhanced effects. The hollow microspheres were resulted either in an additional step by template dissolution and/or during the coating process. The microspheres' surface interactions and the size distribution were optimized by treatment in simulated body fluids, which resulted in the in vitro prediction of bioactivity. The bioassay test indicated that the induced hydroxyapatite resembled in structure to naturally occurring bone apatite. The drug doxorubicin (DOX) was used as a model entity for the evaluation of drug loading and release. The drug release study was performed in two different pH conditions, at acidic (pH=4.5) close to cancer cell environment and at slightly basic pH (pH=7.4) resembling the orthopedic environment. The results of the present study indicated promising hybrid microspheres for the potential application as drug delivery vehicles, for dual orthopedic functionalities in bone defects, bone inflammation, bone cancer and bone repair. Copyright © 2014 Elsevier B.V. All rights reserved.

Physicochemical and mechanical properties of freeze cast hydroxyapatite-gelatin scaffolds with dexamethasone loaded PLGA microspheres for hard tissue engineering applications.

PubMed

Ghorbani, Farnaz; Nojehdehian, Hanieh; Zamanian, Ali

2016-12-01

Hydroxyapatite (HA)-gelatin scaffolds incorporated with dexamethasone-loaded polylactic-co-glycolic acid (PLGA) microspheres were synthesized by freeze casting technique. Scanning electron microscopy (SEM) micrographs demonstrated a unidirectional microstructure and a decrease in the pore size as a function of temperature gradient. Higher amounts of HA resulted in a decrease in the pore size. According to the results, at lower cooling rates, the formation of a lamellar structure decreased the mechanical strength, but at the same time, enhanced the swelling ratio, biodegradation rate and drug release level. On the other hand, higher weight ratios of HA increased the compressive strength, and reduced the swelling ratio, biodegradation rate and drug release level. The results obtained by furrier transform infrared spectroscopy (FTIR) and bioactivity analysis illustrated that the interactions of the materials support the apatite formation in the simulated body fluid (SBF) solution. Based on the obtained results, the synthesized composite scaffolds have the necessary mechanical and physicochemical features to support the regeneration of defects and to maintain their stability during the neo-tissue formation. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of reconstitutable suspensions containing diclofenac sodium-loaded microspheres for pediatric delivery.

PubMed

Oz, Umut Can; Devrim, Burcu; Bozkır, Asuman; Canefe, Kandemir

2015-01-01

Effective clinical utilisation of non-steroidal anti-inflammatory drugs, such as diclofenac sodium (DS) is significantly limited by their ulcerogenic potential and poor bioavailability after oral administration. The objective of this work was to develop reconstitutable pediatric suspensions of DS-loaded microspheres prepared with an acrylic polymer (Eudragit RS) for improved pediatric delivery of DS. The microspheres were prepared by the water-in-oil-in-water or solid-in-oil-in-water emulsion techniques. Enviromental scanning electron microscopy observations clearly showed that microspheres have spherical shape. The drug entrapment efficiency of these microspheres was found 47.96 ± 0.79% to 88.57 ± 0.59% and their average particle sizes were 23.94-60.78 µm, which are within the desired range for the development of suspension formulation. The in vitro dissolution indicated prolonged sustained release of DS over 8 h. The results of preliminary characterisation studies of suspensions show that a liquid pharmaceutical preparation for oral administration capable of providing a sustained release of DS was successfully obtained.

PLGA microspheres encapsulating siRNA.

PubMed

De Rosa, Giuseppe; Salzano, Giuseppina

2015-01-01

The therapeutic use of small interfering RNA (siRNA) represents a new and powerful approach to suppress the expression of pathologically genes. However, biopharmaceutical drawbacks, such as short half-life, poor cellular uptake, and unspecific distribution into the body, hamper the development of siRNA-based therapeutics. Poly(lactide-co-glycolide), (PLGA) microspheres can be a useful tool to overcome these issues. siRNA can be encapsulated into the PLGA microspheres, which protects the loaded nucleic acid against the enzymatic degradation. Moreover, PLGA microspheres can be injected directly into the action site, where the siRNA can be released in controlled manner, thus avoiding the need of frequent invasive administrations. The complete biodegradability of PLGA to monomers easily metabolized by the body, and its approval by FDA and EMA for parenteral administration, assure the safety of this copolymer and do not require the removal of the device after the complete drug release. In chapter, a basic protocol for the preparation of PLGA microspheres encapsulating siRNA is described. This protocol is based on a double emulsion/solvent evaporation technique, a well known and easy to reproduce method. This specific protocol has been developed to encapsulate a siRNA anti-TNFα in PLGA microspheres, and it has been designed and optimized to achieve high siRNA encapsulation efficiency and slow siRNA release in vitro. However, it can be extended also to other siRNA as well as other RNA or DNA-based oligonucleotides (miRNA, antisense, decoy, etc.). Depending on the applications, chemical modifications of the backbone and site-specific modification within the siRNA sequences could be required.

An effective novel delivery strategy of rasagiline for Parkinson's disease.

PubMed

Fernández, Marcos; Negro, Sofía; Slowing, Karla; Fernández-Carballido, Ana; Barcia, Emilia

2011-10-31

This is the first report on the efficacy of a new controlled release system developed for rasagiline mesylate (RM) in a rotenone-induced rat model of Parkinson's disease (PD). PLGA microspheres in vitro released RM at a constant rate of 62.3 μg/day for two weeks. Intraperitoneal injection of rotenone (2 mg/kg/day) to Wistar rats produced typical PD symptoms. Catalepsy, akinesia and swim tests outcomes in animals receiving RM either in solution or within microspheres showed a reversal in descent latency when compared to rotenone-treated animals, being this reversal specially pronounced in animals receiving RM microspheres (dose equivalent to 1 mg/kg/day RM injected i.p. every 15 days). Nissl-staining of brain sections showed selective degeneration of the substantia nigra (SNc) dopaminergic neurons in rotenone-treated animals which was markedly reverted by RM microspheres. PET/CT with (18)F-DG resulted in mean increases of accumulation of radiotracer in striatum and SNc of around 40% in animals treated with RM microspheres which also had significant beneficial effects on Bcl-2, Bax, TNF-α mRNA and SOD2 levels as detected by real-time RT-PCR. Our results confirm the robust effect achieved by the new controlled release system developed for RM which exhibited better in vivo efficacy than RM given in solution. Copyright © 2011 Elsevier B.V. All rights reserved.

Synthesis and characterization of poly(lactic acid-co-glycolic acid) complex microspheres as drug carriers.

PubMed

Wang, Fang; Liu, Xiuxiu; Yuan, Jian; Yang, Siqian; Li, Yueqin; Gao, Qinwei

2016-10-01

Poly(lactic-co-glycolic) acid (PLGA) is synthesized via melt polycondensation directly from lactic acid and glycolic acid with a feed molar ratio of 75/25. Bovine serum albumin, which is used as model protein, is entrapped into the poly(lactic-co-glycolic acid) microspheres with particle size of 260.9 ± 20.0 nm by the double emulsification method. Then it is the first report of producing more carboxyl groups by poly(lactic-co-glycolic acid) surface hydrolysis. The purpose is developing poly(lactic-co-glycolic acid) microspheres surface, which is modified with chitosan by chemical reaction between carboxyl groups and amine groups. The particle size and the positive zeta potential of the poly(lactic-co-glycolic acid)/chitosan microspheres are 388.2 ± 35.6 nm and 10.4 ± 2.9 mV, respectively. The drug loading ratio and encapsulation efficacy of poly(lactic-co-glycolic acid)/chitosan microspheres are 36.3% and 57.5%, which are higher than PLGA microspheres. Furthermore, the drug burst release of poly(lactic-co-glycolic acid)/chitosan microspheres at 10 h is decreased to 21.72% while the corresponding value of the poly(lactic-co-glycolic acid) microsphere is 64.56%. These results reveal that surface hydrolysis modification of poly(lactic-co-glycolic acid) is an efficient method to improve the negative potential and chemical reaction properties of the polymer. And furthermore, this study shows that chitosan-modified poly(lactic-co-glycolic acid) microspheres is a promising system for the controlled release of pharmaceutical proteins. © The Author(s) 2016.

Synthesis of P(AM-co-MAA)/AEM composite microspheres with lichi-like surface structure using porous microgel as template.

PubMed

Yang, Juxiang; Hu, Daodao; Xue, Min; Yang, Xing

2014-03-15

The P(AM-co-MAA)/AEM composite microspheres with lichi-like structure were synthesized by the hydrolysis and condensation of 3-(trimethoxysilyl)-propyldimethyloctadecyl-ammonium chloride (AEM) located within porous poly(acrylamide-co-methylacrylic acid) (P(AM-co-MAA)) microgels in an ammonia water atmosphere. The morphology and composition of the composite microspheres were characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), Fourier transform infrared spectrometer (FI-IR), and X-ray photoelectron spectroscopy (XPS), respectively. The results indicated that the composite microspheres with lichi-like surface structure could be obtained by controlling the loaded amount of AEM, the hydrolysis-condensation time of AEM, and the cross-linking degree of the porous P(AM-co-MAA) microgels. On the basis of the results, the mechanism on the formation of the microspheres with lichi-like surface structure was proposed. The multiple factors play a role in the formation of the specific surface morphology. The pores of the porous microgels make AEM behavior localized; the migration of AEM along with solvent evaporation leads to the structural change; the hydrolysis-condensation of AEM brings the temporarily structural solidification; the surface tension of hydrophobic AEM in hydrophilic atmosphere induces AEM liquid membrane constriction. Although the mechanism is complicated, the method is very simple. Based on the analogous principle, other composite materials with lichi-like structure could be constructed by altering precursor and porous template. Copyright © 2013 Elsevier Inc. All rights reserved.

Sustained release effects of berberine-loaded chitosan microspheres on in vitro chondrocyte culture.

PubMed

Zhou, Yan; Liu, Shiqing; Ming, Jianghua; Li, Yaming; Deng, Ming; He, Bin

2017-10-01

The low bioavailability and short biological half-life of berberine chloride (BBR) negatively affect the protective role of this compound against osteoarthritis (OA). The present study was performed to evaluate the effectiveness of sustained BBR release system. Novel BBR-loaded chitosan microspheres (BBR-loaded CMs) were successfully synthesized using an ionic cross-linking method for sustained release. The basic characteristics of the prepared microspheres were subsequently evaluated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) techniques, encapsulation efficiency (EE), and in vitro release experiments. BBR-loaded CMs displayed spherical forms to encapsulate a considerable quantity of BBR (100.8 ± 2.7 mg/g); these microspheres also exhibited an ideal releasing profile. The FT-IR spectra and XRD results revealed that BBR-loaded CMs were successfully synthesized via electrostatic interaction. In vitro experiments further showed that BBR-loaded CMs significantly inhibited sodium nitroprusside (SNP)-stimulated chondrocyte apoptosis as well as cytoskeletal remodeling, and led to increasing mitochondrial membrane potential and maintaining the nuclear morphology. BBR-loaded CMs exerted markedly higher anti-apoptotic activity in the treatment of OA, and markedly inhibited the protein expression levels of caspase-3, a disintegrin, and metalloproteinase with thrombospondin motifs (ADAMTS)-5 and matrix metalloproteinase (MMP)-13 induced by SNP in rat articular chondrocytes, compared with free BBR at equivalent concentration. Therefore, novel BBR-loaded CMs may offer potential for application in the treatment of OA.

A novel microsphere with a three-layer structure for duodenum-specific drug delivery.

PubMed

Zhu, Xi; Zhou, Dan; Jin, Yun; Song, Yu-pin; Zhang, Zhi-rong; Huang, Yuan

2011-07-15

Owing to the quick elimination of drug from duodenum and the depth of Helicobacter pylori (H. pylori) colonized in mucus, antibiotic therapy often fails in the eradication of H. pylori infection for duodenal ulcer. A novel duodenum-specific microsphere (DSM) consisting of three-layer structure was developed to enhance the drug concentration and retention time in duodenal mucus layer. Firstly a core-shell mucoadhesive microsphere was prepared with a novel emulsification/coagulation coating method by introducing drug loaded Eudragit cores into a thiolated chitosan mucoadhesive layer. Then the obtained core-shell mucoadhesive microspheres were further coated with hydroxypropyl methylcellulose acetate maleate as the pH-sensitive layer for the trigger of mucoadhesion and drug release in duodenum. From the fluorescence microscopic and scanning electron microscopic images, the three-layer structure was successfully established. The microspheres exhibited a duodenum-specific trigger performance, good mucoadhesive property and pH-dependent drug release. In vivo study performed in rats demonstrated that DSM exhibited about 3-fold augmentation of AUC and about 5-fold augmentation of C(max) for duodenal mucus drug concentration compared with free drug suspension. These results suggest that the three-layer structure microspheres may provide a promising approach for duodenum-targeting drug delivery system. Copyright © 2011 Elsevier B.V. All rights reserved.

Porous PLGA microspheres tailored for dual delivery of biomolecules via layer-by-layer assembly.

PubMed

Go, Dewi P; Palmer, Jason A; Mitchell, Geraldine M; Gras, Sally L; O'Connor, Andrea J

2015-05-01

Tissue engineering is a complex and dynamic process that requires varied biomolecular cues to promote optimal tissue growth. Consequently, the development of delivery systems capable of sequestering more than one biomolecule with controllable release profiles is a key step in the advancement of this field. This study develops multilayered polyelectrolyte films incorporating alpha-melanocyte stimulating hormone (α-MSH), an anti-inflammatory molecule, and basic fibroblast growth factor (bFGF). The layers were successfully formed on macroporous poly lactic-co-glycolic acid microspheres produced using a combined inkjet and thermally induced phase separation technique. Release profiles could be varied by altering layer properties including the number of layers and concentrations of layering molecules. α-MSH and bFGF were released in a sustained manner and the bioactivity of α-MSH was shown to be preserved using an activated macrophage cell assay in vitro. The system performance was also tested in vivo subcutaneously in rats. The multilayered microspheres reduced the inflammatory response induced by a carrageenan stimulus 6 weeks after implantation compared to the non-layered microspheres without the anti-inflammatory and growth factors, demonstrating the potential of such multilayered constructs for the controlled delivery of bioactive molecules. © 2014 Wiley Periodicals, Inc.

Composite nuclear fuel fabrication methodology for gas fast reactors

NASA Astrophysics Data System (ADS)

Vasudevamurthy, Gokul

An advanced fuel form for use in Gas Fast Reactors (GFR) was investigated. Criteria for the fuel includes operation at high temperature (˜1400°C) and high burnup (˜150 MWD/MTHM) with effective retention of fission products even during transient temperatures exceeding 1600°C. The GFR fuel is expected to contain up to 20% transuranics for a closed fuel cycle. Earlier evaluations of reference fuels for the GFR have included ceramic-ceramic (cercer) dispersion type composite fuels of mixed carbide or nitride microspheres coated with SiC in a SiC matrix. Studies have indicated that ZrC is a potential replacement for SiC on account of its higher melting point, increased fission product corrosion resistance and better chemical stability. The present work investigated natural uranium carbide microspheres in a ZrC matrix instead of SiC. Known issues of minor actinide volatility during traditional fabrication procedures necessitated the investigation of still high temperature but more rapid fabrication techniques to minimize these anticipated losses. In this regard, fabrication of ZrC matrix by combustion synthesis from zirconium and graphite powders was studied. Criteria were established to obtain sufficient matrix density with UC microsphere volume fractions up to 30%. Tests involving production of microspheres by spark erosion method (similar to electrodischarge machining) showed the inability of the method to produce UC microspheres in the desired range of 300 to 1200 mum. A rotating electrode device was developed using a minimum current of 80A and rotating at speeds up to 1500 rpm to fabricate microspheres between 355 and 1200 mum. Using the ZrC process knowledge, UC electrodes were fabricated and studied for use in the rotating electrode device to produce UC microspheres. Fabrication of the cercer composite form was studied using microsphere volume fractions of 10%, 20%, and 30%. The macrostructure of the composite and individual components at various stages were characterized to understand the required fabrication techniques and at the same time meet the necessary GFR fuel characteristics.

Scaffolds for bone regeneration made of hydroxyapatite microspheres in a collagen matrix.

PubMed

Cholas, Rahmatullah; Kunjalukkal Padmanabhan, Sanosh; Gervaso, Francesca; Udayan, Gayatri; Monaco, Graziana; Sannino, Alessandro; Licciulli, Antonio

2016-06-01

Biomimetic scaffolds with a structural and chemical composition similar to native bone tissue may be promising for bone tissue regeneration. In the present work hydroxyapatite mesoporous microspheres (mHA) were incorporated into collagen scaffolds containing an ordered interconnected macroporosity. The mHA were obtained by spray drying of a nano hydroxyapatite slurry prepared by the precipitation technique. X-ray diffraction (XRD) analysis revealed that the microspheres were composed only of hydroxyapatite (HA) phase, and energy-dispersive x-ray spectroscopy (EDS) analysis revealed the Ca/P ratio to be 1.69 which is near the value for pure HA. The obtained microspheres had an average diameter of 6 μm, a specific surface area of 40 m(2)/g as measured by Brunauer-Emmett-Teller (BET) analysis, and Barrett-Joyner-Halenda (BJH) analysis showed a mesoporous structure with an average pore diameter of 16 nm. Collagen/HA-microsphere (Col/mHA) composite scaffolds were prepared by freeze-drying followed by dehydrothermal crosslinking. SEM observations of Col/mHA scaffolds revealed HA microspheres embedded within a porous collagen matrix with a pore size ranging from a few microns up to 200 μm, which was also confirmed by histological staining of sections of paraffin embedded scaffolds. The compressive modulus of the composite scaffold at low and high strain values was 1.7 and 2.8 times, respectively, that of pure collagen scaffolds. Cell proliferation measured by the MTT assay showed more than a 3-fold increase in cell number within the scaffolds after 15 days of culture for both pure collagen scaffolds and Col/mHA composite scaffolds. Attractive properties of this composite scaffold include the potential to load the microspheres for drug delivery and the controllability of the pore structure at various length scales. Copyright © 2016 Elsevier B.V. All rights reserved.

From harmful Microcystis blooms to multi-functional core-double-shell microsphere bio-hydrochar materials.

PubMed

Bi, Lei; Pan, Gang

2017-11-13

Harmful algal blooms (HABs) induced by eutrophication is becoming a serious global environmental problem affecting public health and aquatic ecological sustainability. A novel strategy for the utilization of biomass from HABs was developed by converting the algae cells into hollow mesoporous bio-hydrochar microspheres via hydrothermal carbonization method. The hollow microspheres were used as microreactors and carriers for constructing CaO 2 core-mesoporous shell-CaO 2 shell microspheres (OCRMs). The CaO 2 shells could quickly increase dissolved oxygen to extremely anaerobic water in the initial 40 min until the CaO 2 shells were consumed. The mesoporous shells continued to act as regulators restricting the release of oxygen from CaO 2 cores. The oxygen-release time using OCRMs was 7 times longer than when directly using CaO 2 . More interestingly, OCRMs presented a high phosphate removal efficiency (95.6%) and prevented the pH of the solution from rising to high levels in comparison with directly adding CaO 2 due to the OH - controlled-release effect of OCRMs. The distinct core-double-shell micro/nanostructure endowed the OCRMs with triple functions for oxygen controlled-release, phosphorus removal and less impact on water pH. The study is to explore the possibility to prepare smarter bio-hydrochar materials by utilizing algal blooms.

Nefopam hydrochloride loaded microspheres for post-operative pain management: synthesis, physicochemical characterization and in-vivo evaluation.

PubMed

Sharma, Neelam; Arora, Sandeep; Madan, Jitender

2018-02-01

Once-daily oral dosage of nefopam hydrochloride loaded sustained release microspheres (NPH-MS) was investigated as novel therapeutic strategy for post-operative pain management. Microspheres were synthesized using poly-3-hydroxybutyrate and poly-(ɛ-caprolactone) by double emulsion solvent evaporation technique. NPH-MS were characterized through FTIR, PXRD and SEM. In-vitro drug release study revealed sustained behavior till 24 h. Haemolysis was <5% which signified haemocompatibility of formulation. ED50 in rat tail-flick anti-nociceptive test was found ∼18.12 mg/kg. In post-operative pain model, reversal of mechanical allodynia and thermal hyperalgesia by NPH-MS was statistically significant (p < .001) as compared with NPH till 24 h post-dose.

One-step growth of nanosheet-assembled BiOCl/BiOBr microspheres for highly efficient visible photocatalytic performance

NASA Astrophysics Data System (ADS)

Zhang, Jinfeng; Lv, Jiali; Dai, Kai; Liang, Changhao; Liu, Qi

2018-02-01

In this work, we have developed a simple synthetic approach of nanosheet-assembled BiOCl/BiOBr microspheres by an ethylene glycol (EG)-assisted hydrothermal method. The crystalline form, morphology, chemical composition, optical performance and surface area of BiOCl/BiOBr microspheres were identified using X-ray diffraction (XRD), transmission electron microscopy (TEM), high resolution TEM (HRTEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy spectra (EDX), UV-vis diffuse reflectance spectroscopy (DRS) analysis, high resolution X-ray photoelectron spectra (XPS) and N2 adsorption-desorption isotherms. BiOCl/BiOBr microspheres were nanosheet-assembled particles, which possessed visible light absorption under LED light irridation. Additionally, the methylene blue (MB) photodegradation performance of different BiOCl/BiOBr microspheres irradiated under 410 nm LED light arrays were investigated, the results exhibited that as-prepared BiOCl/BiOBr products showed higher catalytic effiency than pure BiOCl or BiOBr. By optimizing the composition ration of the BiOCl and BiOBr, up to 93% degradation rate can be obtained in the 40%BiOCl/BiOBr microspheres. Finally, the photocatalytic mechanism of BiOCl/BiOBr microspheres had been proposed.

Novel polystyrene microspheres functionalized by imidazolium and the electrocatalytic activity towards H2O2 of its Prussian blue composite

NASA Astrophysics Data System (ADS)

Mao, Hui; Song, Jinling; Zhang, Qian; Liu, Daliang; Gong, Naiqi; Li, Ying; Wu, Qiong; Verpoort, Francis; Song, Xi-Ming

2013-05-01

Copolymerization of styrene (St) and 1-vinyl-3-ethylimidazolium bromide (VEIB), novel poly(St-co-VEIB) microspheres were generated. Owing to the presence of imidazolium groups, such microspheres having an average diameter of 125 nm, behave electropositively when dispersed in aqueous solution. Furthermore, due to the presence of imidazolium groups, having a capacity of ion-exchange and weak reducibility on the surface of the PS microspheres, [Fe(CN)6]3- was absorbed on the surface of poly(St-co-VEIB) microspheres, and simultaneously, Fe3+ was reduced to Fe2+. Thus, in situ growth of Prussian blue (PB) nanoparticles could occur on the surface of poly(St-co-VEIB) microspheres without the addition of any other reducing agent. This methodology, utilizing the ion-exchange and weak reducibility properties of the imidazolium groups on the surface of micro-/nanostructures is a novel general method for assembling hierarchical nanostructured materials. Finally, the electrochemical property of the strawberry-like PS/PB composite microspheres was also investigated by applying a glassy carbon electrode. A good repeatability of the cyclic voltammetry responses, having a good linearity and sensitivity, for the electrocatalytic reduction of H2O2 was obtained.

A 5-fluorouracil-loaded floating gastroretentive hollow microsphere: development, pharmacokinetic in rabbits, and biodistribution in tumor-bearing mice

PubMed Central

Huang, Yu; Wei, Yumeng; Yang, Hongru; Pi, Chao; Liu, Hao; Ye, Yun; Zhao, Ling

2016-01-01

5-Fluorouracil (5-FU) was loaded in hollow microspheres to improve its oral bioavailability. 5-FU hollow microspheres were developed by a solvent diffusion–evaporation method. The effect of Span 80 concentration, ether/ethanol volume ratio, and polyvinyl pyrrolidone/ethyl cellulose weight ratio on physicochemical characteristics, floating, and in vitro release behaviors of 5-FU hollow microspheres was investigated and optimized. The formulation and technology composed of Span 80 (1.5%, w/v), ether/ethanol (1.0:10.0, v/v), and polyvinyl pyrrolidone/ethyl cellulose (1.0:10.0, w/w) were employed to develop three batch samples, which showed an excellent reproducibility. The microspheres were spherical with a hollow structure with high drug loading amount (28.4%±0.5%) and production yield (74.2%±0.6%); they exhibited excellent floating and sustained release characteristics in simulated gastric and intestinal fluid. Pharmacokinetic studies demonstrated that 5-FU hollow microspheres significantly enhanced oral bioavailability (area under curve, [AUC](0−t): 12.53±1.65 mg/L*h vs 7.80±0.83 and 5.82±0.83 mg/L*h) with longer elimination half-life (t1/2) (15.43±2.12 hours vs 2.25±0.22 and 1.43±0.18 hours) and mean residence time (7.65±0.97 hours vs 3.61±0.41 and 2.34±0.35 hours), in comparison with its solid microspheres and powder. In vivo distribution results from tumor-bearing nude mice demonstrated that the animals administered with 5-FU hollow microspheres had much higher drug content in tumor, plasma, and stomach at 1 and 8 hours except for 0.5 hours sample collection time point in comparison with those administered with 5-FU solid microspheres and its powder. These results suggested that the hollow microspheres would be a promising controlled drug delivery system for an oral chemotherapy agent like 5-FU. PMID:27042001

A 5-fluorouracil-loaded floating gastroretentive hollow microsphere: development, pharmacokinetic in rabbits, and biodistribution in tumor-bearing mice.

PubMed

Huang, Yu; Wei, Yumeng; Yang, Hongru; Pi, Chao; Liu, Hao; Ye, Yun; Zhao, Ling

2016-01-01

5-Fluorouracil (5-FU) was loaded in hollow microspheres to improve its oral bioavailability. 5-FU hollow microspheres were developed by a solvent diffusion-evaporation method. The effect of Span 80 concentration, ether/ethanol volume ratio, and polyvinyl pyrrolidone/ethyl cellulose weight ratio on physicochemical characteristics, floating, and in vitro release behaviors of 5-FU hollow microspheres was investigated and optimized. The formulation and technology composed of Span 80 (1.5%, w/v), ether/ethanol (1.0:10.0, v/v), and polyvinyl pyrrolidone/ethyl cellulose (1.0:10.0, w/w) were employed to develop three batch samples, which showed an excellent reproducibility. The microspheres were spherical with a hollow structure with high drug loading amount (28.4%±0.5%) and production yield (74.2%±0.6%); they exhibited excellent floating and sustained release characteristics in simulated gastric and intestinal fluid. Pharmacokinetic studies demonstrated that 5-FU hollow microspheres significantly enhanced oral bioavailability (area under curve, [AUC](0-t): 12.53±1.65 mg/L(*)h vs 7.80±0.83 and 5.82±0.83 mg/L(*)h) with longer elimination half-life (t1/2) (15.43±2.12 hours vs 2.25±0.22 and 1.43±0.18 hours) and mean residence time (7.65±0.97 hours vs 3.61±0.41 and 2.34±0.35 hours), in comparison with its solid microspheres and powder. In vivo distribution results from tumor-bearing nude mice demonstrated that the animals administered with 5-FU hollow microspheres had much higher drug content in tumor, plasma, and stomach at 1 and 8 hours except for 0.5 hours sample collection time point in comparison with those administered with 5-FU solid microspheres and its powder. These results suggested that the hollow microspheres would be a promising controlled drug delivery system for an oral chemotherapy agent like 5-FU.

Studies of ciprofloxacin encapsulation on alginate/pectin matrixes and its relationship with biodisponibility.

PubMed

Islan, Germán A; de Verti, Ignacio Pérez; Marchetti, Sergio G; Castro, Guillermo R

2012-07-01

Screening of ciprofloxacin (Cip) with selected biopolymers brings about 90% antibiotic interactions with a coacervate composed of alginate/high metoxylated pectin in 2:1 ratio. Fourier transform infrared spectroscopy analysis provides information about the nature of this interaction, revealing ionic and hydrophobic patterns among the molecules. Alginate/high methoxylated pectin gel microspheres developed by ionic gelation encapsulates 46.8 ± 5.0% Cip. The gel matrix can release Cip in a sustained manner, releasing 42.7 ± 0.2% in 2 h under simulated stomach pH conditions, and 83.3 ± 1.1% Cip release in 80 mM phosphate at pH = 7.40 (intestinal). The increase of sodium chloride from 50 to 200 mM implies a Cip release from 69.0 ± 1.5% to 95.1 ± 3.6% respectively in 2 h. Scanning electron microscopy revealed the cohesive effect of HM pectin over alginate molecules on the microsphere surface. Those results guarantee all Cip contained in the alginate/HM pectin microspheres could be released in an established kinetic profile along the gastrointestinal tract, avoiding the Cip undesirable side effects during absorption.

Evaluation of an Extended-Release, Abuse-Deterrent, Microsphere-in-Capsule Analgesic for the Management of Patients with Chronic Pain With Dysphagia (CPD).

PubMed

Fleming, Alison B; Carlson, Douglas R; Varanasi, Ravi K; Grima, Michael; Mayock, Stephen P; Saim, Said; Kopecky, Ernest A

2016-03-01

Patients who have chronic pain with dysphagia (difficulty swallowing) (CPD) often have difficulty taking oral medication and, as such, alter their medications by crushing or chewing in an attempt to make it easier to swallow. Such manipulation of currently marketed, extended-release (ER) opioid analgesics can significantly alter the pharmacokinetic (PK) properties of the formulations, resulting in poor treatment outcome or serious adverse events. There is an unmet medical need for oral ER opioid formulations suitable for patients with CPD. The primary objectives of this study were to conduct in vitro studies to evaluate alternate means of administration of a new, extended-release (ER), abuse-deterrent, microsphere-in-capsule formulation of oxycodone for patients with CPD. Specifically, these studies investigated the in vitro equivalence of drug release rates from Oxycodone DETERx® ER intact capsules (control condition) and administration via alternate modes-opening the capsule and sprinkling the microspheres onto soft foods or administration through enteral tubes. Secondary objectives were to compare alternate modes of administration of Oxycodone DETERx® to a commercially available ER-morphine product. Soft food study: Oxycodone DETERx® microspheres were sprinkled onto and mixed with several soft foods (ie, applesauce, vanilla pudding, strawberry jam, yogurt, and vanilla ice cream); the effect of drug contact time (0, 30, and 60 minutes) on drug release was studied. Enteral tube study: Oxycodone DETERx® microspheres were administered through varying sizes of nasogastric (10 and 12 Fr.) tubes and a 16 Fr. gastrostomy tube using 5 different delivery vehicles (ie, water, liquid nutritional feeds [Jevity®, Ensure®], and milk [whole milk and 2% milk]). Drug release rate was characterized using a standard in vitro dissolution methodology; dissolution of intact Oxycodone DETERx® capsules served as the control for both the soft food and enteral tube studies. Oxycodone concentration was measured using a standardized high-performance liquid chromatography (HPLC) assay. Similarity factor (f2) analysis was used to compare similarity of the dissolution profiles of test and control conditions. The mean dissolution profile of Oxycodone DETERx® microspheres sprinkled onto and mixed with each of the soft foods were similar (f2 > 50) to that of the control. Study drug-food contact time did not impact dissolution profiles. The dissolution data obtained from Oxycodone DETERx® microspheres passed through enteral feeding tubes of varying sizes were similar (f2 > 50) to that of the control. Unlike a marketed morphine sulfate ER pellet formulation, Oxycodone DETERx® did not clog any of the studied enteral tubes. A new ER, abuse-deterrent, microsphere-in-capsule formulation of oxycodone can be administered by sprinkling onto soft food without affecting the drug release profile of the formulation. The formulation can also be administered directly via enteral tubes without affecting drug release and without clogging enteral tubes. Oxycodone DETERx® may offer physicians and patients with CPD an alternate treatment option, especially in those patients who have dysphagia or an aversion to swallowing monolithic tablet/capsule formulations and for whom analgesic patches or other opioid formulations are not a viable therapeutic option. © 2015 World Institute of Pain.

Inhibition by local bupivacaine-releasing microspheres of acute postoperative pain from hairy skin incision.

PubMed

Ohri, Rachit; Wang, Jeffrey Chi-Fei; Blaskovich, Phillip D; Pham, Lan N; Costa, Daniel S; Nichols, Gary A; Hildebrand, William P; Scarborough, Nelson L; Herman, Clifford J; Strichartz, Gary R

2013-09-01

Acute postoperative pain causes physiological deficits and slows recovery. Reduction of such pain by local anesthetics that are delivered for several days postoperatively is a desirable clinical objective, which is approached by a new formulation and applied in animal studies reported here. We subcutaneously injected a new formulation of poly-lactic-co-glycolic acid polymer microspheres, which provides steady drug release for 96+ hours into rats at the dorsal region 2 hours before surgery. A single 1.2-cm-long skin incision was followed by blunt dissection of skin away from the underlying fascia, and closed by 2 sutures, followed by 14 days of testing. Microspheres containing 5, 10, 20, and 40 mg bupivacaine were injected locally 2 hours before surgery; bupivacaine-free microspheres were the vehicle control, and bupivacaine HCl solution (0.5%), the positive control. Mechanical sensitivity was determined by the frequency of local muscle contractions to repeated pokes with nylon monofilaments (von Frey hairs) exerting 4 and 15 g forces, testing, respectively, allodynia and hyperalgesia, and by pinprick. Injection of bupivacaine microspheres (40 mg drug) into intact skin reduced responses to 15 g von Frey hairs for 6 hours and to pinprick for 36 hours. Respective reductions from bupivacaine HCl lasted for 3 and 2 hours. Skin incision and dissection alone caused mechanical allodynia and hyperalgesia for 14 days. Microspheres containing 20 or 40 mg bupivacaine suppressed postoperative hypersensitivity for up to 3 days, reduced integrated allodynia (area under curve of response versus time) over postoperative days 1 to 5 by 51% ± 20% (mean ± SE) and 78% ± 12%, and reduced integrated hyperalgesia by 55% ± 13% and 64% ± 11%, for the respective doses. Five and ten milligrams bupivacaine in microspheres and the 0.5% bupivacaine solution were ineffective in reducing postoperative hypersensitivity, as were 40 mg bupivacaine microspheres injected contralateral to the incision. Significant suppression of postoperative pain by the slow-release bupivacaine preparation outlasts its anesthetic action on intact skin. These findings demonstrate preventive analgesia and indicate the importance of acute processes in the development of chronic postoperative pain.

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.

Phase relationship in three-phase composites which include a void phase

NASA Technical Reports Server (NTRS)

Price, H. L.; Nelson, J. B.

1976-01-01

The paper shows the relationship among polymer, particles, and voids in a three-phase composite and how some of the properties of a composite may be changed by changing the proportions of the phases. The three-phase composite is an aggregate of microspheres bonded together with a small amount of polymer which may not form a continuous matrix. The void space (third phase) is obtained by limiting the amount of polymer which is mixed with the microspheres. A ternary phase diagram is used to show the proportional relationship among the three phases, with each apex representing a volume fraction of unity for a constituent while the side opposite the apex represents a volume fraction of zero for that constituent. The vertical dimension represents some composite property such as density or strength. The effect of composition on composite properties is shown by plotting them on a binary phase diagram which represents a perpendicular plane coincident with the 0.60 volume fraction microsphere line.

A comparison of fibrin, agarose and gellan gum hydrogels as carriers of stem cells and growth factor delivery microspheres for cartilage regeneration.

PubMed

Ahearne, Mark; Kelly, Daniel J

2013-06-01

The limited intrinsic repair capacity of articular cartilage has led to the investigation of different treatment options to promote its regeneration. The delivery of hydrogels containing stem or progenitor cells and growth factor releasing microspheres represents an attractive approach to cartilage repair. In this study, the influence of the encapsulating hydrogel on the ability of progenitor cells coupled with TGF-β3 releasing microspheres to form cartilaginous tissue was investigated. Fibrin, agarose and gellan gum hydrogels containing TGF-β3 loaded gelatin microspheres and progenitor cells derived from the infrapatellar fat-pad of the knee were cultured for 21 days in a chemically defined media. In the presence of TGF-β3 releasing microspheres, gellan gum hydrogels were observed to facilitate greater cell proliferation than fibrin or agarose hydrogels. Histological and biochemical analysis of the hydrogels indicated that fibrin was the least chondro-inductive of the three hydrogels, while agarose and gellan gum appeared to support more robust cartilage formation as demonstrated by greater sGAG accumulation within these constructs. Gellan gum hydrogels also stained more intensely for collagen type II and collagen type I, suggesting that although total collagen synthesis was higher in these constructs, that the phenotype may be more fibrocartilaginous in nature than normal hyaline cartilage. This study demonstrates how the encapsulating hydrogel can have a significant impact on the ability of stem cells to form cartilage when incorporated into a growth factor delivery system.

ROS-Responsive Microspheres for On Demand Antioxidant Therapy in a Model of Diabetic Peripheral Arterial Disease

PubMed Central

Poole, KM; Nelson, CE; Joshi, RV; Martin, JR; Gupta, MK; Haws, SC; Kavanaugh, TE; Skala, MC; Duvall, CL

2014-01-01

A new microparticle-based delivery system was synthesized from reactive oxygen species (ROS)-responsive poly(propylene sulfide) (PPS) and tested for “on demand” antioxidant therapy. PPS is hydrophobic but undergoes a phase change to become hydrophilic upon oxidation and thus provides a useful platform for ROS-demanded drug release. This platform was tested for delivery of the promising anti-inflammatory and antioxidant therapeutic molecule curcumin, which is currently limited in use in its free form due to poor pharmacokinetic properties. PPS microspheres efficiently encapsulated curcumin through oil-in-water emulsion and provided sustained, on demand release that was modulated in vitro by hydrogen peroxide concentration. The cytocompatible, curcumin-loaded microspheres preferentially targeted and scavenged intracellular ROS in activated macrophages, reduced in vitro cell death in the presence of cytotoxic levels of ROS, and decreased tissue-level ROS in vivo in the diabetic mouse hind limb ischemia model of peripheral arterial disease. Interestingly, due to the ROS scavenging behavior of PPS, the blank microparticles also showed inherent therapeutic properties that were synergistic with the effects of curcumin in these assays. Functionally, local delivery of curcumin-PPS microspheres accelerated recovery from hind limb ischemia in diabetic mice, as demonstrated using non-invasive imaging techniques. This work demonstrates the potential for PPS microspheres as a generalizable vehicle for ROS-demanded drug release and establishes the utility of this platform for improving local curcumin bioavailability for treatment of chronic inflammatory diseases. PMID:25522975

In vitro evaluation of chitosan/poly(lactic acid-glycolic acid) sintered microsphere scaffolds for bone tissue engineering.

PubMed

Jiang, Tao; Abdel-Fattah, Wafa I; Laurencin, Cato T

2006-10-01

A three-dimensional (3-D) scaffold is one of the major components in many tissue engineering approaches. We developed novel 3-D chitosan/poly(lactic acid-glycolic acid) (PLAGA) composite porous scaffolds by sintering together composite chitosan/PLAGA microspheres for bone tissue engineering applications. Pore sizes, pore volume, and mechanical properties of the scaffolds can be manipulated by controlling fabrication parameters, including sintering temperature and sintering time. The sintered microsphere scaffolds had a total pore volume between 28% and 37% with median pore size in the range 170-200microm. The compressive modulus and compressive strength of the scaffolds are in the range of trabecular bone making them suitable as scaffolds for load-bearing bone tissue engineering. In addition, MC3T3-E1 osteoblast-like cells proliferated well on the composite scaffolds as compared to PLAGA scaffolds. It was also shown that the presence of chitosan on microsphere surfaces increased the alkaline phosphatase activity of the cells cultured on the composite scaffolds and up-regulated gene expression of alkaline phosphatase, osteopontin, and bone sialoprotein.

Novel Bi/BiOBr/AgBr composite microspheres: Ion exchange synthesis and photocatalytic performance

NASA Astrophysics Data System (ADS)

Lyu, Jianchang; Li, Zhenlu; Ge, Ming

2018-06-01

Novel Bi/BiOBr/AgBr composite microspheres were prepared by a rational in situ ion exchange reaction between Bi/BiOBr microspheres and AgNO3. The characteristic of the as-obtained ternary microspheres was tested by X-ray diffraction (XRD), energy dispersive X-ray spectrometer (EDS), scanning electron microscope (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectroscopy (UV-vis DRS) and photoluminescence (PL). Under visible light irradiation, Bi/BiOBr/AgBr microspheres exhibited an excellent photocatalytic efficiency for rhodamine B (RhB) degradation, which was about 1.4 and 4.9 times as high as that of Bi/BiOBr and BiOBr/AgBr, demonstrating that the highest separation efficiency of charge carriers in the heterostructured Bi/BiOBr/AgBr. The photocatalytic activity of Bi/BiOBr/AgBr microspheres just exhibited a slight decrease after three consecutive cycles. The photocatalytic mechanism investigation confirmed that the superoxide radicals (O2•-) were the dominant reactive oxygen species for RhB degradation in Bi/BiOBr/AgBr suspension.

Controlled drug delivery for glaucoma therapy using montmorillonite/Eudragit microspheres as an ion-exchange carrier

PubMed Central

Tian, Shuangyan; Li, Juan; Tao, Qi; Zhao, Yawen; Lv, Zhufen; Yang, Fan; Duan, Haoyun; Chen, Yanzhong; Zhou, Qingjun; Hou, Dongzhi

2018-01-01

Background Glaucoma is a serious eye disease that can lead to loss of vision. Unfortunately, effective treatments are limited by poor bioavailability of antiglaucoma medicine due to short residence time on the preocular surface. Materials and methods To solve this, we successfully prepared novel controlled-release ion-exchange microparticles to deliver betaxolol hydrochloride (BH). Montmorillonite/BH complex (Mt-BH) was prepared by acidification-intercalation, and this complex was encapsulated in microspheres (Mt-BH encapsulated microspheres [BMEMs]) by oil-in-oil emulsion–solvent evaporation method. The BH loaded into ion-exchange Mt was 47.45%±0.54%. After the encapsulation of Mt-BH into Eudragit microspheres, the encapsulation efficiency of BH into Eudragit microspheres was 94.35%±1.01% and BH loaded into Eudragit microspheres was 14.31%±0.47%. Results Both Fourier transform infrared spectra and X-ray diffraction patterns indicated that BH was successfully intercalated into acid-Mt to form Mt-BH and then Mt-BH was encapsulated into Eudragit microspheres to obtain BMEMs. Interestingly, in vitro release duration of the prepared BMEMs was extended to 12 hours, which is longer than both of the BH solution (2.5 hours) and the conventional BH microspheres (5 hours). Moreover, BMEM exhibited lower toxicity than that of BH solution as shown by the results of cytotoxicity tests, chorioallantoic membrane-trypan blue staining, and Draize rabbit eye test. In addition, both in vivo and in vitro preocular retention capacity study of BMEMs showed a prolonged retention time. The pharmacodynamics showed that BMEMs could extend the drug duration of action. Conclusion The developed BMEMs have the potential to be further applied as ocular drug delivery systems for the treatment of glaucoma. PMID:29391798

Controlled drug delivery for glaucoma therapy using montmorillonite/Eudragit microspheres as an ion-exchange carrier.

PubMed

Tian, Shuangyan; Li, Juan; Tao, Qi; Zhao, Yawen; Lv, Zhufen; Yang, Fan; Duan, Haoyun; Chen, Yanzhong; Zhou, Qingjun; Hou, Dongzhi

2018-01-01

Glaucoma is a serious eye disease that can lead to loss of vision. Unfortunately, effective treatments are limited by poor bioavailability of antiglaucoma medicine due to short residence time on the preocular surface. To solve this, we successfully prepared novel controlled-release ion-exchange microparticles to deliver betaxolol hydrochloride (BH). Montmorillonite/BH complex (Mt-BH) was prepared by acidification-intercalation, and this complex was encapsulated in microspheres (Mt-BH encapsulated microspheres [BMEMs]) by oil-in-oil emulsion-solvent evaporation method. The BH loaded into ion-exchange Mt was 47.45%±0.54%. After the encapsulation of Mt-BH into Eudragit microspheres, the encapsulation efficiency of BH into Eudragit microspheres was 94.35%±1.01% and BH loaded into Eudragit microspheres was 14.31%±0.47%. Both Fourier transform infrared spectra and X-ray diffraction patterns indicated that BH was successfully intercalated into acid-Mt to form Mt-BH and then Mt-BH was encapsulated into Eudragit microspheres to obtain BMEMs. Interestingly, in vitro release duration of the prepared BMEMs was extended to 12 hours, which is longer than both of the BH solution (2.5 hours) and the conventional BH microspheres (5 hours). Moreover, BMEM exhibited lower toxicity than that of BH solution as shown by the results of cytotoxicity tests, chorioallantoic membrane-trypan blue staining, and Draize rabbit eye test. In addition, both in vivo and in vitro preocular retention capacity study of BMEMs showed a prolonged retention time. The pharmacodynamics showed that BMEMs could extend the drug duration of action. The developed BMEMs have the potential to be further applied as ocular drug delivery systems for the treatment of glaucoma.

Chitosan-HPMC-blended microspheres as a vaccine carrier for the delivery of tetanus toxoid.

PubMed

Arthanari, Saravanakumar; Mani, Ganesh; Peng, Mei Mei; Jang, Hyun Tae

2016-01-01

The purpose of this research was to develop a suitable and alternate adjuvant for the tetanus toxoid (TT) vaccine that induces long term immunity after a single-dose immunization. In our study, the preformulation studies were carried out by using different ratios (7/3, 8/2, and 9/1) of chitosan-hydroxypropyl methylcellulose (HPMC)-blended empty microspheres. Moreover, TT was stabilized with heparin (at heparin concentrations of 1%, 2%, 3%, and 4% w/v) and encapsulated in ideal chitosan - HPMC (CHBMS) microspheres, by the water-in-oil-in-water (W/O/W) multiple emulsion method. The vaccine entrapment and the in vitro release efficiency of the CHBMS was evaluated for a period of 90 days. The release of antigens from the microspheres was determined by ELISA. Antigen integrity was investigated by SDS-PAGE. From the optimization studies, it was found that a chitosan/HPMC ratio of 8/2 produced a good yield, with microspheres that were spherical, regular and uniformly-sized. In the CHBMS, a heparin concentration of 3% w/v resulted in well-sustained antigen delivery for a period of 90 days. It was found that the characteristics of initial release could be observed in 2 days, followed by a constant release, and an almost 100% complete release in 90 days. From the in vitro release characteristics, the ideal batch of CHBMS (3% w/v heparin) was evaluated for in vivo studies by the antibody induction method. The antibody levels were measured for different combinations for the period of 9 months, and finally, with a second booster dose after 1 year. In conclusion, it was observed that CHBMS (combination-1) resulted in the antibody level of 4.5 IU/mL of guinea pig serum, and the level was 3.5 IU/mL for the Central Research Institute's alum-adsorbed tetanus toxoid (CRITT) (combination 2), after 1 year, with a second booster dose. This novel approach of using CHBMS may have potential advantages for single-step immunization with vaccines.

Robust superhydrophobic diamond microspheres for no-loss transport of corrosive liquid microdroplets.

PubMed

Wang, Qiang; Bai, Jie; Dai, Bing; Yang, Zhenhuai; Guo, Shuai; Yang, Lei; He, Yurong; Han, Jiecai; Zhu, Jiaqi

2017-02-16

Superhydrophobic surfaces usually lose their characteristics when exposed to a corrosive environment. To solve this issue, we synthesized superhydrophobic diamond microspheres by microwave-plasma-assisted chemical vapor deposition. Commercial epoxy glue was used to bond the microspheres to various substrates. The thus-synthesized composite films exhibited robust superhydrophobicity and an ultrahigh adhesive force.

Formulation and evaluation of Bacillus coagulans-loaded hypromellose mucoadhesive microspheres.

PubMed

Alli, Sk Md Athar

2011-01-01

Development of a novel delivery system has been attempted to deliver viable probiotic cells into the gut for a prolonged period of time while maintaining high numbers of viable cells within the formulation throughout the shelf-life of the product and during the gastrointestinal transit. Core mucoadhesive microspheres of Bacillus coagulans were developed employing several grades of hypromellose, a mucoadhesive polymer, following coacervation and phase separation technique and were subsequently enteric-coated with hypromellose phthalate. Microspheres were evaluated for percent yield; entrapment efficiency; in vitro swelling; surface morphology; particle size, size distribution, and zeta potential; flow property, mucoadhesion property by the ex vivo mucoadhesive strength test and the in vitro wash off test; in vitro release profile and release kinetic; in vivo probiotic activity; and stability. The values for the kinetic constant and regression coefficient of model-dependent approaches and the difference factor (f(1)), the similarity factor (f(2)), and the Rescigno index (ξ(1) and ξ(2)) of model independent approaches were determined for comparing in vitro dissolution profiles. Freeze dried B. coagulans cells were successfully formulated as enteric-coated mucoadhesive microspheres with satisfactory physical structure and yield. The viability of B. coagulans was maintained in the simulated gastric conditions and during processing; in simulated intestinal conditions exhibiting mucoadhesion, and controlling and extending the viable cell release following zero-order; and was satisfactorily stable at room temperature. Test results depict statistically significant effects of the hypromellose grade and their concentration on the performance and release profile of formulations.

Formulation and evaluation of Bacillus coagulans-loaded hypromellose mucoadhesive microspheres

PubMed Central

Alli, Sk Md Athar

2011-01-01

Development of a novel delivery system has been attempted to deliver viable probiotic cells into the gut for a prolonged period of time while maintaining high numbers of viable cells within the formulation throughout the shelf-life of the product and during the gastrointestinal transit. Core mucoadhesive microspheres of Bacillus coagulans were developed employing several grades of hypromellose, a mucoadhesive polymer, following coacervation and phase separation technique and were subsequently enteric-coated with hypromellose phthalate. Microspheres were evaluated for percent yield; entrapment efficiency; in vitro swelling; surface morphology; particle size, size distribution, and zeta potential; flow property, mucoadhesion property by the ex vivo mucoadhesive strength test and the in vitro wash off test; in vitro release profile and release kinetic; in vivo probiotic activity; and stability. The values for the kinetic constant and regression coefficient of model-dependent approaches and the difference factor (f1), the similarity factor (f2), and the Rescigno index (ξ1 and ξ2) of model independent approaches were determined for comparing in vitro dissolution profiles. Freeze dried B. coagulans cells were successfully formulated as enteric-coated mucoadhesive microspheres with satisfactory physical structure and yield. The viability of B. coagulans was maintained in the simulated gastric conditions and during processing; in simulated intestinal conditions exhibiting mucoadhesion, and controlling and extending the viable cell release following zero-order; and was satisfactorily stable at room temperature. Test results depict statistically significant effects of the hypromellose grade and their concentration on the performance and release profile of formulations. PMID:21674019

Insulin delivery through nasal route using thiolated microspheres.

PubMed

Nema, Tarang; Jain, Ashish; Jain, Aviral; Shilpi, Satish; Gulbake, Arvind; Hurkat, Pooja; Jain, Sanjay K

2013-01-01

The aim of the present study was to investigate the potential of developed thiolated microspheres for insulin delivery through nasal route. In the present study, cysteine was immobilized on carbopol using EDAC. A total of 269.93 µmol free thiol groups per gram polymer were determined. The prepared nonthiolated and thiolated microspheres were studied for particle shape, size, drug content, swellability, mucoadhesion and in vitro insulin release. The thiolated microspheres exhibited higher mucoadhesion due to formation of covalent bonds via disulfide bridges with the mucus gel layer. Drug permeation through goat nasal mucosa of nonthiolated and thiolated microspheres were found as 52.62 ± 2.4% and 78.85 ± 3.1% in 6 h, respectively. Thiolated microspheres bearing insulin showed better reduction in blood glucose level (BGL) in comparison to nonthiolated microspheres as 31.23 ± 2.12% and 75.25 ± 0.93% blood glucose of initial BGL were observed at 6 h after nasal delivery of thiolated and nonthiolated microspheres in streptozotocin-induced diabetic rabbits.

Facile synthesis of nanorod-assembled multi-shelled Co3O4 hollow microspheres for high-performance supercapacitors

NASA Astrophysics Data System (ADS)

Wang, Yaping; Pan, Anqiang; Zhu, Qinyu; Nie, Zhiwei; Zhang, Yifang; Tang, Yan; Liang, Shuquan; Cao, Guozhong

2014-12-01

In this work, we report a novel strategy for the controlled synthesis of nanorod assembled multi-shelled cobalt oxide (Co3O4) hollow microspheres (HSs). The Co2CO3(OH)2 NRs are first vertically grown on the carbon microspheres (CS) to form the core-shelled composites by a low-temperature solution route. The multi-shelled hollow interiors within the Co3O4 microspheres are unconventionally obtained by annealing the as-prepared core-shell structured CS@Co2CO3(OH)2 composite in air. When evaluated for supercapacitive performance, the multi-shelled Co3O4 hollow microspheres exhibit high capacitance of 394.4 and 360 F g-1 at the current densities of 2 A g-1 and 10 A g-1, respectively. The superior electrochemical performance can be attributed to the multi-shelled hollow structures, which facilitate the electrolyte penetration and provide more active sites for the electrochemical reactions.

Evaluation of Eudragit® Retard Polymers for the Microencapsulation of Alpha-Lipoic Acid.

PubMed

Pecora, Tiziana M G; Musumeci, Teresa; Musumeci, Lucrezia; Fresta, Massimo; Pignatello, Rosario

2016-01-01

Microencapsulation of natural antioxidants in polymeric systems represents a possible strategy for improving the oral bioavailability of compounds that are otherwise poorly soluble. α-lipoic acid (ALA) was microencapsulated with polymethacrylate polymers (blends at various ratios of Eudragit® RS100 and RL100 resins). Microspheres were produced by solvent displacement of an ethanol cosolution of ALA and polymers; the microsuspensions were then freeze-dried, using trehalose as a cryoprotector. Microspheres were characterized in the solid state for micromeritic properties and drug loading, as well as by infrared spectroscopy, powder X-ray diffractometry and differential scanning calorimetry. The antioxidant activity of free and encapsulated ALA was assessed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In vitro release studies, performed in simulated gastric (pH 1.2) and intestinal fluid (pH 6.8), showed that, depending on polymer composition and drug-to-polymer ratio, ALA release can be slowed down, compared to the dissolution pattern of the free drug. Solid-state characterization confirmed the chemical stability of ALA in the microspheres, suggesting that ALA did not develop strong interactions with the polymer and was present in an amorphous or a disordered-crystalline state within the polymer network. As indicated by the DPPH assay, the microencapsulation of ALA in Eudragit® Retard matrices did not alter its antioxidant activity. ALA was effectively encapsulated in Eudragit® Retard matrices, showing a chemical stability up to 6 months at room conditions and at 40°C. Moreover, since the drug maintained its antioxidant activity in vitro, the potential application of these microparticulate systems for oral administration would deserve further studies.

MAPs/bFGF-PLGA microsphere composite-coated titanium surfaces promote increased adhesion and proliferation of fibroblasts.

PubMed

Wang, Zhongshan; Wu, Guofeng; Bai, Shizhu; Feng, Zhihong; Dong, Yan; Zhou, Jian; Qin, Haiyan; Zhao, Yimin

2014-06-01

Infection and epithelial downgrowth are two major problems with maxillofacial transcutaneous implants, and both are mainly due to lack of stable closure of soft tissues at transcutaneous sites. Fibroblasts have been shown to play a key role in the formation of biological seals. In this work, titanium (Ti) model surfaces were coated with mussel adhesive proteins (MAPs) utilizing its unique adhesion ability on diverse inorganic and organic surfaces in wet environments. Prepared basic fibroblast growth factor (bFGF)-poly(lactic-co-glycolic acid) (PLGA) microspheres can be easily synthesized and combined onto MAPs-coated Ti surfaces, due to the negative surface charges of microspheres in aqueous solution, which is in contrast to the positive charges of MAPs. Titanium model surfaces were divided into three groups. Group A: MAPs/bFGF-PLGA microspheres composite-coated Ti surfaces. Group B: MAPs-coated Ti surfaces. Group C: uncoated Ti surfaces. The effects of coated Ti surfaces on adhesion of fibroblasts, cytoskeletal organization, proliferation, and extracellular matrix (ECM)-related gene expressions were examined. The results revealed increased adhesion (P < 0.05), enhanced actin cytoskeletal organization, and up-regulated ECM-related gene expressions in groups A and B compared with group C. Increased proliferation of fibroblasts during five days of incubation was observed in group A compared with groups B and C (P < 0.05). Collectively, the results from this in vitro study demonstrated that MAPs/bFGF-PLGA microspheres composite-coated Ti surfaces had the ability to increase fibroblast functionality. In addition, MAPs/bFGF-PLGA microsphere composite-coated Ti surfaces should be studied further as a method of promoting formation of stable biological seals around transcutaneous sites.

Time-Dependent Changes in Morphology and Composition of Solid Particles Collected From Heavy Water Electrolyte after Electrolysis with a Palladium Cathode

NASA Astrophysics Data System (ADS)

Dash, John; Wang, Q.

2009-03-01

Recently, we have observed particles floating on the surfaces of electrolytes after electrolysis, in four cells, each of which contained a heavy water electrolyte and a Pd cathode. Solid particles were unexpected from electrolysis, so it seemed important to characterize these particles. Cu grids were used to collect particles from the electrolyte surface. Then, a scanning electron microscope ( SEM ) and an energy dispersive spectrometer ( EDS ) were used to study the surfaces of these particles and to record time-dependent changes which were occurring. The morphology and composition of the particles were determined . After storage at ambient for 11 days, there were large changes in the morphology and composition of the particles. For example, one portion of the particles contained a large number of microspheres. A typical microsphere contained mostly carbon and palladium, whereas the matrix near the microsphere contained mostly palladium with less carbon and a significant amount of silver. One day later the same microsphere had increased carbon and reduced palladium, but there was no significant change in the composition of the matrix. Results for other particles from other cells will also be presented.

Polymeric microsphere-facilitated site-specific delivery of quercetin prevents senescence of pancreatic islets in vivo and improves transplantation outcomes in mouse model of diabetes.

PubMed

Pathak, Shiva; Regmi, Shobha; Nguyen, Tiep Tien; Gupta, Biki; Gautam, Milan; Yong, Chul Soon; Kim, Jong Oh; Son, Youlim; Kim, Jae-Ryong; Park, Min Hui; Bae, Young Kyung; Park, So Young; Jeong, Daewon; Yook, Simmyung; Jeong, Jee-Heon

2018-06-05

Attenuation of senescence progression may be attractive way to preserve the functionality of pancreatic islets (PI) after transplantation. In this study, we developed a model for in vitro induction of premature senescence in rat PI and showed the effectiveness of quercetin (QU) to prevent the senescence. To provide targeted-delivery of QU to the PI after transplantation, we prepared the hybrid clusters (HC) of islet single cells (ISC) and QU-loaded polymeric microspheres (QU; ∼7.55 ng HC -1 ). Long-term culture of the HC revealed reduced levels of reactive oxygen species and decreased expression of senescence-associated beta galactosidase, Rb, p53, p16, and p21 compared to that of the control islets. Transplantation of HC into subcutaneous space of the immune-deficient mice produced better glycemic control compared to the control islets or the ICC-transplanted mice. SA-β-Gal staining of the in vivo transplanted HC sample showed lower intensity compared to that of the control islets or the islet cell clusters. Thus, in situ delivery of therapeutic agent may be a promising approach to improve therapeutic outcomes in cell therapy. In this study, we aimed to improve outcomes in islet transplantation using in situ delivery of quercetin to pancreatic islets, using polymeric microspheres. We prepared prolonged release-type microspheres and constructed hybrid clusters of pancreatic islets and the microspheres using hanging drop method. The presence of quercetin in the cellular microenvironment attenuated the progression of senescence in the pancreatic islets in a long-term in vitro culture. Moreover, transplantation of the hybrid clusters in the diabetic mice produced better glycemic control compared to that of the control islets. In addition, quercetin delayed the progression of senescence in the pancreatic islets after in vivo transplantation. Thus, local delivery of antioxidants like quercetin may be an attractive way to improve outcomes in cell therapy. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Preparation of Nano-TiO₂-Coated SiO₂ Microsphere Composite Material and Evaluation of Its Self-Cleaning Property.

PubMed

Sun, Sijia; Deng, Tongrong; Ding, Hao; Chen, Ying; Chen, Wanting

2017-11-03

In order to improve the dispersion of nano-TiO₂ particles and enhance its self-cleaning properties, including photocatalytic degradation of pollutants and surface hydrophilicity, we prepared nano-TiO₂-coated SiO₂ microsphere composite self-cleaning materials (SiO₂-TiO₂) by co-grinding SiO₂ microspheres and TiO₂ soliquid and calcining the ground product. The structure, morphology, and self-cleaning properties of the SiO₂-TiO₂ were characterized. The characterization results showed that the degradation efficiency of methyl orange by SiO₂-TiO₂ was 97%, which was significantly higher than that obtained by pure nano-TiO₂. The minimum water contact angle of SiO₂-TiO₂ was 8°, indicating strong hydrophilicity and the good self-cleaning effect. The as-prepared SiO₂-TiO₂ was characterized by the nano-TiO₂ particles uniformly coated on the SiO₂ microspheres and distributed in the gap among the microspheres. The nano-TiO₂ particles were in an anatase phase with the particle size of 15-20 nm. The nano-TiO₂ particles were combined with SiO₂ microspheres via the dehydroxylation of hydroxyl groups on their surfaces.

Disposable swim diaper retention of Cryptosporidium-sized particles on human subjects in a recreational water setting.

PubMed

Amburgey, James E; Anderson, J Brian

2011-12-01

Cryptosporidium is a chlorine-resistant protozoan parasite responsible for the majority of waterborne disease outbreaks in recreational water venues in the USA. Swim diapers are commonly used by diaper-aged children participating in aquatic activities. This research was intended to evaluate disposable swim diapers for retaining 5-μm diameter polystyrene microspheres, which were used as non-infectious surrogates for Cryptosporidium oocysts. A hot tub recirculating water without a filter was used for this research. The microsphere concentration in the water was monitored at regular intervals following introduction of microspheres inside of a swim diaper while a human subject undertook normal swim/play activities. Microsphere concentrations in the bulk water showed that the majority (50-97%) of Cryptosporidium-sized particles were released from the swim diaper within 1 to 5 min regardless of the swim diaper type or configuration. After only 10 min of play, 77-100% of the microspheres had been released from all swim diapers tested. This research suggests that the swim diapers commonly used by diaper-aged children in swimming pools and other aquatic activities are of limited value in retaining Cryptosporidium-sized particles. Improved swim diaper solutions are necessary to efficiently retain pathogens and effectively safeguard public health in recreational water venues.

Melamine-assisted one-pot synthesis of hierarchical nitrogen-doped carbon@MoS2 nanowalled core-shell microspheres and their enhanced Li-storage performances

NASA Astrophysics Data System (ADS)

Sun, Fugen; Wei, Yanju; Chen, Jianzhuang; Long, Donghui; Ling, Licheng; Li, Yongsheng; Shi, Jianlin

2015-07-01

A facile and scalable one-pot approach has been developed to synthesize carbon@MoS2 core-shell microspheres by a hydrothermal method, which involves the fast formation of melamine-resorcinol-formaldehyde polymeric microspheres in situ, followed by direct growth of the MoS2 nanowalls on them. The results give unequivocal proof that melamine could be the key to forming the core-shell microspherical morphology, and the contents of MoS2 shells can be easily tuned by initial ratios of the precursors. After a simple heat treatment, the obtained carbon@MoS2 microspheres simultaneously integrate the nitrogen-doped carbon cores and the hierarchical shells which consist of few-layered MoS2 nanowalls with an expanded interlayer spacing. Their unique architectures are favourable for high electronic/ionic conductivity and accommodate volume strain during the electrochemical reaction of the MoS2 anodes in lithium-ion batteries. Thus, a very high reversibility capacity of 771 mA h g-1 at 100 mA g-1 after 100 cycles, and a rate capacity of 598 mA h g-1 at 2000 mA g-1 could be achieved for the carbon@MoS2 core-shell microspheres with the optimal composition. Furthermore, a thin carbon coating on the carbon@MoS2 microspheres could further increase the reversible capacity to 856 mA h g-1 after 100 cycles at 100 mA g-1. These encouraging results suggest that such a facile and efficient protocol can provide a new pathway to produce hierarchical core-shell microspheres which integrate the structural, morphological and compositional design rationales for advanced lithium-ion batteries.A facile and scalable one-pot approach has been developed to synthesize carbon@MoS2 core-shell microspheres by a hydrothermal method, which involves the fast formation of melamine-resorcinol-formaldehyde polymeric microspheres in situ, followed by direct growth of the MoS2 nanowalls on them. The results give unequivocal proof that melamine could be the key to forming the core-shell microspherical morphology, and the contents of MoS2 shells can be easily tuned by initial ratios of the precursors. After a simple heat treatment, the obtained carbon@MoS2 microspheres simultaneously integrate the nitrogen-doped carbon cores and the hierarchical shells which consist of few-layered MoS2 nanowalls with an expanded interlayer spacing. Their unique architectures are favourable for high electronic/ionic conductivity and accommodate volume strain during the electrochemical reaction of the MoS2 anodes in lithium-ion batteries. Thus, a very high reversibility capacity of 771 mA h g-1 at 100 mA g-1 after 100 cycles, and a rate capacity of 598 mA h g-1 at 2000 mA g-1 could be achieved for the carbon@MoS2 core-shell microspheres with the optimal composition. Furthermore, a thin carbon coating on the carbon@MoS2 microspheres could further increase the reversible capacity to 856 mA h g-1 after 100 cycles at 100 mA g-1. These encouraging results suggest that such a facile and efficient protocol can provide a new pathway to produce hierarchical core-shell microspheres which integrate the structural, morphological and compositional design rationales for advanced lithium-ion batteries. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr03708e

The Effects of rhBMP-2 Released from Biodegradable Polyurethane/Microsphere Composite Scaffolds on New Bone Formation in Rat Femora

DTIC Science & Technology

2009-09-17

bone morphogenetic protein ) Bone regeneration Drug delivery In vivo test Polyurethane a b s t r a c t Scaffolds prepared from biodegradable...Toshitaka Yoshii b, c ,2, Andrea E. Hafeman a,b,3, Jeffry S. Nyman b, c ,d,4, Joseph C . Wenke e,5, Scott A. Guelcher a,b,* aDepartment of Chemical and...Houston, TX, USA a r t i c l e i n f o Article history: Received 18 June 2009 Accepted 26 August 2009 Available online 17 September 2009 Keywords: BMP

Ternary particles for effective vaccine delivery to the pulmonary system

NASA Astrophysics Data System (ADS)

Terry, Treniece La'shay

Progress in the fields of molecular biology and genomics has provided great insight into the pathogenesis of disease and the defense mechanisms of the immune system. This knowledge has lead to the classification of an array of abnormal genes, for which, treatment relies on cellular expression of proteins. The utility of DNA-based vaccines hold great promise for the treatment of genetically based and infectious diseases, which ranges from hemophilia, cystic fibrosis, and HIV. Synthetic delivery systems consisting of cationic polymers, such as polyethylenimine (PEI), are capable of condensing DNA into compact structures, maximizing cellular uptake of DNA and yielding high levels of protein expression. To date, short term expression is a major obstacle in the development of gene therapies and has halted their expansion in clinical applications. This study intends to develop a sustained release vaccine delivery system using PLA-PEG block copolymers encapsulating PEI:DNA polyplexes. To enhance the effectiveness of such DNA-based vaccines, resident antigen presenting cells, macrophages and dendritic cells, will be targeted within the alveoli regions of the lungs. Porous microspheres will be engineered with aerodynamic properties capable of achieving deep lung deposition. A fabrication technique using concentric nozzles will be developed to produce porous microspheres. It was observed that modifications in the dispersed to continuous phase ratios have the largest influence on particle size distributions, release rates and encapsulation efficiency which ranged form 80--95% with fourteen days of release. Amphiphilic block copolymers were also used to fabricate porous microspheres. The confirmation of PEG within the biodegradable polymer backbone was found to have a tremendous impact on the microsphere morphology and encapsulation efficiency which varied from 50--90%. Porous microspheres were capable of providing sustained gene expression when tested in vitro using the luciferase reporter gene plasmid DNA. Prolonged expression was obtained for 9 days. PLGA and PLA-PEG microspheres were administered in vivo by intra-tracheal instillation and produced an acute inflammatory response, as observed from the large presence of neutrophils. The response using PLA-PEG microspheres yielded a lower total cell count signifying the incorporation of PEG into the copolymer backbone enhances the biocompatibility of the delivery system.

Assessing the influence of media composition and ionic strength on drug release from commercial immediate-release and enteric-coated aspirin tablets.

PubMed

Karkossa, Frank; Klein, Sandra

2017-10-01

The objective of this test series was to elucidate the importance of selecting the right media composition for a biopredictive in-vitro dissolution screening of enteric-coated dosage forms. Drug release from immediate-release (IR) and enteric-coated (EC) aspirin formulations was assessed in phosphate-based and bicarbonate-based media with different pH, electrolyte composition and ionic strength. Drug release from aspirin IR tablets was unaffected by media composition. In contrast, drug release from EC aspirin formulations was affected by buffer species and ionic strength. In all media, drug release increased with increasing ionic strength, but in bicarbonate-based buffers was delayed when compared with that in phosphate-based buffers. Interestingly, the cation species in the dissolution medium had also a clear impact on drug release. Drug release profiles obtained in Blank CarbSIF, a new medium simulating pH and average ionic composition of small intestinal fluid, were different from those obtained in all other buffer compositions studied. Results from this study in which the impact of various media parameters on drug release of EC aspirin formulations was systematically screened clearly show that when developing predictive dissolution tests, it is important to simulate the ionic composition of intraluminal fluids as closely as possible. © 2017 Royal Pharmaceutical Society.

Apparatus and process to enhance the uniform formation of hollow glass microspheres

DOEpatents

Schumacher, Ray F

2013-10-01

A process and apparatus is provided for enhancing the formation of a uniform population of hollow glass microspheres. A burner head is used which directs incoming glass particles away from the cooler perimeter of the flame cone of the gas burner and distributes the glass particles in a uniform manner throughout the more evenly heated portions of the flame zone. As a result, as the glass particles are softened and expand by a released nucleating gas so as to form a hollow glass microsphere, the resulting hollow glass microspheres have a more uniform size and property distribution as a result of experiencing a more homogenous heat treatment process.

Estimation of antigenic tetanus toxoid extracted from biodegradable microspheres.

PubMed

Xing, D K; McLellan, K; Corbel, M J; Sesardic, D

1996-03-01

Microspheres made from poly (lactic/glycolic acid) polymers have been considered as a new delivery system for single-dose tetanus toxoid (TT) vaccines. One of the most critical properties of the proposed vaccines is the loading and distribution of TT as this will have a profound effect on immunogenicity. As the concentration of TT in microspheres is very low sensitive assay methods are required. An assay incorporating monoclonal antibody (MAb) recognizing a neutralizing epitope and cross-reacting with TT was developed (MAp capture ELISA) which provided a sensitivity of 0.001 Lf/ml. An extraction procedure was devised which did not destroy the antigenicity and gave a recovery of 90.6 +/- 3.39% when applied to different preparations. The extracted TT was then quantified by MAb capture ELISA which was estimated to be 250-fold more sensitive than single-site ELISA for toxoid. The loading of 20 microspheres preparations (12 filled and 8 placebo) was determined by both protein micro-BCA assay and the developed assay for TT. The TT content obtained for the 12 filled microspheres preparations from different sources varied up to 400-fold (range 0.01-4.0 Lf/mg microspheres). The utility of the MAb capture ELISA for detection of total antigenic content in microspheres was confirmed by the observation that the determine TT loading correlated with the theoretical loading predicted from the protein content for the best preparations. Preparations with high loading gave the greatest peak response. There was no relationship between dose and the in vivo immunogenic response, suggesting that encapsulated vaccines with differential loading, release properties and presence of excipients will have different response curves in vivo. Hence, the present assay, when combined with information on toxoid release rate and presence and effect of excipients may be of value in predicting in vivo response.

Template-etching route to construct uniform rattle-type Fe3O4@SiO2 hollow microspheres as drug carrier.

PubMed

Cheng, Lin; Liu, Yuanyuan; Zou, Bingfang; Yu, Yong; Ruan, Weimin; Wang, Yongqiang

2017-06-01

Template-etching strategy was put forward to synthesize rattle-type magnetic silica (Fe 3 O 4 @SiO 2 ) hollow microspheres in a controlled way. During the experiment, monodisperse Fe 2 O 3 microspheres were fabricated as physical template to generate uniform Fe 2 O 3 @SiO 2 with controlled shell thicknesses through sol-gel method, and the subsequent Fe 2 O 3 template etching process created variable space between Fe 2 O 3 core and SiO 2 shell, and the final calcination process transformed rattle-type Fe 2 O 3 @SiO 2 hollow microspheres into corresponding Fe 3 O 4 @SiO 2 product in hydrogen/nitrogen atmosphere. Compared with traditional physical template, here template-etching synthesis of rattle-type hollow microspheres saved the insertion of middle shells and their removal, which simplified the synthesis process with controllable core size and shell thickness. The rattle-type Fe 3 O 4 @SiO 2 hollow microspheres as drug carrier show efficient doxorubicin (DOX) loading, and the release rate of DOX loaded the rattle-type Fe 3 O 4 @SiO 2 hollow microspheres exhibit a surprising shell-thickness-dependent and a pH responsive drug release features. Additionally, MTT assays in HeLa cells demonstrated that the Fe 3 O 4 @SiO 2 nanocarriers were non-toxic even at the concentration of 250µgmL -1 for 48h. Thus, our results revealed that the Fe 3 O 4 @SiO 2 -DOX could play an important role in the development of intracellular delivery nanodevices for cancer therapy. Copyright © 2017. Published by Elsevier B.V.

[Preparation of vanilline cross-linked rhBMP-2/chitosan microspheres and its effect on mesenchymal stem cells].

PubMed

Wu, Gui; Wang, Hai; Qiu, Guixing; Yu, Xin; Su, Xinlin; Ma, Pei; Yin, Bo; Wu, Zhihong

2015-06-02

To prepare rhBMP-2/chitosan microspheres (rhBMP-2 CMs) with vanilline as a cross-linking reagent and study the biocompatibility and drug release characteristic of microspheres in vitro. Emulsion cross-linking method was utilized to prepare rhBMP-2 CMs, Scanning electron microscope (SEM) was used to observe the microstructure of microspheres.Leaching solution of microspheres and blank culture medium were designated as experimental and control groups respectively. Both groups were cultured with human mesenchymal stem cells (hMSCs) to determine its cytotoxicity and its effect on the proliferation of hMSCs. Dynamic immersion method was used to examine the in vitro release characteristic of rhBMP-2. And the alkaline phosphatase (ALP) activity of hMSCs was determined to reveal the bioactivity of released rhBMP-2. The rhBMP-2 CMs were spherical under SEM.After treating with leaching solution for 24 and 48 h, there was no inter-group statistical difference in optical density (OD) values at both timepoints (24 h:0.72 ± 0.07 vs 0.73 ± 0.05, P > 0.05; 48 h:1.19 ± 0.11 vs 1.27 ± 0.06, P > 0.05). After culturing with leaching solution for 1, 3 and 7 days, the number of cells increased with time for both groups. And the OD values were not statistically different at each timepoint. Five milligram rhBMP-2 CMs soaked for 19 days with a gradual release of rhBMP-2. The concentration of rhBMP-2 was 216.1 ± 20.0 ng/ml at Day 19. At Days 3 and 7, the ALP activities of hMSCs were (0.50 ± 0.07) and (0.68 ± 0.06) µmol pNPP·min⁻¹·mg⁻¹ protein respectively and both were higher than that of blank culture medium group (0.14 ± 0.01) (P < 0.05). With an excellent biocompatibility, rhBMP-2 CMs may be an ideal carrier for control-released rhBMP-2 and encapsulated rhBMP-2 remains bioactive.

Hierarchical Microspheres Constructed from Chitin Nanofibers Penetrated Hydroxyapatite Crystals for Bone Regeneration.

PubMed

Duan, Bo; Shou, Kangquan; Su, Xiaojuan; Niu, Yahui; Zheng, Guan; Huang, Yao; Yu, Aixi; Zhang, Yu; Xia, Hong; Zhang, Lina

2017-07-10

Chitin exists abundantly in crab and shrimp shells as the template of the minerals, which inspired us to mineralize it for fabricating bone grafting materials. In the present work, chitin nanofibrous microspheres were used as the matrix for in situ synthesis of hydroxyapatite (HA) crystals including microflakes, submicron-needles, and submicron-spheres, which were penetrated by long chitin nanofibers, leading to the hierarchical structure. The shape and size of the HA crystals could be controlled by changing the HA synthesis process. The tight interface adhesion between chitin and HA through the noncovanlent bonds occurred in the composite microspheres, and HAs were homogeneously dispersed and bounded to the chitin nanofibers. In our findings, the inherent biocompatibilities of the both chitin and HA contributed the bone cell adhesion and osteoconduction. Moreover, the chitin microsphere with submicron-needle and submicron-sphere HA crystals remarkably promoted in vitro cell adhesion and in vivo bone healing. It was demonstrated that rabbits with 1.5 cm radius defect were almost cured completely within three months in a growth factor- and cell-free state, as a result of the unique surface microstructure and biocompatibilities of the composite microspheres. The microsphere scaffold displayed excellent biofunctions and an appropriate biodegradability. This work opened up a new avenue to construct natural polymer-based organic-inorganic hybrid microspheres for bone regeneration.

Microspherical polyaniline/graphene nanocomposites for high performance supercapacitors

NASA Astrophysics Data System (ADS)

Cao, Hailiang; Zhou, Xufeng; Zhang, Yiming; Chen, Liang; Liu, Zhaoping

2013-12-01

Polyaniline/graphene nanocomposites with microspherical morphology and porous structure are prepared as electrode materials for supercapacitors. Using few-layer graphene obtained by liquid phase exfoliation of graphite as the raw material, porous graphene microspheres are produced by spray drying, and are then employed as the substrates for the growth of polyaniline nanowire arrays by in situ polymerization. In the composite, interconnected graphene sheets with few structural defects constitute a high-efficient conductive network to improve the electrical conductivity of polyaniline. Furthermore, the microspherical architecture prevents restacking of polyaniline/graphene composite nanosheets, thus facilitates fast diffusion of electrolytes. Consequently, the nanocomposite exhibits excellent electrochemical performance. A specific capacitance of 338 F g-1 is reached in 1 M H2SO4 at a scan rate of 20 mV s-1, and a high capacity retention rate of 87.4% after 10,000 cycles at a current density of 3 A g-1 can be achieved, which suggests that the polyaniline/graphene composite with such kind of 3D architecture is a promising electrode material for high-performance supercapacitors.

Light diffusing films fabricated by strawberry-like PMMA/SiO₂ composite microspheres for LED application.

PubMed

Guo, Shuang; Zhou, Shuxue; Li, Huijing; You, Bo

2015-06-15

This paper presents a facile method to fabricate volumetric light diffusing films with high transmittance and haze simultaneously by mimicking the micro- and nanostructure of compound eyes. Strawberry-like polymethyl methacrylate/SiO2 composite microspheres were first prepared via the electrostatic attraction between positively charged PMMA spheres and negatively charged SiO2 nanoparticles, and further blended with polyacrylate latex to produce light diffusing coatings. A novel light diffusing film with hemispherical surface was built by casting the light diffusing coatings on optical-grade PET film. Effects of the sizes of PMMA spheres and SiO2 nanoparticles on the optical properties of light diffusing film were investigated by a haze meter and application on a LED lamp. The best result (transmittance 94.6% and haze 84.2%) was achieved for the strawberry-like composite microspheres based on 1 μm PMMA spheres and 50 nm SiO2 nanoparticles. The light-diffusing mechanism of the strawberry-like microspheres in the film was discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

"Smart tattoo" glucose biosensors and effect of coencapsulated anti-inflammatory agents.

PubMed

Srivastava, Rohit; Jayant, Rahul Dev; Chaudhary, Ayesha; McShane, Michael J

2011-01-01

Minimally invasive glucose biosensors with increased functional longevity form one of the most promising techniques for continuous glucose monitoring. In the present study, we developed a novel nanoengineered microsphere formulation comprising alginate microsphere glucose sensors and anti-inflammatory-drug-loaded alginate microspheres. The formulation was prepared and characterized for size, shape, in vitro drug release, biocompatibility, and in vivo acceptability. Glucose oxidase (GOx)- and Apo-GOx-based glucose sensors were prepared and characterized. Sensing was performed both in distilled water and simulated interstitial body fluid. Layer-by-layer self-assembly techniques were used for preventing drug and sensing chemistry release. Finally, in vivo studies, involving histopathologic examination of subcutaneous tissue surrounding the implanted sensors using Sprague-Dawley rats, were performed to test the suppression of inflammation and fibrosis associated with glucose sensor implantation. The drug formulation showed 100% drug release with in 30 days with zero-order release kinetics. The GOx-based sensors showed good enzyme retention and enzyme activity over a period of 1 month. Apo-GOx-based visible and near-infrared sensors showed good sensitivity and analytical response range of 0-50 mM glucose, with linear range up to 12 mM glucose concentration. In vitro cell line studies proved biocompatibility of the material used. Finally, both anti-inflammatory drugs were successful in controlling the implant-tissue interface by suppressing inflammation at the implant site. The incorporation of anti-inflammatory drug with glucose biosensors shows promise in improving sensor biocompatibility, thereby suggesting potential application of alginate microspheres as "smart tattoo" glucose sensors with increased functional longevity. © 2010 Diabetes Technology Society.

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.

SPHRINT - Printing Drug Delivery Microspheres from Polymeric Melts.

PubMed

Shpigel, Tal; Uziel, Almog; Lewitus, Dan Y

2018-06-01

This paper describes a simple, straightforward, and rapid method for producing microspheres from molten polymers by merely printing them in an inkjet-like manner onto a superoleophobic surface (microsphere printing, hence SPHRINT). Similar to 3D printing, a polymer melt is deposited onto a surface; however, in contrast to 2D or 3D printing, the surface is not wetted (i.e. exhibiting high contact angles with liquids, above 150°, due to its low surface energy), resulting in the formation of discrete spherical microspheres. In this study, microspheres were printed using polycaprolactone and poly(lactic-co-glycolic acid) loaded with a model active pharmaceutical ingredient-ibuprofen (IBU). The formation of microspheres was captured by high-speed imaging and was found to involve several physical phenomena characterized by non-dimensional numbers, including the thinning and breakup of highly viscous, weakly elastic filaments, which are first to be described in pure polymer melts. The resulting IBU-loaded microspheres had higher sphericity, reproducible sizes and shapes, and superior drug encapsulation efficiencies with a distinctly high process yield (>95%) as compared to the conservative solvent-based methods used presently. Furthermore, the microspheres showed sustained release profiles. Copyright © 2018 Elsevier B.V. All rights reserved.

Development and gamma-scintigraphy study of Hibiscus rosasinensis polysaccharide-based microspheres for nasal drug delivery.

PubMed

Sharma, Nitin; Tyagi, Shanu; Gupta, Satish Kumar; Kulkarni, Giriraj Thirupathirao; Bhatnagar, Aseem; Kumar, Neeraj

2016-11-01

This work describes the application of natural plant polysaccharide as pharmaceutical mucoadhesive excipients in delivery systems to reduce the clearance rate through nasal cavity. Novel natural polysaccharide (Hibiscus rosasinensis)-based mucoadhesive microspheres were prepared by using emulsion crosslinking method for the delivery of rizatriptan benzoate (RB) through nasal route. Mucoadhesive microspheres were characterized for different parameters and nasal clearance of technetium-99m ((99m)Tc)-radiolabeled microspheres was determined by using gamma-scintigraphy. Their Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) studies showed that the drug was stable during preparation of microspheres. Aerodynamic diameter of microspheres was in the range 13.23 ± 1.83-33.57 ± 3.69 µm. Change in drug and polysaccharide ratio influenced the mucoadhesion, encapsulation efficiency and in-vitro release property. Scintigraphs taken at regular interval indicate that control solution was cleared rapidly from nasal cavity, whereas microspheres showed slower clearance (p < 0.005) with half-life of 160 min. Natural polysaccharide-based microspheres achieved extended residence by minimizing effect of mucociliary clearance with opportunity of sustained delivery for longer duration.

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

Liu, Shuling, E-mail: shulingliu@aliyun.com; College of Chemistry & Chemical Engineering, Shaanxi University of Science & Technology, Xi’an, Shaanxi 710021; Ma, Lanbing

Highlights: • ZnS/Ni{sub 2}P composites have been firstly synthesized via a gentle hydrothermal route. • The composites have been characterized by XRD, SEM and TEM. • ZnS/Ni{sub 2}P showed enhanced photocatalytic degradation activity for pyronine B. • The reason for the enhanced photocatalytic activity has been discussed. - Abstract: ZnS/Ni{sub 2}P core/shell composites were successfully synthesized using a hydrothermal method. The composites have been characterized by XRD, SEM, TEM and the corresponding results showed that the composites were composed of the cubic ZnS microspheres, which were made up of ZnS nanoparticles, and Ni{sub 2}P nanoparticles coated on the surfaces ofmore » ZnS microspheres. Compared with ZnS microspheres, ZnS/Ni{sub 2}P core/shell composites showed enhanced photocatalytic degradation activity for pyronine B under UV irradiation. This may be related to the effective separation of photogenerated electron–hole pairs in ZnS/Ni{sub 2}P composites which can greatly reduce the chance of their recombination. Furthermore, superoxide ions and hydroxyl radical can be more easily produced through ZnS/Ni{sub 2}P composites, which is also beneficial for the degradation of pyronine B.« less

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.

Intracellular degradation of microspheres based on cross-linked dextran hydrogels or amphiphilic block copolymers: A comparative Raman microscopy study

PubMed Central

van Manen, Henk-Jan; van Apeldoorn, Aart A; Verrijk, Ruud; van Blitterswijk, Clemens A; Otto, Cees

2007-01-01

Micro- and nanospheres composed of biodegradable polymers show promise as versatile devices for the controlled delivery of biopharmaceuticals. Whereas important properties such as drug release profiles, biocompatibility, and (bio)degradability have been determined for many types of biodegradable particles, information about particle degradation inside phagocytic cells is usually lacking. Here, we report the use of confocal Raman microscopy to obtain chemical information about cross-linked dextran hydrogel microspheres and amphiphilic poly(ethylene glycol)-terephthalate/poly(butylene terephthalate) (PEGT/PBT) microspheres inside RAW 264.7 macrophage phagosomes. Using quantitative Raman microspectroscopy, we show that the dextran concentration inside phagocytosed dextran microspheres decreases with cell incubation time. In contrast to dextran microspheres, we did not observe PEGT/PBT microsphere degradation after 1 week of internalization by macrophages, confirming previous studies showing that dextran microsphere degradation proceeds faster than PEGT/PBT degradation. Raman microscopy further showed the conversion of macrophages to lipid-laden foam cells upon prolonged incubation with both types of microspheres, suggesting that a cellular inflammatory response is induced by these biomaterials in cell culture. Our results exemplify the power of Raman microscopy to characterize microsphere degradation in cells and offer exciting prospects for this technique as a noninvasive, label-free optical tool in biomaterials histology and tissue engineering. PMID:17722552

Doped zinc oxide microspheres

DOEpatents

Arnold, Jr., Wesley D.; Bond, Walter D.; Lauf, Robert J.

1993-01-01

A new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel.

Effect of Polymer Porosity on Aqueous Self-Healing Encapsulation of Proteins in PLGA Microspheres

PubMed Central

Reinhold, Samuel E.

2014-01-01

Self-healing (SH) poly(lactic-co-glycolic acid) (PLGA) microspheres are a unique class of functional biomaterials capable of microencapsulating process-sensitive proteins by simple mixing and heating the drug-free polymer in aqueous protein solution. Drug-free SH microspheres of PLGA 50/50 with percolating pore networks of varying porosity (ε = 0.49–73) encapsulate increasing lysozyme (~1–10% w/w) with increasing ε, with typically ~20–25% pores estimated assessible to entry by the enzyme from the external solution. Release kinetics of lysozyme under physiological conditions is continuous over > 2 weeks and most strongly influenced by ε and protein loading before reaching a lag phase until 28 days at the study completion. Recovered enzyme after release is typically predominantly monomeric and active. Formulations containing acid-neutralizing MgCO3 at >4.3% exhibit >97% monomeric and active protein after the release with full mass balance recovery. Hence, control of SH polymer ε is a key parameter to development of this new class of biomaterials. PMID:24285573

Highly sensitive analysis of polycyclic aromatic hydrocarbons in environmental water with porous cellulose/zeolitic imidazolate framework-8 composite microspheres as a novel adsorbent coupled with high-performance liquid chromatography.

PubMed

Liang, Xiaotong; Liu, Shengquan; Zhu, Rong; Xiao, Lixia; Yao, Shouzhuo

2016-07-01

In this work, novel cellulose/zeolitic imidazolate frameworks-8 composite microspheres have been successfully fabricated and utilized as sorbent for environmental polycyclic aromatic hydrocarbons efficient extraction and sensitive analysis. The composite microspheres were synthesized through the in situ hydrothermal growth of zeolitic imidazolate frameworks-8 on cellulose matrix, and exhibited favorable hierarchical structure with chemical composition as assumed through scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction patterns, and Brunauer-Emmett-Teller surface areas characterization. A robust and highly efficient method was then successfully developed with as-prepared composite microspheres as novel solid-phase extraction sorbent with optimum extraction conditions, such as sorbent amount, sample volume, extraction time, desorption conditions, volume of organic modifier, and ionic strength. The method exhibited high sensitivity with low limit of detection down to 0.1-1.0 ng/L and satisfactory linearity with correlation coefficients ranging from 0.9988 to 0.9999, as well as good recoveries of 66.7-121.2% with relative standard deviations less than 10% for environmental polycyclic aromatic hydrocarbons analysis. Thus, our method was convenient and efficient for polycyclic aromatic hydrocarbons extraction and detection, potential for future environmental water samples analysis. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Surfactant-free synthesis, luminescent properties, and drug-release properties of LaF3 and LaCO3F hollow microspheres.

PubMed

Lv, Ruichan; Gai, Shili; Dai, Yunlu; He, Fei; Niu, Na; Yang, Piaoping

2014-01-21

Uniform LaF3 and LaCO3F hollow microspheres were successfully synthesized through a surfactant-free route by employing La(OH)CO3 colloidal microspheres as a sacrificial template and NaBF4 as the fluorine source. The synthetic process consists of two steps: the preparation of a La(OH)CO3 precursor via a facile urea-based precipitation and the following formation of lanthanide fluoride hollow microspheres under aqueous conditions at low temperature (50 °C) and short reaction time (3 h), without using any surfactant and catalyst. The formation of hollow spheres with controlled size can be assigned to the Kirkendall effect. It is found that the phase and structure of the products can be simply tuned by changing the pH values of the solution. Time-dependent experiments were employed to study the possible formation process. N2 adsorption/desorption results indicate the mesoporous nature of LaF3 hollow spheres. Yb(3+)/Er(3+) (Ho(3+)) and Yb(3+)/Tm(3+)-doped LaF3 hollow spheres exhibit characteristic up-conversion (UC) emissions of Er(3+) (Ho(3+)) and Tm(3+) under 980 nm laser-diode excitation, and Ce(3+)/Tb(3+)-doped LaF3 and LaCO3F emit bright yellow-green and near-white light under UV irradiation, respectively. In particular, LaF3:Yb/Er and LaCO3F:Ce/Tb hollow microspheres exhibit obvious sustained and pH-dependent doxorubicin release properties. The luminescent properties of the carriers allow them to be tracked or monitored during the release or therapy process, suggesting their high potential in the biomedical field.

Biodegradable polymeric microsphere-based vaccines and their applications in infectious diseases.

PubMed

Lin, Chi-Ying; Lin, Shih-Jie; Yang, Yi-Chen; Wang, Der-Yuan; Cheng, Hwei-Fang; Yeh, Ming-Kung

2015-01-01

Vaccination, which provides effective, safe infectious disease protection, is among the most important recent public health and immunological achievements. However, infectious disease remains the leading cause of death in developing countries because several vaccines require repeated administrations and children are often incompletely immunized. Microsphere-based systems, providing controlled release delivery, can obviate the need for repeat immunizations. Here, we review the function of sustained and pulsatile release of biodegradable polymeric microspheres in parenteral and mucosal single-dose vaccine administration. We also review the active-targeting function of polymeric particles. With their shield and co-delivery functions, polymeric particles are applied to develop single-dose and mucosally administered vaccines as well as to improve subunit vaccines. Because polymeric particles are easily surface-modified, they have been recently used in vaccine development for cancers and many infectious diseases without effective vaccines (e.g., human immunodeficiency virus infection). These polymeric particle functions yield important vaccine carriers and multiple benefits.

Controlling protein release using biodegradable microparticles

NASA Astrophysics Data System (ADS)

Kline, Benjamin Patrick

Research in the field of protein therapeutics has exploded over the past decade and continues to grow in both academia and in industry. Protein drugs have advantages of being highly specific and highly active making them coveted targets for high profile disease states like cancer and multiple sclerosis. Unfortunately, their many advantages are complemented by their obstacles. Because proteins are highly active and highly specific, the window between efficacy and toxicity is very narrow and drug development can be long and arduous. In addition, protein activity is dependent on its specific folding conformation that is easily disrupted by a variety of development processes. This research aimed to identify microparticle formulations to control protein release and also to determine which formulation parameters affected burst release, encapsulation, and steady-state release the most. It was found that polymer type and composition were two of the most important factors. Long-term controlled release of bovine serum albumin (BSA) was achieved as well as a wide variety of release profiles. A method was identified for micronizing protein at low cost to retain activity and coacervation was evaluated as a method for preparing protein loaded microspheres. This research provides a basis from which researchers can create better controlled release formulations for future protein therapeutics.

Doped zinc oxide microspheres

DOEpatents

Arnold, W.D. Jr.; Bond, W.D.; Lauf, R.J.

1993-12-14

A new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel. 4 figures.

Renal Function in De Novo Liver Transplant Recipients Receiving Different Prolonged-Release Tacrolimus Regimens-The DIAMOND Study.

PubMed

TruneČka, P; Klempnauer, J; Bechstein, W O; Pirenne, J; Friman, S; Zhao, A; Isoniemi, H; Rostaing, L; Settmacher, U; Mönch, C; Brown, M; Undre, N; Tisone, G

2015-07-01

DIAMOND: multicenter, 24-week, randomized trial investigating the effect of different once-daily, prolonged-release tacrolimus dosing regimens on renal function after de novo liver transplantation. Arm 1: prolonged-release tacrolimus (initial dose 0.2mg/kg/day); Arm 2: prolonged-release tacrolimus (0.15-0.175mg/kg/day) plus basiliximab; Arm 3: prolonged-release tacrolimus (0.2mg/kg/day delayed until Day 5) plus basiliximab. All patients received MMF plus a bolus of corticosteroid (no maintenance steroids). eGFR (MDRD4) at Week 24. Secondary endpoints: composite efficacy failure, BCAR and AEs. Baseline characteristics were comparable. Tacrolimus trough levels were readily achieved posttransplant; initially lower in Arm 2 versus 1 with delayed initiation in Arm 3. eGFR (MDRD4) was higher in Arms 2 and 3 versus 1 (p = 0.001, p = 0.047). Kaplan-Meier estimates of composite efficacy failure-free survival were 72.0%, 77.6%, 73.9% in Arms 1-3. BCAR incidence was significantly lower in Arm 2 versus 1 and 3 (p = 0.016, p = 0.039). AEs were comparable. Prolonged-release tacrolimus (0.15-0.175mg/kg/day) immediately posttransplant plus basiliximab and MMF (without maintenance corticosteroids) was associated with lower tacrolimus exposure, and significantly reduced renal function impairment and BCAR incidence versus prolonged-release tacrolimus (0.2mg/kg/day) administered immediately posttransplant. Delayed higher-dose prolonged-release tacrolimus initiation significantly reduced renal function impairment compared with immediate posttransplant administration, but BCAR incidence was comparable. © 2015 The Authors. American Journal of Transplantation published by Wiley Periodicals Inc.

Delivery of bioactive lipids from composite microgel-microsphere injectable scaffolds enhances stem cell recruitment and skeletal repair.

PubMed

Das, Anusuya; Barker, Daniel A; Wang, Tiffany; Lau, Cheryl M; Lin, Yong; Botchwey, Edward A

2014-01-01

In this study, a microgel composed of chitosan and inorganic phosphates was used to deliver poly(lactic-co-glycolic acid) (PLAGA) microspheres loaded with sphingolipid growth factor FTY720 to critical size cranial defects in Sprague Dawley rats. We show that sustained release of FTY720 from injected microspheres used alone or in combination with recombinant human bone morphogenic protein-2 (rhBMP2) improves defect vascularization and bone formation in the presence and absence of rhBMP2 as evaluated by quantitative microCT and histological measurements. Moreover, sustained delivery of FTY720 from PLAGA and local targeting of sphingosine 1-phosphate (S1P) receptors reduces CD45+ inflammatory cell infiltration, promotes endogenous recruitment of CD29+CD90+ bone progenitor cells and enhances the efficacy of rhBMP2 from chitosan microgels. Companion in vitro studies suggest that selective activation of sphingosine receptor subtype-3 (S1P3) via FTY720 treatment induces smad-1 phosphorylation in bone-marrow stromal cells. Additionally, FTY720 enhances stromal cell-derived factor-1 (SDF-1) mediated chemotaxis of CD90+CD11B-CD45- bone progenitor cells in vitro after stimulation with rhBMP2. We believe that use of such small molecule delivery formulations to recruit endogenous bone progenitors may be an attractive alternative to exogenous cell-based therapy.

Delivery of Bioactive Lipids from Composite Microgel-Microsphere Injectable Scaffolds Enhances Stem Cell Recruitment and Skeletal Repair

PubMed Central

Das, Anusuya; Barker, Daniel A.; Wang, Tiffany; Lau, Cheryl M.; Lin, Yong; Botchwey, Edward A.

2014-01-01

In this study, a microgel composed of chitosan and inorganic phosphates was used to deliver poly(lactic-co-glycolic acid) (PLAGA) microspheres loaded with sphingolipid growth factor FTY720 to critical size cranial defects in Sprague Dawley rats. We show that sustained release of FTY720 from injected microspheres used alone or in combination with recombinant human bone morphogenic protein-2 (rhBMP2) improves defect vascularization and bone formation in the presence and absence of rhBMP2 as evaluated by quantitative microCT and histological measurements. Moreover, sustained delivery of FTY720 from PLAGA and local targeting of sphingosine 1-phosphate (S1P) receptors reduces CD45+ inflammatory cell infiltration, promotes endogenous recruitment of CD29+CD90+ bone progenitor cells and enhances the efficacy of rhBMP2 from chitosan microgels. Companion in vitro studies suggest that selective activation of sphingosine receptor subtype-3 (S1P3) via FTY720 treatment induces smad-1 phosphorylation in bone-marrow stromal cells. Additionally, FTY720 enhances stromal cell-derived factor-1 (SDF-1) mediated chemotaxis of CD90+CD11B-CD45- bone progenitor cells in vitro after stimulation with rhBMP2. We believe that use of such small molecule delivery formulations to recruit endogenous bone progenitors may be an attractive alternative to exogenous cell-based therapy. PMID:25077607

The effects of biodegradable poly(lactic-co-glycolic acid)-based microspheres loaded with quercetin on stemness, viability and osteogenic differentiation potential of stem cell spheroids.

PubMed

Lee, H; Nguyen, T T; Kim, M; Jeong, J-H; Park, J-B

2018-05-31

Quercetin has been reported to exert many beneficial effects on the protection against various diseases, such as diabetes, cancer, and inflammation. The aim of this study is to evaluate the potential osteogenic differentiation ability of mesenchymal stem cells in the presence of quercetin. Quercetin-loaded poly(lactic-co-glycolic acid) microspheres were prepared using an electrospraying technique. Characterization of the microspheres was evaluated with a scanning electron microscope and release profile. Three-dimensional cell spheroids were fabricated using silicon elastomer-based concave microwells. Qualitative results of cellular viability were seen under a confocal microscope, and quantitative cellular viability was evaluated using the Cell Counting Kit-8 assay. The alkaline phosphatase activity and Alizarin Red S staining were performed. A quantitative real-time polymerase chain reaction and a western blot analysis were performed. Spheroids were well formed irrespective of quercetin concentration. Most of the cells in spheroids emitted green fluorescence, and the morphology was round without significant changes. The application of quercetin-loaded microspheres produced a significant increase in the alkaline phosphatase activity. The real-time polymerase chain reaction results showed a significant increase in Runx2, and western blot results showed higher expression of Runx2 protein expression. Biodegradable microspheres loaded with quercetin produced prolonged release profiles with increased mineralization. Microspheres loaded with quercetin can be used for the enhancement of osteoblastic differentiation in cell therapy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[An experimental study on a slow-release complex with rifampicin-polylactic-co-glycolic acid-calcium 
phosphate cement].

PubMed

Wu, Jianhuang; Ding, Zhou; Lei, Qing; Li, Miao; Liang, Yan; Lu, Tao

2016-09-28

To prepare the slow-release complex with rifampicin (RFP)-polylactic-co-glycolic acid (PLGA)-calcium phosphate cement (CPC) (RFP-PLGA-CPC complex), and to study its physical and chemical properties and drug release properties in vitro.
 The emulsification-solvent evaporation method was adopted to prepare rifampicin polylactic acid-glycolic acid (RFP-PLGA) slow-release microspheres, which were divided into 3 groups: a calcium phosphate bone cement group (CPC group), a CPC embedded with RFP group (RFP-CPC group), and a PLGA slow-release microspheres carrying RFP and the self-curing CPC group (RFP- PLGA-CPC complex group). The solidification time and porosity of materials were determined. The drug release experiments in vitro were carried out to observe the compressive strength, the change of section morphology before and after drug release. 
 The CPC group showed the shortest solidification time, while the RFP-PLGA-CPC complex group had the longest one. There was statistical difference in the porosity between the CPC group and the RFP-CPC group (P<0.05); Compared to the RFP-PLGA-CPC complex group, the porosity in the CPC group and the RFP-CPC group were significantly changed (both P<0.01). There was significant difference in the compressive strength between the RFP- PLGA-CPC complex group and the CPC group (P<0.01), while there was significant difference in the compressive strength between the RFP-CPC group and the CPC group (3 days: P<0.05; 30 and 60 days: P<0.01). The change of the compressive strength in the CPC was not significant in the whole process of degradation. The sizes of PLGA microspheres were uniform, with the particle size between 100-150 μm. The microspheres were spheres or spheroids, and their surface was smooth without the attached impurities. There was no significant change in the section gap in the CPC group after soaking for 3 to 60 days. The microstructure change in the RFP-CPC group was small, and the cross section was formed by small particles. The pores of section in the RFP-PLGA-CPC complex group increased obviously, and PLGA microspheres gradually disappeared until the 60th day when there were only empty cavities left. The RFP-PLGA-CPC complex group had no obvious drugs sudden release, and the cumulative drug release rate was nearly 95% in the 60 days. The linear fitting was conducted for the drug release behavior of the complex, which was in accordance with zero order kinetics equation F=0.168×t.
 The porosity of RFP-PLGA-CPC complex is significantly higher than that of CPC, and it can keep slow release of the effective anti-tuberculosis drugs and maintain a certain mechanical strength for a long time.

Development of a cell transducible RhoA inhibitor TAT-C3 transferase and its encapsulation in biocompatible microspheres to promote survival and enhance regeneration of severed neurons.

PubMed

Tan, Elaine Y M; Law, Janice W S; Wang, Chi-Hwa; Lee, Alan Y W

2007-12-01

Neurons in post-traumatized mammalian central nervous system show only limited degree of regeneration, which can be attributed to the presence of neurite outgrowth inhibitors in damaged myelin and glial scar, and to the apoptosis of severed central neurons and glial cells during secondary Wallerian degeneration. RhoA GTPase has been implicated as the common denominator in these counter-regeneration events, which shows significant and persistent up-regulation for weeks in injured spinal cord and cerebral infarct after stroke. While the exoenzyme C3 transferase is a potent RhoA inhibitor, its extremely low efficiency of cell entry and degradation in vivo has restricted the therapeutic value. This study aims to circumvent these problems by developing a membrane-permeating form of C3 transferase and a biopolymer-based microsphere depot system for sustainable controlled release of the protein. A membrane-permeating form of C3 transferase was developed by fusing a Tat (trans-activating transcription factor) transduction domain of human immunodeficiency virus to its amino terminal using standard molecular cloning techniques. After confirming efficient cell entry into epithelial and neuroblastoma cells, the resulting recombinant protein TAT-C3 was encapsulated in biocompatible polymer poly(D,L -lactide-co-glycolide) in the form of microspheres by a water-in-oil-in-water (W/O/W) emulsion method. By blending capped and uncapped form of the polymer at different ratios, TAT-C3 protein release profile was modified to suit the expression pattern of endogenous RhoA during CNS injuries. Bioactivity of TAT-C3 released from microspheres was assessed by RhoA ribosylation assay. In contrast to wild-type C3 transferase, the modified TAT-C3 protein was found to efficiently enter NIH3T3 and N1E-115 neuroblastoma cells as early as 6 hours of incubation. The fusion of TAT sequence to C3 transferase imposed no appreciable effects on its biological activity in promoting neurite outgrowth through RhoA inhibition. Characterization of TAT-C3 encapsulation in various blends of capped/uncapped PLGA polymer revealed the 30:70 formulation to be optimal in attaining a mild initial burst release of 25%, followed by a subsequent average daily release of 2.3% of encapsulated protein over one month, matching the change in RhoA level in severed brain and spinal cord. Importantly, TAT-C3 released from the microspheres remained active up to the first three weeks of incubation. Enhanced cell entry of TAT-C3 circumvents the need to administer high dose of the protein to site of injury. The encapsulation of TAT-C3 in different blends of capped/uncapped PLGA microspheres allows adjustment of protein release profile to suit the pattern of RhoA expression in injured CNS.

Technology of stable, prolonged-release eye-drops containing Cyclosporine A, distributed between lipid matrix and surface of the solid lipid microspheres (SLM).

PubMed

Wolska, Eliza; Sznitowska, Małgorzata

2013-01-30

The aim of this study was to prepare solid lipid microspheres (SLM) with incorporated Cyclosporine A (Cs), suitable for ocular application. For this purpose, SLM were formulated by using different lipids and three different nonionic surfactants. The SLM were produced using a hot emulsification method. The SLM dispersions contained 10, 20 or 30% of lipid (w/w) and up to 2% (w/w) of Cs. The size of the microspheres with Cs ranged from 1 to 15 μm. Physically stable SLM with Cs were prepared using Compritol, as a lipid matrix, and Tween 80, as a surfactant. In contrast, dispersion with Precirol alone, formed semi-solid gels during storage, while in formulations with Precirol and Miglyol, crystals of Cs were observed. In vitro release profile of Compritol formulations showed that 40% of Cs is released within 1h, while the release of the following 40% takes more time, depending on lipid content in the formulations. The large part of Cs, added to SLM formulations (from 45 to 80%), was found on the surface of microparticles, but no drug crystallization occurred during a long-term storage. Copyright © 2012 Elsevier B.V. All rights reserved.

Characteristics and degradation of chitosan/cellulose acetate microspheres with different model drugs

NASA Astrophysics Data System (ADS)

Zhou, Hui-yun; Chen, Xi-guang

2008-12-01

In this study, chitosan/cellulose acetate microspheres (CCAM) were prepared by W/O/W emulsification and solvent evaporation as a drug delivery system. The microspheres were spherical, free-flowing and non-aggregated. The CCAM had good flow and suspension ability. The loading efficiency of different model drugs increased with the increasing hydrophobicity of the drug. The loading efficiency of 6-mercaptopurine (6-MP) was more than 30% whereas that of ranitidine hydrochloride (RT) or acetaminophen (ACP) was only 10%. The pH values of solution affected the swelling ability of CCAM and the relative humidity had little effect on the characteristics of CCAM when it was not more than 75%. The CCAM system had a good effect on the controlled release of different model drugs. However, the release rate became slower with the increase of the hydrophobicity of drugs. The release rate of CCAM loaded with hydrophilic RT was almost 60% during 48 h and the release rate of CCAM loaded with hydrophobic drug of 6-MP was not more than 30%. In the meantime, the CCAM system was degradable in vitro and the degradation rate was faster in lysozyme solution than that in the medium of PBS. So the CCAM system was a degradable promising drug delivery system especially for hydrophobic drugs.

Process for fabricating doped zinc oxide microsphere gel

DOEpatents

Arnold, Jr., Wesley D.; Bond, Walter D.; Lauf, Robert J.

1991-01-01

A new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel.

Rational Construction of Uniform CoNi-Based Core-Shell Microspheres with Tunable Electromagnetic Wave Absorption Properties.

PubMed

Chen, Na; Jiang, Jian-Tang; Xu, Cheng-Yan; Yan, Shao-Jiu; Zhen, Liang

2018-02-16

Core-shell particles with integration of ferromagnetic core and dielectric shell are attracting extensive attention for promising microwave absorption applications. In this work, CoNi microspheres with conical bulges were synthesized by a simple and scalable liquid-phase reduction method. Subsequent coating of dielectric materials was conducted to acquire core-shell structured CoNi@TiO 2 composite particles, in which the thickness of TiO 2 is about 40 nm. The coating of TiO 2 enables the absorption band of CoNi to effectively shift from K u to S band, and endows CoNi@TiO 2 microspheres with outstanding electromagnetic wave absorption performance along with a maximum reflection loss of 76.6 dB at 3.3 GHz, much better than that of bare CoNi microspheres (54.4 dB at 17.8 GHz). The enhanced EMA performance is attributed to the unique core-shell structures, which can induce dipole polarization and interfacial polarization, and tune the dielectric properties to achieve good impedance matching. Impressively, TiO 2 coating endows the composites with better microwave absorption capability than CoNi@SiO 2 microspheres. Compared with SiO 2 , TiO 2 dielectric shells could protect CoNi microspheres from merger and agglomeration during annealed. These results indicate that CoNi@TiO 2 core-shell microspheres can serve as high-performance absorbers for electromagnetic wave absorbing application.

Co-delivery of vascular endothelial growth factor and angiopoietin-1 using injectable microsphere/hydrogel hybrid systems for therapeutic angiogenesis.

PubMed

Shin, Seung-Hwa; Lee, Jangwook; Ahn, Dong-Gyun; Lee, Kuen Yong

2013-08-01

We hypothesized that combined delivery of vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) using microsphere/hydrogel hybrid systems could enhance mature vessel formation compared with administration of each factor alone. Hybrid delivery systems composed of alginate hydrogels and poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres containing angiogenic factors were prepared. The release behavior of angiogenic factors from hybrid systems was monitored in vitro. The hybrid systems were injected into an ischemic rodent model, and blood vessel formation at the ischemic site was evaluated. The sustained release over 4 weeks of both VEGF and Ang-1 from hybrid systems was achieved in vitro. Co-delivery of VEGF and Ang-1 was advantageous to retain muscle tissues and significantly induced vessel enlargement at the ischemic site, compared to mice treated with either VEGF or Ang-1 alone. Sustained and combined delivery of VEGF and Ang-1 significantly enhances vessel enlargement at the ischemic site, compared with sustained delivery of either factor alone. Microsphere/hydrogel hybrid systems may be a promising vehicle for delivery of multiple drugs for many therapeutic applications.

Carbon Cryogel and Carbon Paper-Based Silicon Composite Anode Materials for Lithium-Ion Batteries

NASA Technical Reports Server (NTRS)

Woodworth, James; Baldwin, Richard; Bennett, William

2010-01-01

A variety of materials are under investigation for use as anode materials in lithium-ion batteries, of which, the most promising are those containing silicon. 6 One such material is a composite formed via the dispersion of silicon in a resorcinol-formaldehyde (RF) gel followed by pyrolysis. Two silicon-carbon composite materials, carbon microspheres and nanofoams produced from nano-phase silicon impregnated RF gel precursors have been synthesized and investigated. Carbon microspheres are produced by forming the silicon-containing RF gel into microspheres whereas carbon nano-foams are produced by impregnating carbon fiber paper with the silicon containing RF gel to create a free standing electrode. 1-5 Both materials have demonstrated their ability to function as anodes and utilize the silicon present in the material. Stable reversible capacities above 400 mAh/g for the bulk material and above 1000 mAh/g of Si have been observed.

Silicon Composite Anode Materials for Lithium Ion Batteries Based on Carbon Cryogels and Carbon Paper

NASA Technical Reports Server (NTRS)

Woodworth, James; Baldwin, Richard; Bennett, William

2010-01-01

A variety of materials are under investigation for use as anode materials in lithium-ion batteries, of which, the most promising are those containing silicon. One such material is a composite formed via the dispersion of silicon in a resorcinol-formaldehyde (RF) gel followed by pyrolysis. Two silicon-carbon composite materials, carbon microspheres and nanofoams produced from nano-phase silicon impregnated RF gel precursors have been synthesized and investigated. Carbon microspheres are produced by forming the silicon-containing RF gel into microspheres whereas carbon nanofoams are produced by impregnating carbon fiber paper with the silicon containing RF gel to create a free standing electrode. Both materials have demonstrated their ability to function as anodes and utilize the silicon present in the material. Stable reversible capacities above 400 mAh/g for the bulk material and above 1000 mAh/g of Si have been observed.

Carbon Cryogel Silicon Composite Anode Materials for Lithium Ion Batteries

NASA Technical Reports Server (NTRS)

Woodworth James; Baldwin, Richard; Bennett, William

2010-01-01

A variety of materials are under investigation for use as anode materials in lithium-ion batteries, of which, the most promising are those containing silicon. 10 One such material is a composite formed via the dispersion of silicon in a resorcinol-formaldehyde (RF) gel followed by pyrolysis. Two silicon-carbon composite materials, carbon microspheres and nanofoams produced from nano-phase silicon impregnated RF gel precursors have been synthesized and investigated. Carbon microspheres are produced by forming the silicon-containing RF gel into microspheres whereas carbon nano-foams are produced by impregnating carbon fiber paper with the silicon containing RF gel to create a free standing electrode. 1-4,9 Both materials have demonstrated their ability to function as anodes and utilize the silicon present in the material. Stable reversible capacities above 400 mAh/g for the bulk material and above 1000 mAh/g of Si have been observed.

Morphological characterization of microspheres, films and implants prepared from poly(lactide-co-glycolide) and ABA triblock copolymers: is the erosion controlled by degradation, swelling or diffusion?

PubMed

Witt, C; Kissel, T

2001-05-01

Erosion of biodegradable parenteral delivery systems (PDS) based on ABA copolymers consisting of poly(L-lactide-co-glycolide) (PLGA) A-blocks attached to polyethylene oxide (PEO) B-blocks, or PLGA is important for the release of macromolecular drugs. The degradation behavior of four types of PDS, namely extruded rods, tablets, films and microspheres, was studied with respect to molecular weight, mass, polymer composition and shape and microstructure of the PDS. For each device the onset time of bulk erosion (t(on)) and the apparent rate of mass loss (k(app)) were calculated. In the case of PLGA, the t(on) was 16.2 days for microspheres, 19.2 days for films and 30.1 days for cylindrical implants and tablets. The k(app) was 0.04 days(-1) for microspheres, 0.09 days(-1) for films, 0.11 days(-1) for implants and 0.10 days(-1) for tablets. The degradation rates were in the same range irrespective of the geometry and the micrographs of eroding PDS demonstrated pore formation; therefore, a complex pore diffusion mechanism seems to control the erosion of PLGA devices. In contrast, PDS based on ABA copolymers showed swelling, followed by a parallel process of molecular weight degradation and polymer erosion, independent of the geometry. The contact angles of ABA films increased either with decreasing PEO content or with increasing chain length of the PEO B-blocks. In summary, the insertion of a hydrophilic B-block leads to an erosion controlled by degradation of ABA copolymers, whereas for PLGA a complex pore diffusion of degradation products controls the rate of bulk erosion.

Polystyrene-based Hollow Microsphere Synthesized by γ-ray Irradiation-assisted Polymerization and Self-Assembly and Its Application in Detection of Ionizing Radiation

NASA Astrophysics Data System (ADS)

Fan, Wenhui; Li, Qing; Hu, Liang; Yan, Siqi; Wen, Wanxin; Chai, Zhifang; Liu, Hanzhou

2017-01-01

To simply and multitudinously synthesize hollow microspheres in a pure system is important for relevant research and application. Here, a simple and novel one-pot synthetic strategy to prepare polystyrene (PS) hollow microspheres via irradiation-assisted free-radical polymerizing and self-assembly (IFPS) approach under γ-ray irradiation with no additives introduced into the system is presented. And PS/2,5-Diphenyloxazole (PPO) fluorescent microspheres have been prepared successfully by IFPS reaction, which can be used as scintillators for the detection of ionizing radiation. A linear relationship between emitted luminescence and dose-activity in water is obtained, which suggests that composite microspheres could be used as liquid scintillation in specific environment.

Development of serratiopeptidase and metronidazole based alginate microspheres for wound healing.

PubMed

Rath, G; Johal, E S; Goyal, Amit K

2011-02-01

The objective of this study was to establish an effective therapy system for wound management. The present work describes preparation of metronidazole/serratiopeptidase loaded alginate microspheres by emulsification method. In vitro characterizations like particle size analysis, % yield, % encapsulation, and in vitro release were carried out. Wound healing assessment was determined by physical, histological, and biochemical methods. Wound healing performance of experimental formulations was compared with marketed product in rabbits. Result obtained for alginate microspheres showed good loading efficiency with spherical in shape. Experimentation suggests wound healing is improved by using serratiopeptidase and metronidazole in full thickness wounds in rabbits.

Preparation, characterization, and infrared emissivity property of optically active polyurethane/TiO{sub 2}/SiO{sub 2} multilayered microspheres

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

Yang Yong; Zhou Yuming, E-mail: ymzhou@seu.edu.cn; Ge Jianhua

Optically active polyurethane/titania/silica (LPU/TiO{sub 2}/SiO{sub 2}) multilayered core-shell composite microspheres were prepared by the combination of titania deposition on the surface of silica spheres and subsequent polymer grafting. LPU/TiO{sub 2}/SiO{sub 2} was characterized by FT-IR, UV-vis spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), SEM and TEM, and the infrared emissivity value (8-14 {mu}m) was investigated in addition. The results indicated that titania and polyurethane had been successfully coated onto the surfaces of silica microspheres. LPU/TiO{sub 2}/SiO{sub 2} exhibited clearly multilayered core-shell construction. The infrared emissivity values reduced along with the increase of covering layers thus provedmore » that the interfacial interactions had direct influence on the infrared emissivity. Besides, LPU/TiO{sub 2}/SiO{sub 2} multilayered microspheres based on the optically active polyurethane took advantages of the orderly secondary structure and strengthened interfacial synergistic actions. Consequently, it possessed the lowest infrared emissivity value. - Graphical Abstract: Optically active polyurethane/titania/silica (LPU/TiO{sub 2}/SiO{sub 2}) multilayered core-shell composite microspheres were prepared by the combination of titania deposition on the surface of silica spheres and subsequent polymer grafting. Highlights: > Optically active polyurethane based on tyrosine was used for the modification of nanoparticles. > LPU/TiO{sub 2}/SiO{sub 2} multilayered core-shell microspheres were prepared and characterized. > Interfacial interactions and secondary structure affected the infrared emissivity of composite.« less

Preparation of cellulose based microspheres by combining spray coagulating with spray drying.

PubMed

Wang, Qiao; Fu, Aiping; Li, Hongliang; Liu, Jingquan; Guo, Peizhi; Zhao, Xiu Song; Xia, Lin Hua

2014-10-13

Porous microspheres of regenerated cellulose with size in range of 1-2 μm and composite microspheres of chitosan coated cellulose with size of 1-3 μm were obtained through a two-step spray-assisted approach. The spray coagulating process must combine with a spray drying step to guarantee the formation of stable microspheres of cellulose. This approach exhibits the following two main virtues. First, the preparation was performed using aqueous solution of cellulose as precursor in the absence of organic solvent and surfactant; Second, neither crosslinking agent nor separated crosslinking process was required for formation of stable microspheres. Moreover, the spray drying step also provided us with the chance to encapsulate guests into the resultant cellulose microspheres. The potential application of the cellulose microspheres acting as drug delivery vector has been studied in two PBS (phosphate-buffered saline) solution with pH values at 4.0 and 7.4 to mimic the environments of stomach and intestine, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

Plackett-Burman experimental design to facilitate syntactic foam development

DOE PAGES

Smith, Zachary D.; Keller, Jennie R.; Bello, Mollie; ...

2015-09-14

The use of an eight-experiment Plackett–Burman method can assess six experimental variables and eight responses in a polysiloxane-glass microsphere syntactic foam. The approach aims to decrease the time required to develop a tunable polymer composite by identifying a reduced set of variables and responses suitable for future predictive modeling. The statistical design assesses the main effects of mixing process parameters, polymer matrix composition, microsphere density and volume loading, and the blending of two grades of microspheres, using a dummy factor in statistical calculations. Responses cover rheological, physical, thermal, and mechanical properties. The cure accelerator content of the polymer matrix andmore » the volume loading of the microspheres have the largest effects on foam properties. These factors are the most suitable for controlling the gel point of the curing foam, and the density of the cured foam. The mixing parameters introduce widespread variability and therefore should be fixed at effective levels during follow-up testing. Some responses may require greater contrast in microsphere-related factors. As a result, compared to other possible statistical approaches, the run economy of the Plackett–Burman method makes it a valuable tool for rapidly characterizing new foams.« less

Process for fabricating doped zinc oxide microsphere gel

DOEpatents

Arnold, W.D. Jr.; Bond, W.D.; Lauf, R.J.

1991-11-05

Disclosed are a new composition and method of making same for a doped zinc oxide microsphere and articles made therefrom for use in an electrical surge arrestor which has increased solid content, uniform grain size and is in the form of a gel. 4 figures.

Influence of clay particles on microfluidic-based preparation of hydrogel composite microsphere

NASA Astrophysics Data System (ADS)

Hong, Joung Sook

2016-05-01

For the successful fabrication of a hydrogel composite microsphere, this study aimed to investigate the influence of clay particles on microsphere formation in a microfluidic device which has flow focusing and a 4.5:1 contraction channel. A poly alginic acid solution (2.0 wt.%) with clay particles was used as the dispersed phase to generate drops in an oil medium, which then merged with drops of a CaCl2 solution for gelation. Drop generations were observed with different flow rates and particles types. When the flow rate increased, drop generation was enhanced and drop size decreased by the build-up of more favorable hydrodynamic flow conditions to detach the droplets. The addition of a small amount of particles insignificantly changed the drop generation behavior even though it reduced interfacial tension and increased the viscosity of the solution. Instead, clays particles significantly affected hydro-gelation depending on the hydrophobicity of particles, which produced further heterogeneity in the shape and size of microsphere.

Preparation of Nano-TiO2-Coated SiO2 Microsphere Composite Material and Evaluation of Its Self-Cleaning Property

PubMed Central

Sun, Sijia; Deng, Tongrong; Ding, Hao; Chen, Ying; Chen, Wanting

2017-01-01

In order to improve the dispersion of nano-TiO2 particles and enhance its self-cleaning properties, including photocatalytic degradation of pollutants and surface hydrophilicity, we prepared nano-TiO2-coated SiO2 microsphere composite self-cleaning materials (SiO2–TiO2) by co-grinding SiO2 microspheres and TiO2 soliquid and calcining the ground product. The structure, morphology, and self-cleaning properties of the SiO2–TiO2 were characterized. The characterization results showed that the degradation efficiency of methyl orange by SiO2–TiO2 was 97%, which was significantly higher than that obtained by pure nano-TiO2. The minimum water contact angle of SiO2–TiO2 was 8°, indicating strong hydrophilicity and the good self-cleaning effect. The as-prepared SiO2–TiO2 was characterized by the nano-TiO2 particles uniformly coated on the SiO2 microspheres and distributed in the gap among the microspheres. The nano-TiO2 particles were in an anatase phase with the particle size of 15–20 nm. The nano-TiO2 particles were combined with SiO2 microspheres via the dehydroxylation of hydroxyl groups on their surfaces. PMID:29099774

QbD-enabled systematic development of gastroretentive multiple-unit microballoons of itopride hydrochloride.

PubMed

Bansal, Sanjay; Beg, Sarwar; Asthana, Abhay; Garg, Babita; Asthana, Gyati Shilakari; Kapil, Rishi; Singh, Bhupinder

2016-01-01

The objectives of present studies were to develop the systematically optimized multiple-unit gastroretentive microballoons, i.e. hollow microspheres of itopride hydrochloride (ITH) employing quality by design (QbD)-based approach. Initially, the patient-centric QTPP and CQAs were earmarked, and preliminary studies were conducted to screen the suitable polymer, solvent, solvent ratio, pH and temperature conditions. Microspheres were prepared by non-aqueous solvent evaporation method employing Eudragit S-100. Risk assessment studies carried out by constructing Ishikawa cause-effect fish-bone diagram, and techniques like risk estimation matrix (REM) and failure mode effect analysis (FMEA) facilitated the selection of plausible factors affecting the drug product CQAs, i.e. percent yield, entrapment efficiency (EE) and percent buoyancy. A 3(3) Box-Behnken design (BBD) was employed for optimizing CMAs and CPPs selected during factor screening studies employing Taguchi design, i.e. drug-polymer ratio (X1), stirring temperature (X2) and stirring speed (X3). The hollow microspheres, as per BBD, were evaluated for EE, particle size and drug release characteristics. The optimum formulation was embarked upon using numerical desirability function yielding excellent floatation characteristics along with adequate drug release control. Drug-excipient compatibility studies employing FT-IR, DSC and powder XRD revealed absence of significant interaction among the formulation excipients. The SEM studies on the optimized formulation showed hollow and spherical nature of the prepared microspheres. In vivo X-ray imaging studies in rabbits confirmed the buoyant nature of the hollow microspheres for 8 h in the upper GI tract. In a nutshell, the current investigations report the successful development of gastroretentive floating microspheres for once-a-day administration of ITH.

A novel approach for the preparation of highly loaded polymeric controlled release dosage forms of diltiazem HCl and diclofenac sodium.

PubMed

Kakish, Hanan F; Tashtoush, Bassam; Ibrahim, Hussein G; Najib, Naji M

2002-07-01

In this investigation, modified-release dosage forms of diltiazem HCl (DT) and diclofenac sodium (DS) were prepared. The development work comprised two main parts: (a) loading the drug into ethylene vinyl acetate (EVA) polymer, and (b) generation of a non-uniform concentration distribution of the drug within the polymer matrix. Phase separation technique was successfully used to load DT and DS into the polymer at significantly high levels, up to 81 and 76%, respectively. Size diameter of the resultant microspheres was between 1.6 and 2.0mm. Controlled-extraction of loaded microspheres and high vacuum freeze-drying were used to generate the non-uniform concentration distribution and to immobilize the new drug distribution within the matrix. Parameters controlling the different processes were investigated, and hence optimal processing conditions were used to prepare the dosage forms. Rates of drug release from the two dosage forms in water and in media having different pH were found to be constant for an appreciable length of time (>8h) followed by a slow decline; a characteristic of a non-Fickian diffusion process. Scanning electron microscopy studies suggested that the resultant release behavior was the outcome of the combined effects of the non-uniform distribution of the drug in the matrix and the apparent changes in the pores and surface characteristics of the microspheres. Comparison of release rate-time plots of dissolution data of marketed products with the newly developed dosage forms indicated the ability of the latter to sustain more zero order release.

Synthesis and catalytic performance of SiO2@Ni and hollow Ni microspheres

NASA Astrophysics Data System (ADS)

Liu, Xin; Liu, Yanhua; Shi, Xueting; Yu, Zhengyang; Feng, Libang

2016-11-01

Nickel (Ni) catalyst has been widely used in catalytic reducing reactions such as catalytic hydrogenation of organic compounds and catalytic reduction of organic dyes. However, the catalytic efficiency of pure Ni is low. In order to improve the catalytic performance, Ni nanoparticle-loaded microspheres can be developed. In this study, we have prepared Ni nanoparticle-loaded microspheres (SiO2@Ni) and hollow Ni microspheres using two-step method. SiO2@Ni microspheres with raspberry-like morphology and core-shell structure are synthesized successfully using SiO2 microsphere as a template and Ni2+ ions are adsorbed onto SiO2 surfaces via electrostatic interaction and then reduced and deposited on surfaces of SiO2 microspheres. Next, the SiO2 cores are removed by NaOH etching and the hollow Ni microspheres are prepared. The NaOH etching time does no have much influence on the crystal structure, shape, and surface morphology of SiO2@Ni; however, it can change the phase composition evidently. The hollow Ni microspheres are obtained when the NaOH etching time reaches 10 h and above. The as-synthesized SiO2@Ni microspheres exhibit much higher catalytic performance than the hollow Ni microspheres and pure Ni nanoparticles in the catalytic reduction of methylene blue. Meanwhile, the SiO2@Ni catalyst has high stability and hence it can be recycled for reuse.

Methods for producing monodispersed particles of barium titanate

DOEpatents

Hu, Zhong-Cheng

2001-01-01

The present invention is a low-temperature controlled method for producing high-quality, ultrafine monodispersed nanocrystalline microsphere powders of barium titanate and other pure or composite oxide materials having particles ranging from nanosized to micronsized particles. The method of the subject invention comprises a two-stage process. The first stage produces high quality monodispersed hydrous titania microsphere particles prepared by homogeneous precipitation via dielectric tuning in alcohol-water mixed solutions of inorganic salts. Titanium tetrachloride is used as an inorganic salt precursor material. The second stage converts the pure hydrous titania microsphere particles into crystalline barium titanate microsphere powders via low-temperature, hydrothermal reactions.

A protein/antibiotic releasing poly(lactic-co-glycolic acid)/lecithin scaffold for bone repair applications.

PubMed

Shi, Xuetao; Wang, Yingjun; Ren, Li; Huang, Wei; Wang, Dong-An

2009-05-21

Novel poly(lactic-co-glycolic acid) (PLGA)-hybridizing-lecithin scaffolds loaded with drug or protein were prepared with water/oil/water techniques and sintering microspheres technique. In such fabricated composite scaffolds (abbreviated "PLGA/Lec-SMS"), the introduction of lecithin component has been proven capable of largely enhancing Gentamicin (GS) and protein (Bovine Serum Albumin) encapsulation efficiency. The in vitro GS and BSA releasing profiles of PLGA/Lec-SMS system were plotted basing over 60 days' and 18 days' data collection, respectively. It indicates a sustained releasing tendency despite a burst at the very beginning. The antibacterial properties of GS-laden scaffolds were determined in vitro, and the antibacterial activity of scaffolds was enhanced by incorporating lecithin into PLGA bulks. Additionally, mesenchymal stem cells (MSCs) were seeded onto PLGA-SMS and PLGA/Lec-SMS in vitro. The outcome confirmed PLGA/Lec(5%)-SMS functions to improve MSC proliferation and also to enhance general ALP production and calcium secretion which is the vital markers for osteogenesis. In conclusion, this newly designed antibiotic releasing PLGA/Lec-SMS is promising for bone-repairing therapeutics.

Sustained reduction of intraocular pressure by supraciliary delivery of brimonidine-loaded poly(lactic acid) microspheres for the treatment of glaucoma

PubMed Central

Chiang, B.; Kim, Y.C.; Doty, A.C.; Grossniklaus, H.E.; Schwendeman, S.P.; Prausnitz, M.R.

2016-01-01

Although effective drugs that lower intraocular pressure (IOP) in the management of glaucoma exist, their efficacy is limited by poor patient adherence to the prescribed eye drop regimen. To replace the need for eye drops, in this study we tested the hypothesis that IOP can be reduced for one month after a single targeted injection using a microneedle for administration of a glaucoma medication (i.e., brimonidine) formulated for sustained release in the supraciliary space of the eye adjacent to the drug’s site of action at the ciliary body. To test this hypothesis, brimonidine-loaded microspheres were formulated using poly(lactic acid) (PLA) to release brimonidine at a constant rate for 35 days and microneedles were designed to penetrate through the sclera, without penetrating into the choroid/retina, in order to target injection into the supraciliary space. A single administration of these microspheres using a hollow microneedle was performed in the eye of New Zealand White rabbits and was found to reduce IOP initially by 6 mm Hg and then by progressively smaller amounts for more than one month. All administrations were well tolerated without significant adverse events, although histological examination showed a foreign-body reaction to the microspheres. This study demonstrates, for the first time, that the highly-targeted delivery of brimonidine-loaded microspheres into the supraciliary space using a microneedle is able to reduce IOP for one month as an alternative to daily eye drops. PMID:26930266

Urchin-like TiO₂@C core-shell microspheres: coupled synthesis and lithium-ion battery applications.

PubMed

Liu, Zhenyu; Liu, Jing; Liu, Junfeng; Wang, Li; Zhang, Guoxin; Sun, Xiaoming

2014-05-21

Carbon coated urchin-like TiO2 microspheres were prepared through coupled hydrolysis of titanium tetrachloride and catalyzed carbonization of glucose. Carbon coating endowed the composite with unusual structural stability at high temperature and reasonable Li-ion battery performance.

Influence of time delay on the estimated lung shunt fraction on 99mTc-labeled MAA scintigraphy for 90Y microsphere treatment planning.

PubMed

De Gersem, Ruth; Maleux, Geert; Vanbilloen, Hubert; Baete, Kristof; Verslype, Chris; Haustermans, Karin; Verbruggen, Alfons; Van Cutsem, Eric; Deroose, Christophe Michel

2013-12-01

90Y-microspheres therapy is used to treat selected patients with primary or metastatic liver tumors in a safe and effective way. As a preparation for 90Y-microspheres treatment, a 99mTc-macroaggregated albumin (99mTc-MAA) simulation procedure is essential to evaluate particle shunting to the lung or gastrointestinal tract. We investigated the effect of interval between injection of 99mTc-MAA and time of scanning on the lung shunt fraction (LSF). In 4 patients with secondary hepatic malignancies who underwent repeated whole-body scintigraphy up to 5 hours after injection of 99mTc-MAA, a marked change in LSF was observed. It appears that tracer degradation leads to an important overestimation of LSF at later time points. An overestimation of LSF can lead to dose reduction or canceling of the planned 90Y-microspheres treatment. It is concluded that the interval between injection and scanning should be kept as short as possible.

Stabilization of Tetanus Toxoid Encapsulated in PLGA Microspheres

PubMed Central

Jiang, Wenlei; Schwendeman, Steven P.

2014-01-01

Delivery of vaccine antigens from controlled-release poly(lactic/glycolic acid) (PLGA) microspheres is a novel approach to reduce the number of antigen doses required for protection against infection. A major impediment to developing single-shot vaccines is encapsulated antigen instability during months of exposure to physiological conditions. For example, efforts to control neonatal tetanus in developing countries with a single-dose TT vaccine have been plagued by poor stability of the 150 kDa formaldehyde-detoxified protein antigen, tetanus toxoid (TT) in PLGA microspheres. We examined the denatured states of PLGA-encapsulated TT, revealing two primary TT instability mechanisms: 1) protein aggregation mediated by formaldehyde and 2) acid-induced protein unfolding and epitope damage. Further, we systemically identified excipients which can efficiently inhibit TT aggregation and retain TT antigenicity under simulated deleterious conditions, i.e., elevated temperature and humidity. By employing these novel additives in the PLGA system, we report the slow and continuous release of high doses of TT for one month with retained antigen stability during bioerosion of PLGA. PMID:18710256

Biodegradable polymeric microsphere-based vaccines and their applications in infectious diseases

PubMed Central

Lin, Chi-Ying; Lin, Shih-Jie; Yang, Yi-Chen; Wang, Der-Yuan; Cheng, Hwei-Fang; Yeh, Ming-Kung

2015-01-01

Vaccination, which provides effective, safe infectious disease protection, is among the most important recent public health and immunological achievements. However, infectious disease remains the leading cause of death in developing countries because several vaccines require repeated administrations and children are often incompletely immunized. Microsphere-based systems, providing controlled release delivery, can obviate the need for repeat immunizations. Here, we review the function of sustained and pulsatile release of biodegradable polymeric microspheres in parenteral and mucosal single-dose vaccine administration. We also review the active-targeting function of polymeric particles. With their shield and co-delivery functions, polymeric particles are applied to develop single-dose and mucosally administered vaccines as well as to improve subunit vaccines. Because polymeric particles are easily surface-modified, they have been recently used in vaccine development for cancers and many infectious diseases without effective vaccines (e.g., human immunodeficiency virus infection). These polymeric particle functions yield important vaccine carriers and multiple benefits. PMID:25839217

Biocompatible and biodegradable fibrinogen microspheres for tumor-targeted doxorubicin delivery

PubMed Central

Joo, Jae Yeon; Park, Gil Yong; An, Seong Soo A

2015-01-01

In the development of effective drug delivery carriers, many researchers have focused on the usage of nontoxic and biocompatible materials and surface modification with targeting molecules for tumor-specific drug delivery. Fibrinogen (Fbg), an abundant glycoprotein in plasma, could be a potential candidate for developing drug carriers because of its biocompatibility and tumor-targeting property via arginine–glycine–aspartate (RGD) peptide sequences. Doxorubicin (DOX), a chemotherapeutic agent, was covalently conjugated to Fbg, and the microspheres were prepared. Acid-labile and non-cleavable linkers were used for the conjugation of DOX to Fbg, resulting in an acid-triggered drug release under a mild acidic condition and a slow-controlled drug release, respectively. In vitro cytotoxicity tests confirmed low cytotoxicity in normal cells and high antitumor effect toward cancer cells. In addition, it was discovered that a longer linker could make the binding of cells to Fbg drug carriers easier. Therefore, DOX–linker–Fbg microspheres could be a suitable drug carrier for safer and effective drug delivery. PMID:26366073

Mucoadhesive microspheres for gastroretentive delivery of acyclovir: in vitro and in vivo evaluation.

PubMed

Dhaliwal, Sumeet; Jain, Subheet; Singh, Hardevinder P; Tiwary, A K

2008-06-01

The aim of the present investigation was to evaluate the potential use of mucoadhesive microspheres for gastroretentive delivery of acyclovir. Chitosan, thiolated chitosan, Carbopol 71G and Methocel K15M were used as mucoadhesive polymers. Microsphere formulations were prepared using emulsion-chemical crosslinking technique and evaluated in vitro, ex-vivo and in-vivo. Gelatin capsules containing drug powder showed complete dissolution (90.5 +/- 3.6%) in 1 h. The release of drug was prolonged to 12 h (78.8 +/- 3.9) when incorporated into mucoadhesive microspheres. The poor bioavailability of acyclovir is attributed to short retention of its dosage form at the absorption sites (in upper gastrointestinal tract to duodenum and jejunum). The results of mucoadhesion study showed better retention of thiolated chitosan microspheres (8.0 +/- 0.8 h) in duodenal and jejunum regions of intestine. The results of qualitative and quantitative GI distribution study also showed significant higher retention of mucoadhesive microspheres in upper GI tract. Pharmacokinetic study revealed that administration of mucoadhesive microspheres could maintain measurable plasma concentration of acyclovir through 24 h, as compared to 5 h after its administration in solution form. Thiolated chitosan microsphere showed superiority over the other formulations as observed with nearly 4.0-fold higher AUC(0-24) value (1,090 +/- 51 ng h/ml) in comparison to drug solution (281 +/- 28 ng h/ml). Overall, the result indicated prolonged delivery with significant improvement in oral bioavailability of acyclovir from mucoadhesive microspheres due to enhanced retention in the upper GI tract.

Process for preparing metal-carbide-containing microspheres from metal-loaded resin beads

DOEpatents

Beatty, Ronald L.

1976-01-01

An improved method for treating metal-loaded resin microspheres is described which comprises heating a metal-loaded resin charge in an inert atmosphere at a pre-carbide-forming temperature under such conditions as to produce a microsphere composition having sufficient carbon as to create a substantially continuous carbon matrix and a metal-carbide or an oxide-carbide mixture as a dispersed phase(s) during carbide-forming conditions, and then heating the thus treated charge to a carbide-forming temperature.

Oral delivery of exenatide via microspheres prepared by cross-linking of alginate and hyaluronate.

PubMed

Zhang, Baojie; He, Dongyang; Fan, Yu; Liu, Nan; Chen, Yijun

2014-01-01

Exenatide is an FDA-approved glucose-lowering peptide drug for the treatment of type 2 diabetes by subcutaneous injection. To address the issues on the inconvenience for patient use and the difficulty of oral administration of peptide drugs, chemical cross-linking of two pH-responsive biomaterials, alginate and hyaluronate, was carried out to prepare a new material for the encapsulation of exenatide as a form of microspheres. The exenatide-loaded microspheres exhibited spherical structures with excellent loading and release behaviors in the simulated gastrointestinal tract environments. After oral administration of the microspheres in db/db mice, maximum plasma concentration of exenatide appeared at 4 hours, and blood glucose was effectively reduced to a normal level within 2 hours and maintained for another 4 hours. The bioavailability of the exenatide-loaded microspheres, relative to subcutaneous injection of exenatide, reached 10.2%. Collectively, the present study demonstrated the feasibility of orally delivering exenatide with the new cross-linked biomaterial and formulation, and showed therapeutic potential for clinical applications.

Oral Delivery of Exenatide via Microspheres Prepared by Cross-Linking of Alginate and Hyaluronate

PubMed Central

Zhang, Baojie; He, Dongyang; Fan, Yu; Liu, Nan; Chen, Yijun

2014-01-01

Exenatide is an FDA-approved glucose-lowering peptide drug for the treatment of type 2 diabetes by subcutaneous injection. To address the issues on the inconvenience for patient use and the difficulty of oral administration of peptide drugs, chemical cross-linking of two pH-responsive biomaterials, alginate and hyaluronate, was carried out to prepare a new material for the encapsulation of exenatide as a form of microspheres. The exenatide-loaded microspheres exhibited spherical structures with excellent loading and release behaviors in the simulated gastrointestinal tract environments. After oral administration of the microspheres in db/db mice, maximum plasma concentration of exenatide appeared at 4 hours, and blood glucose was effectively reduced to a normal level within 2 hours and maintained for another 4 hours. The bioavailability of the exenatide-loaded microspheres, relative to subcutaneous injection of exenatide, reached 10.2%. Collectively, the present study demonstrated the feasibility of orally delivering exenatide with the new cross-linked biomaterial and formulation, and showed therapeutic potential for clinical applications. PMID:24465870

Novel control methods for insect pests: development of a microencapsulation procedure for proteinaceous bioactives intended for oral delivery.

PubMed

Richards, Elaine H; Wontner-Smith, Tim; Bradish, Hannah; Dani, M Paulina; Cotterill, Jane V

2015-09-01

The objective was to develop an environmentally favourable microcapsule suitable for delivery of proteinaceous bioactive agents ('bioinsecticides') to pest insects. Utilising feeding bioassays, we determined that microspheres made of alginate can be produced in a variety of sizes and are palatable and non-toxic to larvae of the lepidopteran pest Lacanobia oleracea. Dehydrated microspheres were also readily ingested by larvae. Using a novel feeding bioassay and alginate microspheres containing a fluorescent marker material (coumarin 7 encapsulated in styrene maleic anhydride beads), we determined that the microspheres successfully deliver the marker to the insect gut. Moreover, the alginate microspheres rapidly break down in the alkaline conditions of the insect gut and release their contents, the beads passing through the gut in 2-3 h. Using bovine serum albumin as a test protein and western blotting, it was determined that alginate can successfully encapsulate protein, and that the microspheres can be stored in a CaCl2 solution for up to 24 days without extensive leakage. Importantly, it was also determined that alginate and the microsphere-making procedure developed do not inactivate rVPr1 (an insect immunosuppressive protein and potential bioinsecticide). An alginate-based microsphere has potential to deliver the proteinaceous bioactive rVPr1 to pest insects. © 2014 Crown copyright. Pest Management Science © 2014 Society of Chemical Industry.

Synthesis of Fe3O4 cluster microspheres/graphene aerogels composite as anode for high-performance lithium ion battery

NASA Astrophysics Data System (ADS)

Zhou, Shuai; Zhou, Yu; Jiang, Wei; Guo, Huajun; Wang, Zhixing; Li, Xinhai

2018-05-01

Iron oxides are considered as attractive electrode materials because of their capability of lithium storage, but their poor conductivity and large volume expansion lead to unsatisfactory cycling stability. We designed and synthesized a novel Fe3O4 cluster microspheres/Graphene aerogels composite (Fe3O4/GAs), where Fe3O4 nanoparticles were assembled into cluster microspheres and then embedded in 3D graphene aerogels framework. In the spheres, the sufficient free space between Fe3O4 nanoparticles could accommodate the volume change during cycling process. Graphene aerogel works as flexible and conductive matrix, which can not only significantly increase the mechanical stress, but also further improve the storage properties. The Fe3O4/GAs composite as an anode material exhibits high reversible capability and excellent cyclic capacity for lithium ion batteries (LIBs). A reversible capability of 650 mAh g-1 after 500 cycles at a current density of 1 A g-1 can be maintained. The superior storage capabilities of the composites make them potential anode materials for LIBs.

Effect of particle size, polydispersity and polymer degradation on progesterone release from PLGA microparticles: Experimental and mathematical modeling.

PubMed

Busatto, Carlos; Pesoa, Juan; Helbling, Ignacio; Luna, Julio; Estenoz, Diana

2018-01-30

Poly(lactic-co-glycolic acid) (PLGA) microparticles containing progesterone were prepared by the solvent extraction/evaporation and microfluidic techniques. Microparticles were characterized by their size distribution, encapsulation efficiency, morphology and thermal properties. The effect of particle size, polydispersity and polymer degradation on the in vitro release of the hormone was studied. A triphasic release profile was observed for larger microparticles, while smaller microspheres showed a biphasic release profile. This behavior is related to the fact that complete drug release was achieved in a few days for smaller microparticles, during which polymer degradation effects are still negligible. A mathematical model was developed that predicts the progesterone release profiles from different-sized PLGA microspheres. The model takes into account both the dissolution and diffusion of the drug in the polymeric matrix as well as the autocatalytic effect of polymer degradation. The model was adjusted and validated with novel experimental data. Simulation results are in very good agreement with experimental results. Copyright © 2017 Elsevier B.V. All rights reserved.

Multi-functional carbon microspheres with double shell layers for flame retardant poly (ethylene terephthalate)

NASA Astrophysics Data System (ADS)

Xue, Baoxia; Niu, Mei; Yang, Yongzhen; Bai, Jie; Song, Yinghao; Peng, Yun; Liu, Xuguang

2018-03-01

Carbon microspheres (CMSs) as a core material had been coated by two capsule walls: an inorganic material of magnesium hydroxide (MH) as inner shell layer and an organic material of poly (ethylene terephthalate) (PET) as outer shell layer. MH coating CMSs (MCMSs) were fabricated by liquid phase deposition method, then grafted 3-Aminopropyltriethoxysilane (APTS) to obtain the Si-MCMSs. Microencapsulated Si-MCMSs (PMCMSs) was prepared by in situ polymerization method. Morphology structure, dispersion, flame retardant and other properties of PMCMSs have been investigated. A series of PET blends were prepared by melt compounding. The results showed that MH and PET as two layers were coated on CMSs surface with the optimal thickness of about 70 nm. The PMCMSs owned better dispersion in PET matrix. Compared with MCMSs/PET composites, the mechanical property of PMCMSs/PET composites had significantly increased because of the strong interface binding force between PMCMSs and PET matrix. Moreover, PMCMSs was proved to be an effective flame retardant. For PMCMSs/PET with 2 wt% PMCMSs, the limiting oxygen index (LOI) value increased from 21.0% (pristine PET) to 27.2%, and the peak heat release rate (pk-HRR) decreased from 513.22 kW/m2 to 352.14 kW/m2. The decreased smoke production rate (SPR) and total smoke production (TSP) values demonstrated PMCMSs suppressed the smoke production. The increased Fire performance index (FPI) value illustrated PMCMSs significantly reduced the fire risk of PET. Overall, the two capsular walls endowed the PMCMSs/PET composites with good mechanical and flame-retardant properties.

Pinhole shifting lifetime imaging microscopy

PubMed Central

Ramshesh, Venkat K.; Lemasters, John J.

2009-01-01

Lifetime imaging microscopy is a powerful tool to probe biological phenomena independent of luminescence intensity and fluorophore concentration. We describe time-resolved imaging of long-lifetime luminescence with an unmodified commercial laser scanning confocal/multiphoton microscope. The principle of the measurement is displacement of the detection pinhole to collect delayed luminescence from a position lagging the rasting laser beam. As proof of principle, luminescence from microspheres containing europium (Eu3+), a red emitting probe, was compared to that of short-lifetime green-fluorescing microspheres and/or fluorescein and rhodamine in solution. Using 720-nm two-photon excitation and a pinhole diameter of 1 Airy unit, the short-lifetime fluorescence of fluorescein, rhodamine and green microspheres disappeared much more rapidly than the long-lifetime phosphorescence of Eu3+ microspheres as the pinhole was repositioned in the lagging direction. In contrast, repositioning of the pinhole in the leading and orthogonal directions caused equal loss of short- and long-lifetime luminescence. From measurements at different lag pinhole positions, a lifetime of 270 μs was estimated for the Eu3+ microspheres, consistent with independent measurements. This simple adaptation is the basis for quantitative 3-D lifetime imaging microscopy. PMID:19123648

Adipose-Derived Stem Cell Delivery into Collagen Gels Using Chitosan Microspheres

DTIC Science & Technology

2010-02-17

Porous CSM of uniform size and composition were prepared and used as a stem cell carrier. ASC were allowed to attach to the microspheres and infiltrate...and viable, could be retrieved from the spheres, and maintained expression of stem - cell -specific markers. Electron microscopic evaluation of the cell

New hydrazonoindolin-2-ones: Synthesis, exploration of the possible anti-proliferative mechanism of action and encapsulation into PLGA microspheres.

PubMed

Attia, Mohamed I; Eldehna, Wagdy M; Afifi, Samar A; Keeton, Adam B; Piazza, Gary A; Abdel-Aziz, Hatem A

2017-01-01

The synthesis and molecular characterization of new isatin-based hydrazonoindolin-2-ones 4a-o and 7a-e are reported. The in vitro anti-proliferative potential of the synthesized compounds 4a-o and 7a-e was examined against HT-29 (colon), ZR-75 (breast) and A549 (lung) human cancer cell lines. Compounds 7b, 7d and 7e were the most active congeners against the tested human cancer cell lines with average IC50 values of 4.77, 3.39 and 2.37 μM, respectively, as compared with the reference isatin-based drug, sunitinib, which exhibited an average IC50 value of 8.11 μM. Compound 7e was selected for further pharmacological evaluation in order to gain insight into its possible mechanism of action. It increased caspase 3/7 activity by 2.4- and 1.85-fold between 4 and 8 h of treatment, respectively, at 10 μM and it caused a decrease in the percentage of cells in the G1 phase of the cell cycle with a corresponding increase in the S-phase. In addition, compound 7e increased phosphorylated tyrosine (p-Tyr) levels nearly two-fold with an apparent IC50 value of 3.8 μM. The 7e-loaded PLGA microspheres were prepared using a modified emulsion-solvent diffusion method. The average encapsulation efficiency of the 7e-loaded PLGA microspheres was 85% ± 1.3. While, the in vitro release profile of the 7e-loaded microspheres was characterized by slow and continuous release of compound 7e during 21 days and the release curve was fitted to zero order kinetics. Incorporation of 7e into PLGA microspheres improved its in vitro anti-proliferative activity toward the human cancer cell line A549 after 120 h incubation period with an IC50 value less than 0.8 μM.

Review Article: Fabricated Microparticles: An Innovative Method to Minimize the Side Effects of NSAIDs in Arthritis.

PubMed

Abadi, Shaivad Shabee Hulhasan; Moin, Afrasim; Veerabhadrappa, Gangadharappa Hosahalli

2016-01-01

Microparticles are polymeric bodies ranging 1-1000 µm that constitute a variety of forms such as microcapsules, microspheres, microcages, microshells, microrods, biosensors microparticles, radiolabeled microparticles, and so forth. This review focuses on general microparticles, mainly microcapsules and microspheres. Nonsteriodal anti-inflammatory drugs (NSAIDs) are one of the mostcommonly prescribed medications in the world. Most of the NSAIDs available have severe side effects. With increased awareness of NSAID-induced gastrointestinal (GI) side effects, safety has become a priority in treatment of arthritis and other inflammatory diseases with NSAIDs. A trend in NSAID development has been to improve therapeutic efficacy while reducing the severity of GI side effects by altering dosage through modified release to optimize drug delivery. One such approach is the use of fabricated microparticles such as microcapsules and microspheres as carriers of drugs. Microparticles provide delivery of macromolecules and micromolecules via different routes and effectively control the release profile of such drugs. Microcapsules and microspheres are compatible with most natural and synthetic polymers and can be used for several routes of administration, including parenteral, oral, nasal, intra-ocular, topical, and the like. Because of greater stability and multiple manufacturing techniques, microspheres and microcapsules are preferred as drug carriers over other colloidal drug delivery systems. Microparticles provide effective protection of the encapsulated agent against degradation by enzymatic activities, controlled and confined delivery of drugs from a few hours to months, and ingenious administration compared to alternative forms of controlled-release parenteral dosages, such as macro-sized implants. This comprehensive overview of fabricated microparticles describes microencapsulation technologies to produce microparticles for targeted therapy of arthritis and other inflammatory diseases which provide constant and prolonged therapeutic effects that reduce dosing frequency and thereby minimize potential adverse effects of NSAIDs such as GI irritation and insufficient patient compliance. The present review describes the latest developments in microparticulate drug delivery systems and the best alternatives for safe and effective microcapsular systems in a controlled manner for the delivery of NSAIDs.

[Preparation of scopolamine hydrobromide nanoparticles-in-microsphere system].

PubMed

Lü, Wei-ling; Hu, Jin-hong; Zhu, Quan-gang; Li, Feng-qian

2010-07-01

This study is to prepare scopolamine hydrobromide nanoparticles-in-microsphere system (SH-NiMS) and evaluate its drug release characteristics in vitro. SH nanoparticles were prepared by ionic crosslinking method with tripolyphosphate (TPP) as crosslinker and chitosan as carrier. Orthogonal design was used to optimize the formulation of SH nanoparticles, which took the property of encapsulation efficiency and drug loading as evaluation parameters. With HPMC as carrier, adjusted the parameters of spray drying technique and sprayed the SH nanoparticles in microspheres encaposulated by HPMC was formed and which is called nanoparticles-in-microsphere system (NiMS). SH-NiMS appearances were observed by SEM, structure was obsearved by FT-IR and the release characteristics in vitro were evaluated. The optimized formulation of SH nanoparticles was TPP/CS 1:3 (w/w), HPMC 0.3%, SH 0.2%. The solution peristaltic speed of the spray drying technique was adjusted to 15%, and the temperature of inlet was 110 degrees C. The encapsulation product yeild, drug loading and particle sizes of SH-NiMS were 94.2%, 20.4%, and 1256.5 nm, respectively. The appearances and the structure of SH-NiMS were good. The preparation method of SH-NiMS is stable and reliable to use, which provide a new way to develop new dosage form.

Production of GMP-grade radioactive holmium loaded poly(L-lactic acid) microspheres for clinical application.

PubMed

Zielhuis, S W; Nijsen, J F W; de Roos, R; Krijger, G C; van Rijk, P P; Hennink, W E; van het Schip, A D

2006-03-27

Radioactive holmium-166 loaded poly(L-lactic acid) microspheres are promising systems for the treatment of liver malignancies. The microspheres are loaded with holmium acetylacetonate (HoAcAc) and prepared by a solvent evaporation method. After preparation, the microspheres (Ho-PLLA-MS) are activated by neutron irradiation in a nuclear reactor. In this paper, the aspects of the production of a (relatively) large-scale GMP batch (4 g, suitable for treatment of 5-10 patients) of Ho-PLLA-MS are described. The critical steps of the Ho-PLLA-MS production process (sieving procedure, temperature control during evaporation and raw materials) were considered and the pharmaceutical quality of the microspheres was evaluated. The pharmaceutical characteristics (residual solvents, possible bacterial contaminations and endotoxins) of the produced Ho-PLLA-MS batches were in compliance with the requirements of the European Pharmacopoeia. Moreover, neutron irradiated Ho-PLLA-MS retained their morphological integrity and the holmium remained stably associated with the microspheres; it was observed that after 270h (10 times the half-life of Ho-166) only 0.3+/-0.1% of the loading was released from the microspheres in an aqueous solution. In conclusion, Ho-PLLA-MS which are produced as described in this paper, can be clinically applied, with respect to their pharmaceutical quality.

SiO2/TiO2/Ag multilayered microspheres: Preparation, characterization, and enhanced infrared radiation property

NASA Astrophysics Data System (ADS)

Ye, Xiaoyun; Cai, Shuguang; Zheng, Chan; Xiao, Xueqing; Hua, Nengbin; Huang, Yanyi

2015-08-01

SiO2/TiO2/Ag core-shell multilayered microspheres were successfully synthesized by the combination of anatase of TiO2 modification on the surfaces of SiO2 spheres and subsequent Ag nanoparticles deposition and Ag shell growth with face-centered cubic (fcc) Ag. The composites were characterized by TEM, FT-IR, UV-vis, Raman spectroscopy and XRD, respectively. The infrared emissivity values during 8-14 μm wavelengths of the composites were measured. The results revealed that TiO2 thin layers with the thickness of ∼10 nm were coated onto the SiO2 spheres of ∼220 nm in diameter. The thickness of the TiO2 layers was controlled by varying the amount of TBOT precursor. Homogeneous Ag nanoparticles of ∼20 nm in size were successfully deposited by ultrasound on the surfaces of SiO2/TiO2 composites, followed by complete covering of Ag shell. The infrared emissivity value of the SiO2/TiO2 composites was decreased than that of pure SiO2. Moreover, the introduction of the Ag brought the remarkably lower infrared emissivity value of the SiO2/TiO2/Ag multilayered microspheres with the lowest value down to 0.424. Strong chemical effects in the interface of SiO2/TiO2 core-shell composites and high reflection performance of the metal Ag are two decisive factors for the improved infrared radiation performance of the SiO2/TiO2/Ag multilayered microspheres.

Physicochemical characterization of camptothecin membrane binding properties and polymeric microsphere formulations

NASA Astrophysics Data System (ADS)

Selvi, Bilge

In an effort to design novel formulation strategies to optimize the antitumor activity of camptothecin (CPT), the physicochemical and membrane binding properties of the drug, were investigated by various techniques in acidic and physiological pH. The intrinsic solubility of the CPT-lactone free base was determined to be 3.44 muM and 5.11 muM at 22°C and 37°C, respectively. The equilibrium solubility of the drug was found to increase with increasing temperature and decreasing pH. The enhanced solubility of the drug at very low pH is attributed to the protonation of the nitrogen atom in the ring B and the increased solvency of the highly acidic media. The logarithmic value of the intrinsic partition coefficient P of the free base CPT-lactone form was estimated to be 1.65, characteristic of a molecule suitable for oral absorption. The association constants Kf of the drug for bilayers composed of the zwitterionic 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and the negatively-charged 1,2-dioleoyl-sn-glycero-3-phospho- rac-(1-glycerol) (DOPG) were studied at acidic pH by fluorescence anisotropy and determined to be 35.4 +/- 4.5 M-1 and 93.1 +/- 11.0 M-1 for DOPC and DOPG, respectively, indicating a tendency of CPT to preferentially bind to negatively charged membranes. The energy of activation for the hydrolysis of CPT at physiological pH was found to be 114.3 +/- 33.4 kj/mole. The calculated t½ of the reaction at pH 7.2 at temperatures 25°C and 10°C was found to be 0.07 days and 5.12 days, respectively, whereas the time required for 1% of CPT-lactone to hydrolyze to CPT-carboxylate (t99%) was determined to be 1.8 hours, thus offering enough time to safely handle CPT-lactone at low temperatures. The preformulation results indicated that at highly acidic media CPT is positively charged and exists at its stable lactone form of increased solubility and has a capacity to bind to negatively charged membranes. Taking advantage of the increased stability of CPT in acidic media CPT-loaded microspheres were prepared in a 10 N HCl-methylene chloride mixture using the H-series of poly(D,L-lactide-co-glycolide) (H-PLGA). The system was then compared with a standard microsphere formation method and the results were evaluated with respect to particle morphology and drug release profile. Rough surface of the particles were obtained from the preparation method where a 10 N HCl solution was used. The release pattern of CPT was biphasic comprising a first burst effect followed by zero order release for all the formulations. However, the release of the drug was slightly faster from the microspheres formed with the modified method compared to the standard. Until now clinical application of CPT has been highly restricted by the insolubility and instability of the drug in its active lactone form, resulting in less antitumor potency and poor bioavailability. The pH-dependent release of the CPT-loaded microspheres was also compared and faster initial release (burst phase) was found at neutral pH, whereas at low pH the release was zero order for all the formulations. The results indicate that the stabilization and sustained release of CPT from H-PLGA microspheres might reduce local toxicity while simultaneously prolonging efficiency, suggesting new perspectives in CPT chemotherapy.

Cellulose acetate-based SiO2/TiO2 hybrid microsphere composite aerogel films for water-in-oil emulsion separation

NASA Astrophysics Data System (ADS)

Yang, Xue; Ma, Jianjun; Ling, Jing; Li, Na; Wang, Di; Yue, Fan; Xu, Shimei

2018-03-01

The cellulose acetate (CA)/SiO2-TiO2 hybrid microsphere composite aerogel films were successfully fabricated via water vapor-induced phase inversion of CA solution and simultaneous hydrolysis/condensation of 3-aminopropyltrimethoxysilane (APTMS) and tetrabutyl titanate (TBT) at room temperature. Micro-nano hierarchical structure was constructed on the surface of the film. The film could separate nano-sized surfactant-stabilized water-in-oil emulsions only under gravity. The flux of the film for the emulsion separation was up to 667 L m-2 h-1, while the separation efficiency was up to 99.99 wt%. Meanwhile, the film exhibited excellent stability during multiple cycles. Moreover, the film performed excellent photo-degradation performance under UV light due to the photocatalytic ability of TiO2. Facile preparation, good separation and potential biodegradation maked the CA/SiO2-TiO2 hybrid microsphere composite aerogel films a candidate in oil/water separation application.

Coacervate-like microspheres from lysine-rich proteinoid

NASA Technical Reports Server (NTRS)

Rohlfing, D. L.

1975-01-01

Microspheres form isothermally from lysine-rich proteinoid when the ionic strength of the solution is increased with NaCl or other salts. Studies with different monovalent anions and with polymers of different amino acid composition indicate that charge neutralization and hydrophobic bonding contribute to microsphere formation. The particles also form in sea water, especially if heated or made slightly alkaline. The microspheres differ from those made from acidic proteinoid but resemble coacervate droplets in some ways (isothermal formation, limited stability, stabilization by quinone, uptake of dyes). Because the constituent lysine-rich proteinoid is of simulated prebiotic origin, the study is interpreted to add emphasis to and suggest an evolutionary continuity for coacervation phenomena.

Effects of spray drying conditions on the physicochemical properties of the Tramadol-Hcl microparticles containing Eudragit(®) RS and RL.

PubMed

Patel, A S; Soni, T; Thakkar, V; Gandhi, T

2012-03-01

The preparation of Tramadol-HCL spray-dried microspheres can be affected by the long drug recrystallization time. Polymer type and drug-polymer ratio as well as manufacturing parameters affect the preparation. The purpose of this work was to evaluate the possibility to obtain tramadol spray-dried microspheres using the Eudragit(®) RS and RL; the influence of the spray-drying parameters on morphology, dimension, and physical stability of microspheres was studied. The effects of matrix composition on microparticle properties were characterized by Laser Light scattering, differential scanning calorimetry (DSC), X-ray diffraction study, FT-infrared and UV-visible spectroscopy. The spray-dried microparticles were evaluated in terms of shape (SEM), size distribution (Laser light scattering method), production yield, drug content, initial drug loding and encapsulation efficiency. The results of X-ray diffraction and thermal analysis reveals the conversion of crystalline drug to amorphous. FTIR analysis confirmed the absence of any drug polymer interaction. The results indicated that the entrapment efficiency (EE), and product yield were depended on polymeric composition and polymeric ratios of the microspheres prepared. Tramadol microspheres based on Eudragit(®) blend can be prepared by spray-drying and the nebulization parameters do not influence significantly on particle properties.

Processing and size range separation of pristine and magnetic poly(l-lactic acid) based microspheres for biomedical applications.

PubMed

Correia, D M; Sencadas, V; Ribeiro, C; Martins, P M; Martins, P; Gama, F M; Botelho, G; Lanceros-Méndez, S

2016-08-15

Biodegradable poly(l-lactic acid) (PLLA) and PLLA/CoFe2O4 magnetic microspheres with average sizes ranging between 0.16-3.9μm and 0.8-2.2μm, respectively, were obtained by an oil-in-water emulsion method using poly(vinyl alcohol) (PVA) solution as the emulsifier agent. The separation of the microspheres in different size ranges was then performed by centrifugation and the colloidal stability assessed at different pH values. Neat PLLA spheres are more stable in alkaline environments when compared to magnetic microspheres, both types being stable for pHs higher than 4, resulting in a colloidal suspension. On the other hand, in acidic environments the microspheres tend to form aggregates. The neat PLLA microspheres show a degree of crystallinity of 40% whereas the composite ones are nearly amorphous (17%). Finally, the biocompatibility was assessed by cell viability studies with MC3T3-E1 pre-osteoblast cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Development and characterization of colon specific drug delivery system bearing 5-ASA and Camylofine dihydrochloride for the treatment of ulcerative colitis.

PubMed

Dubey, Rupal; Dubey, Rounak; Omrey, Pratibha; Vyas, S P; Jain, S K

2010-09-01

The treatment of ulcerative colitis (inflammatory bowel disease, IBD) has been achieved by using colon specific drug delivery system bearing 5-ASA and Camylofine dihydrochloride. Chitosan microspheres were prepared separately for both the drugs using emulsion method followed by enteric coating with EudragitS-100. The in vitro drug release was investigated in different simulated GIT medium. The drug release in PBS (pH7.4) and simulated gastric fluid has shown almost similar pattern and rate, whereas a significant increase in drug release (70.3 +/- 1.36 and 72.5 +/- 1.33% of 5-ASA and Camylofine, respectively) was observed in medium containing 3% rat caecal matter, after 24 h. In control study, 57.1 +/- 1.13% of 5-ASA and 59.2 +/- 1.2% of Camylofine release was observed in 24 h. For enzyme induction, rats were orally administered with 1 mL of 1% w/v dispersion of chitosan for 5 days and release rate studies were conducted in SCF with 3% w/v of caecal matter. An enhanced drug release (i.e., 92.3 +/- 3.81 and 95.5 +/- 3.52% 5-ASA and Camylofine, respectively) was observed after 24 h in dissolution medium containing 3% caecal content obtained from enzyme induced animals. In vivo data showed that microspheres delivered most of its drug load (76.55 +/- 2.13%) to the colon after 9 h, which reflects its targeting potential to the colon. It is concluded that orally administered microspheres of both drugs can be used together for the specific delivery of drug to the colon and reduce symptoms of ulcerative colitis.

Marine structure derived calcium phosphate-polymer biocomposites for local antibiotic delivery.

PubMed

Macha, Innocent J; Cazalbou, Sophie; Ben-Nissan, Besim; Harvey, Kate L; Milthorpe, Bruce

2015-01-20

Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with medically active substances were used to develop polylactic acid (PLA) thin film composites for slow drug delivery systems. The effects of HAp particles within PLA matrix on the gentamicin (GM) release and release kinetics were studied. The gentamicin release kinetics seemed to follow Power law Korsmeyer Peppas model with mainly diffusional process with a number of different drug transport mechanisms. Statistical analysis shows very significant difference on the release of gentamicin between GM containing PLA (PLAGM) and GM containing HAp microspheres within PLA matrix (PLAHApGM) devices, which PLAHApGM displays lower release rates. The use of HAp particles improved drug stabilization and higher drug encapsulation efficiency of the carrier. HAp is also the source of Ca2+ for the regeneration and repair of diseased bone tissue. The release profiles, exhibited a steady state release rate with significant antimicrobial activity against Staphylococcus aureus (S. aureus) (SH1000) even at high concentration of bacteria. The devices also indicated significant ability to control the growth of bacterial even after four weeks of drug release. Clinical release profiles can be easily tuned from drug-HAp physicochemical interactions and degradation kinetics of polymer matrix. The developed systems could be applied to prevent microbial adhesion to medical implant surfaces and to treat infections mainly caused by S. aureus in surgery.

Marine Structure Derived Calcium Phosphate–Polymer Biocomposites for Local Antibiotic Delivery

PubMed Central

Macha, Innocent J.; Cazalbou, Sophie; Ben-Nissan, Besim; Harvey, Kate L.; Milthorpe, Bruce

2015-01-01

Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with medically active substances were used to develop polylactic acid (PLA) thin film composites for slow drug delivery systems. The effects of HAp particles within PLA matrix on the gentamicin (GM) release and release kinetics were studied. The gentamicin release kinetics seemed to follow Power law Korsmeyer Peppas model with mainly diffusional process with a number of different drug transport mechanisms. Statistical analysis shows very significant difference on the release of gentamicin between GM containing PLA (PLAGM) and GM containing HAp microspheres within PLA matrix (PLAHApGM) devices, which PLAHApGM displays lower release rates. The use of HAp particles improved drug stabilization and higher drug encapsulation efficiency of the carrier. HAp is also the source of Ca2+ for the regeneration and repair of diseased bone tissue. The release profiles, exhibited a steady state release rate with significant antimicrobial activity against Staphylococcus aureus (S. aureus) (SH1000) even at high concentration of bacteria. The devices also indicated significant ability to control the growth of bacterial even after four weeks of drug release. Clinical release profiles can be easily tuned from drug-HAp physicochemical interactions and degradation kinetics of polymer matrix. The developed systems could be applied to prevent microbial adhesion to medical implant surfaces and to treat infections mainly caused by S. aureus in surgery. PMID:25608725

In vitro evaluation of three-dimensional single-walled carbon nanotube composites for bone tissue engineering.

PubMed

Gupta, Ashim; Main, Benjamin J; Taylor, Brittany L; Gupta, Manu; Whitworth, Craig A; Cady, Craig; Freeman, Joseph W; El-Amin, Saadiq F

2014-11-01

The purpose of this study was to develop three-dimensional single-walled carbon nanotube composites (SWCNT/PLAGA) using 10-mg single-walled carbon nanotubes (SWCNT) for bone regeneration and to determine the mechanical strength of the composites, and to evaluate the interaction of MC3T3-E1 cells via cell adhesion, growth, survival, proliferation, and gene expression. PLAGA (polylactic-co-glycolic acid) and SWCNT/PLAGA microspheres and composites were fabricated, characterized, and mechanical testing was performed. MC3T3-E1 cells were seeded and cell adhesion/morphology, growth/survival, proliferation, and gene expression analysis were performed to evaluate biocompatibility. Imaging studies demonstrated microspheres with uniform shape and smooth surfaces, and uniform incorporation of SWCNT into PLAGA matrix. The microspheres bonded in a random packing manner while maintaining spacing, thus resembling trabeculae of cancellous bone. Addition of SWCNT led to greater compressive modulus and ultimate compressive strength. Imaging studies revealed that MC3T3-E1 cells adhered, grew/survived, and exhibited normal, nonstressed morphology on the composites. SWCNT/PLAGA composites exhibited higher cell proliferation rate and gene expression compared with PLAGA. These results demonstrate the potential of SWCNT/PLAGA composites for musculoskeletal regeneration, for bone tissue engineering, and are promising for orthopedic applications as they possess the combined effect of increased mechanical strength, cell proliferation, and gene expression. © 2014 Wiley Periodicals, Inc.

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.

Spatiotemporal Programing for the On-Demand Release of Bupivacaine Based on an Injectable Composite Hydrogel.

PubMed

Dinh, Van Vuong; Suh, Yun-Suhk; Yang, Han-Kwang; Lim, Yong Taik

2016-12-01

We report a programed drug delivery system that can tailor the release of anesthetic bupivacaine in a spatiotemporally controlled manner. The drug delivery system was developed through the combination of a collagen-based injectable hydrogel and 2 types of poly(lactic-co-glycolic acid) (PLGA) particles. As a rapid-release platform (90% release after 24 h), bupivacaine hydrochloride was incorporated into collagen/poly(γ-glutamic acid) hydrogel, which exhibited gel formation at body temperature. PLGA microparticles (diameter 1-3 μm) containing bupivacaine base showed a very slow release of bupivacaine (95% after 240 h), whereas PLGA nanoparticles (124 ± 30 nm) containing bupivacaine base demonstrated an intermediate release rate (95% after 160 h). By changing the relative composition ratio between the 3 components in these injectable composite hydrogels, the release of bupivacaine could be easily controlled from very rapid (within 1 day) to very delayed (up to 9 days). The experimental results on the release data (cumulative release, time point release, average release rate) were coincident with the release profile generated by computer simulation. These injectable composite hydrogels with systematically tunable mixing ratios are expected to serve as a promising technology for the on-demand release of bupivacaine in pain management. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Low-melting elemental metal or fusible alloy encapsulated polymerization initiator for delayed initiation

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

Hermes, Robert E.

2017-08-15

An encapsulated composition for polymerization includes an initiator composition for initiating a polymerization reaction, and a capsule prepared from an elemental metal or fusible alloy having a melting temperature from about 20.degree. C. to about 200.degree. C. A fluid for polymerization includes the encapsulated composition and a monomer. When the capsule melts or breaks open, the initiator is released.

Preparation of sodium fluoride-loaded gelatin microspheres, characterization and cariostatic studies.

PubMed

Wu, H; Zhang, Z X; Zhao, H P; Wu, D C; Wu, B L; Cong, R

2004-12-01

Sodium fluoride-loaded gelatin microspheres (NaF-GMS) were prepared using double-phase emulsified condensation polymerization. The average diameter of microspheres was (11.33+/-5.56) microm. The drug content and encapsulation efficiency were 8.80% and 76.73%, respectively. The fluoride releasing profiles of NaF-GMS in physiological saline and artificial saliva (pH 4.5, pH 6.8) showed that NaF-GMS had a sustained-release property and fluoride release rate was increased in pH 4.5 artificial saliva. Experiments conducted in rabbits' oral cavity using NaF-GMS and NaF solution as control revealed NaF-GMS could maintain oral fluoride retention longer than NaF solution. Cariostatic abilities of NaF-GMS including demineralization prohibition in vitro, fluoride deposition in artificial dental plaque and the ability of targeting to cariogenic bacteria were investigated in artificial dental plaque. The results indicated NaF-GMS with lower fluoride concentrations could achieve equivalent cariostatic effect to the concentrated NaF solution, at the same time, could prolong fluoride retention in dental plaque. Microscopic observation showed that NaF-GMS carrying fusion protein of glucan-binding domain could adhere more bacteria than NaF-GMS and this might indicate the possibility of targeting to cariogenic bacteria when NaF-GMS were properly modified.

Microspheres Assembled from Chitosan-Graft-Poly(lactic acid) Micelle-Like Core-Shell Nanospheres for Distinctly Controlled Release of Hydrophobic and Hydrophilic Biomolecules.

PubMed

Niu, Xufeng; Liu, Zhongning; Hu, Jiang; Rambhia, Kunal J; Fan, Yubo; Ma, Peter X

2016-07-01

To simultaneously control inflammation and facilitate dentin regeneration, a copolymeric micelle-in-microsphere platform is developed in this study, aiming to simultaneously release a hydrophobic drug to suppress inflammation and a hydrophilic biomolecule to enhance odontogenic differentiation of dental pulp stem cells in a distinctly controlled fashion. A series of chitosan-graft-poly(lactic acid) copolymers is synthesized with varying lactic acid and chitosan weight ratios, self-assembled into nanoscale micelle-like core-shell structures in an aqueous system, and subsequently crosslinked into microspheres through electrostatic interaction with sodium tripolyphosphate. A hydrophobic biomolecule either coumarin-6 or fluocinolone acetonide (FA) is encapsulated into the hydrophobic cores of the micelles, while a hydrophilic biomolecule either bovine serum albumin or bone morphogenetic protein 2 (BMP-2) is entrapped in the hydrophilic shells and the interspaces among the micelles. Both hydrophobic and hydrophilic biomolecules are delivered with distinct and tunable release patterns. Delivery of FA and BMP-2 simultaneously suppresses inflammation and enhances odontogenesis, resulting in significantly enhanced mineralized tissue regeneration. This result also demonstrates the potential for this novel delivery system to deliver multiple therapeutics and to achieve synergistic effects. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Delivery of S1P Receptor-Targeted Drugs via Biodegradable Polymer Scaffolds Enhances Bone Regeneration in a Critical Size Cranial Defect*

PubMed Central

Das, Anusuya; Tanner, Shaun; Barker, Daniel A.; Green, David; Botchwey, Edward A.

2014-01-01

Biodegradable polymer scaffolds can be used to deliver soluble factors to enhance osseous remodeling in bone defects. To this end, we designed a poly(lactic-co-glycolic acid) (PLAGA) microsphere scaffold to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors. The microsphere scaffolds were created from fast degrading 50:50 PLAGA and/or from slow-degrading 85:15 PLAGA. Temporal and spatial regulation of bone remodeling depended on the use of appropriate scaffolds for drug delivery. The release profiles from the scaffolds were used to design an optimal delivery system to treat critical size cranial defects in a rodent model. The ability of local FTY720 delivery to maximize bone regeneration was evaluated with microcomputed tomography (microCT) and histology. Following 4 weeks of defect healing, FTY720 delivery from 85:15 PLAGA scaffolds resulted in a significant increase in bone volumes in the defect region compared to the controls. 85:15 microsphere scaffolds maintain their structural integrity over a longer period of time, and cause an initial burst release of FTY720 due to surface localization of the drug. This encourages cellular in-growth and an increase in new bone formation. PMID:23640833

Delivery of S1P receptor-targeted drugs via biodegradable polymer scaffolds enhances bone regeneration in a critical size cranial defect.

PubMed

Das, Anusuya; Tanner, Shaun; Barker, Daniel A; Green, David; Botchwey, Edward A

2014-04-01

Biodegradable polymer scaffolds can be used to deliver soluble factors to enhance osseous remodeling in bone defects. To this end, we designed a poly(lactic-co-glycolic acid) (PLAGA) microsphere scaffold to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors. The microsphere scaffolds were created from fast degrading 50:50 PLAGA and/or from slow-degrading 85:15 PLAGA. Temporal and spatial regulation of bone remodeling depended on the use of appropriate scaffolds for drug delivery. The release profiles from the scaffolds were used to design an optimal delivery system to treat critical size cranial defects in a rodent model. The ability of local FTY720 delivery to maximize bone regeneration was evaluated with micro-computed tomography (microCT) and histology. Following 4 weeks of defect healing, FTY720 delivery from 85:15 PLAGA scaffolds resulted in a significant increase in bone volumes in the defect region compared to the controls. A 85:15 microsphere scaffolds maintain their structural integrity over a longer period of time, and cause an initial burst release of FTY720 due to surface localization of the drug. This encourages cellular in-growth and an increase in new bone formation. Copyright © 2013 Wiley Periodicals, Inc.

Nanomechanics of biocompatible hollow thin-shell polymer microspheres.

PubMed

Glynos, Emmanouil; Koutsos, Vasileios; McDicken, W Norman; Moran, Carmel M; Pye, Stephen D; Ross, James A; Sboros, Vassilis

2009-07-07

The nanomechanical properties of biocompatible thin-shell hollow polymer microspheres with approximately constant ratio of shell thickness to microsphere diameter were measured by nanocompression tests in aqueous conditions. These microspheres encapsulate an inert gas and are used as ultrasound contrast agents by releasing free microbubbles in the presence of an ultrasound field as a result of free gas leakage from the shell. The tests were performed using an atomic force microscope (AFM) employing the force-distance curve technique. An optical microscope, on which the AFM was mounted, was used to guide the positioning of tipless cantilevers on top of individual microspheres. We performed a systematic study using several cantilevers with spring constants varying from 0.08 to 2.3 N/m on a population of microspheres with diameters from about 2 to 6 microm. The use of several cantilevers with various spring constants allowed a systematic study of the mechanical properties of the microsphere thin shell at different regimes of force and deformation. Using thin-shell mechanics theory for small deformations, the Young's modulus of the thin wall material was estimated and was shown to exhibit a strong size effect: it increased as the shell became thinner. The Young's modulus of thicker microsphere shells converged to the expected value for the macroscopic bulk material. For high applied forces, the force-deformation profiles showed a reversible and/or irreversible nonlinear behavior including "steps" and "jumps" which were attributed to mechanical instabilities such as buckling events.

Improvement in autologous human fat transplant survival with SVF plus VEGF-PLA nano-sustained release microspheres.

PubMed

Li, Liqun; Pan, Shengsheng; Ni, Binting; Lin, Yuanshao

2014-08-01

Early neovascularization is important for autologous fat transplant survival. SVF cells are ideal seed cells. Both vascular endothelial growth factor (VEGF) and SVF cells can promote neovascularization. However, the half-life (about 50 min) of VEGF is too short to sustain an adequate local concentration. We have investigated whether VEGF-polylactic acid (PLA) nano-sustained release microspheres plus SVF cells can improve neovascularization and survival of transplanted fat tissues. SVF cells were harvested and constructed VEGF-PLA nano-sustained release microspheres in vitro. Human fat tissues was mixed with SVF cells plus VEGF-PLA, SVF cells alone or Dulbecco's modified Eagle's medium as the control. These three mixtures were injected into random sites in 18 nude mice. Two months later, the transplants were weighed and examined histologically; and capillaries were counted to quantify neovascularization. Hematoxylin-eosin (HE) and anti-VEGF stains were applied to reveal cell infiltration. The mean wet weight of fat in the SVF plus VEGF-PLA, SVF alone, and control transplants were 0.18 ± 0.013 g, 0.16 ± 0.015 g, and 0.071 ± 0.12 g, respectively; the differences between groups were statistically significant. More vessels were present in the SVF plus VEGF-PLA transplants than in the other two types. Transplants mixed with SVF cells also had an acceptable density of capillaries. Histological analysis revealed that both the SVF plus VEGF-PLA and SVF alone transplants, but not the control transplants, were composed of adipose tissue, and had less fat necrosis and less fibrosis than control specimens. SVF plus VEGF-PLA transplants had significantly greater capillary density and VEGF expression than the other two transplant groups. Thus transplanted fat tissue survival and quality can be enhanced by the addition of VEGF-PLA nano-sustained release microspheres plus SVF cells. © 2014 International Federation for Cell Biology.

Facile synthesis of blue-emitting carbon dots@mesoporous silica composite spheres

NASA Astrophysics Data System (ADS)

Guo, Ziying; Zhu, Zhenpeng; Zhang, Xinguo; Chen, Yibo

2018-02-01

This paper reported a facile and effective approach towards high-efficient composite luminophores by embedding blue-emitting N-doped carbon dots into spherical SiO2 matrix (CDs@SiO2). Mesoporous silica microspheres (r-CDs@MSN) with strong luminescence were synthesized by removing CTAB templates in CDs@SiO2 using reflux with acetone. The r-CDs@MSN possess a spherical morphology with smooth surface and a diameter of 130 nm, while it exhibits an excitation-independent blue emission peak at 440 nm with an internal quantum yield of 21.5%. BET result shows that the corresponding surface area and adsorption total pore volume are 156.27 m2/g and 0.682 cm3/g, which is suitable for the drugs loading and release. The results indicate that r-CDs@MSN might act as a potential fluorescent drug carrier.

Hydroxyapatite-armored poly(ε-caprolactone) microspheres and hydroxyapatite microcapsules fabricated via a Pickering emulsion route.

PubMed

Fujii, Syuji; Okada, Masahiro; Nishimura, Taiki; Maeda, Hayata; Sugimoto, Tatsuya; Hamasaki, Hiroyuki; Furuzono, Tsutomu; Nakamura, Yoshinobu

2012-05-15

Hydroxyapatite (HAp) nanoparticle-armored poly(ε-caprolactone) (PCL) microspheres were fabricated via a "Pickering-type" emulsion solvent evaporation method in the absence of any molecular surfactants. It was clarified that the interaction between carbonyl/carboxylic acid groups of PCL and the HAp nanoparticles at an oil-water interface played a crucial role in the preparation of the stable Pickering-type emulsions and the HAp nanoparticle-armored microspheres. The HAp nanoparticle-armored PCL microspheres were characterized in terms of size, size distribution, morphology, and chemical compositions using scanning electron microscopy, laser diffraction, energy dispersive X-ray microanalysis, and thermogravimetric analysis. The presence of HAp nanoparticles at the surface of the microspheres was confirmed by scanning electron microscopy and energy dispersive X-ray microanalysis. Pyrolysis of the PCL cores led to the formation of the corresponding HAp hollow microcapsules. Copyright © 2012 Elsevier Inc. All rights reserved.

In situ fabrication of hollow hydroxyapatite microspheres by phosphate solution immersion

NASA Astrophysics Data System (ADS)

Wang, Yingchun; Yao, Aihua; Huang, Wenhai; Wang, Deping; zhou, Jun

2011-07-01

Hollow hydroxyapatite (HAP) microspheres with pores on their surfaces were prepared by converting Li 2O-CaO-B 2O 3 (LCB) glass microspheres in phosphate solution. The structure, phase composition, surface morphology, and porosity of the hollow HAP microspheres were characterized by SEM, SEM-EDS, XRD, FTIR, ICP-AES, and N 2 adsorption-desorption techniques. The formation and conversion mechanism of the hollow HAP microspheres during immersion process were discussed. The as-prepared microspheres consisted of calcium deficient carbonated hydroxyapatite, which is biomimetic. FTIR spectra indicated that the resulting apatite were B-type CO 3HAP, in which carbonate ions occupied the phosphate sites. After 600 °C heating treatment, hollow microspheres were completely composed of calcium deficient hydroxyapatite crystals including CO32-. The pore size distribution of the as-prepared hollow HAP microspheres were mainly the mesopores in the range of 2-40 nm with the pore volume 0.5614 cm 3/g, and the mean pore size 10.5 nm, respectively. The results confirmed that LCB glass were transformed to hydroxyapatite without changing the external shape and dimension of the original glass object and the resulting microspheres possessed good hollow structures. Once immersed in phosphate solution, Ca-P-OH hydrates were in situ formed on the surface of the glass and precipitated in the position occupied by Ca 2+, while the pores were formed in the position occupied by Li + and B 3+. These hollow HAP microspheres with such structures may be used as promising drug delivery devices.

Evaluation of a combined drug-delivery system for proteins assembled with polymeric nanoparticles and porous microspheres; characterization and protein integrity studies.

PubMed

Alcalá-Alcalá, Sergio; Benítez-Cardoza, Claudia G; Lima-Muñoz, Enrique J; Piñón-Segundo, Elizabeth; Quintanar-Guerrero, David

2015-07-15

This work presents an evaluation of the adsorption/infiltration process in relation to the loading of a model protein, α-amylase, into an assembled biodegradable polymeric system, free of organic solvents and made up of poly(D,L-lactide-co-glycolide) acid (PLGA). Systems were assembled in a friendly aqueous medium by adsorbing and infiltrating polymeric nanoparticles into porous microspheres. These assembled systems are able to load therapeutic amounts of the drug through adsorption of the protein onto the large surface area characteristic of polymeric nanoparticles. The subsequent infiltration of nanoparticles adsorbed with the protein into porous microspheres enabled the controlled release of the protein as a function of the amount of infiltrated nanoparticles, since the surface area available on the porous structure is saturated at different levels, thus modifying the protein release rate. Findings were confirmed by both the BET technique (N2 isotherms) and in vitro release studies. During the adsorption process, the pH of the medium plays an important role by creating an environment that favors adsorption between the surfaces of the micro- and nano-structures and the protein. Finally, assays of α-amylase activity using 2-chloro-4-nitrophenyl-α-D-maltotrioside (CNP-G3) as the substrate and the circular dichroism technique confirmed that when this new approach was used no conformational changes were observed in the protein after release. Copyright © 2015 Elsevier B.V. All rights reserved.

BMP2-loaded hollow hydroxyapatite microspheres exhibit enhanced osteoinduction and osteogenicity in large bone defects.

PubMed

Xiong, Long; Zeng, Jianhua; Yao, Aihua; Tu, Qiquan; Li, Jingtang; Yan, Liang; Tang, Zhiming

2015-01-01

The regeneration of large bone defects is an osteoinductive, osteoconductive, and osteogenic process that often requires a bone graft for support. Limitations associated with naturally autogenic or allogenic bone grafts have demonstrated the need for synthetic substitutes. The present study investigates the feasibility of using novel hollow hydroxyapatite microspheres as an osteoconductive matrix and a carrier for controlled local delivery of bone morphogenetic protein 2 (BMP2), a potent osteogenic inducer of bone regeneration. Hollow hydroxyapatite microspheres (100±25 μm) with a core (60±18 μm) and a mesoporous shell (180±42 m(2)/g surface area) were prepared by a glass conversion technique and loaded with recombinant human BMP2 (1 μg/mg). There was a gentle burst release of BMP2 from microspheres into the surrounding phosphate-buffered saline in vitro within the initial 48 hours, and continued at a low rate for over 40 days. In comparison with hollow hydroxyapatite microspheres without BMP2 or soluble BMP2 without a carrier, BMP2-loaded hollow hydroxyapatite microspheres had a significantly enhanced capacity to reconstitute radial bone defects in rabbit, as shown by increased serum alkaline phosphatase; quick and complete new bone formation within 12 weeks; and great biomechanical flexural strength. These results indicate that BMP2-loaded hollow hydroxyapatite microspheres could be a potential new option for bone graft substitutes in bone regeneration.

[Preparation of large-pore silica microspheres using templating method and their applications to protein separation with high performance liquid chromatography].

PubMed

Niu, Mengna; Ma, Hongyan; Hu, Fei; Wang, Shige; Liu, Lu; Chang, Haizhou; Huang, Mingxian

2017-06-08

Large-pore silica microspheres were synthesized by utilizing weak cation exchange polymer beads as templates, N -trimethoxysilylpropyl- N,N,N -trimethylammonium chloride (TMSPTMA) as a structure-directing agent, tetraethoxysilane (TEOS) as a silica precursor, and triethanolamine as a weak base catalyst. The hydrolysis and condensation of the silica precursors occurred inside the templating polymer beads yielded polymer/silica composite microspheres. After the organic polymer templates were removed in the calcination step, large-pore silica microspheres were produced. The effects of different reaction conditions on the morphology, structure and dispersibility of the formed silica microspheres were investigated. It has been shown that when the volume ratio of TMSPTMA, TEOS and triethanolamine was 1:2:2, silica microspheres with pore size range of 50-150 nm and particle size around 2 μm were obtained. The as-prepared silica microspheres were then bonded with chlorodimethyloctadecylsilane (C18), packed into a 50 mm×4.6 mm column, and evaluated for the separations of some common standard proteins and soybean isolation proteins. The results showed that the large-pore silica spheres from this work have potentials for protein separation in HPLC.

Novel synthesis strategy for composite hydrogel of collagen/hydroxyapatite-microsphere originating from conversion of CaCO3 templates.

PubMed

Wei, Qingrong; Lu, Jian; Wang, Qiaoying; Fan, Hongsong; Zhang, Xingdong

2015-03-20

Inspired by coralline-derived hydroxyapatite, we designed a methodological route to synthesize carbonated-hydroxyapatite microspheres from the conversion of CaCO3 spherulite templates within a collagen matrix under mild conditions and thus constructed the composite hydrogel of collagen/hydroxyapatite-microspheres. Fourier transform infrared spectroscopy (FTIR) and x-ray diffraction (XRD) were employed to confirm the successful generation of the carbonated hydroxyapatite phase originating from CaCO3, and the ratios of calcium to phosphate were tracked over time. Variations in the weight portion of the components in the hybrid gels before and after the phase transformation of the CaCO3 templates were identified via thermogravimetric analysis (TGA). Scanning electron microscopy (SEM) shows these composite hydrogels have a unique multiscale microstructure consisting of a collagen nanofibril network and hydroxyapatite microspheres. The relationship between the hydroxyapatite nanocrystals and the collagen fibrils was revealed by transmission electron microscopy (TEM) in detail, and the selected area electron diffraction (SAED) pattern further confirmed the results of the XRD analyses which show the typical low crystallinity of the generated hydroxyapatite. This smart synthesis strategy achieved the simultaneous construction of microscale hydroxyapatite particles and collagen fibrillar hydrogel, and appears to provide a novel route to explore an advanced functional hydrogel materials with promising potentials for applications in bone tissue engineering and reconstruction medicine.

Stabilization of tetanus toxoid encapsulated in PLGA microspheres.

PubMed

Jiang, Wenlei; Schwendeman, Steven P

2008-01-01

Delivery of vaccine antigens from controlled-release poly(lactic/glycolic acid) (PLGA) microspheres is a novel approach to reduce the number of antigen doses required for protection against infection. A major impediment to developing single-shot vaccines is encapsulated antigen instability during months of exposure to physiological conditions. For example, efforts to control neonatal tetanus in developing countries with a single-dose TT vaccine based on PLGA microspheres have been plagued by poor stability of the 150 kDa formaldehyde-detoxified protein antigen, tetanus toxoid (TT), in the polymer. We examined the denatured states of PLGA-encapsulated TT, revealing two primary TT instability mechanisms: (1) protein aggregation mediated by formaldehyde and (2) acid-induced protein unfolding and epitope damage. Further, we systematically identified excipients, which can efficiently inhibit TT aggregation and retain TT antigenicity under simulated deleterious conditions, i.e., elevated temperature and humidity. By employing these novel additives in the PLGA system, we report the slow and continuous release of high doses of TT for one month with retained antigen stability during bioerosion of PLGA.

Coating and release of an anti-inflammatory hormone from PLGA microspheres for tissue engineering.

PubMed

Go, Dewi P; Palmer, Jason A; Gras, Sally L; O'Connor, Andrea J

2012-02-01

Many biomaterials used in tissue engineering cause a foreign body response in vivo, which left untreated can severely reduce the effectiveness of tissue regeneration. In this study, an anti-inflammatory hormone α-melanocyte stimulating hormone (α-MSH) was physically adsorbed to the surface of biodegradable poly (lactic-co-glycolic) acid (PLGA) microspheres to reduce inflammatory responses to this material. The stability and adsorption isotherm of peptide binding were characterized. The peptide secondary structure was not perturbed by the adsorption and subsequent desorption process. The α-MSH payload was released over 72 h and reduced the expression of the inflammatory cytokine, Tumor necrosis factor-α (TNF-α) in lipopolysaccharide activated RAW 264.7 macrophage cells, indicating that the biological activity of α-MSH was preserved. α-MSH coated PLGA microspheres also appeared to reduce the influx of inflammatory cells in a subcutaneous implantation model in rats. This study demonstrates the potential of α-MSH coatings for anti-inflammatory delivery and this approach may be applied to other tissue engineering applications. Copyright © 2011 Wiley Periodicals, Inc.

Investigations Concerning Hydrolysis and Stabilization of Antiradiation Compounds

DTIC Science & Technology

1982-01-01

Stability of Unencapsulated WR 2721 31 V. DISCUSSION 35 A. Microencapsulation 35 1. Microspheres 35 2. Microcapsules 35 B. Hydrolytic Stability of...in 1.5 hours at 370C in buffered solutions of pH 1.0 or 3.0. 3^ The more promising microspheres and microcapsules released the WR 2721 within two...hours at pH 7.5 in buffered solutions. 4) Analytical procedures were developed for: "♦ WR 2721 (directly) in microcapsules using an HPLC

Kefiran-alginate gel microspheres for oral delivery of ciprofloxacin.

PubMed

Blandón, Lina M; Islan, German A; Castro, Guillermo R; Noseda, Miguel D; Thomaz-Soccol, Vanete; Soccol, Carlos R

2016-09-01

Ciprofloxacin is a broad-spectrum antibiotic associated with gastric and intestinal side effects after extended oral administration. Alginate is a biopolymer commonly employed in gel synthesis by ionotropic gelation, but unstable in the presence of biological metal-chelating compounds and/or under dried conditions. Kefiran is a microbial biopolymer able to form gels with the advantage of displaying antimicrobial activity. In the present study, kefiran-alginate gel microspheres were developed to encapsulate ciprofloxacin for antimicrobial controlled release and enhanced bactericidal effect against common pathogens. Scanning electron microscopy (SEM) analysis of the hybrid gel microspheres showed a spherical structure with a smoother surface compared to alginate gel matrices. In vitro release of ciprofloxacin from kefiran-alginate microspheres was less than 3.0% and 5.0% at pH 1.2 (stomach), and 5.0% and 25.0% at pH 7.4 (intestine) in 3 and 21h, respectively. Fourier transform infrared spectroscopy (FTIR) of ciprofloxacin-kefiran showed the displacement of typical bands of ciprofloxacin and kefiran, suggesting a cooperative interaction by hydrogen bridges between both molecules. Additionally, the thermal analysis of ciprofloxacin-kefiran showed a protective effect of the biopolymer against ciprofloxacin degradation at high temperatures. Finally, antimicrobial assays of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhymurium, and Staphylococcus aureus demonstrated the synergic effect between ciprofloxacin and kefiran against the tested microorganisms. Copyright © 2016 Elsevier B.V. All rights reserved.

Material Characterization of Microsphere-Based Scaffolds with Encapsulated Raw Materials

PubMed Central

Sridharan, BanuPriya; Mohan, Neethu; Berkland, Cory J.; Detamore, Michael S.

2016-01-01

“Raw materials,” or materials capable of serving both as building blocks and as signals, which are often but not always natural materials, are taking center stage in biomaterials for contemporary regenerative medicine. In osteochondral tissue engineering, a field leveraging the underlying bone to facilitate cartilage regeneration, common raw materials include chondroitin sulfate (CS) for cartilage and β-tricalcium phosphate (TCP) for bone. Building on our previous work with gradient scaffolds based on microspheres, here we delved deeper into the characterization of individual components. In the current study, the release of CS and TCP from poly(D,L-lactic-co-glycolic acid) (PLGA) microsphere-based scaffolds was evaluated over a time period of 4 weeks. Raw material encapsulated groups were compared to ‘blank’ groups and evaluated for surface topology, molecular weight, and mechanical performance as a function of time. The CS group may have led to increased surface porosity, and the addition of CS improved the mechanical performance of the scaffold. The finding that CS was completely released into the surrounding media by 4 weeks has a significant impact on future in vivo studies, given rapid bioavailability. The addition of TCP seemed to contribute to the rough external appearance of the scaffold. The current study provides an introduction to degradation patterns of homogenous raw material encapsulated scaffolds, providing characterization data to advance the field of microsphere-based scaffolds in tissue engineering. PMID:27040236

[Preparation of citrulline microspheres by spray drying technique for colonic targeting].

PubMed

Bahri, S; Zerrouk, N; Lassoued, M-A; Tsapis, N; Chaumeil, J-C; Sfar, S

2014-03-01

Citrulline is an amino acid that becomes essential in situations of intestinal insufficiency such as short bowel syndrome. It is therefore interesting to provide the patients with dosage forms for routing citrulline to the colon. The aim of this work is to formulate microspheres of citrulline for colonic targeting by the technique of spray drying. Eudragit(®) FS 30D was selected as polymer to encapsulate citrulline using the spray drying technique. Citrulline and Eudragit(®) FS 30D were dissolved in water and ethanol, respectively. The aqueous and the ethanolic solutions were then mixed in 1:2 (v/v) ratio. Microspheres were obtained by nebulizing the citrulline-Eudragit(®) FS 30D solution using a Mini spray dryer equipped with a 0.7mm nozzle. The microspheres have been formulated using citrulline and Eudragit(®) FS 30D. The size distribution of microspheres was determined by light diffraction. The morphology of the microspheres was studied by electron microscopy. Manufacturing yields, encapsulation rate and dissolution profiles were also studied. The microspheres obtained had a spherical shape with a smooth surface and a homogeneous size except for the microspheres containing the highest concentration of polymer (90 %). The formulation showed that the size and morphology of the microspheres are influenced by the polymer concentration. Manufacturing yields were about 51 % but encapsulation rate were always very high (above 90 %). The in vitro dissolution study showed that the use of the Eudragit(®) FS 30D under these conditions is not appropriate to change the dissolution profile of the citrulline. This technique has led to the formulation of microspheres with good physical properties in terms of morphology and size. The compression of the microspheres should help to control citrulline release for colonic targeting. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Shell thickness-dependent microwave absorption of core-shell Fe3O4@C composites.

PubMed

Du, Yunchen; Liu, Wenwen; Qiang, Rong; Wang, Ying; Han, Xijiang; Ma, Jun; Xu, Ping

2014-08-13

Core-shell composites, Fe3O4@C, with 500 nm Fe3O4 microspheres as cores have been successfully prepared through in situ polymerization of phenolic resin on the Fe3O4 surface and subsequent high-temperature carbonization. The thickness of carbon shell, from 20 to 70 nm, can be well controlled by modulating the weight ratio of resorcinol and Fe3O4 microspheres. Carbothermic reduction has not been triggered at present conditions, thus the crystalline phase and magnetic property of Fe3O4 micropsheres can be well preserved during the carbonization process. Although carbon shells display amorphous nature, Raman spectra reveal that the presence of Fe3O4 micropsheres can promote their graphitization degree to a certain extent. Coating Fe3O4 microspheres with carbon shells will not only increase the complex permittivity but also improve characteristic impedance, leading to multiple relaxation processes in these composites, thus the microwave absorption properties of these composites are greatly enhanced. Very interestingly, a critical thickness of carbon shells leads to an unusual dielectric behavior of the core-shell structure, which endows these composites with strong reflection loss, especially in the high frequency range. By considering good chemical homogeneity and microwave absorption, we believe the as-fabricated Fe3O4@C composites can be promising candidates as highly effective microwave absorbers.

Effects of oleic acid surface coating on the properties of nickel ferrite nanoparticles/PLA composites.

PubMed

Yin, Hong; Chow, Gan-Moog

2009-11-01

Nickel ferrite nanoparticles with or without oleic acid surface coating were mixed with poly(D,L-lactide) (PLA) by double emulsion method. If the nanoparticles were prepared without oleic acid coating, they adsorbed on the PLA surface. If the nanoparticles were coated with oleic acid, they could be readily encapsulated within the PLA microspheres. A slight depression in glass transition temperature was found in all composites and it could be related to the interfacial energies between nanoparticles and PLA. Optimum mixed composite was achieved by reducing interfacial energy. However, loading capacity was limited in this composite. Increasing the amount of nickel ferrite nanoparticles was not useful to increase loading capacity. Cytotoxicity of the composite decreased significantly when nickel ferrite nanoparticles were effectively encapsulated in PLA microspheres. (c) 2008 Wiley Periodicals, Inc.

Extended ocular drug delivery systems for the anterior and posterior segments: biomaterial options and applications.

PubMed

Kang-Mieler, Jennifer J; Dosmar, Emily; Liu, Wenqiang; Mieler, William F

2017-05-01

The development of new therapies for treating various eye conditions has led to a demand for extended release delivery systems, which would lessen the need for frequent application while still achieving therapeutic drug levels in the target tissues. Areas covered: Following an overview of the different ocular drug delivery modalities, this article surveys the biomaterials used to develop sustained release drug delivery systems. Microspheres, nanospheres, liposomes, hydrogels, and composite systems are discussed in terms of their primary materials. The advantages and disadvantages of each drug delivery system are discussed for various applications. Recommendations for modifications and strategies for improvements to these basic systems are also discussed. Expert opinion: An ideal sustained release drug delivery system should be able to encapsulate and deliver the necessary drug to the target tissues at a therapeutic level without any detriment to the drug. Drug encapsulation should be as high as possible to minimize loss and unless it is specifically desired, the initial burst of drug release should be kept to a minimum. By modifying various biomaterials, it is possible to achieve sustained drug delivery to both the anterior and posterior segments of the eye.

Designing biopolymer microgels to encapsulate, protect and deliver bioactive components: Physicochemical aspects.

PubMed

McClements, David Julian

2017-02-01

Biopolymer microgels have considerable potential for their ability to encapsulate, protect, and release bioactive components. Biopolymer microgels are small particles (typically 100nm to 1000μm) whose interior consists of a three-dimensional network of cross-linked biopolymer molecules that traps a considerable amount of solvent. This type of particle is also sometimes referred to as a nanogel, hydrogel bead, biopolymer particles, or microsphere. Biopolymer microgels are typically prepared using a two-step process involving particle formation and particle gelation. This article reviews the major constituents and fabrication methods that can be used to prepare microgels, highlighting their advantages and disadvantages. It then provides an overview of the most important characteristics of microgel particles (such as size, shape, structure, composition, and electrical properties), and describes how these parameters can be manipulated to control the physicochemical properties and functional attributes of microgel suspensions (such as appearance, stability, rheology, and release profiles). Finally, recent examples of the utilization of biopolymer microgels to encapsulate, protect, or release bioactive agents, such as pharmaceuticals, nutraceuticals, enzymes, flavors, and probiotics is given. Copyright © 2016 Elsevier B.V. All rights reserved.

Gold nanoparticles coated polystyrene/reduced graphite oxide microspheres with improved dispersibility and electrical conductivity for dopamine detection.

PubMed

Qian, Tao; Yu, Chenfei; Wu, Shishan; Shen, Jian

2013-12-01

Gold nanoparticles coated polystyrene/reduced graphite oxide (AuNPs@PS/RGO) microspheres have been successfully prepared via a facile process, and the decorative gold nanoparticles could prevent the aggregation of RGO by electrostatic repulsive interaction, and lead to high dispersibility of the composite. The prepared composite has a highly increased conductivity of 129Sm(-1) due to the unique electrical properties of citrate reduced gold nanoparticles. Being employed as an electrochemical sensor for detection of dopamine, the modified electrode exhibits remarkable sensitivity (3.44μA/μM) and lower detection limit (5nM), with linear response in a range of 0.05-20μM. Moreover, valid response to dopamine obtained in present work also indicates the prospective performances of AuNPs@PS/RGO microspheres to other biological molecules, such as nucleic acids, proteins and enzymes. Copyright © 2013 Elsevier B.V. All rights reserved.

Tailoring the morphology of raspberry-like carbon black/polystyrene composite microspheres for fabricating superhydrophobic surface

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

Bao, Yubin; Li, Qiuying, E-mail: liqy@ecust.edu.cn; Shanghai Key Laboratory Polymeric Materials

In our previous report, raspberry-like carbon black/polystyrene (CB/PS) composite microsphere was prepared through heterocoagulation process. Based on the previous study, in the present work, the morphology of raspberry-like CB/PS particle is tailored through adjusting the polarity and the concentration ratio of CB/PS colloidal suspension with the purpose to prepare particulate film for the fabrication of superhydrophobic surface. Scanning electron microscope (SEM) confirms the morphology of raspberry-like particle and the coverage of CB. Rough surfaces fabricated by raspberry-like particles with proper morphology are observed by SEM and clear evidence of superhydrophobic surface is shown. The structure of raspberry-like particle is analyzedmore » by atom force microscope. The proposed relationship between the hydrophobicity and the structure of CB aggregates on the surface of PS microsphere is discussed in details.« less

In Vivo Osteogenic Potential of Biomimetic Hydroxyapatite/Collagen Microspheres: Comparison with Injectable Cement Pastes

PubMed Central

Manzanares, Maria-Cristina; Ginebra, Maria-Pau; Franch, Jordi

2015-01-01

The osteogenic capacity of biomimetic calcium deficient hydroxyapatite microspheres with and without collagen obtained by emulsification of a calcium phosphate cement paste has been evaluated in an in vivo model, and compared with an injectable calcium phosphate cement with the same composition. The materials were implanted into a 5 mm defect in the femur condyle of rabbits, and bone formation was assessed after 1 and 3 months. The histological analysis revealed that the cements presented cellular activity only in the margins of the material, whereas each one of the individual microspheres was covered with osteogenic cells. Consequently, bone ingrowth was enhanced by the microspheres, with a tenfold increase compared to the cement, which was associated to the higher accessibility for the cells provided by the macroporous network between the microspheres, and the larger surface area available for osteoconduction. No significant differences were found in terms of bone formation associated with the presence of collagen in the materials, although a more extensive erosion of the collagen-containing microspheres was observed. PMID:26132468

Hierarchical NiO-SiO2 composite hollow microspheres with enhanced adsorption affinity towards Congo red in water.

PubMed

Lei, Chunsheng; Zhu, Xiaofeng; Zhu, Bicheng; Yu, Jiaguo; Ho, Wingkei

2016-03-15

Hollow microspheres and hierarchical porous nanostructured materials with desired morphologies have gained remarkable attention for their potential applications in environmental technology. In this study, NiO-SiO2 hollow microspheres were prepared by co-precipitation with SiO2 and nickel salt as precursors, followed by dipping in alkaline solution and calcination. The samples were characterized by X-ray diffraction, field-emission scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, nitrogen adsorption, and X-ray photoelectron spectroscopy. The synthesized hollow spheres were composed of a SiO2 shell and hierarchical porous NiO nanosheets on the surface. Adsorption experiments suggested that NiO-SiO2 composite particles were powerful adsorbents for removal of Congo red from water, with a maximum adsorption capacity of 204.1 mg/g. The high specific surface areas, hollow structures, and hierarchical porous surfaces of the hollow composite particles are suitable for various applications, including adsorption of pollutants, chemical separation, and water purification. Copyright © 2015 Elsevier Inc. All rights reserved.

[Adsorption of the TiO2 @ yeast composite microspheres for adsorbing Fluorescent Whitening Agent-VBL in fixed bed].

PubMed

Wu, Fei; Zhang, Kai-Qiang; Bai, Bo; Wang, Hong-Lun; Suo, You-Rui

2015-02-01

In this work, the adsorption potential of TiO2@ yeast composite microspheres to remove Fluorescent Whitening Agent-VBL (FWA-VBL) from aqueous solution was investigated using fixed-bed adsorption column. The effects of pH(2.0-8.0), bed height (1-3 cm), inlet concentration (20-80 mg x L(-1)) and feed flow rate (5-11 mL x min(-1)) on the breakthrough characteristics of the adsorption system were determined. The results showed that the highest bed capacity of 223.80 mg x g(-1) was obtained under the condition of pH 2.0, 80 mg x L(-1) inlet dye concentration, 1.0 cm bed height and 5 mL x min(-1) flow rate. The adsorption data were fitted to three well-established fixed-bed adsorption models, namely, BDST model, Thomas model and Yoon-Nelson model. The results fitted well to the three models with coefficients of correlation R2 > 0.980 in different conditions. The TiO2 @ yeast composite microspheres have desired regeneration ability and could be reused for four times.

Scalable and sustainable synthesis of carbon microspheres via a purification-free strategy for sodium-ion capacitors

NASA Astrophysics Data System (ADS)

Wang, Shijie; Wang, Rutao; Zhang, Yabin; Jin, Dongdong; Zhang, Li

2018-03-01

Sodium-based energy storage receives a great deal of interest due to the virtually inexhaustible sodium reserve, while the scalable and sustainable strategies to synthesize carbon-based materials with suitable interlayer spaces and large sodium storage capacities are yet to be fully investigated. Carbon microspheres, with regular geometry, non-graphitic characteristic, and stable nature are promising candidates, yet the synthetic methods are usually complex and energy consuming. In this regard, we report a scalable purification-free strategy to synthesize carbon microspheres directly from 5 species of fresh juice. As-synthesized carbon microspheres exhibit dilated interlayer distance of 0.375 nm and facilitate Na+ uptake and release. For example, such carbon microsphere anodes have a specific capacity of 183.9 mAh g-1 at 50 mA g-1 and exhibit ultra-stability (99.0% capacity retention) after 10000 cycles. Moreover, via facile activation, highly porous carbon microsphere cathodes are fabricated and show much higher energy density at high rate than commercial activated carbon. Coupling the compelling anodes and cathodes above, novel sodium-ion capacitors show the high working potential up to 4.0 V, deliver a maximum energy density of 52.2 Wh kg-1, and exhibit an acceptable capacity retention of 85.7% after 2000 cycles.

Preparation and characterization of monodisperse large-porous silica microspheres as the matrix for protein separation.

PubMed

Xia, Hongjun; Wan, Guangping; Zhao, Junlong; Liu, Jiawei; Bai, Quan

2016-11-04

High performance liquid chromatography (HPLC) is a kind of efficient separation technology and has been used widely in many fields. Micro-sized porous silica microspheres as the most popular matrix have been used for fast separation and analysis in HPLC. In this paper, the monodisperse large-porous silica microspheres with controllable size and structure were successfully synthesized with polymer microspheres as the templates and characterized. First, the poly(glycidyl methacrylate-co-ethyleneglycol dimethacrylate) microspheres (P GMA-EDMA ) were functionalized with tetraethylenepentamine (TEPA) to generate amino groups which act as a catalyst in hydrolysis of tetraethyl orthosilicate (TEOS) to form Si-containing low molecular weight species. Then the low molecular weight species diffused into the functionalized P GMA-EDMA microspheres by induction force of the amino groups to form polymer/silica hybrid microspheres. Finally, the organic polymer templates were removed by calcination, and the large-porous silica microspheres were obtained. The compositions, morphology, size distribution, specific surface area and pore size distribution of the porous silica microspheres were characterized by infrared analyzer, scanning-electron microscopy, dynamic laser scattering, the mercury intrusion method and thermal gravimetric analysis, respectively. The results show that the agglomeration of the hybrid microspheres can be overcome when the templates were functionalized with TEPA as amination reagent, and the yield of 95.7% of the monodisperse large-porous silica microspheres can be achieved with high concentration of polymer templates. The resulting large-porous silica microspheres were modified with octadecyltrichlorosilane (ODS) and the chromatographic evaluation was performed by separating the proteins and the digest of BSA. The baseline separation of seven kinds of protein standards was achieved, and the column delivered a better performance when separating BSA digests comparing with the commercial one currently available. The high column efficiency and good reproducibility present that the large-porous silica microspheres obtained can be used as a matrix for peptide and protein separation. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel hollow Pt-ZnO nanocomposite microspheres with hierarchical structure and enhanced photocatalytic activity and stability

NASA Astrophysics Data System (ADS)

Yu, Changlin; Yang, Kai; Xie, Yu; Fan, Qizhe; Yu, Jimmy C.; Shu, Qing; Wang, Chunying

2013-02-01

Noble metal/semiconductor nanocomposites play an important role in high efficient photocatalysis. Herein, we demonstrate a facile strategy for fabrication of hollow Pt-ZnO nanocomposite microspheres with hierarchical structure under mild solvothermal conditions using Zn (CH3COO)2.2H2O and HPtCl4 as the precursors, and polyethylene glycol-6000 (PEG-6000) and ethylene glycol as the reducing agent and solvent, respectively. The as-synthesized ZnO and Pt-ZnO composite nanocrystals were well characterized by powder X-ray diffraction (XRD), nitrogen-physical adsorption, scanning electron microscopy (SEM), energy dispersive X-ray (EDX), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectra (DRS), and photoluminescence (PL) emission spectroscopy. It was found that Pt content greatly influences the morphology of Pt-ZnO composite nanocrystals. Suitable concentration of HPtCl4 in the reaction solution system can produce well hierarchically hollow Pt-ZnO nanocomposite microspheres, which are composed of an assembly of fine Pt-ZnO nanocrystals. Photocatalytic tests of the Pt-ZnO microspheres for the degradation of the dye acid orange II revealed extremely high photocatalytic activity and stability compared with those of pure ZnO and corresponding Pt deposited ZnO. The remarkable photocatalytic performance of hollow Pt-ZnO microspheres mainly originated from their unique nanostructures and the low recombination rate of the e-/h+ pairs by the platinum nanoparticles embedded in ZnO nanocrystals.Noble metal/semiconductor nanocomposites play an important role in high efficient photocatalysis. Herein, we demonstrate a facile strategy for fabrication of hollow Pt-ZnO nanocomposite microspheres with hierarchical structure under mild solvothermal conditions using Zn (CH3COO)2.2H2O and HPtCl4 as the precursors, and polyethylene glycol-6000 (PEG-6000) and ethylene glycol as the reducing agent and solvent, respectively. The as-synthesized ZnO and Pt-ZnO composite nanocrystals were well characterized by powder X-ray diffraction (XRD), nitrogen-physical adsorption, scanning electron microscopy (SEM), energy dispersive X-ray (EDX), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), UV-vis diffuse reflectance spectra (DRS), and photoluminescence (PL) emission spectroscopy. It was found that Pt content greatly influences the morphology of Pt-ZnO composite nanocrystals. Suitable concentration of HPtCl4 in the reaction solution system can produce well hierarchically hollow Pt-ZnO nanocomposite microspheres, which are composed of an assembly of fine Pt-ZnO nanocrystals. Photocatalytic tests of the Pt-ZnO microspheres for the degradation of the dye acid orange II revealed extremely high photocatalytic activity and stability compared with those of pure ZnO and corresponding Pt deposited ZnO. The remarkable photocatalytic performance of hollow Pt-ZnO microspheres mainly originated from their unique nanostructures and the low recombination rate of the e-/h+ pairs by the platinum nanoparticles embedded in ZnO nanocrystals. Electronic supplementary information (ESI) available: Fig. S1-S3. See DOI: 10.1039/c2nr33595f

Facile Synthesis of Carbon Nanosphere/NiCo2O4 Core-shell Sub-microspheres for High Performance Supercapacitor

PubMed Central

Li, Delong; Gong, Youning; Zhang, Yupeng; Luo, Chengzhi; Li, Weiping; Fu, Qiang; Pan, Chunxu

2015-01-01

This paper introduced a process to prepare the carbon nanosphere (CNS)/NiCo2O4 core-shell sub-microspheres. That is: 1) CNSs were firstly prepared via a simple hydrothermal method; 2) a layer of NiCo2O4 precursor was coated on the CNS surface; 3) finally the composite was annealed at 350 °C for 2 hours in the air, and the CNS/NiCo2O4 core-shell sub-microspheres were obtained. This core-shell sub-microsphere was prepared with a simple, economical and environmental-friendly hydrothermal method, and was suitable for large-scale production, which expects a promising electrode candidate for high performance energy storage applications. Electrochemical experiments revealed that the composite exhibited remarkable electrochemical performances with high capacitance and desirable cycle life at high rates, such as: 1) the maximum specific capacitance was up to 1420 F/g at 1 A/g; 2) about 98.5% of the capacitance retained after 3000 charge-discharge cycles; 3) the capacitance retention was about 72% as the current density increase from 1 A/g to 10 A/g. PMID:26245982

Characterization of protein release from photocrosslinkable hyaluronic acid-polyethylene glycol hydrogel tissue engineering scaffolds.

PubMed

Leach, Jennie B; Schmidt, Christine E

2005-01-01

The goal of this work was to utilize the naturally derived bioactive polymer hyaluronic acid (HA) to create a combination tissue engineering scaffold and protein delivery device. HA is a non-immunogenic, non-adhesive glycosaminoglycan that plays significant roles in several cellular processes, including angiogenesis and the regulation of inflammation. In previous work, we created photopolymerizable glycidyl methacrylate-hyaluronic acid (GMHA) hydrogels that had controlled degradation rates, were cytocompatible, and were able to be modified with peptide moieties. In the present studies, we characterized the release of a model protein, bovine serum albumin (BSA), from GMHA and GMHA-polyethylene glycol (PEG) hydrogels. Although BSA could be released rapidly (> 60% within 6 h) from 1% GMHA hydrogels, we found that increasing either the GMHA or the PEG concentrations could lengthen the duration of protein delivery. Preliminary size exclusion chromatography studies indicated that the released BSA was almost entirely in its native monomeric form. Lastly, protein release was extended to several weeks by suspending BSA-poly(lactic-co-glycolic acid) microspheres within the hydrogel bulk. These initial studies indicate that the naturally derived biopolymer HA can be employed to design novel photopolymerizable composites that are suitable for delivering stable proteins from scaffolding in tissue engineering applications.

The application of novel nano-thermal and imaging techniques for monitoring drug microstructure and distribution within PLGA microspheres.

PubMed

Yang, Fan; Chen, De; Guo, Zhe-Fei; Zhang, Yong-Ming; Liu, Yi; Askin, Sean; Craig, Duncan Q M; Zhao, Min

2017-04-30

Poly (d,l-lactic-co-glycolic) acid (PLGA) based microspheres have been extensively used as controlled drug release systems. However, the burst effect has been a persistent issue associated with such systems, especially for those prepared by the double emulsion technique. An effective approach to preventing the burst effect and achieving a more ideal drug release profile is to improve the drug distribution within the polymeric matrix. Therefore, it is of great importance to establish a rapid and robust tool for screening and optimizing the drug distribution during pre-formulation. Transition Temperature Microscopy (TTM), a novel nano-thermal and imaging technique, is an extension of nano-thermal analysis (nano-TA) whereby a transition temperature is detected at a localized region of a sample and then designated a color based on a particular temperature/color palette, finally resulting in a coded map based on transition temperatures detected by carrying out a series of nanoTA measurements across the surface of the sample. In this study, we investigate the feasibility of applying the aforementioned technique combined with other thermal, imaging and structural techniques for monitoring the drug microstructure and spatial distribution within bovine serum albumin (BSA) loaded and nimodipine loaded PLGA microspheres, with a view to better predicting the in vitro drug release performance. Copyright © 2017 Elsevier B.V. All rights reserved.

An investigation into the mechanisms of drug release from taste-masking fatty acid microspheres.

PubMed

Qi, Sheng; Deutsch, David; Craig, Duncan Q M

2008-09-01

Fatty acid microspheres based on stearic and palmitic acids are known to form effective taste masking systems, although the mechanisms by which the drug is preferentially released in the lower gastrointestinal tract are not known. The objective of the present study was to identify the mechanisms involved, with a particular view to clarify the role of acid soap formation in the dissolution process. Microspheres were prepared by a spray chilling process. Using benzoic acid as a model drug and an alkaline dissolution medium, a faster drug release was observed in the mixed fatty acid formulation (50:50 stearic:palmitic acid (w/w)) compared to the single fatty acid component systems. Thermal and powder X-ray diffraction studies indicated a greater degree of acid soap formation for the mixed formulation in alkaline media compared to the single fatty acid systems. Particle size and porosity studies indicated a modest reduction in size for the mixed systems and an increase in porosity on immersion in the dissolution medium. It is proposed that the mixed fatty acid system form a mixed crystal system which in turn facilitates interaction with the dissolution medium, thereby leading to a greater propensity for acid soap formation which in turn forms a permeable liquid crystalline phase through which the drug may diffuse. The role of dissolution of palmitic acid into the dissolution medium is also discussed as a secondary mechanism.

Micro-Spherical Sulfur/Graphene Oxide Composite via Spray Drying for High Performance Lithium Sulfur Batteries.

PubMed

Tian, Yuan; Sun, Zhenghao; Zhang, Yongguang; Wang, Xin; Bakenov, Zhumabay; Yin, Fuxing

2018-01-18

An efficient, industry-accepted spray drying method was used to synthesize micro-spherical sulfur/graphene oxide (S/GO) composites as cathode materials within lithium sulfur batteries. The as-designed wrapping of the sulfur-nanoparticles, with wrinkled GO composites, was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The unique morphological design of this material enabled superior discharge capacity and cycling performance, demonstrating a high initial discharge capacity of 1400 mAh g -1 at 0.1 C. The discharge capacity remained at 828 mAh g -1 after 150 cycles. The superior electrochemical performance indicates that the S/GO composite improves electrical conductivity and alleviates the shuttle effect. This study represents the first time such a facile spray drying method has been adopted for lithium sulfur batteries and used in the fabrication of S/GO composites.

Micro-Spherical Sulfur/Graphene Oxide Composite via Spray Drying for High Performance Lithium Sulfur Batteries

PubMed Central

Tian, Yuan; Sun, Zhenghao; Zhang, Yongguang; Yin, Fuxing

2018-01-01

An efficient, industry-accepted spray drying method was used to synthesize micro-spherical sulfur/graphene oxide (S/GO) composites as cathode materials within lithium sulfur batteries. The as-designed wrapping of the sulfur-nanoparticles, with wrinkled GO composites, was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The unique morphological design of this material enabled superior discharge capacity and cycling performance, demonstrating a high initial discharge capacity of 1400 mAh g−1 at 0.1 C. The discharge capacity remained at 828 mAh g−1 after 150 cycles. The superior electrochemical performance indicates that the S/GO composite improves electrical conductivity and alleviates the shuttle effect. This study represents the first time such a facile spray drying method has been adopted for lithium sulfur batteries and used in the fabrication of S/GO composites. PMID:29346303

Sustained delivery of biomolecules from gelatin carriers for applications in bone regeneration.

PubMed

Song, Jiankang; Leeuwenburgh, Sander Cg

2014-08-01

Local delivery of therapeutic biomolecules to stimulate bone regeneration has matured considerably during the past decades, but control over the release of these biomolecules still remains a major challenge. To this end, suitable carriers that allow for tunable spatial and temporal delivery of biomolecules need to be developed. Gelatin is one of the most widely used natural polymers for the controlled and sustained delivery of biomolecules because of its biodegradability, biocompatibility, biosafety and cost-effectiveness. The current study reviews the applications of gelatin as carriers in form of bulk hydrogels, microspheres, nanospheres, colloidal gels and composites for the programmed delivery of commonly used biomolecules for applications in bone regeneration with a specific focus on the relationship between carrier properties and delivery characteristics.

BMP2-loaded hollow hydroxyapatite microspheres exhibit enhanced osteoinduction and osteogenicity in large bone defects

PubMed Central

Xiong, Long; Zeng, Jianhua; Yao, Aihua; Tu, Qiquan; Li, Jingtang; Yan, Liang; Tang, Zhiming

2015-01-01

The regeneration of large bone defects is an osteoinductive, osteoconductive, and osteogenic process that often requires a bone graft for support. Limitations associated with naturally autogenic or allogenic bone grafts have demonstrated the need for synthetic substitutes. The present study investigates the feasibility of using novel hollow hydroxyapatite microspheres as an osteoconductive matrix and a carrier for controlled local delivery of bone morphogenetic protein 2 (BMP2), a potent osteogenic inducer of bone regeneration. Hollow hydroxyapatite microspheres (100±25 μm) with a core (60±18 μm) and a mesoporous shell (180±42 m2/g surface area) were prepared by a glass conversion technique and loaded with recombinant human BMP2 (1 μg/mg). There was a gentle burst release of BMP2 from microspheres into the surrounding phosphate-buffered saline in vitro within the initial 48 hours, and continued at a low rate for over 40 days. In comparison with hollow hydroxyapatite microspheres without BMP2 or soluble BMP2 without a carrier, BMP2-loaded hollow hydroxyapatite microspheres had a significantly enhanced capacity to reconstitute radial bone defects in rabbit, as shown by increased serum alkaline phosphatase; quick and complete new bone formation within 12 weeks; and great biomechanical flexural strength. These results indicate that BMP2-loaded hollow hydroxyapatite microspheres could be a potential new option for bone graft substitutes in bone regeneration. PMID:25609957

Evaluation of zinc-doped mesoporous hydroxyapatite microspheres for the construction of a novel biomimetic scaffold optimized for bone augmentation

PubMed Central

Yu, Weilin; Sun, Tuan-Wei; Qi, Chao; Ding, Zhenyu; Zhao, Huakun; Zhao, Shichang; Shi, Zhongmin; Zhu, Ying-Jie; Chen, Daoyun; He, Yaohua

2017-01-01

Biomaterials with high osteogenic activity are desirable for sufficient healing of bone defects resulting from trauma, tumor, infection, and congenital abnormalities. Synthetic materials mimicking the structure and composition of human trabecular bone are of considerable potential in bone augmentation. In the present study, a zinc (Zn)-doped mesoporous hydroxyapatite microspheres (Zn-MHMs)/collagen scaffold (Zn-MHMs/Coll) was developed through a lyophilization fabrication process and designed to mimic the trabecular bone. The Zn-MHMs were synthesized through a microwave-hydrothermal method by using creatine phosphate as an organic phosphorus source. Zn-MHMs that consist of hydroxyapatite nanosheets showed relatively uniform spherical morphology, mesoporous hollow structure, high specific surface area, and homogeneous Zn distribution. They were additionally investigated as a drug nanocarrier, which was efficient in drug delivery and presented a pH-responsive drug release behavior. Furthermore, they were incorporated into the collagen matrix to construct a biomimetic scaffold optimized for bone tissue regeneration. The Zn-MHMs/Coll scaffolds showed an interconnected pore structure in the range of 100–300 μm and a sustained release of Zn ions. More importantly, the Zn-MHMs/Coll scaffolds could enhance the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells. Finally, the bone defect repair results of critical-sized femoral condyle defect rat model demonstrated that the Zn-MHMs/Coll scaffolds could enhance bone regeneration compared with the Coll or MHMs/Coll scaffolds. The results suggest that the biomimetic Zn-MHMs/Coll scaffolds may be of enormous potential in bone repair and regeneration. PMID:28392688

Evaluation of zinc-doped mesoporous hydroxyapatite microspheres for the construction of a novel biomimetic scaffold optimized for bone augmentation.

PubMed

Yu, Weilin; Sun, Tuan-Wei; Qi, Chao; Ding, Zhenyu; Zhao, Huakun; Zhao, Shichang; Shi, Zhongmin; Zhu, Ying-Jie; Chen, Daoyun; He, Yaohua

2017-01-01

Biomaterials with high osteogenic activity are desirable for sufficient healing of bone defects resulting from trauma, tumor, infection, and congenital abnormalities. Synthetic materials mimicking the structure and composition of human trabecular bone are of considerable potential in bone augmentation. In the present study, a zinc (Zn)-doped mesoporous hydroxyapatite microspheres (Zn-MHMs)/collagen scaffold (Zn-MHMs/Coll) was developed through a lyophilization fabrication process and designed to mimic the trabecular bone. The Zn-MHMs were synthesized through a microwave-hydrothermal method by using creatine phosphate as an organic phosphorus source. Zn-MHMs that consist of hydroxyapatite nanosheets showed relatively uniform spherical morphology, mesoporous hollow structure, high specific surface area, and homogeneous Zn distribution. They were additionally investigated as a drug nanocarrier, which was efficient in drug delivery and presented a pH-responsive drug release behavior. Furthermore, they were incorporated into the collagen matrix to construct a biomimetic scaffold optimized for bone tissue regeneration. The Zn-MHMs/Coll scaffolds showed an interconnected pore structure in the range of 100-300 μm and a sustained release of Zn ions. More importantly, the Zn-MHMs/Coll scaffolds could enhance the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells. Finally, the bone defect repair results of critical-sized femoral condyle defect rat model demonstrated that the Zn-MHMs/Coll scaffolds could enhance bone regeneration compared with the Coll or MHMs/Coll scaffolds. The results suggest that the biomimetic Zn-MHMs/Coll scaffolds may be of enormous potential in bone repair and regeneration.

One-pot synthesis of hierarchical Cu{sub 2}O/Cu hollow microspheres with enhanced visible-light photocatalytic activity

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

Hong, Tianjie; Tao, Feifei, E-mail: feifeitao@usx.edu.cn; Lin, Jiudong

2015-08-15

The hierarchical Cu{sub 2}O/Cu hollow microspheres have been fabricated by the one-pot solvothermal redox method, which is one-step approach without any surfactant and template. By using the HRTEM, XRD, XPS and UV–vis spectroscopy, the as-prepared product is composed of Cu{sub 2}O and Cu with energy band gap of 1.72 eV. Based on the time-dependent experiments, the content of Cu{sub 2}O and Cu compositions can be effectively controlled by adjusting the reaction time and a possible mechanism is proposed. In addition, using various dye molecules to stimulate pollutants, the hierarchical Cu{sub 2}O/Cu hollow microspheres reacted for 8 h exhibit excellent visible-lightmore » photocatalytic activities, which is much higher than those of the Cu{sub 2}O/Cu catalysts formed at the shorter reaction time, commercial Cu{sub 2}O powder and the mixture of alone Cu{sub 2}O and Cu. This enhanced photocatalytic performance makes these hierarchical Cu{sub 2}O/Cu hollow microspheres a kind of efficient visible-light photocatalyst in removing some organic compounds in wastewater. - Graphical abstract: The hierarchical Cu{sub 2}O/Cu hollow microspheres with adjustable components have been synthesized by one-step solvothermal redox approach. The special structures and composition lead to the excellent visible-light photocatalytic activity. - Highlights: • The hierarchical Cu{sub 2}O/Cu hollow microspheres are fabricated by one-step approach. • The content of Cu{sub 2}O and Cu can be controlled by adjusting the reaction time. • The material exhibits a better visible-light photocatalytic activity and stability. • Degradation kinetics of MO by Cu{sub 2}O/Cu fits the pseudo first-order model.« less

Adsorption and covalent binding of fibrinogen as a method for probing the chemical composition of poly(styrene/α-tert-butoxy-ω-vinylbenzyl-polyglycidol) microsphere surfaces.

PubMed

Gosecka, Monika; Chehimi, Mohamed M; Basinska, Teresa; Slomkowski, Stanislaw; Makowski, Tomasz

2017-12-01

We investigated the distribution of polyglycidol and polystyrene on the surface of poly(styrene/α-tert-butoxy-ω-vinylbenzyl-polyglycidol) microspheres (random distribution or segregated into hydrophilic and hydrophobic patches), using fibrinogen (Fb) as a macromolecular probe. The fibrinogen was adsorbed or covalently attached to the surface of the poly(styrene-co-α-tert-butoxy-ω-vinylbenzyl-polyglycidol) (P(S/PGLy)) microspheres. The P(S/PGLy) particles were prepared by emulsion copolymerization of styrene and α-tert-butoxy-ω-vinylbenzyl-polyglycidol (PGLy) macromonomer initiated with potassium persulfate. The polymerizations yielded P(S/PGLy) particles with various surface fractions of polyglycidol, depending on the amount of added macromonomer and the addition process. In some syntheses, the entire macromonomer amount was added once at the beginning of the polymerization, while in others, the macromonomer was added gradually after the formation of particle seeds from pure polystyrene. XPS studies revealed that the fraction of polyglycidol in the interfacial layer of the microspheres was larger when the entire amount of macromonomer was added at the beginning of the polymerization than when it was added after formation of the polystyrene seeds. Studies of fibrinogen adsorption provided the first evidence of segregation of the hydrophobic (polystyrene) and hydrophilic (polyglycidol) components at the surface of the composite P(S/PGLy) microspheres into patches. The hydrophobic patches are composed mainly of polystyrene. However, they also contain a small amount of polyglycidol chains, making the adsorption of fibrinogen weaker than the adsorption onto the pure polystyrene. Studies of covalent immobilization of fibrinogen on the microspheres via 1,3,5-trichlorotriazine confirmed these findings. Copyright © 2017 Elsevier B.V. All rights reserved.

Fabrication of hierarchical porous ZnO-Al2O3 microspheres with enhanced adsorption performance

NASA Astrophysics Data System (ADS)

Lei, Chunsheng; Pi, Meng; Xu, Difa; Jiang, Chuanjia; Cheng, Bei

2017-12-01

Hierarchical porous ZnO-Al2O3 microspheres were fabricated through a simple hydrothermal route. The as-prepared hierarchical porous ZnO-Al2O3 composites were utilized as adsorbents to remove organic dye Congo red (CR) from water. The ZnO-Al2O3 composites had morphology of microspheres with diameters in the range of 12-16 μm, which were assembled by nanosheets with thicknesses of approximately 60 nm. The adsorption kinetics of CR onto the ZnO-Al2O3 composites was properly fitted by the pseudo-second-order kinetic model. The equilibrium adsorption data were perfectly described by the Langmuir isotherm and had a maximum adsorption capacity that reached 397 mg/g, which was significantly higher than the value of the pure alumina (Al2O3) and zinc oxide (ZnO) samples. The superior CR removal efficiency of the ZnO-Al2O3 composites was attributed to its well-developed hierarchical porous structures and larger specific surface area (201 m2/g), which were conducive to the diffusion and adsorption of CR molecules. Moreover, the regeneration study reveals that the ZnO-Al2O3 composites have suitable stability and reusability. The results also indicate that the as-prepared sample can act as a highly effective adsorbent in anionic dye removal from wastewater.

Development and characterisation of polymeric microparticle of poly(d,l-lactic acid) loaded with holmium acetylacetonate.

PubMed

de Azevedo, Mariangela de Burgos M; de Melo, Vitor H S; Soares, Carlos Roberto J; Miyamoto, Douglas M; Katayama, Ricardo A; Squair, Peterson L; Barros, Caio H N; Tasic, Ljubica

2018-06-14

Biodegradable polymers containing radioactive isotopes such as Holmium 166 ( 166 Ho) have potential applications as beta particle emitters in tumour tissues. It is also a gamma ray emitter, allowing nuclear imaging of any tissue to be acquired. It is frequently used in the form of complexes such as holmium acetylacetonate (HoAcAc), which may cause damages in tissues next to the targets cancer cells, as it is difficult to control its linkage or healthy tissues radiotherapy effects. Poly(d,l-lactic acid), PDLLA, was used to encapsulate holmium acetylacetonate (HoAcAc) using an emulsion solvent extraction/evaporation technique. Microspheres with sizes between 20-53 µm were extensively characterised. HoAcAc release from the microspheres was assessed through studies using Inductively Coupled Plasma - Optical Emission Spectroscopy, and the microspheres showed no holmium leakage after a period of 10 half-lives and following gamma irradiation. Thus, HoAcAc loaded microspheres are here presented as a potential system for brachytherapy and imaging purposes.

Trowelable ablative coating composition and method of use

NASA Technical Reports Server (NTRS)

Headrick, Stephen E. (Inventor); Hill, Roger L. (Inventor)

1989-01-01

A trowelable ablative coating composition is disclosed. The composition comprises an epoxy resin, an amide curing agent, glass microspheres and ground cork. A method for protecting a substrate is also disclosed. The method comprises applying the trowelable ablative coating discussed above to a substrate and curing the coating composition.

Trowelable ablative coating composition and method of use

NASA Technical Reports Server (NTRS)

Headrick, Stephen E. (Inventor); Hill, Roger L. (Inventor)

1988-01-01

A trowelable ablative coating composition is disclosed. The composition comprises an epoxy resin, an amide curing agent, glass microspheres and ground cork. A method for protecting a substrate is also disclosed. The method comprises applying the trowelable ablative coating discussed above to a substrate and curing the coating composition.

Raloxifene microsphere-embedded collagen/chitosan/β-tricalcium phosphate scaffold for effective bone tissue engineering.

PubMed

Zhang, Ming-Lei; Cheng, Ji; Xiao, Ye-Chen; Yin, Ruo-Feng; Feng, Xu

2017-02-25

Engineering novel scaffolds that can mimic the functional extracellular matrix (ECM) would be a great achievement in bone tissue engineering. This paper reports the fabrication of novel collagen/chitosan/β-tricalcium phosphate (CCTP) based tissue engineering scaffold. In order to improve the regeneration ability of scaffold, we have embedded raloxifene (RLX)-loaded PLGA microsphere in the CCTP scaffold. The average pore of scaffold was in the range of 150-200μm with ideal mechanical strength and swelling/degradation characteristics. The release rate of RLX from the microsphere (MS) embedded scaffold was gradual and controlled. Also a significantly enhanced cell proliferation was observed in RLX-MS exposed cell group suggesting that microsphere/scaffold could be an ideal biomaterial for bone tissue engineering. Specifically, RLX-MS showed a significantly higher Alizarin red staining indicating the higher mineralization capacity of this group. Furthermore, a high alkaline phosphatase (ALP) activity for RLX-MS exposed group after 15days incubation indicates the bone regeneration capacity of MC3T3-E1 cells. Overall, present study showed that RLX-loaded microsphere embedded scaffold has the promising potential for bone tissue engineering applications. Copyright © 2016. Published by Elsevier B.V.

Calcium phosphate-phosphorylated adenosine hybrid microspheres for anti-osteosarcoma drug delivery and osteogenic differentiation.

PubMed

Zhou, Zi-Fei; Sun, Tuan-Wei; Chen, Feng; Zuo, Dong-Qing; Wang, Hong-Sheng; Hua, Ying-Qi; Cai, Zheng-Dong; Tan, Jun

2017-03-01

Biocompatibility, biodegradability and bioactivity are significantly important in practical applications of various biomaterials for bone tissue engineering. Herein, we develop a functional inorganic-organic hybrid system of calcium phosphate-phosphorylated adenosine (CPPA). Both calcium phosphate and phosphorylated adenosine molecules in CPPA are fundamental components in mammalians and play important roles in biological metabolism. In this work, we report our three leading research qualities: (1) CPPA hybrid microspheres with hollow and porous structure are synthesized by a facile one-step microwave-assisted solvothermal method; (2) CPPA hybrid microspheres show high doxorubicin loading capacity and pH-responsive drug release properties, and demonstrate positive therapeutic effects on six osteosarcoma cell lines in vitro and a mouse model of 143B osteosarcoma subcutaneous tumor in vivo; (3) CPPA hybrid microspheres are favorable to promote osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) by activating the AMPK pathway, with satisfactory evidences from cellular alkaline phosphatase staining, alizarin red staining, real time PCR and western analysis. The as-prepared CPPA hybrid microspheres are promising in anti-osteosarcoma and bone regeneration, which simultaneously display excellent properties on drug delivery and osteogenic differentiation of hBMSCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Local therapeutic efficacy with reduced systemic side effects by rapamycin-loaded subcapsular microspheres.

PubMed

Falke, Lucas L; van Vuuren, Stefan H; Kazazi-Hyseni, Filis; Ramazani, Farshad; Nguyen, Tri Q; Veldhuis, Gert J; Maarseveen, Erik M; Zandstra, Jurjen; Zuidema, Johan; Duque, Luisa F; Steendam, Rob; Popa, Eliane R; Kok, Robbert Jan; Goldschmeding, Roel

2015-02-01

Kidney injury triggers fibrosis, the final common pathway of chronic kidney disease (CKD). The increase of CKD prevalence worldwide urgently calls for new therapies. Available systemic treatment such as rapamycin are associated with serious side effects. To study the potential of local antifibrotic therapy, we administered rapamycin-loaded microspheres under the kidney capsule of ureter-obstructed rats and assessed the local antifibrotic effects and systemic side effects of rapamycin. After 7 days, microsphere depots were easily identifiable under the kidney capsule. Both systemic and local rapamycin treatment reduced intrarenal mTOR activity, myofibroblast accumulation, expression of fibrotic genes, and T-lymphocyte infiltration. Upon local treatment, inhibition of mTOR activity and reduction of myofibroblast accumulation were limited to the immediate vicinity of the subcapsular pocket, while reduction of T-cell infiltration was widespread. In contrast to systemically administered rapamycin, local treatment did not induce off target effects such as weight loss. Thus subcapsular delivery of rapamycin-loaded microspheres successfully inhibited local fibrotic response in UUO with less systemic effects. Therapeutic effect of released rapamycin was most prominent in close vicinity to the implanted microspheres. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fabrication, characterization, and in vitro evaluation of poly(lactic acid glycolic acid)/nano-hydroxyapatite composite microsphere-based scaffolds for bone tissue engineering in rotating bioreactors.

PubMed

Lv, Qing; Nair, Lakshmi; Laurencin, Cato T

2009-12-01

Dynamic flow culture bioreactor systems have been shown to enhance in vitro bone tissue formation by facilitating mass transfer and providing mechanical stimulation. Our laboratory has developed a biodegradable poly (lactic acid glycolic acid) (PLAGA) mixed scaffold consisting of lighter-than-water (LTW) and heavier-than-water (HTW) microspheres as potential matrices for engineering tissue using a high aspect ratio vessel (HARV) rotating bioreactor system. We have demonstrated enhanced osteoblast differentiation and mineralization on PLAGA scaffolds in the HARV rotating bioreactor system when compared with static culture. The objective of the present study is to improve the mechanical properties and bioactivity of polymeric scaffolds by designing LTW polymer/ceramic composite scaffolds suitable for dynamic culture using a HARV bioreactor. We employed a microsphere sintering method to fabricate three-dimensional PLAGA/nano-hydroxyapatite (n-HA) mixed scaffolds composed of LTW and HTW composite microspheres. The mechanical properties, pore size and porosity of the composite scaffolds were controlled by varying parameters, such as sintering temperature, sintering time, and PLAGA/n-HA ratio. The PLAGA/n-HA (4:1) scaffold sintered at 90 degrees C for 3 h demonstrated the highest mechanical properties and an appropriate pore structure for bone tissue engineering applications. Furthermore, evaluation human mesenchymal stem cells (HMSCs) response to PLAGA/n-HA scaffolds was performed. HMSCs on PLAGA/n-HA scaffolds demonstrated enhanced proliferation, differentiation, and mineralization when compared with those on PLAGA scaffolds. Therefore, PLAGA/n-HA mixed scaffolds are promising candidates for HARV bioreactor-based bone tissue engineering applications. Copyright 2008 Wiley Periodicals, Inc.

Synthesis of plastic scintillation microspheres: Evaluation of scintillators

NASA Astrophysics Data System (ADS)

Santiago, L. M.; Bagán, H.; Tarancón, A.; Garcia, J. F.

2013-01-01

The use of plastic scintillation microspheres (PSm) appear to be an alternative to liquid scintillation for the quantification of alpha and beta emitters because it does not generate mixed wastes after the measurement (organic and radioactive). In addition to routine radionuclide determinations, PSm can be used for further applications, e.g. for usage in a continuous monitoring equipment, for measurements of samples with a high salt concentration and for an extractive scintillation support which permits the separation, pre-concentration and measurement of the radionuclides without additional steps of elution and sample preparation. However, only a few manufacturers provide PSm, and the low number of regular suppliers reduces its availability and restricts the compositions and sizes available. In this article, a synthesis method based on the extraction/evaporation methodology has been developed and successfully used for the synthesis of plastic scintillation microspheres. Seven different compositions of plastic scintillation microspheres have been synthesised; PSm1 with polystyrene, PSm2 with 2,5-Diphenyloxazol(PPO), PSm3 with p-terphenyl (pT), PSm4 with PPO and 1,4-bis(5-phenyloxazol-2-yl) (POPOP), PSm5 pT and (1,4-bis [2-methylstyryl] benzene) (Bis-MSB), PSm6 with PPO, POPOP and naphthalene and PSm7 with pT, Bis-MSB and naphthalene. The synthesised plastic scintillation microspheres have been characterised in terms of their morphology, detection capabilities and alpha/beta separation capacity. The microspheres had a median diameter of approximately 130 μm. Maximum detection efficiency values were obtained for the PSm4 composition as follows 1.18% for 3H, 51.2% for 14C, 180.6% for 90Sr/90Y and 76.7% for 241Am. Values of the SQP(E) parameter were approximately 790 for PSm4 and PSm5. These values show that the synthesised PSm exhibit good scintillation properties and that the spectra are at channel numbers higher than in commercial PSm. Finally, the addition of naphthalene modifies the shape of the pulses produced by alpha and beta particles leading to better alpha/beta separation.

Control of silk microsphere formation using polyethylene glycol (PEG).

PubMed

Wu, Jianbing; Zheng, Zhaozhu; Li, Gang; Kaplan, David L; Wang, Xiaoqin

2016-07-15

A one step, rapid method to prepare silk microspheres was developed, with particle size controlled by the addition of polyethylene glycol (PEG). PEG molecular weight (4.0K-20.0KDa) and concentration (20-50wt%), as well as silk concentration (5-20wt%), were key factors that determined particle sizes varying in a range of 1-100μm. Addition of methanol to the PEG-silk combinations increased the content of crystalline β-sheet in the silk microspheres. To track the distribution and degradation of silk microspheres in vivo, 3-mercaptopropionic acid (MPA)-coated CdTe quantum dots (QDs) were physically entrapped in the silk microspheres. QDs tightly bound to the β-sheet domains of silk via hydrophobic interactions, with over 96% of the loaded QDs remaining in the silk microspheres after exhaustive extraction. The fluorescence of QDs-incorporated silk microspheres less stable in cell culture medium than in phosphate buffer solution (PBS) and water. After subcutaneous injection in mice, microspheres prepared from 20% silk (approx. 30μm diameter particles) still fluoresced at 24h, while those prepared from 8% silk (approx. 4μm diameter particles) and free QDs were not detectable, reflecting the QDs quenching and particle size effect on microsphere clearance in vivo. The larger microspheres were more resistant to cell internalization and degradation. Since PEG is an FDA-approved polymer, and silk is FDA approved for some medical devices, the methods developed in the present study will be useful in a variety of biomedical applications where simple, rapid and scalable preparation of silk microspheres is required. The work is of significance to the biomaterial and controlled release society because it provides a new option for fabricating silk microspheres in one simple step of mixing silk and polyethylene glycol (PEG), with the size and properties of microspheres controllable by PEG molecular weight as well as PEG and silk concentrations. Although fabrication of silk microspheres have been reported previously using spray-drying, liposome-templating, polyvinyl alcohol (PVA) emulsification, etc., applications were hindered due to harsh conditions (temperature, solvents, etc.) and complicated procedures used as well as low yield and less controllable particle size (usually <10μm). Since PEG is an FDA-approved polymer, and silk is FDA approved for some medical devices, the methods developed in the present study will be useful in a variety of biomedical applications where simple, rapid and scalable preparation of silk microspheres is required. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Synthesis of novel quaternary silica hybrid bioactive microspheres.

PubMed

Angelopoulou, A; Efthimiadou, E Κ; Kordas, G

2018-01-01

To survey the preparation of novel hybrid microspheres of quaternary silicate glassy composition (SiO 2 P 2 O 5 CaONa 2 O) and the prospect of using them as an osteogenic system with enhanced bioactive properties for the development of hydroxyapatite. In line with our previous synthetic procedure a two-step process was followed, wherein polystyrene (PS) microspheres were prepared by the emulsifier free-emulsion polymerization method and constituted the core for the sol-gel coating of the silicate inorganic shell. The development of the hybrid microspheres was based on silane and phosphate precursors and was assesses at different ratio of ethanol/water (of 9/1, 4/1, and 2/1, in mL) and at varied ammonia concentration of 4.8-1.0 mL. The hybrid microspheres had an average size ranged between 350 and 550 nm according to SEM, depending on the ethanol/water solution rate and ammonia content. The final microspheres probably exhibited a porous-like structure through the formation of diffused voids along with the low carbon content of the EDX analysis, which could be regulated by the catalyst content. The hybrid microspheres exhibited effective in vitro bioactivity assessed in simulated body fluids (SBF). Quaternary hybrid silica microspheres were effectively synthesized. The bioassay evaluation of the final microspheres revealed the rapid in vitro formation of a bone-like apatite layer. The results verify the bioactivity of the microspheres and promote further research of their suitability on regenerative treatment of bone abnormalities. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 112-120, 2018. © 2016 Wiley Periodicals, Inc.

Bioacceptable and calcification-resistant membranes and interfaces for implantable sensors and devices

NASA Astrophysics Data System (ADS)

Galeska, Izabela Ewa

The rational design and characterization of biocompatible, semipermeable and calcification resistant materials to serve as an outer membrane for implantable glucose biosensors, was the primary focus of this research. Multilayered films of polyanions (i.e. Nafion(TM), a perfluorinated ionomer, and Humic Acids (HAs), naturally occurring biopolymers), fabricated by layer-by-layer self-assembly with oppositely charged ferric ions were investigated as potential membranes. Spectroscopic ellipsometry and quartz crystal microbalance studies point towards a stepwise film growth, with growth rates of 47 and 24.3 nm per layer (for Nafion and HAs respectively) that can be altered depending on the pH and ionic strength of the polyanion solution. Nafion/Fe3+ assembled films exhibited an order of magnitude lower calcification as compared to dip-coated Nafion films and did not require annealing to impart insolubility. Similarly the HAs/Fe3+ films were also devoid of calcification, even after four-week immersion in DMEM cell culture media. Significantly, in vivo studies on the HAs/Fe3 films point to their biocompatibility as demonstrated by mild tissue reaction. These results, along with controllable glucose permeability, could prove vital in prolonging the lifetime of implantable biosensors. Additionally in effort to minimize tissue trauma upon implantation, novel poly(lactic-co-glycolic acid) (PLGA) microsphere/poly(vinyl alcohol) (PVA) hydrogel composites were investigated for dexamethasone delivery. A release rate of 25 to 40% over one month, following a zero order profile, was achieved by preferential adsorption of surface active polyacids (poly(acrylic acid), Nafion and HAs) on the hydrogel dispersed microspheres. Environmental scanning electron microscopy investigation on the degradation mechanism of the microspheres pointed towards their slow homogeneous degradation in the PVA hydrogels that was significantly surface-accelerated in the presence of polyacids. The physico-mechanical properties (fluid uptake and Young's modulus) and release of unencapsulated dexamethasone (80 to 100%) from the hydrogels were related to their crystallinity. Significantly, with Young's modulus in the range of 0.1 to 4 MPa, comparable to human sub-dermal tissue, the hydrated gels provide soft and flexible tissue/sensor interface.

Release of paclitaxel from polylactide-co-glycolide (PLGA) microparticles and discs under irradiation.

PubMed

Wang, J; Ng, C W; Win, K Y; Shoemakers, P; Lee, T K Y; Feng, S S; Wang, C H

2003-01-01

Paclitaxel is a promising anti-cancer drug as well as a radiosensitizer for chemotherapy and radiotherapy applications. Because of the poor solubility of paclitaxel in water and most pharmaceutical reagents, it is usually formulated with an adjuvant called Cremophor EL, which causes severe side effects. This work develops new dosage forms of paclitaxel for controlled release application, which do not require the adjuvant and, thus, can avoid its associated side effects. Paclitaxel was encapsulated into the PLGA matrix with various additives such as polyethylene glycol (PEG), isopropyl myristate (IPM) and d-alpha tocopheryl polyethylene glycol (Vitamin E TPGS). These additives were used to enhance the release rate of paclitaxel from the polymer matrix. Spray-drying and an hydraulic press were used to prepare paclitaxel-PLGA microspheres and discs. The microspheres and discs were given different irradiation doses to investigate their effects on the surface morphology (characterized by SEM, AFM and XPS) and in vitro release properties. There seems to be a small effect of the ionizing radiation on various formulations. Although the irradiation did not cause observable changes on the morphology of the polymer matrix, the release rate can be enhanced by a few per cent. It was found that PEG has the highest enhancement effect for release rate among all the additives investigated in this study.

The Preparation of Capsaicin-Chitosan Microspheres (CCMS) Enteric Coated Tablets

PubMed Central

Chen, Jian; Huang, Gui-Dong; Tan, Si-Rong; Guo, Jiao; Su, Zheng-Quan

2013-01-01

This study aimed to research the preparation and content determination of capsaicin-chitosan microspheres (CCMS) enteric coated tablets. The core tablets were prepared with the method of wet granulation. Nine formulae were designed to determine the optimal formula of the core tablet. Eudragit L100 was used to prepare the CCMS enteric-coated tablets. The effect of enteric coated formulation variables such as content of talc (10%, 25% and 40%), plasticisers (TEC and DBS), dosage of plasticiser (10%, 20% and 30%) and coating weight (2%, 3% and 5%) were evaluated for drug release characteristics. The in vitro release was studied using 0.1 N HCl and pH 6.8 phosphate buffer. Enteric coated tablets without ruptures or swelling behaviour over 2 h in 0.1 N HCl indicated that these tablets showed acid resistance. The accumulated release rate in phosphate buffer (pH 6.8) revealed that the prepared tablets were able to sustain drug release into the intestine and a first-order release was obtained for capsaicin. This research is the first report of the preparation and content determination of CCMS enteric coated tablets. The sustained release behavior of enteric coated formulations in pH 6.8 phosphate buffer demonstrated that it would be a potential drug delivery platform for sustained delivery of gastric irritant drugs. PMID:24351818

Hydrophilic porous magnetic poly(GMA-MBAA-NVP) composite microspheres containing oxirane groups: An efficient carrier for immobilizing penicillin G acylase

NASA Astrophysics Data System (ADS)

Xue, Ping; Su, Weiguang; Gu, Yaohua; Liu, Haifeng; Wang, Julan

2015-03-01

Magnetic hydrophilic polymeric microspheres containing oxirane groups were prepared by inverse suspension polymerization of glycidyl methacrylate (GMA), N, N‧-methylene bisacrylamide (MBAA) and N-vinyl pyrrolidone (NVP) in the existence of formamide, which were denoted as magnetic poly(GMA-MBAA-NVP) microspheres. The magnetic poly(GMA-MBAA-NVP) microspheres were characterized by scanning electron microscopy (SEM), FT-IR spectroscopy, X-ray diffraction (XRD), vibrating sample magnetometer (VSM) and so on. The results showed that poly(GMA-MBAA-NVP) microspheres possessed well spherical shape, narrow size distribution, abundant porous structure, reactive oxirane groups and superparamagnetic properties. Formamide used in the present work served as a modifier, a dispersant and a porogen to form final porous polymer microspheres. The penicillin G acylase (PGA) was covalently immobilized onto the magnetic microspheres through the reaction between the amino groups of enzyme and the oxirane groups on the microspheres for producing 6-aminopenicillanic acid (6-APA). The effects of GMA/NVP ratio and crosslink density on the activity of immobilized PGA were investigated. The highest apparent activity, enzyme loading and coupling yield of immobilized PGA were 821 IU/g, 65.3 mg/g and 42.3% respectively when the mass ratio of GMA/NVP was 1:1 and crosslink density was 60%. Compared with the free PGA, immobilized PGA showed a wider range of pH value and reaction temperature. The relative activity and reaction rate of immobilized PGA remained almost constant after 20 recycles. The magnetic poly(GMA-MBAA-NVP) microspheres would be very promising carriers for immobilizing enzymes in industrial application.

Preparation and characterization of biodegradable magnetic carriers by single emulsion-solvent evaporation

NASA Astrophysics Data System (ADS)

Liu, Xianqiao; Kaminski, Michael D.; Riffle, Judy S.; Chen, Haitao; Torno, Michael; Finck, Martha R.; Taylor, LaToyia; Rosengart, Axel J.

2007-04-01

This paper describes a single emulsion-solvent evaporation protocol to prepare PEGylated biodegradable/biocompatible magnetic carriers by utilizing hydrophobic magnetite and a mixture of poly( D,L lactide-co-glycolide) (PLGA) and poly(lactic acid-block-polyethylene glycol) (PLA-PEG) (26:1 by mass) polymers. We characterized the magnetic microspheres in terms of morphology, composite microstructure, size and size distribution, and magnetic properties. Results show that the preparation produces magnetic microspheres with a good spherical morphology, small size (mean diameter of 1.2-1.5 μm) by means of large size distributions, and magnetizations up to 20-30 emu/g of microspheres.

Leflunomide biodegradable microspheres intended for intra-articular administration: Development, anti-inflammatory activity and histopathological studies.

PubMed

El-Setouhy, Doaa Ahmed; Abdelmalak, Nevine Shawky; Anis, Shady E; Louis, Dina

2015-11-30

Leflunomide, the disease-modifying anti-rheumatic drug was formulated as microspheres for prolonged drug release in the form of intraarticular injection. Eight formulations were developed using three biodegradable PDLG polymers (lactide/glycolide copolymer) and polycaprolactone (PLC) at two drug:polymer ratios (1:2 and 1:4). Solvent evaporation method was employed using polyvinyl alcohol or hydropxypropyl methylcellulose as stabilizers. Formulations were assessed for encapsulation efficiency, yield, particle size, release pattern and SEM. F6 (PDLG 5010), with appropriate particle size and prolonged drug release, was chosen for in-vivo studies using arthritis induced rats, which were intrarticularly injected with F6 or took oral Avara(®). Nuclear factor-kappa B measurements and histopathologic studies were conducted. There was significant reduction of inflammation caused by both F6 and oral Avara(®). Histopathologic studies showed minimal infiltration by chronic inflammatory cells and no angiogenesis in F6 compared to Avara(®). Results also revealed biocompatibility of the polymer used. Copyright © 2015 Elsevier B.V. All rights reserved.

Release of Cyclic Phosphatidic Acid from Gelatin-based Hydrogels Inhibit Colon Cancer Cell Growth and Migration

PubMed Central

Tsukahara, Tamotsu; Murakami-Murofushi, Kimiko

2012-01-01

Microparticle and nanoparticle formulations are widely used to improve the bioavailability of low-solubility drugs and as vehicles for organ- and tissue-specific targeted drug delivery. We investigated the effect of a novel, controlled-release form of a bioactive lipid, cyclic phosphatidic acid (cPA), on human colon cancer cell line functions. We encapsulated cPA in gelatin-based hydrogels and examined its ability to inhibit the viability and migration of HT-29 and DLD-1 cells in vitro and the LPA-induced activity of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ). The hydrogel delivery system prolonged cPA release into the culture medium. Accordingly, cPA-hydrogel microspheres substantially inhibited LPA-induced PPARγ activity and cell growth and migration compared with that of cells cultured with cPA alone. Thus, hydrogel microspheres are a potential system for stable and efficient delivery of bioactive lipids such as cPA and may offer a new strategy for targeted colon cancer treatment. PMID:23008752

Simple and Sensitive Quantification of MicroRNAs via PS@Au Microspheres-Based DNA Probes and DSN-Assisted Signal Amplification Platform.

PubMed

Zhao, Qian; Piao, Jiafang; Peng, Weipan; Wang, Yang; Zhang, Bo; Gong, Xiaoqun; Chang, Jin

2018-01-31

Identifying the microRNA (miRNA) expression level can provide critical information for early diagnosis of cancers or monitoring the cancer therapeutic efficacy. This paper focused on a kind of gold-nanoparticle-coated polystyrene microbeads (PS@Au microspheres)-based DNA probe as miRNA capture and duplex-specific nuclease (DSN) signal amplification platform based on an RGB value readout for detection of miRNAs. In virtue of the outstanding selectivity and simple experimental operation, 5'-fluorochrome-labeled molecular beacons (MBs) were immobilized on PS@Au microspheres via their 3'-thiol, in the wake of the fluorescence quenching by nanoparticle surface energy transfer (NSET). Target miRNAs were captured by the PS@Au microspheres-based DNA probe through DNA/RNA hybridization. DSN enzyme subsequently selectively cleaved the DNA to recycle the target miRNA and release of fluorophores, thereby triggering the signal amplification with more free fluorophores. The RGB value measurement enabled a detection limit of 50 fM, almost 4 orders of magnitude lower than PS@Au microspheres-based DNA probe detection without DSN. Meanwhile, by different encoding of dyes, miRNA-21 and miRNA-10b were simultaneously detected in the same sample. Considering the ability for quantitation, high sensitivity, and convenient merits, the PS@Au microspheres-based DNA probe and DSN signal amplification platform supplied valuable information for early diagnosis of cancers.

Solvent/non-solvent sintering: a novel route to create porous microsphere scaffolds for tissue regeneration.

PubMed

Brown, Justin L; Nair, Lakshmi S; Laurencin, Cato T

2008-08-01

Solvent/non-solvent sintering creates porous polymeric microsphere scaffolds suitable for tissue engineering purposes with control over the resulting porosity, average pore diameter, and mechanical properties. Five different biodegradable biocompatible polyphosphazenes exhibiting glass transition temperatures from -8 to 41 degrees C and poly (lactide-co-glycolide), (PLAGA) a degradable polymer used in a number of biomedical settings, were examined to study the versatility of the process and benchmark the process to heat sintering. Parameters such as: solvent/non-solvent sintering solution composition and submersion time effect the sintering process. PLAGA microsphere scaffolds fabricated with solvent/non-solvent sintering exhibited an interconnected porosity and pore size of 31.9% and 179.1 mum, respectively which was analogous to that of conventional heat sintered PLAGA microsphere scaffolds. Biodegradable polyphosphazene microsphere scaffolds exhibited a maximum interconnected porosity of 37.6% and a maximum compressive modulus of 94.3 MPa. Solvent/non-solvent sintering is an effective strategy for sintering polymeric microspheres, with a broad spectrum of glass transition temperatures, under ambient conditions making it an excellent fabrication route for developing tissue engineering scaffolds and drug delivery vehicles. (c) 2007 Wiley Periodicals, Inc.

Solvent/Non-Solvent Sintering: A Novel Route to Create Porous Microsphere Scaffolds For Tissue Regeneration

PubMed Central

Brown, Justin L.; Nair, Lakshmi S.; Laurencin, Cato T.

2009-01-01

Solvent/non-solvent sintering creates porous polymeric microsphere scaffolds suitable for tissue engineering purposes with control over the resulting porosity, average pore diameter and mechanical properties. Five different biodegradable biocompatible polyphosphazenes exhibiting glass transition temperatures from −8°C to 41oC and poly(lactide-co-glycolide), (PLAGA) a degradable polymer used in a number of biomedical settings, were examined to study the versatility of the process and benchmark the process to heat sintering. Parameters such as: solvent/non-solvent sintering solution composition and submersion time effect the sintering process. PLAGA microsphere scaffolds fabricated with solvent/non-solvent sintering exhibited an interconnected porosity and pore size of 31.9% and 179.1µm respectively which was analogous to that of conventional heat sintered PLAGA microsphere scaffolds. Biodegradable polyphosphazene microsphere scaffolds exhibited a maximum interconnected porosity of 37.6% and a maximum compressive modulus of 94.3MPa. Solvent/non-solvent sintering is an effective strategy for sintering polymeric microspheres, with a broad spectrum of glass transition temperatures, under ambient conditions making it an excellent fabrication route for developing tissue engineering scaffolds and drug delivery vehicles. PMID:18161819

Finite Element Modeling of Tensile Deformation Behaviors of Iron Syntactic Foam with Hollow Glass Microspheres

PubMed Central

Cho, Yi Je; Lee, Wookjin; Park, Yong Ho

2017-01-01

The elastoplastic deformation behaviors of hollow glass microspheres/iron syntactic foam under tension were modeled using a representative volume element (RVE) approach. The three-dimensional microstructures of the iron syntactic foam with 5 wt % glass microspheres were reconstructed using the random sequential adsorption algorithm. The constitutive behavior of the elastoplasticity in the iron matrix and the elastic-brittle failure for the glass microsphere were simulated in the models. An appropriate RVE size was statistically determined by evaluating elastic modulus, Poisson’s ratio, and yield strength in terms of model sizes and boundary conditions. The model was validated by the agreement with experimental findings. The tensile deformation mechanism of the syntactic foam considering the fracture of the microspheres was then investigated. In addition, the feasibility of introducing the interfacial deboning behavior to the proposed model was briefly investigated to improve the accuracy in depicting fracture behaviors of the syntactic foam. It is thought that the modeling techniques and the model itself have major potential for applications not only in the study of hollow glass microspheres/iron syntactic foams, but also for the design of composites with a high modulus matrix and high strength reinforcement. PMID:29048346

Poly-ε-caprolactone microspheres as a drug delivery system for cannabinoid administration: development, characterization and in vitro evaluation of their antitumoral efficacy.

PubMed

Hernán Pérez de la Ossa, D; Ligresti, A; Gil-Alegre, M E; Aberturas, M R; Molpeceres, J; Di Marzo, V; Torres Suárez, A I

2012-08-10

Cannabinoids show promise for the treatment of various medical conditions such as emesis, anorexia, pain, cancer, multiple sclerosis, Parkinson's disease and glaucoma. However, their high lipohilicity and instability complicate their handling and dosing, and restrict their use as pharmaceuticals. The objective of the present work was to assess the feasibility of developing cannabinoid loaded poly-ε-caprolactone (PCL) microparticles prepared by the oil-in-water emulsion-solvent evaporation technique as a suitable dosage form for their administration. Spherical microparticles with a size range of 20-50 μm, and high entrapment efficiency (around 100%) were obtained. Cannabidiol (CBD) dissolved in the polymeric matrix of the microspheres was slowly released in vitro within 10 days. In vitro cell viability studies demonstrated the antitumoral activity of CBD released from microparticles. After 4 and 7 days of incubation, CBD in microspheres significantly inhibited the growth of MDA-MB-231 cells by 60% as compared to the 50% attained with free drug. The results suggest that PCL microparticles could be an alternative delivery system for long-term cannabinoid administration, showing potential therapeutic advantages over free drug. Copyright © 2012 Elsevier B.V. All rights reserved.

Development and evaluation of floating alginate microspheres for oral delivery of anthocyanins - A preliminary investigation.

PubMed

Celli, Giovana B; Ghanem, Amyl; Brooks, Marianne S

2017-05-01

The goal of this study was to develop floating microspheres that could be used as gastroretentive systems for the delivery of anthocyanins (ACNs). These compounds are absorbed in the stomach and small intestine, and insufficient residence time in these organs could result in limited absorption and contribute to degradation. The microparticles containing freeze-dried haskap berry extract (321.96 ± 8.35 mg cyanidin 3-glucoside equivalents per g) were prepared by ionotropic gelation of alginate (9%, w/w) with calcium ions (CaCl 2 at 2%, w/v) in the gelation bath, with calcium carbonate as the gas-generating compound (added at different ratios in the alginate/extract mixture). The effect of acetic acid concentration (2 and 10%, v/v) in the gelation medium was investigated. Increasing the carbonate : alginate weigh ratio from 0 to 3:4 resulted in different degrees of floatability, larger particles, higher encapsulation efficiency, and lower amount of ACN released. The power law equation fitted the experimental data well, indicating that release occurred mainly by diffusion. This is the first time floating microspheres are proposed as gastroretentive platforms for the delivery of ACNs.

Controlled drug delivery through a novel PEG hydrogel encapsulated silica aerogel system.

PubMed

Giray, Seda; Bal, Tuğba; Kartal, Ayse M; Kızılel, Seda; Erkey, Can

2012-05-01

A novel composite material consisting of a silica aerogel core coated by a poly(ethylene) glycol (PEG) hydrogel was developed. The potential of this novel composite as a drug delivery system was tested with ketoprofen as a model drug due to its solubility in supercritical carbon dioxide. The results indicated that both drug loading capacity and drug release profiles could be tuned by changing hydrophobicity of aerogels, and that drug loading capacity increased with decreased hydrophobicity, while slower release rates were achieved with increased hydrophobicity. Furthermore, higher concentration of PEG diacrylate in the prepolymer solution of the hydrogel coating delayed the release of the drug which can be attributed to the lower permeability at higher PEG diacrylate concentrations. The novel composite developed in this study can be easily implemented to achieve the controlled delivery of various drugs and/or proteins for specific applications. Copyright © 2012 Wiley Periodicals, Inc.

Hierarchical, porous CuS microspheres integrated with carbon nanotubes for high-performance supercapacitors

NASA Astrophysics Data System (ADS)

Lu, Yang; Liu, Xianming; Wang, Weixiao; Cheng, Jinbing; Yan, Hailong; Tang, Chengchun; Kim, Jang-Kyo; Luo, Yongsong

2015-11-01

Carbon nanotubes (CNTs) incorporated porous 3-dimensional (3D) CuS microspheres have been successfully synthesized via a simple refluxing method assisted by PVP. The composites are composed of flower-shaped CuS secondary microspheres, which in turn are assembled with primary nanosheets of 15-30 nm in thickness and fully integrated with CNT. The composites possess a large specific surface area of 189.6 m2 g-1 and a high conductivity of 0.471 S cm-1. As electrode materials for supercapacitors, the nanocomposites show excellent cyclability and rate capability and deliver an average reversible capacitance as high as 1960 F g-1 at a current density of 10 mA cm-2 over 10000 cycles. The high electrochemical performance can be attributed to the synergistic effect of CNTs and the unique microstructure of CuS. The CNTs serve as not only a conductive agent to accelerate the transfer of electrons in the composites, but also as a buffer matrix to restrain the volume change and stabilize the electrode structure during the charge/discharge process. The porous structure of CuS also helps to stabilize the electrode structure and facilitates the transport for electrons.

Method and composition for molding low-density desiccant syntactic-foam articles

DOEpatents

Not Available

1981-12-07

These and other objects of the invention are achieved by a process for molding to size a desiccant syntactic foam article having a density of 0.2 to 0.9 g/cc and a moisture capacity of 1 to 12% by weight, comprising the steps of: charging a mold with a powdery mixture of an activated desiccant, microspheres and a thermosetting resin, the amount of the desiccant being sufficient to provide the required moisture capacity, and the amounts of the microspheres and resin being such that the microspheres/desiccant volume fraction exceeds the packing factor by an amount sufficient to substantially avoid shrinkage without causing excessively high molding pressures; covering the mold and heating the covered mold to a temperature and for an amount of time sufficient to melt the resin; and tightly closing the mold and heating the closed mold to a temperature and for an amount of time sufficient to cure the resin, and removing the resultant desiccant syntactic foam article from the mold. In a composition of matter aspect, the present invention provides desiccant syntactic foam articles, and a composition of matter for use in molding the same.

Hierarchical, porous CuS microspheres integrated with carbon nanotubes for high-performance supercapacitors.

PubMed

Lu, Yang; Liu, Xianming; Wang, Weixiao; Cheng, Jinbing; Yan, Hailong; Tang, Chengchun; Kim, Jang-Kyo; Luo, Yongsong

2015-11-16

Carbon nanotubes (CNTs) incorporated porous 3-dimensional (3D) CuS microspheres have been successfully synthesized via a simple refluxing method assisted by PVP. The composites are composed of flower-shaped CuS secondary microspheres, which in turn are assembled with primary nanosheets of 15-30 nm in thickness and fully integrated with CNT. The composites possess a large specific surface area of 189.6 m(2) g(-1) and a high conductivity of 0.471 S cm(-1). As electrode materials for supercapacitors, the nanocomposites show excellent cyclability and rate capability and deliver an average reversible capacitance as high as 1960 F g(-1) at a current density of 10 mA cm(-2) over 10000 cycles. The high electrochemical performance can be attributed to the synergistic effect of CNTs and the unique microstructure of CuS. The CNTs serve as not only a conductive agent to accelerate the transfer of electrons in the composites, but also as a buffer matrix to restrain the volume change and stabilize the electrode structure during the charge/discharge process. The porous structure of CuS also helps to stabilize the electrode structure and facilitates the transport for electrons.

The influence of spray-drying parameters on phase behavior, drug distribution, and in vitro release of injectable microspheres for sustained release.

PubMed

Meeus, Joke; Lenaerts, Maité; Scurr, David J; Amssoms, Katie; Davies, Martyn C; Roberts, Clive J; Van Den Mooter, Guy

2015-04-01

For ternary solid dispersions, it is indispensable to characterize their structure, phase behavior, and the spatial distribution of the dispersed drug as this might influence the release profile and/or stability of these formulations. This study shows how formulation (feed concentration) and process (feed rate, inlet air temperature, and atomizing air pressure) parameters can influence the characteristics of ternary spray-dried solid dispersions. The microspheres considered here consist of a poly(lactic-co-glycolic acid) (PLGA) surface layer and an underlying polyvinylpyrrolidone (PVP) phase. A poorly soluble active pharmaceutical ingredient (API) was molecularly dispersed in this matrix. Differences were observed in component miscibility, phase heterogeneity, particle size, morphology, as well as API surface coverage for selected spray-drying parameters. Observed differences are likely because of changes in the droplet generation, evaporation, and thus particle formation processes. However, varying particle characteristics did not influence the drug release of the formulations studied, indicating the robustness of this approach to produce particles of consistent drug release characteristics. This is likely because of the fact that the release is dominated by diffusion from the PVP layer through pores in the PLGA surface layer and that observed differences in the latter have no influence on the release. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Flower-like BiOI microsphere/Ni@C nanocapsule hybrid composites and their efficient microwave absorbing activity

NASA Astrophysics Data System (ADS)

Liu, Xianguo; Yu, Jieyi; Cui, Caiyun; Sun, Yuping; Li, Xiaolong; Li, Zhenxing

2018-07-01

At present, microwave absorbers are prepared by dispersing absorbing nanomaterials in a binder, which can lead to the aggregation of nanomaterials in the binder and further affect the optimization of the absorption performances. Hybrid micro/nano-scale structures are beneficial for buffering agglomeration phenomena and the construction of multiple interfaces. Here, Ni@C nanocapsules are conjugated onto flower-like BiOI microspheres, forming micro/nano-scale hybrid composites. The multiple interfaces between BiOI microspheres and Ni@C nanocapsules can bring enhanced dielectric loss and increased attenuation constant, resulting in the enhancement of absorption capacity (the optimal reflection loss reaches  ‑61.35 dB), increased width of the effective absorption band (the maximum effective bandwidth, f Emax , is 5.86 GHz) and the reduction of absorption thickness (the thickness corresponding to f Emax is 1.7 mm). This study highlights a simple idea for the optimization of electromagnetic absorbing performance, which is of great significance in the development of microwave absorbers.

Cross-linked polyvinyl pyridine coated glass particle catalyst support and aqueous composition or polyvinyl pyridine adducted microspheres

NASA Technical Reports Server (NTRS)

Rembaum, Alan (Inventor); Gupta, Amitava (Inventor); Volksen, Willi (Inventor)

1981-01-01

Microspheres are produced by cobalt gamma radiation initiated polymerization of a dilute aqueous vinyl pyridine solution. Addition of cross-linking agent provides higher surface area beads. Addition of monomers such as hydroxyethylmethacrylate acrylamide or methacrylamide increases hydrophilic properties and surface area of the beads. High surface area catalytic supports are formed in the presence of controlled pore glass substrate.

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

Basaldella, E.I.; Bonetto, R.; Tara, J.C.

The synthesis of NaY zeolite was carried out on fired kaolinite microspheres. Changes in porosity, chemical composition, and crystallinity of the solid show zeolite growth on both internal and external microsphere surfaces. It was also observed that, as a consequence of the alkaline treatment, the SiO[sub 2]/Al[sub 2]O[sub 3] ratio in the solid diminishes prior to the appearance of the zeolite, but increases when the zeolite begins to crystallize.

Fe3O4@Polypyrrole Microspheres with High Magnetization and Superparamagnetism for Efficient and Fast Removal of Pb(II) Ions

NASA Astrophysics Data System (ADS)

Zhang, Wei; Zhu, Wanyan; Xu, Wutong; Wang, Yan; Li, Ning; Zhang, Tingting; Wang, Hui

2017-12-01

Core-shell structured Fe3O4@PPy microspheres are synthesized successfully through a facile polyol reduction method in combination with a modified Stöber method. We show that the as-prepared Fe3O4@PPy microspheres with high saturation magnetization, superparamagnetism, and good dispersibility have a high efficient adsorption capacity for high efficient removal of Pb(II) ions of up to 391.71 mg g-1 and a fast adsorption equilibrium time of 20 min. Furthermore, the lead-adsorbed Fe3O4@PPy microspheres can be rapidly separated from solution because of the excellent superparamagnetic properties. The composite Fe3O4@PPy microspheres are characterized using X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and vibrating sample magnetometer (VSM). The adsorption data from our experiments show that the adsorption process fits well with the pseudosecond- order kinetic model and the adsorption isotherm follows the Langmuir isotherm model. The thermodynamic studies show that the adsorption of Pb(II) on Fe3O4@PPy microspheres is an endothermic and spontaneous process. Comprehensive comparison among adsorbents for the removal of Pb(II) ions that literature reported, reusability, high adsorption efficiency, fast adsorption equilibrium, and rapid magnetic separation make these Fe3O4@PPy microspheres very promising application for removal of Pb(II) ions from contaminated water.

Prolonged nerve block by microencapsulated bupivacaine prevents acute postoperative pain in rats.

PubMed

Ohri, Rachit; Blaskovich, Phillip; Wang, Jeffrey Chi-Fei; Pham, Lan; Nichols, Gary; Hildebrand, William; Costa, Daniel; Scarborough, Nelson; Herman, Clifford; Strichartz, Gary

2012-01-01

To minimize acute postoperative pain, a new formulation of slowly released bupivacaine was developed. Bupivacaine was microencapsulated at 60% (wt/wt) in poly-lactide-co-glycolide polymers and characterized for physicochemical properties and bupivacaine release kinetics. This formulation was injected around the rat sciatic nerve to produce an antinociceptive effect to toe pinch. Mechanical hyperalgesia following lateral plantar paw incision in rats was assessed for 7 to 14 days when the bupivacaine slow-release formulation was placed at the ipsilateral sciatic nerve and compared with the hyperalgesia that developed with various controls. Bupivacaine was released in vitro at a relatively constant rate over a period of ≈ 72 to 96 hours. Complete antinociception, shown as no response to toe pinch, lasted for 23 ± 7 hours, with a half-recovery time of 42 ± 8 hours after sciatic nerve injection of 0.4 mL of the microspheres delivering 34 mg of bupivacaine. Solutions of 0.5% (wt/vol) bupivacaine-HCl (0.1 mL) produced complete antinociception for less than 2 hours and recovery half-times of 2 hours. Postincisional mechanical hyperalgesia, shown by increased withdrawal responses to von Frey filaments, was absent for 24 hours and was lower than control for 96 hours, when the sciatic nerve was blocked by bupivacaine microspheres, whereas the 0.5% bupivacaine solution reduced postincisional pain for only 4 hours. Corresponding to its far greater functional blocking time, the microsphere-bupivacaine formulation was able to significantly reduce postoperative pain below control levels for up to 4 days. These findings of several days of postoperative pain relief, for an injectable formulation containing a single active agent, present an improved and potentially promising therapy to prevent acute pain after surgery.

Doxorubicin-Loaded QuadraSphere Microspheres: Plasma Pharmacokinetics and Intratumoral Drug Concentration in an Animal Model of Liver Cancer

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

Lee, Kwang-Hun; Liapi, Eleni A.; Cornell, Curt

The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20more » ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.« less

Doxorubicin-loaded QuadraSphere microspheres: plasma pharmacokinetics and intratumoral drug concentration in an animal model of liver cancer.

PubMed

Lee, Kwang-Hun; Liapi, Eleni A; Cornell, Curt; Reb, Philippe; Buijs, Manon; Vossen, Josephina A; Ventura, Veronica Prieto; Geschwind, Jean-Francois H

2010-06-01

The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

Hierarchical TiO2/C micro-nano spheres as high-performance anode materials for sodium ion batteries

NASA Astrophysics Data System (ADS)

Ma, Xiao; Zhang, Zhihui; Tian, Jianliya; Xu, Beibei; Ping, Qiushi; Wang, Baofeng

The hierarchical TiO2/C microspheres were obtained via a facile method of in-situ hydrolysis and spray drying. Antase TiO2 nanoparticles were coherent to microspheres TiO2/C due to the pyrolysis of carbon source (PVP). Besides, the favorable electron transfer from carbon to TiO2 improves the electronic conductivity of TiO2 via the presence of Ti-C bond within TiO2/C composite. Charge-discharge tests show that TiO2/C microspheres delivered a good rate capability of 106.1mAhg‑1 at the high current density of 5Ag‑1 and an enhanced cyclic capacity. The superior electrochemical performance could be ascribed to the porous micro-nano structure, smaller crystal size and increased conductivity. The synthesis of TiO2/C microspheres is easy to scale up for satisfying high-performance sodium storage.

Construction of Nitrogen-Doped Carbon-Coated MoSe2 Microspheres with Enhanced Performance for Lithium Storage.

PubMed

Tang, Wangjia; Xie, Dong; Shen, Tong; Wang, Xiuli; Wang, Donghuang; Zhang, Xuqing; Xia, Xinhui; Wu, Jianbo; Tu, Jiangping

2017-09-18

Exploring advanced anode materials with highly reversible capacity have gained great interests for large-scale lithium storage. A facile two-step method is developed to synthesize nitrogen-doped carbon coated MoSe 2 microspheres via hydrothermal plus thermal polymerization. The MoSe 2 microspheres composed of interconnected nanoflakes are homogeneously coated by a thin nitrogen-doped carbon (N-C) layer. As an anode for lithium ion batteries, the MoSe 2 /N-C composite shows better reversibility, smaller polarization, and higher electrochemical reactivity as compared to the unmodified MoSe 2 microspheres. The MoSe 2 /N-C electrode delivers a high specific capacity of 698 mAh g -1 after 100 cycles at a current density of 100 mA g -1 and good high rate performance (471 mAh g -1 at a high current density of 2000 mA g -1 ). The improved electrochemical performance is attributed to the conductive N-C coating and hierarchical microsphere structure with fast ion/electron transfer characteristics. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Popcorn balls-like ZnFe2O4-ZrO2 microsphere for photocatalytic degradation of 2,4-dinitrophenol

NASA Astrophysics Data System (ADS)

Chen, Xi; Liu, Yutang; Xia, Xinnian; Wang, Longlu

2017-06-01

In this paper, novel popcorn balls-like ZnFe2O4-ZrO2 composite microspheres were successfully fabricated by a simple hydrothermal method. The morphology, structure and optical property of the microspheres were characterized. The microspheres were used as the photocatalysts to degrade 2,4-dinitrophenol, and exhibited superior photocatalytic performance. Under simulated solar visible light irradiation, the degradation rate of ZnFe2O4-ZrO2 photocatalyst (mass ratio of ZnFe2O4/ZrO2 = 2:1) was almost 7.4 and 2.4 times higher than those of pure ZnFe2O4 and ZrO2. The enhancement could attribute to stronger light absorption, lower carrier recombination and multi-porous structure of the microspheres. Moreover, the popcorn balls-like photocatalysts can be easily separated, because of the magnetism of the samples. After five times runs, the photocatalyst still showed 90% of its photocatalytic degradation efficiency. This work demonstrated a good prospect for removing organic pollutants in water.

Preparation of UC0.07-0.10N0.90-0.93 spheres for TRISO coated fuel particles

NASA Astrophysics Data System (ADS)

Hunt, R. D.; Silva, C. M.; Lindemer, T. B.; Johnson, J. A.; Collins, J. L.

2014-05-01

The US Department of Energy is considering a new nuclear fuel that would be less susceptible to ruptures during a loss-of-coolant accident. The fuel would consist of tristructural isotropic coated particles with dense uranium nitride (UN) kernels with diameters of 650 or 800 μm. The objectives of this effort are to make uranium oxide microspheres with adequately dispersed carbon nanoparticles and to convert these microspheres into UN spheres, which could be then sintered into kernels. Recent improvements to the internal gelation process were successfully applied to the production of uranium gel spheres with different concentrations of carbon black. After the spheres were washed and dried, a simple two-step heat profile was used to produce porous microspheres with a chemical composition of UC0.07-0.10N0.90-0.93. The first step involved heating the microspheres to 2023 K in a vacuum, and in the second step, the microspheres were held at 1873 K for 6 h in flowing nitrogen.

Highly Efficient visible-light-induced photoactivity of magnetically retrievable Fe3O4@SiO2@Bi2WO6@g-C3N4 hierarchical microspheres for the degradation of organic pollutant and production of hydrogen

NASA Astrophysics Data System (ADS)

Lu, Dingze; Wang, Hongmei; Shen, Qingqing; Kondamareddy, Kiran Kumar; Neena D

2017-07-01

The new multifunctional composite Fe3O4@SiO2@Bi2WO6@g-C3N4 (FSBG) hierarchical microspheres with Bi2WO6/g-C3N4 heterostructure as an outer shell and Fe3O4@SiO2 as a magnetic core have been synthesized and characterized for photocatalytic applications. An efficient and adoptable approach of synthesizing magnetic Bi2WO6/g-C3N4 hierarchical microspheres of grape-like morphology is realized. The as-synthesized structures exhibit highly efficient visible-light absorption and separation efficiency of photo-induced charge. The visible-light-induced photocatalytic activity of g-C3N4, Fe3O4@SiO2@Bi2WO6, and FSBG is evaluated by investigating the photodegradation of Rhodamine B (RhB) and hydrogen (H2) out of water. The comparative study reveals that the FSBG microspheres exhibit an optimum visible-light-induced photocatalytic activity in degrading Rhodamin B (RhB), which is 3.06 and 1.92 times to that of g-C3N4 and Fe3O4@SiO2@Bi2WO6 systems respectively and 3.89 and 2.31 times in the production of hydrogen (H2) out of water, respectively. The FSBG composite microspheres also exhibit good magnetic recoverability. An alternate mechanism for the enhanced visible-light photocatalytic activity is given in the present manuscript.

Fabrication of (U,Am)O2 pellet with controlled porosity from oxide microspheres

NASA Astrophysics Data System (ADS)

Ramond, Laure; Coste, Philippe; Picart, Sébastien; Gauthé, Aurélie; Bataillea, Marc

2017-08-01

U1-xAmxO2±δ mixed-oxides are considered as promising compounds for americium heterogeneous transmutation in Sodium Fast Neutron Reactor. Porous microstructure is envisaged in order to facilitate helium and fission gas release and to reduce pellet swelling during irradiation and under self-irradiation. In this study, the porosity is created by reducing (U,Am)3O8 microspheres into (U,Am)O2 during the sintering. This reduction is accompanied by a decrease of the lattice volume that leads to the creation of open porosity. Finally, an (U0.90Am0.10)O2 porous ceramic pellet (D∼89% of the theoretical density TD) with controlled porosity (≥8% open porosity) was obtained from mixed-oxide microspheres obtained by the Weak Acid Resin (WAR) process.

Polyvinyl Alcohol Microspheres Reinforced Thermoplastic Starch Composites

PubMed Central

Zha, Dongdong; Li, Bengang; Yin, Peng; Li, Panxin

2018-01-01

We reported a new method to prepare polyvinyl alcohol (PVA)/thermoplastic starch (TPS) composites by using polyvinyl alcohol microspheres (PVAMS). The PVAMS/TPS composites were characterized using tensile test, scanning electron microscopy (SEM), dynamic mechanical thermal analysis (DMTA) and thermogravimetric analysis (TGA). The results exhibited that adding small amounts of PVAMSs can effectively improve the mechanical strength and toughness of the composites, especially for the 1 wt %PVAMS in TPS matrix, with a tensile strength of 3.5 MPa, an elongation at break at 71.73% and an impact strength of 33.4 kJ/m2. Furthermore, the SEM and shift in the tan δ peak (Tα and Tβ) at the maximum value of 69.87 and −36.52 °C indicates that the PVAMS decreased the mobility of the amorphous starch molecules due to the strong intermolecular hydrogen bonds between PVAMS and TPS. The peak temperature of maximum decomposition rate (Tp) of 1 wt % PVAMS/TPS composites increased about 5 °C compared with TPS in TGA curves. PMID:29690506

K88 Fimbrial Adhesin Targeting of Microspheres Containing Gentamicin Made with Albumin Glycated with Lactose.

PubMed

Sarabia-Sainz, Andre-I; Sarabia-Sainz, Hector Manuel; Montfort, Gabriela Ramos-Clamont; Mata-Haro, Veronica; Guzman-Partida, Ana María; Guzman, Roberto; Garcia-Soto, Mariano; Vazquez-Moreno, Luz

2015-09-16

The formulation and characterization of gentamicin-loaded microspheres as a delivery system targeting enterotoxigenic Escherichia coli K88 (E. coli K88) was investigated. Glycated albumin with lactose (BSA-glucose-β (4-1) galactose) was used as the microsphere matrix (MS-Lac) and gentamicin included as the transported antibiotic. The proposed target strategy was that exposed galactoses of MS-Lac could be specifically recognized by E. coli K88 adhesins, and the delivery of gentamicin would inhibit bacterial growth. Lactosylated microspheres (MS-Lac1, MS-Lac2 and MS-Lac3) were obtained using a water-in-oil emulsion, containing gentamicin, followed by crosslinking with different concentrations of glutaraldehyde. Electron microscopy displayed spherical particles with a mean size of 10-17 µm. In vitro release of gentamicin from MS-Lac was best fitted to a first order model, and the antibacterial activity of encapsulated and free gentamicin was comparable. MS-Lac treatments were recognized by plant galactose-specific lectins from Ricinus communis and Sophora japonica and by E. coli K88 adhesins. Results indicate MS-Lac1, produced with 4.2 mg/mL of crosslinker, as the best treatment and that lactosylated microsphere are promising platforms to obtain an active, targeted system against E. coli K88 infections.

K88 Fimbrial Adhesin Targeting of Microspheres Containing Gentamicin Made with Albumin Glycated with Lactose

PubMed Central

Sarabia-Sainz, Andre-i; Sarabia-Sainz, Hector Manuel; Ramos-Clamont Montfort, Gabriela; Mata-Haro, Veronica; Guzman-Partida, Ana María; Guzman, Roberto; Garcia-Soto, Mariano; Vazquez-Moreno, Luz

2015-01-01

The formulation and characterization of gentamicin-loaded microspheres as a delivery system targeting enterotoxigenic Escherichia coli K88 (E. coli K88) was investigated. Glycated albumin with lactose (BSA-glucose-β (4-1) galactose) was used as the microsphere matrix (MS-Lac) and gentamicin included as the transported antibiotic. The proposed target strategy was that exposed galactoses of MS-Lac could be specifically recognized by E. coli K88 adhesins, and the delivery of gentamicin would inhibit bacterial growth. Lactosylated microspheres (MS-Lac1, MS-Lac2 and MS-Lac3) were obtained using a water-in-oil emulsion, containing gentamicin, followed by crosslinking with different concentrations of glutaraldehyde. Electron microscopy displayed spherical particles with a mean size of 10–17 µm. In vitro release of gentamicin from MS-Lac was best fitted to a first order model, and the antibacterial activity of encapsulated and free gentamicin was comparable. MS-Lac treatments were recognized by plant galactose-specific lectins from Ricinus communis and Sophora japonica and by E. coli K88 adhesins. Results indicate MS-Lac1, produced with 4.2 mg/mL of crosslinker, as the best treatment and that lactosylated microsphere are promising platforms to obtain an active, targeted system against E. coli K88 infections. PMID:26389896

Preload of slowly digestible carbohydrate microspheres decreases gastric emptying rate of subsequent meal in humans.

PubMed

Cisse, Fatimata; Pletsch, Elizabeth A; Erickson, Daniel P; Chegeni, Mohammad; Hayes, Anna M R; Hamaker, Bruce R

2017-09-01

Gastric emptying rate influences how fast the nutrients of a meal are delivered to the body, and when slow, it moderates glycemic response and may impact satiety. Carbohydrates are one of the macronutrients that trigger the ileal brake, and we hypothesized that slowly digestible carbohydrate (SDC) administered in a premeal load would delay gastric emptying. A crossover design study was conducted with 10 healthy adults using fabricated SDC-microspheres (cooked) that were given 20 minutes before a non-nutritive viscous paste meal. There were 4 treatment arms, each separated by a 1-week washout period, consisting of (1) the paste alone, (2) a rapidly digesting maltodextrin (Polycose) preload followed by the paste 20 minutes later, (3) an SDC-microsphere preload followed by the paste, and (4) a comparably slower SDC-microsphere preload followed by the paste. A 13 C-labeled octanoic acid breath test method was used to measure gastric emptying, with the label incorporated into the non-nutritive paste. The microspheres were less than 1 mm in diameter (a size that does not require breakdown in the stomach before emptying) and, after cooking, were of the same density value. Compared with the paste alone, both of the SDC-microsphere preloads (slow and comparably slower digesting) decreased gastric emptying rate of the paste, with the latter having the most effect (half-emptying times of 1.7, 2.3, and 2.8 hours, respectively [each different at P<.05]). In conclusion, SDCs decreased gastric emptying rate, and this was suggested to be due to a triggering of the ileal brake. Copyright © 2017 Elsevier Inc. All rights reserved.

Physicochemical characterization of spray-dried PLGA/PEG microspheres, and preliminary assessment of biological response.

PubMed

Javiya, Curie; Jonnalagadda, Sriramakamal

2016-09-01

The use of spray-drying to prepare blended PLGA:PEG microspheres with lower immune detection. To study physical properties, polymer miscibility and alveolar macrophage response for blended PLGA:PEG microspheres prepared by a laboratory-scale spray-drying process. Microspheres were prepared by spray-drying 0-20% w/w ratios of PLGA 65:35 and PEG 3350 in dichloromethane. Particle size and morphology was studied using scanning electron microscopy. Polymer miscibility and residual solvent levels evaluated by thermal analysis (differential scanning calorimetry - DSC and thermogravimetric analysis - TGA). Immunogenicity was assessed in vitro by response of rat alveolar macrophages (NR8383) by the MTT-based cell viability assay and reactive oxygen species (ROS) detection. The spray dried particles were spherical, with a size range of about 2-3 µm and a yield of 16-60%. Highest yield was obtained at 1% PEG concentration. Thermal analysis showed a melting peak at 59 °C (enthalpy: 170.61 J/g) and a degradation-onset of 180 °C for PEG 3350. PLGA 65:35 was amorphous, with a Tg of 43 °C. Blended PLGA:PEG microspheres showed a delayed degradation-onset of 280 °C, and PEG enthalpy-loss corresponding to 15% miscibility of PEG in PLGA. NR8383 viability studies and ROS detection upon exposure to these cells suggested that blended PLGA:PEG microspheres containing 1 and 5% PEG are optimal in controling cell proliferation and activation. This research establishes the feasibility of using a spray-drying process to prepare spherical particles (2-3 µm) of molecularly-blended PLGA 65:35 and PEG 3350. A PEG concentration of 1-5% was optimal to maximize process yield, with minimal potential for immune detection.

Nanoparticle and Gelation Stabilized Functional Composites of an Ionic Salt in a Hydrophobic Polymer Matrix

PubMed Central

Kanyas, Selin; Aydın, Derya; Kizilel, Riza; Demirel, A. Levent; Kizilel, Seda

2014-01-01

Polymer composites consisted of small hydrophilic pockets homogeneously dispersed in a hydrophobic polymer matrix are important in many applications where controlled release of the functional agent from the hydrophilic phase is needed. As an example, a release of biomolecules or drugs from therapeutic formulations or release of salt in anti-icing application can be mentioned. Here, we report a method for preparation of such a composite material consisted of small KCOOH salt pockets distributed in the styrene-butadiene-styrene (SBS) polymer matrix and demonstrate its effectiveness in anti-icing coatings. The mixtures of the aqueous KCOOH and SBS-cyclohexane solutions were firstly stabilized by adding silica nanoparticles to the emulsions and, even more, by gelation of the aqueous phase by agarose. The emulsions were observed in optical microscope to check its stability in time and characterized by rheological measurements. The dry composite materials were obtained via casting the emulsions onto the glass substrates and evaporations of the organic solvent. Composite polymer films were characterized by water contact angle (WCA) measurements. The release of KCOOH salt into water and the freezing delay experiments of water droplets on dry composite films demonstrated their anti-icing properties. It has been concluded that hydrophobic and thermoplastic SBS polymer allows incorporation of the hydrophilic pockets/phases through our technique that opens the possibility for controlled delivering of anti-icing agents from the composite. PMID:24516593

Ketorolac Administration Attenuates Retinal Ganglion Cell Death After Axonal Injury.

PubMed

Nadal-Nicolás, Francisco M; Rodriguez-Villagra, Esther; Bravo-Osuna, Irene; Sobrado-Calvo, Paloma; Molina-Martínez, Irene; Villegas-Pérez, Maria Paz; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Herrero-Vanrell, Rocío

2016-03-01

To assess the neuroprotective effects of ketorolac administration, in solution or delivered from biodegradable microspheres, on the survival of axotomized retinal ganglion cells (RGCs). Retinas were treated intravitreally with a single injection of tromethamine ketorolac solution and/or with ketorolac-loaded poly(D,L-lactide-co-glycolide) (PLGA) microspheres. Ketorolac treatments were administered either 1 week before optic nerve crush (pre-ONC) or right after the ONC (simultaneous). In all cases, animals were euthanized 7 days after the ONC. As control, nonloaded microspheres or vehicle (balanced salt solution, BSS) were administered in parallel groups. All retinas were dissected as flat mounts; RGCs were immunodetected with brain-specific homeobox/POU domain protein 3A (Brn3a), and their number was automatically quantified. The percentage of Brn3a+RGCs was 36% to 41% in all control groups (ONC with or without BSS or nonloaded microparticles). Ketorolac solution administered pre-ONC resulted in 63% survival of RGCs, while simultaneous administration promoted a 53% survival. Ketorolac-loaded microspheres were not as efficient as ketorolac solution (43% and 42% of RGC survival pre-ONC or simultaneous, respectively). The combination of ketorolac solution and ketorolac-loaded microspheres did not have an additive effect (54% and 55% survival pre-ONC and simultaneous delivery, respectively). Treatment with the nonsteroidal anti-inflammatory drug ketorolac delays RGC death triggered by a traumatic axonal insult. Pretreatment seems to elicit a better output than simultaneous administration of ketorolac solution. This may be taken into account when performing procedures resulting in RGC axonal injury.

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.

One-Pot Green Synthesis of Ag-Decorated SnO2 Microsphere: an Efficient and Reusable Catalyst for Reduction of 4-Nitrophenol.

PubMed

Hu, Min; Zhang, Zhenwei; Luo, Chenkun; Qiao, Xiuqing

2017-12-01

In this paper, hierarchical Ag-decorated SnO 2 microspheres were synthesized by a facile one-pot hydrothermal method. The resulting composites were characterized by XRD, SEM, TEM, XPS, BET, and FTIR analysis. The catalytic performances of the samples were evaluated with the reduction of 4-nitrophenol to 4-aminophenol by potassium borohydride (KBH 4 ) as a model reaction. Time-dependent experiments indicated that the hierarchical microspheres assembled from SnO 2 and Ag nanoparticles can be formed when the react time is less than 10 h. With the increase of hydrothermal time, SnO 2 nanoparticles will self-assemble into SnO 2 nanosheets and Ag nanoparticles decorated SnO 2 nanosheets were obtained. When evaluated as catalyst, the obtained Ag-decorated SnO 2 microsphere prepared for 36 h exhibited excellent catalytic performance with normalized rate constant (κ nor ) of 6.20 min -1 g -1 L, which is much better than that of some previous reported catalysts. Moreover, this Ag-decorated SnO 2 microsphere demonstrates good reusability after the first five cycles. In addition, we speculate the formation mechanism of the hierarchical Ag-decorated SnO 2 microsphere and discussed the possible origin of the excellent catalytic activity.

Amorphous Ni(OH)2/CQDs microspheres for highly sensitive non-enzymatic glucose detection prepared via CQDs induced aggregation process

NASA Astrophysics Data System (ADS)

Zhu, Jiajie; Yin, Haoyong; Cui, Zhenzhen; Qin, Dongyu; Gong, Jianying; Nie, Qiulin

2017-10-01

Non-enzymatic electrochemical sensors for the detection of glucose were designed based on amorphous Ni(OH)2/CQDs microspheres. The amorphous Ni(OH)2/CQDs microspheres were prepared by a CQDs assistant crystallization inhibition process. The morphologies and composition of the microspheres were characterized by SEM, TEM, XRD, EDS, and TG/DSC. The results showed that the microspheres had uniform heterogeneous phases with amorphous Ni(OH)2 and CQDs. The sensor based on amorphous Ni(OH)2/CQDs microspheres showed remarkable electrocatalytic activity towards glucose oxidation comparing to the conventional crystalline Ni(OH)2, which included two linear range (20 μM-350 μM and 0.45mM-2.5 mM) with high selectivity of 2760.05 and 1853.64 μA mM-1cm-2. Moreover, the interference from the commonly interfering species such as urea, ascorbic acid, NaCl, L-proline and L-Valine, can be effectively avoided. The high sensitivity, wide glucose detection range and good selectivity of the electrode may be due to their synergistic effect of amorphous phase and CQDs incorporation. These findings may promote the application of amorphous Ni(OH)2 as advanced electrochemical glucose sensing materials.

Synthesis of phase-pure U 2N 3 microspheres and its decomposition into UN

DOE PAGES

Silva, Chinthaka M.; Hunt, Rodney Dale; Snead, Lance Lewis; ...

2014-12-12

Uranium mononitride (UN) is important as a nuclear fuel. Fabrication of UN in its microspherical form also has its own merits since the advent of the concept of accident-tolerant fuel, where UN is being considered as a potential fuel in the form of TRISO particles. But, not many processes have been well established to synthesize kernels of UN. Therefore, a process for synthesis of microspherical UN with a minimum amount of carbon is discussed herein. First, a series of single-phased microspheres of uranium sesquinitride (U 2N 3) were synthesized by nitridation of UO 2+C microspheres at a few different temperatures.more » Resulting microspheres were of low-density U 2N 3 and decomposed into low-density UN. The variation of density of the synthesized sesquinitrides as a function of its chemical composition indicated the presence of extra (interstitial) nitrogen atoms corresponding to its hyperstoichiometry, which is normally indicated as α-U 2N 3. Average grain sizes of both U 2N 3 and UN varied in a range of 1–2.5 μm. In addition, these had a considerably large amount of pore spacing, indicating the potential sinterability of UN toward its use as a nuclear fuel.« less

Sequential delivery of BMP-2 and IGF-1 using a chitosan gel with gelatin microspheres enhances early osteoblastic differentiation

PubMed Central

Kim, Sungwoo; Kang, Yunqing; Krueger, Chad A.; Sen, Milan; Holcomb, John B.; Chen, Di; Wenke, Joseph C.; Yang, Yunzhi

2012-01-01

The purpose of this study was to develop and characterize a chitosan gel/gelatin microspheres (MSs) dual delivery system for sequential release of bone morphogenetic protein-2 (BMP-2) and insulin-like growth factor-1 (IGF-1) to enhance osteoblast differentiation in vitro. We made and characterized the delivery system based on its degree of cross-linking, degradation, and release kinetics. We also evaluated the cytotoxicity of the delivery system and the effect of growth factors on cell response using pre-osteoblast W-20-17 mouse bone marrow stromal cells. IGF-1 was first loaded into MSs, and then the IGF-1 containing MSs were encapsulated into the chitosan gel which contained BMP-2. Cross-linking of gelatin with glyoxal via Schiff bases significantly increased thermal stability and decreased the solubility of the MSs, leading to a significant decrease in the initial release of IGF-1. Encapsulation of the MSs into the chitosan gel generated polyelectrolyte complexes by intermolecular interactions, which further affected the release kinetics of IGF-1. This combinational delivery system provided an initial release of BMP-2 followed by a slow and sustained release of IGF-1. Significantly greater alkaline phosphatase activity was found in W-20-17 cells treated with the sequential delivery system than other treatments (p<0.05) after a week of culture. PMID:22293583

Hollow microspheres of diclofenac sodium - a gastroretentive controlled delivery system.

PubMed

Bv, Basavaraj; R, Deveswaran; S, Bharath; Abraham, Sindhu; Furtado, Sharon; V, Madhavan

2008-10-01

Most of the floating systems have an inherent drawback of high variability in the GI transit time, invariably affecting the bioavailability of drug. To overcome it, a multiple unit floating system with extended GI transit time, capable of distributing widely throughout the GIT for effective enteric release of the drug has been sought. Microballoons loaded with drug in their outer polymer shells were prepared by novel emulsion solvent diffusion method. The ethanol: dicloromethane solution of drug and Eudragit-S were poured into an aqueous solution of PVA that was thermally controlled at 40 degrees C. The gas phase generated in the dispersed polymer droplet by the evaporation of solvent formed an internal cavity in the microsphere of the polymer with the drug. The flowability of the resulting microballoons improved when compared to pure drug. The microballoons on floatation along with the surfactant, floated continuously for more than 12 hours in the acidic medium in-vitro conditions. The in-vitro drug release profile of the formulation in the simulated gastric buffer showed no drug release, which emphasizes the enteric release property and in simulated intestinal buffer, a slow and controlled drug release of 60 to 84% was obtained over a period of 8 hours. Drug release was significantly affected by increased drug to polymer concentration at pH 6.8. The formulation was found to be physically and chemically stable as per the ICH guidelines.

Hollow microspheres based on - Folic acid modified - Hydroxypropyl Cellulose and synthetic multi-responsive bio-copolymer for targeted cancer therapy: controlled release of daunorubicin, in vitro and in vivo studies.

PubMed

Metaxa, Aikaterini-Foteini; Efthimiadou, Eleni K; Boukos, Nikos; Fragogeorgi, Eirini A; Loudos, George; Kordas, George

2014-12-01

Conventional chemotherapy drugs such as anthracyclines show no specific activity. They destroy cancer cells but also and the healthy ones, and for that reason exhibit high toxicity. In order to alleviate the toxic effects of chemotherapeutic drugs, the administration dose is being minimized, while their reactivity against tumor cells is lessened. This problem can be overcome or at least reduced by using nanoscale drug delivery systems to target the pathogenic area. The present work deals with the synthesis, characterization and biological evaluation of multi-responsive hollow microspheres coated with Hydroxypropyl Cellulose (HPC)-a biocompatible and thermosensitive polysaccharide-conjugated with folic acid as well promising drug vehicles for targeted cancer therapy. The synthetic route consists of two steps. In the first step, a single layer of sensitive copolymers is ((Methacrylic acid (MAA), N-(2-Hydroxypropyl) methacrylamide (HPMA) and N,N'-(disulfanediylbis(ethane-2,1-diyl))bis(2-methylacrylamide) (DSBMA)) fabricated on a sacrificial template of SiO2 and in the second step, an additional layer of the folic acid modified HPC coat the microspheres' surface. The layers fabrication is performed through a combination of distillation precipitation co-polymerization and chemical deposition method. The loading capacity (% LC) and encapsulation efficiency (% EE) percentages of the chemotherapeutic agent daunorubicin (DNR) in the fabricated microspheres were calculated through the standard curve methodology. In addition, the releasing properties of the resulting spheres are investigated, using the above mentioned methodology. It is worth mentioning that, spheres release the entrapped drug under combined conditions such acidic and reductive environment along with conventional hyperthermia. Cytotoxic activity of the synthesized spheres was investigated by using the well-established method of MTT assay in MCF-7 (breast cancer), HeLa (cervical cancer) and HEK 293 (Human Embryonic Kidney healthy cells) cell lines. Confocal and fluorescence microscopy were used to confirm the in vitro targeted ability of folic acid modified drug loaded microspheres in HeLa, to that overexpress folate receptors, MCF-7 and 3T3 cells, as negative folate cell substrate. Finally, radiolabelling of the spheres is performed, with a gamma emitting radionuclide ((99m)Tc), to assess their in vivo profile by means of scintigraphic imaging and biodistribution studies. Hollow spheres release the encapsulated drug under acidic environment, conventional hyperthermia or in the presence of glutathione (reductive environment). The ability of modified drug carriers to target the HeLa cells, was confirmed by confocal and fluorescence microscopy. The resulting spheres are observed to be promising drug-carriers for cancer treatment due to their releasing properties under tumor's environment and high concentration in HeLa cells via endocytosis. In addition, the empty vehicles have no toxicity in healthy cells and present antimicrobial activity. Copyright © 2014 Elsevier Inc. All rights reserved.

Trisacryl Gelatin Microspheres Versus Polyvinyl Alcohol Particles in the Preoperative Embolization of Bone Neoplasms

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

Basile, Antonio; Rand, Thomas; Lomoschitz, Fritz

2004-09-15

The aim of this study was to compare the efficacy of trisacryl gelatin microspheres versus polyvinyl alcohol particles (PVA) in the preoperative embolization of bone neoplasms, on the basis of intraoperative blood loss quantified by the differences in preoperative and postoperative hematic levels of hemoglobin, hematocrit and erythrocytes count. From January 1997 to December 2002, preoperative embolization of bone tumors (either primary or secondary) was carried out in 49 patients (age range 12/78), 20 of whom were treated with trysacril gelatin microspheres (group A) and 29 with PVA particles (group B). The delay between embolization and surgery ranged from 1more » to 13 days in group A and 1 to 4 days in group B. As used in international protocols, we considered hematic levels of hemoglobin, hematocrit and erythrocytes count for the measurement of intraoperative blood loss then the differences in pre- and postoperative levels were used as statistical comparative parameters. We compared the values of patients treated with embospheres (n = 10) and PVA (n = 18) alone, and patients treated with (group A = 10; group B = 11) versus patients treated without other additional embolic materials in each group (group A = 10; group B = 18). According to the Student's t-test (p < 0.05), the difference of hematic parameters between patients treated by embospheres and PVA alone were significant; otherwise there was no significant difference between patients treated with only one embolic material (embospheres and PVA) versus those treated with other additional embolic agents in each group. The patients treated with microspheres had a minor quantification of intraoperative blood loss compared to those who received PVA particles. Furthermore, they had a minor increase of bleeding related to the delay time between embolization and surgery. The use of additional embolic material did not improve the efficacy of the procedure in either group of patients.« less

Dissolved Organic Matter Compositional Change and Biolability During Two Storm Runoff Events in a Small Agricultural Watershed

NASA Astrophysics Data System (ADS)

Eckard, Robert S.; Pellerin, Brian A.; Bergamaschi, Brian A.; Bachand, Philip A. M.; Bachand, Sandra M.; Spencer, Robert G. M.; Hernes, Peter J.

2017-10-01

Agricultural watersheds are globally pervasive, supporting fundamentally different organic matter source, composition, and concentration profiles in comparison to natural systems. Similar to natural systems, agricultural storm runoff exports large amounts of organic carbon from agricultural land into waterways. But intense management of upper soil layers, waterway channelization, wetland and riparian habitat removal, and postharvest vegetation removal promise to uniquely drive organic matter release to waterways. During a winter first flush and a subsequent storm event, this study investigated the influence of a small agricultural watershed on dissolved organic matter (DOM) source, composition, and biolability. Storm water discharge released strongly terrestrial yet biolabile (23 to 32%) dissolved organic carbon (DOC). Following a 21 day bioassay, a parallel factor analysis identified an 80% reduction in a protein-like (phenylpropyl) component (C2) that was previously correlated to lignin phenol concentration, and a 10% reduction in a humic-like, terrestrially sourced component (C4). Storm-driven releases tripled DOC concentration (from 2.8 to 8.7 mg L-1) during the first flush event in comparison to base flow and were terrestrially sourced, with an eightfold increase in vascular plant derived lignin phenols (23.0 to 185 μg L-1). As inferred from system hydrology, lignin composition, and nitrate as a groundwater tracer, an initial pulse of dilute water from the upstream watershed caused a counterclockwise DOC hysteresis loop. DOC concentrations peaked after 3.5 days, with the delay between peak discharge and peak DOC attributed to storm water hydrology and a period of initial water repellency of agricultural soils, which delayed DOM leaching.

Combined sustained release of BMP2 and MMP10 accelerates bone formation and mineralization of calvaria critical size defect in mice.

PubMed

Reyes, Ricardo; Rodríguez, Jose Antonio; Orbe, Josune; Arnau, María Rosa; Évora, Carmen; Delgado, Araceli

2018-11-01

The effect of dual delivery of bone morphogenetic protein-2 (BMP-2) and matrix metalloproteinase 10 (MMP10) on bone regeneration was investigated in a murine model of calvarial critical-size defect, hypothesizing that it would result in an enhanced bone formation. Critical-size calvarial defects (4 mm diameter) were created in mice and PLGA microspheres preloaded with either BMP-2, MMP10 or a microsphere combination of both were transplanted into defect sites at different doses. Empty microspheres were used as the negative control. Encapsulation efficiency was assessed and in vivo release kinetics of BMP-2 and MMP10 were examined over 14 days. Histological analyses were used to analyze bone formation after four and eight weeks. Combination with MMP10 (30 ng) significantly enhanced BMP-2 (600 ng)-mediated osteogenesis, as confirmed by the increase in percentage of bone fill (p < .05) at four weeks. Moreover, it also increased mineral apposition rate (p < .05), measured by double labeling with tetracycline and calceine. MMP10 accelerates bone repair by enhancing BMP-2-promoted bone healing and improving the mineralization rate. In conclusion combination of MMP10 and BMP-2 may become a promising strategy for repair and regeneration of bone defects.

Study on the fabrication of composite photonic crystals with high structural stability by co-sedimentation self-assembly on fabric substrates

NASA Astrophysics Data System (ADS)

Li, Yichen; Zhou, Lan; Liu, Guojin; Chai, Liqin; Fan, Qinguo; Shao, Jianzhong

2018-06-01

The Silica/Poly(methylmethacrylate-butylacrylate)[SiO2/P(MMA-BA)] photonic crystals(PCs) with brilliant structural colors were fabricated on fabric substrates by co-sedimentation self-assembly, in which the relatively smaller P(MMA-BA) copolymer particles filled in the interstices among the larger SiO2 microspheres. The fabricated composite PCs were mechanically robust and strongly bonded to the substrate because of the cementing effect caused by the soft P(MMA-BA) copolymer particles filling in the interstices of the SiO2 microspheres like cement filling in the gap and tightly holding stones in a sturdy cement wall. The volume fraction and the size ratios of the two components significantly influenced the structural colors of the composite PCs, and the larger volume fraction could improve the structural stability of the composite PCs, while the smaller size ratios could enhance the brightness of the structural colors of the composite PCs. The composite PCs with both high structural stability and brilliant structural colors have great application prospect for structural coloration of textiles.

Hierarchical, porous CuS microspheres integrated with carbon nanotubes for high-performance supercapacitors

PubMed Central

Lu, Yang; Liu, Xianming; Wang, Weixiao; Cheng, Jinbing; Yan, Hailong; Tang, Chengchun; Kim, Jang-Kyo; Luo, Yongsong

2015-01-01

Carbon nanotubes (CNTs) incorporated porous 3-dimensional (3D) CuS microspheres have been successfully synthesized via a simple refluxing method assisted by PVP. The composites are composed of flower-shaped CuS secondary microspheres, which in turn are assembled with primary nanosheets of 15–30 nm in thickness and fully integrated with CNT. The composites possess a large specific surface area of 189.6 m2 g−1 and a high conductivity of 0.471 S cm−1. As electrode materials for supercapacitors, the nanocomposites show excellent cyclability and rate capability and deliver an average reversible capacitance as high as 1960 F g−1 at a current density of 10 mA cm−2 over 10000 cycles. The high electrochemical performance can be attributed to the synergistic effect of CNTs and the unique microstructure of CuS. The CNTs serve as not only a conductive agent to accelerate the transfer of electrons in the composites, but also as a buffer matrix to restrain the volume change and stabilize the electrode structure during the charge/discharge process. The porous structure of CuS also helps to stabilize the electrode structure and facilitates the transport for electrons. PMID:26568518

A tissue engineering approach for prenatal closure of myelomeningocele: comparison of gelatin sponge and microsphere scaffolds and bioactive protein coatings.

PubMed

Watanabe, Miho; Li, Hiaying; Roybal, Jessica; Santore, Matthew; Radu, Antonetta; Jo, Jun-Ichiro; Kaneko, Michio; Tabata, Yasuhiko; Flake, Alan

2011-04-01

Myelomeningocele (MMC) is a common and devastating malformation. As an alternative to fetal surgical repair, tissue engineering has the potential to provide a less invasive approach for tissue coverage applicable at an earlier stage of gestation. We have previously evaluated the use of gelatin hydrogel composites composed of gelatin sponges and sheets as a platform for tissue coverage of the MMC defect in the retinoic acid induced fetal rat model of MMC. In the current study, we compare our previous composite with gelatin microspheres as a scaffold for tissue ingrowth and cellular adhesion within the amniotic fluid environment. We also examine the relative efficacy of various bioactive protein coatings on the adhesion of amniotic fluid cells to the construct within the amniotic cavity. We conclude from this study that gelatin microspheres are as effective as gelatin sponges as a scaffold for cellular ingrowth and amniotic fluid cell adhesion and that collagen type I and fibronectin coatings enhance amniotic fluid cell adhesion to the gelatin-based scaffolds. These findings support the potential for the development of a tissue-engineered injectable scaffold that could be applied by ultrasound-guided injection, much earlier and less invasively than sponge or sheet-based composites.

Active self-healing encapsulation of vaccine antigens in PLGA microspheres

PubMed Central

Desai, Kashappa-Goud H.; Schwendeman, Steven P.

2013-01-01

Herein, we describe the detailed development of a simple and effective method to microencapsulate vaccine antigens in poly(lactic-co-glycolic acid) (PLGA) by simple mixing of preformed active self-microencapsulating (SM) PLGA microspheres in a low concentration aqueous antigen solution at modest temperature (10-38 °C). Co-encapsulating protein-sorbing vaccine adjuvants and polymer plasticizers were used to “actively” load the protein in the polymer pores and facilitate polymer self-healing at temperature > hydrated polymer glass transition temperature, respectively. The microsphere formulation parameters and loading conditions to provide optimal active self-healing microencapsulation of vaccine antigen in PLGA was investigated. Active self-healing encapsulation of two vaccine antigens, ovalbumin and tetanus toxoid (TT), in PLGA microspheres was adjusted by preparing blank microspheres containing different vaccine adjuvant (aluminum hydroxide (Al(OH)3) or calcium phosphate). Active loading of vaccine antigen in Al(OH)3-PLGA microspheres was found to: a) increase proportionally with an increasing loading of Al(OH)3 (0.88-3 wt%) and addition of porosigen, b) decrease when the inner Al(OH)3/trehalose phase to 1 mL outer oil phase and size of microspheres was respectively > 0.2 mL and 63 μm, and c) change negligibly by PLGA concentration and initial incubation (loading) temperature. Encapsulation of protein sorbing Al(OH)3 in PLGA microspheres resulted in suppression of self-healing of PLGA pores, which was then overcome by improving polymer chain mobility, which in turn was accomplished by coincorporating hydrophobic plasticizers in PLGA. Active self-healing microencapsulation of manufacturing process-labile TT in PLGA was found to: a) obviate micronization- and organic solvent-induced TT degradation, b) improve antigen loading (1.4-1.8 wt% TT) and encapsulation efficiency (~ 97%), c) provide nearly homogeneous distribution and stabilization of antigen in polymer, and d) provide improved in vitro controlled release of antigenic TT. PMID:23103983

Hydroxyapatite hierarchically nanostructured porous hollow microspheres: rapid, sustainable microwave-hydrothermal synthesis by using creatine phosphate as an organic phosphorus source and application in drug delivery and protein adsorption.

PubMed

Qi, Chao; Zhu, Ying-Jie; Lu, Bing-Qiang; Zhao, Xin-Yu; Zhao, Jing; Chen, Feng; Wu, Jin

2013-04-22

Hierarchically nanostructured porous hollow microspheres of hydroxyapatite (HAP) are a promising biomaterial, owing to their excellent biocompatibility and porous hollow structure. Traditionally, synthetic hydroxyapatite is prepared by using an inorganic phosphorus source. Herein, we report a new strategy for the rapid, sustainable synthesis of HAP hierarchically nanostructured porous hollow microspheres by using creatine phosphate disodium salt as an organic phosphorus source in aqueous solution through a microwave-assisted hydrothermal method. The as-obtained products are characterized by powder X-ray diffraction (XRD), Fourier-transform IR (FTIR) spectroscopy, SEM, TEM, Brunauer-Emmett-Teller (BET) nitrogen sorptometry, dynamic light scattering (DLS), and thermogravimetric analysis (TGA). SEM and TEM micrographs show that HAP hierarchically nanostructured porous hollow microspheres consist of HAP nanosheets or nanorods as the building blocks and DLS measurements show that the diameters of HAP hollow microspheres are within the range 0.8-1.5 μm. The specific surface area and average pore size of the HAP porous hollow microspheres are 87.3 m(2) g(-1) and 20.6 nm, respectively. The important role of creatine phosphate disodium salt and the influence of the experimental conditions on the products were systematically investigated. This method is facile, rapid, surfactant-free and environmentally friendly. The as-prepared HAP porous hollow microspheres show a relatively high drug-loading capacity and protein-adsorption ability, as well as sustained drug and protein release, by using ibuprofen as a model drug and hemoglobin (Hb) as a model protein, respectively. These experiments indicate that the as-prepared HAP porous hollow microspheres are promising for applications in biomedical fields, such as drug delivery and protein adsorption. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Formation and oral administration of alginate microspheres loaded with pDNA coding for lymphocystis disease virus (LCDV) to Japanese flounder.

PubMed

Tian, Ji-Yuan; Sun, Xiu-Qin; Chen, Xi-Guang

2008-05-01

Oral delivery of plasmid DNA (pDNA) is a desirable approach for fish immunization in intensive culture. However, its effectiveness is limited because of possible degradation of pDNA in the fish's digestive system. In this report, alginate microspheres loaded with pDNA coding for fish lymphocystis disease virus (LCDV) and green fluorescent protein were prepared with a modified oil containing water (W/O) emulsification method. Yield, loading percent and encapsulation efficiency of alginate microspheres were 90.5%, 1.8% and 92.7%, respectively. The alginate microspheres had diameters of less than 10 microm, and their shape was spherical. As compared to sodium alginate, a remarkable increase of DNA-phosphodiester and DNA-phosphomonoester bonds was observed for alginate microspheres loaded with pDNA by Fourier transform infrared (FTIR) spectroscopic analysis. Agarose gel electrophoresis showed a little supercoiled pDNA was transformed to open circular and linear pDNA during encapsulation. The cumulative release of pDNA in alginate microspheres was or=0.3) for anti-LCDV antibody from week 3 to week 16 for fish orally vaccinated with alginate microspheres loaded with pDNA, in comparison with fish orally vaccinated with naked pDNA. Our results display that alginate microspheres obtained by W/O emulsification are promising carriers for oral delivery of pDNA. This encapsulation technique has the potential for DNA vaccine delivery applications due to its ease of operation, low cost and significant immune effect.

High-surface-area mesoporous TiO2 microspheres via one-step nanoparticle self-assembly for enhanced lithium-ion storage

NASA Astrophysics Data System (ADS)

Wang, Hsin-Yi; Chen, Jiazang; Hy, Sunny; Yu, Linghui; Xu, Zhichuan; Liu, Bin

2014-11-01

Mesoporous TiO2 microspheres assembled from TiO2 nanoparticles with specific surface areas as high as 150 m2 g-1 were synthesized via a facile one-step solvothermal reaction of titanium isopropoxide and anhydrous acetone. Aldol condensation of acetone gradually releases structural H2O, which hydrolyzes and condenses titanium isopropoxide, forming TiO2 nanocrystals. Simultaneous growth and aggregation of TiO2 nanocrystals leads to the formation of high-surface-area TiO2 microspheres under solvothermal conditions. After a low-temperature post-synthesis calcination, carbonate could be incorporated into TiO2 as a dopant with the carbon source coming from the organic byproducts during the synthesis. Carbonate doping modifies the electronic structure of TiO2 (e.g., Fermi level, Ef), and thus influences its electrochemical properties. Solid electrolyte interface (SEI) formation, which is not common for titania, could be initiated in carbonate-doped TiO2 due to elevated Ef. After removing carbonate dopants by high-temperature calcination, the mesoporous TiO2 microspheres showed much improved performance in lithium insertion and stability at various current rates, attributed to a synergistic effect of high surface area, large pore size and good anatase crystallinity.Mesoporous TiO2 microspheres assembled from TiO2 nanoparticles with specific surface areas as high as 150 m2 g-1 were synthesized via a facile one-step solvothermal reaction of titanium isopropoxide and anhydrous acetone. Aldol condensation of acetone gradually releases structural H2O, which hydrolyzes and condenses titanium isopropoxide, forming TiO2 nanocrystals. Simultaneous growth and aggregation of TiO2 nanocrystals leads to the formation of high-surface-area TiO2 microspheres under solvothermal conditions. After a low-temperature post-synthesis calcination, carbonate could be incorporated into TiO2 as a dopant with the carbon source coming from the organic byproducts during the synthesis. Carbonate doping modifies the electronic structure of TiO2 (e.g., Fermi level, Ef), and thus influences its electrochemical properties. Solid electrolyte interface (SEI) formation, which is not common for titania, could be initiated in carbonate-doped TiO2 due to elevated Ef. After removing carbonate dopants by high-temperature calcination, the mesoporous TiO2 microspheres showed much improved performance in lithium insertion and stability at various current rates, attributed to a synergistic effect of high surface area, large pore size and good anatase crystallinity. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr04729j

Molybdenum-base cermet fuel development

NASA Astrophysics Data System (ADS)

Pilger, James P.; Gurwell, William E.; Moss, Ronald W.; White, George D.; Seifert, David A.

Development of a multimegawatt (MMW) space nuclear power system requires identification and resolution of several technical feasibility issues before selecting one or more promising system concepts. Demonstration of reactor fuel fabrication technology is required for cermet-fueled reactor concepts. The MMW reactor fuel development activity at Pacific Northwest Laboratory (PNL) is focused on producing a molybdenum-matrix uranium-nitride (UN) fueled cermte. This cermet is to have a high matrix density (greater than or equal to 95 percent) for high strength and high thermal conductance coupled with a high particle (UN) porosity (approximately 25 percent) for retention of released fission gas at high burnup. Fabrication process development involves the use of porous TiN microspheres as surrogate fuel material until porous Un microspheres become available. Process development was conducted in the areas of microsphere synthesis, particle sealing/coating, and high-energy-rate forming (HERF) and the vacuum hot press consolidation techniques. This paper summarizes the status of these activities.

In-situ synthesis of monodisperse micro-nanospherical LiFePO4/carbon cathode composites for lithium-ion batteries

NASA Astrophysics Data System (ADS)

Gong, Hao; Xue, Hairong; Wang, Tao; He, Jianping

2016-06-01

The LiFePO4 is recognized as the promising cathode material, due to its high specific capacity, excellent, structural stability and environmental benignity. However, it is blamed for the low tap density and poor rate performance when served as the cathode materials for a long time. Here, the microspheric LiFePO4/C composites are successfully synthesized through a one-step in-situ solvothermal method combined with carbothermic reduction. These LiFePO4/C microspheres are assembled by LiFePO4 nanoparticles (∼100 nm) and uniformly coated by the carbon, which show a narrow diameter distribution of 4 μm. As a cathode material for lithium ion batteries, the LiFePO4/C composites can deliver an initiate charge capacity of 155 mAh g-1 and retain 90% of initial capacity after 200 cycles at 0.1 C. When cycled at high current densities up to 20 C, it shows a discharge capacity of ∼60 mAh g-1, exhibiting superior rate performance. The significantly improved electrochemical performance of LiFePO4/C composites material can be attributed to its special micro-nano hierarchical structure. Microspheric LiFePO4/C composites exhibit a high tap density about 1.3 g cm-3. What's more, the well-coated carbon insures the high electrical conductivity and the nano-sized LiFePO4/C particles shorten lithium ion transport, thus exhibiting the high specific capacity, high cycling stability and good rate performance.

Insight into the core-shell structures of Cu-In-S microspheres

NASA Astrophysics Data System (ADS)

Wochnik, Angela S.; Frank, Anna; Heinzl, Christoph; Häusler, Jonas; Schneider, Julian; Hoffmann, Ramona; Matich, Sonja; Scheu, Christina

2013-12-01

In this study we report about the inner and outer structure of CuInS2 microspheres which might be used e.g. in pastes for simple, low-cost solar cell preparation, as well as in electrodes for light-driven water splitting. The microspheres are synthesized via a mild, template-free solvothermal synthesis route and characterised by electron and focused ion beam microscopy, X-ray diffraction, inductively coupled plasma atomic emission and energy dispersive X-ray spectroscopy. The investigations of cross sections prepared by focused ion beam showed that the spheres consist of compact cores and flaky surface structures. Depending on the reaction time, the core possesses a stoichiometric or Cu-rich chemical composition surrounded by an In-rich shell. The flaky surface always comprises a stoichiometric composition in tetragonal chalcopyrite crystal structure, whereas the other areas additionally show minor contributions of CuS, and CuInS2 in hexagonal wurtzite structure. The presence of different phases can be beneficial for future applications since they offer different absorption behaviour in the visible range.

New bioactive bone-like microspheres with intrinsic magnetic properties obtained by bio-inspired mineralisation process.

PubMed

Fernandes Patrício, Tatiana Marisa; Panseri, Silvia; Sandri, Monica; Tampieri, Anna; Sprio, Simone

2017-08-01

A bio-inspired mineralisation process was investigated and applied to develop novel hybrid magnetic materials by heterogeneous nucleation of Fe 2+ /Fe 3+ -doped hydroxyapatite nanocrystals onto a biopolymeric matrix made of a Type I collagen-based recombinant peptide (RCP). The effect of the synthesis temperature on the phase composition, crystallinity and magnetic properties of the nucleated inorganic phase was studied. The as-obtained magnetic materials were then engineered, by using a water-in-oil emulsification process, into hybrid magnetic microspheres, which were stabilized by de-hydrothermal treatment yielding cross-linking of the macromolecular matrix. Thorough investigation of the physicochemical, morphological and biological properties of the new hybrid microspheres, as induced by the presence of the inorganic nanophase and controlled iron substitution into hydroxyapatite lattice, revealed bone-like composition, good cytocompatibility, designed shape and size, and tailored magnetization. Such features are interesting and promising for application as new biomaterials with ability of remote activation and control by using external magnetic fields, for smart and personalized applications in medicine, particularly in bone tissue regeneration. Copyright © 2017 Elsevier B.V. All rights reserved.

Balancing mechanical strength with bioactivity in chitosan-calcium phosphate 3D microsphere scaffolds for bone tissue engineering: air- vs. freeze-drying processes.

PubMed

Nguyen, D T; McCanless, J D; Mecwan, M M; Noblett, A P; Haggard, W O; Smith, R A; Bumgardner, J D

2013-01-01

The objective of this study was to evaluate the potential benefit of 3D composite scaffolds composed of chitosan and calcium phosphate for bone tissue engineering. Additionally, incorporation of mechanically weak lyophilized microspheres within those air-dried (AD) was considered for enhanced bioactivity. AD microsphere, alone, and air- and freeze-dried microsphere (FDAD) 3D scaffolds were evaluated in vitro using a 28-day osteogenic culture model with the Saos-2 cell line. Mechanical testing, quantitative microscopy, and lysozyme-driven enzymatic degradation of the scaffolds were also studied. FDAD scaffold showed a higher concentration (p < 0.01) in cells per scaffold mass vs. AD constructs. Collagen was ∼31% greater (p < 0.01) on FDAD compared to AD scaffolds not evident in microscopy of microsphere surfaces. Alternatively, AD scaffolds demonstrated a superior threefold increase in compressive strength over FDAD (12 vs. 4 MPa) with minimal degradation. Inclusion of FD spheres within the FDAD scaffolds allowed increased cellular activity through improved seeding, proliferation, and extracellular matrix production (as collagen), although mechanical strength was sacrificed through introduction of the less stiff, porous FD spheres.

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

Silva, Chinthaka M.; Hunt, Rodney Dale; Snead, Lance Lewis

Uranium mononitride (UN) is important as a nuclear fuel. Fabrication of UN in its microspherical form also has its own merits since the advent of the concept of accident-tolerant fuel, where UN is being considered as a potential fuel in the form of TRISO particles. But, not many processes have been well established to synthesize kernels of UN. Therefore, a process for synthesis of microspherical UN with a minimum amount of carbon is discussed herein. First, a series of single-phased microspheres of uranium sesquinitride (U 2N 3) were synthesized by nitridation of UO 2+C microspheres at a few different temperatures.more » Resulting microspheres were of low-density U 2N 3 and decomposed into low-density UN. The variation of density of the synthesized sesquinitrides as a function of its chemical composition indicated the presence of extra (interstitial) nitrogen atoms corresponding to its hyperstoichiometry, which is normally indicated as α-U 2N 3. Average grain sizes of both U 2N 3 and UN varied in a range of 1–2.5 μm. In addition, these had a considerably large amount of pore spacing, indicating the potential sinterability of UN toward its use as a nuclear fuel.« less

In-situ preparation and unique electrochemical behavior of pore-embedding CoO/Co3O4 intermixed composite for Li+ rechargeable battery electrodes

NASA Astrophysics Data System (ADS)

Kim, Jin Kyu; Ju, Ji Young; Choi, Seul Ki; Unithrattil, Sanjith; Lee, Sun Sook; Kang, Yongku; Kim, Yongseon; Im, Won Bin; Choi, Sungho

2018-02-01

Electrochemically active CoO/Co3O4 co-existing microspheres with morphology-inherited porous particles is successfully synthesized via a simple solvothermal method. The as-prepared intermixed composite undergoes a monoxide CoO-preferred conversion reaction with an extremely enhanced capacity retention, ∼905 mA h g-1 after 250 cycles for discharge state, which is 1.6 times higher than the conventional CoOx-based anodes. Moreover, stable catalytic behavior of the electrocatalysts in Li-air cathodes of the given composites is also demonstrated. We believe that the extraordinarily enhanced electrode performance might be due to the novel pore-tempered microspheres packed with double electrochemically active centers of the CoO/Co3O4 composite effectively confine the detrimental volume exchange during the reversible cyclic reactions as well as the preserved multiple reactive sites for a reversible Li+ ⇄ LiOx reaction, which is advantageous for advanced Li rechargeable battery.

Fabrication of poly(o-anisidine) coated silica core-shell microspheres and their electrorheological response

NASA Astrophysics Data System (ADS)

Lee, Chul Joo; Choi, Hyoung Jin

2017-11-01

In this work, silica/poly(o-anisidine) (POA) core-shell structured microspheres were synthesized by coating the silica core surface with POA with a help of a chemical grafting agent, N-[(3-trimethoxylsilyl)-propyl] aniline. The synthesized silica microspheres were then applied as a polymer/inorganic composite particle-based electrorheological (ER) fluid. The morphology of the silica/POA microspheres was examined by using both transmission electron microscopy and scanning electron microscopy, while their thermal properties and chemical structure were checked by thermogravimetric analysis and Fourier-transform infrared spectroscopy, respectively. The ER properties of the silica/POA particle-based ER fluid were examined by using a Couette-type rotational rheometer equipped with a high-voltage power supplier and analyzed by the Bingham model and modified Mason number. In order to obtain additional information about the electrical polarization properties, the dielectric spectra were measured by an LCR meter and fitted by using the Cole-Cole equation. Furthermore, suspension stability of the ER fluid was tested using Turbiscan.

Synthesis and characterization of magnetic poly(divinyl benzene)/Fe3O4, C/Fe3O4/Fe, and C/Fe onionlike fullerene micrometer-sized particles with a narrow size distribution.

PubMed

Snovski, Ron; Grinblat, Judith; Margel, Shlomo

2011-09-06

Magnetic poly(divinyl benzene)/Fe(3)O(4) microspheres with a narrow size distribution were produced by entrapping the iron pentacarbonyl precursor within the pores of uniform porous poly(divinyl benzene) microspheres prepared in our laboratory, followed by the decomposition in a sealed cell of the entrapped Fe(CO)(5) particles at 300 °C under an inert atmosphere. Magnetic onionlike fullerene microspheres with a narrow size distribution were produced by annealing the obtained PDVB/Fe(3)O(4) particles at 500, 600, 800, and 1100 °C, respectively, under an inert atmosphere. The formation of carbon graphitic layers at low temperatures such as 500 °C is unique and probably obtained because of the presence of the magnetic iron nanoparticles. The annealing temperature allowed control of the composition, size, size distribution, crystallinity, porosity, and magnetic properties of the produced magnetic microspheres. © 2011 American Chemical Society

Acceleration of hard and soft tissue healing in the oral cavity by a single transmucosal injection of fluvastatin-impregnated poly (lactic-co-glycolic acid) microspheres. An in vitro and rodent in vivo study.

PubMed

Yasunami, Noriyuki; Ayukawa, Yasunori; Furuhashi, Akihiro; Atsuta, Ikiru; Rakhmatia, Yunia Dwi; Moriyama, Yasuko; Masuzaki, Tomohiro; Koyano, Kiyoshi

2015-12-23

Antihyperlipidemic drug statins reportedly promote both bone formation and soft tissue healing. We examined the effect of sustained-release, fluvastatin-impregnated poly(lactic-co-glycolic acid) (PLGA) microspheres on the promotion of bone and gingival healing at an extraction socket in vivo, and the effect of fluvastatin on epithelial cells and fibroblasts in vitro. The maxillary right first molar was extracted in rats, then one of the following was immediately injected, as a single dose, into the gingivobuccal fold: control (no administration), PLGA microspheres without a statin (active control), or PLGA microspheres containing 20 or 40 μg kg(-1) of fluvastatin. At days 1, 3, 7, 14, and 28 after injection, bone and soft tissue healing were histologically evaluated. Cell proliferation was measured under the effect of fluvastatin at dosages of 0, 0.01, 0.1, 1.0, 10, and 50 μM. Cell migration and morphology were observed at dosages of 0 and 0.1 μM. Following tooth extraction, the statin significantly enhanced bone volume and density, connective tissue volume, and epithelial wound healing. In the in vitro study, it promoted significant proliferation and migration of epithelial cells and fibroblasts. A single dose of topically administered fluvastatin-impregnated PLGA microspheres promoted bone and soft tissue healing at the extraction site.

VEGF-incorporated biomimetic poly(lactide-co-glycolide) sintered microsphere scaffolds for bone tissue engineering.

PubMed

Jabbarzadeh, Ehsan; Deng, Meng; Lv, Qing; Jiang, Tao; Khan, Yusuf M; Nair, Lakshmi S; Laurencin, Cato T

2012-11-01

Regenerative engineering approaches utilizing biomimetic synthetic scaffolds provide alternative strategies to repair and restore damaged bone. The efficacy of the scaffolds for functional bone regeneration critically depends on their ability to induce and support vascular infiltration. In the present study, three-dimensional (3D) biomimetic poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds were developed by sintering together PLAGA microspheres followed by nucleation of minerals in a simulated body fluid. Further, the angiogenic potential of vascular endothelial growth factor (VEGF)-incorporated mineralized PLAGA scaffolds were examined by monitoring the growth and phenotypic expression of endothelial cells on scaffolds. Scanning electron microscopy micrographs confirmed the growth of bone-like mineral layers on the surface of microspheres. The mineralized PLAGA scaffolds possessed interconnectivity and a compressive modulus of 402 ± 61 MPa and compressive strength of 14.6 ± 2.9 MPa. Mineralized scaffolds supported the attachment and growth and normal phenotypic expression of endothelial cells. Further, precipitation of apatite layer on PLAGA scaffolds resulted in an enhanced VEGF adsorption and prolonged release compared to nonmineralized PLAGA and, thus, a significant increase in endothelial cell proliferation. Together, these results demonstrated the potential of VEGF-incorporated biomimetic PLAGA sintered microsphere scaffolds for bone tissue engineering as they possess the combined effects of osteointegrativity and angiogenesis. Copyright © 2012 Wiley Periodicals, Inc.

In situ characterization of uranium and americium oxide solid solution formation for CRMP process: first combination of in situ XRD and XANES measurements.

PubMed

Caisso, Marie; Picart, Sébastien; Belin, Renaud C; Lebreton, Florent; Martin, Philippe M; Dardenne, Kathy; Rothe, Jörg; Neuville, Daniel R; Delahaye, Thibaud; Ayral, André

2015-04-14

Transmutation of americium in heterogeneous mode through the use of U1-xAmxO2±δ ceramic pellets, also known as Americium Bearing Blankets (AmBB), has become a major research axis. Nevertheless, in order to consider future large-scale deployment, the processes involved in AmBB fabrication have to minimize fine particle dissemination, due to the presence of americium, which considerably increases the risk of contamination. New synthesis routes avoiding the use of pulverulent precursors are thus currently under development, such as the Calcined Resin Microsphere Pelletization (CRMP) process. It is based on the use of weak-acid resin (WAR) microspheres as precursors, loaded with actinide cations. After two specific calcinations under controlled atmospheres, resin microspheres are converted into oxide microspheres composed of a monophasic U1-xAmxO2±δ phase. Understanding the different mechanisms during thermal conversion, that lead to the release of organic matter and the formation of a solid solution, appear essential. By combining in situ techniques such as XRD and XAS, it has become possible to identify the key temperatures for oxide formation, and the corresponding oxidation states taken by uranium and americium during mineralization. This paper thus presents the first results on the mineralization of (U,Am) loaded resin microspheres into a solid solution, through in situ XAS analysis correlated with HT-XRD.

21 CFR 343.90 - Dissolution and drug release testing.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin delayed-release tablets. Aspirin delayed-release capsules and aspirin delayed-release tablets must meet...

21 CFR 343.90 - Dissolution and drug release testing.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin delayed-release tablets. Aspirin delayed-release capsules and aspirin delayed-release tablets must meet...

21 CFR 343.90 - Dissolution and drug release testing.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin delayed-release tablets. Aspirin delayed-release capsules and aspirin delayed-release tablets must meet...

21 CFR 343.90 - Dissolution and drug release testing.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin delayed-release tablets. Aspirin delayed-release capsules and aspirin delayed-release tablets must meet...

21 CFR 343.90 - Dissolution and drug release testing.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin delayed-release tablets. Aspirin delayed-release capsules and aspirin delayed-release tablets must meet...

Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo.

PubMed

Santos, Daniel; Giudetti, Guido; Micera, Silvestro; Navarro, Xavier; Del Valle, Jaume

2016-04-01

Neurotrophic factors (NTFs) promote nerve regeneration and neuronal survival after peripheral nerve injury. However, drawbacks related with administration and bioactivity during long periods limit their therapeutic application. In this study, PLGA microspheres (MPs) were used to locally release different NTFs and evaluate whether they accelerate axonal regeneration in comparison with free NTFs or controls. ELISA, SEM, UV/visible light microscopy, organotypic cultures of DRG explants and spinal cord slices were used to characterize MP properties and the bioactivity of the released NTFs. Results of organotypic cultures showed that encapsulated NTFs maintain longer bioactivity and enhance neurite regeneration of both sensory and motor neurons compared with free NTFs. For in vivo assays, the rat sciatic nerve was transected and repaired with a silicone tube filled with collagen gel or collagen mixed with PBS encapsulated MPs (control groups) and with free or encapsulated NGF, BDNF, GDNF or FGF-2. After 20 days, a retrotracer was applied to the regenerated nerve to quantify motor and sensory axonal regeneration. NTF encapsulation in MPs improved regeneration of both motor and sensory axons, as evidenced by increased numbers of retrolabeled neurons. Hence, our results show that slow release of NTFs with PLGA MP enhance nerve regeneration. Copyright © 2016 Elsevier B.V. All rights reserved.

Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review

PubMed Central

Islam, Mohammad Ariful; Firdous, Jannatul; Choi, Yun-Jaie; Yun, Cheol-Heui; Cho, Chong-Su

2012-01-01

Chitosan, a natural biodegradable polymer, is of great interest in biomedical research due to its excellent properties including bioavailability, nontoxicity, high charge density, and mucoadhesivity, which creates immense potential for various pharmaceutical applications. It has gelling properties when it interacts with counterions such as sulfates or polyphosphates and when it crosslinks with glutaraldehyde. This characteristic facilitates its usefulness in the coating or entrapment of biochemicals, drugs, antigenic molecules as a vaccine candidate, and microorganisms. Therefore, chitosan together with the advance of nanotechnology can be effectively applied as a carrier system for vaccine delivery. In fact, chitosan microspheres have been studied as a promising carrier system for mucosal vaccination, especially via the oral and nasal route to induce enhanced immune responses. Moreover, the thiolated form of chitosan is of considerable interest due to its improved mucoadhesivity, permeability, stability, and controlled/extended release profile. This review describes the various methods used to design and synthesize chitosan microspheres and recent updates on their potential applications for oral and nasal delivery of vaccines. The potential use of thiolated chitosan microspheres as next-generation mucosal vaccine carriers is also discussed. PMID:23271909

The behaviour of selected yttrium containing bioactive glass microspheres in simulated body environments.

PubMed

Cacaina, D; Ylänen, H; Simon, S; Hupa, M

2008-03-01

The study aims at the manufacture and investigation of biodegradable glass microspheres incorporated with yttrium potentially useful for radionuclide therapy of cancer. The glass microspheres in the SiO2-Na2O-P2O5-CaO-K2O-MgO system containing yttrium were prepared by conventional melting and flame spheroidization. The behaviour of the yttrium silicate glass microspheres was investigated under in vitro conditions using simulated body fluid (SBF) and Tris buffer solution (TBS), for different periods of time, according to half-life time of the Y-90. The local structure of the glasses and the effect of yttrium on the biodegradability process were evaluated by Fourier Transform Infrared (FT-IR) spectroscopy and Back Scattered Electron Imaging of Scanning Electron Microscopy (BEI-SEM) equipped with Energy Dispersive X-ray (EDX) analysis. UV-VIS spectrometry and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used for analyzing the release behaviour of silica and yttrium in the two used solutions. The results indicate that the addition of yttrium to a bioactive glass increases its structural stability which therefore, induced a different behaviour of the glasses in simulated body environments.

Morphology-dependent resonances of a microsphere-optical fiber system

NASA Astrophysics Data System (ADS)

Griffel, Giora; Arnold, Stephen; Taskent, Dogan; Serpengüzel, Ali; Connolly, John; Morris, Nancy

1996-05-01

Morphology-dependent resonances of microspheres sitting upon an index-matched single-mode fiber half-coupler are excited by a tunable 753-nm distributed-feedback laser. Resonance peaks in the scattering spectra and associated dips in the transmission spectra for the TE and TM modes are observed. We present a new model that describes this interaction in terms of the fiber-sphere coupling coefficient and the microsphere's intrinsic quality factor Q0 . This model enables us to obtain expressions for the finesse and the Q factor of the composite particle-fiber system, the resonance width, and the depth of the dips measured in the transmission spectra. Our model shows that index matching improves the coupling efficiency by more than a factor of 2 compared with that of a non-index-matched system.

Morphology-dependent resonances of a microsphere-optical fiber system.

PubMed

Griffel, G; Arnold, S; Taskent, D; Serpengüzel, A; Connolly, J; Morris, N

1996-05-15

Morphology-dependent resonances of microspheres sitting upon an index-matched single-mode fiber half-coupler are excited by a tunable 753-nm distributed-feedback laser. Resonance peaks in the scattering spectra and associated dips in the transmission spectra for the TE and TM modes are observed. We present a new model that describes this interaction in terms of the fiber-sphere coupling coefficient and the microsphere's intrinsic quality factor Q(0). This model enables us to obtain expressions for the finesse and the Q factor of the composite particle-fiber system, the resonance width, and the depth of the dips measured in the transmission spectra. Our model shows that index matching improves the coupling efficiency by more than a factor of 2 compared with that of a non-index-matched system.

Stimuli-responsive polyaniline coated silica microspheres and their electrorheology

NASA Astrophysics Data System (ADS)

Park, Dae Eun; Choi, Hyoung Jin; Vu, Cuong Manh

2016-05-01

Silica/polyaniline (PANI) core-shell structured microspheres were synthesized by coating the surface of silica micro-beads with PANI and applied as a candidate inorganic/polymer composite electrorheological (ER) material. The silica micro-beads were initially modified using N-[(3-trimethoxysilyl)-propyl] aniline to activate an aniline functional group on the silica surface for a better PANI coating. The morphology of the PANI coating on the silica surface was examined by scanning electron microscopy and the silica/PANI core-shell structure was confirmed by transmission electron microscopy. The chemical structure of the particles was confirmed by Fourier transform infrared spectroscopy. Rotational rheometry was performed to confirm the difference in the ER properties between pure silica and silica/PANI microsphere-based ER fluids when dispersed in silicone oil.

Fluxgate magnetorelaxometry: a new approach to study the release properties of hydrogel cylinders and microspheres.

PubMed

Wöhl-Bruhn, S; Heim, E; Schwoerer, A; Bertz, A; Harling, S; Menzel, H; Schilling, M; Ludwig, F; Bunjes, H

2012-10-15

Hydrogels are under investigation as long term delivery systems for biomacromolecules as active pharmaceutical ingredients. The release behavior of hydrogels can be tailored during the fabrication process. This study investigates the applicability of fluxgate magnetorelaxometry (MRX) as a tool to characterize the release properties of such long term drug delivery depots. MRX is based on the use of superparamagnetic core-shell nanoparticles as model substances. The feasibility of using superparamagnetic nanoparticles to study the degradation of and the associated release from hydrogel cylinders and hydrogel microspheres was a major point of interest. Gels prepared from two types of photo crosslinkable polymers based on modified hydroxyethylstarch, specifically hydroxyethyl starch-hydroxyethyl methacrylate (HES-HEMA) and hydroxyethyl starch-polyethylene glycol methacrylate (HES-P(EG)(6)MA), were analyzed. MRX analysis of the incorporated nanoparticles allowed to evaluate the influence of different crosslinking conditions during hydrogel production as well as to follow the increase in nanoparticle mobility as a result of hydrogel degradation during release studies. Conventional release studies with fluorescent markers (half-change method) were performed for comparison. MRX with superparamagnetic nanoparticles as model substances is a promising method to analyze pharmaceutically relevant processes such as the degradation of hydrogel drug carrier systems. In contrast to conventional release experiments MRX allows measurements in closed vials (reducing loss of sample and sampling errors), in opaque media and at low magnetic nanoparticle concentrations. Magnetic markers possess a better long-term stability than fluorescent ones and are thus also promising for the use in in vivo studies. Copyright © 2012 Elsevier B.V. All rights reserved.

The first microbiological contamination assessment by deep-sea drilling and coring by the D/V Chikyu at the Iheya North hydrothermal field in the Mid-Okinawa Trough (IODP Expedition 331)

PubMed Central

Yanagawa, Katsunori; Nunoura, Takuro; McAllister, Sean M.; Hirai, Miho; Breuker, Anja; Brandt, Leah; House, Christopher H.; Moyer, Craig L.; Birrien, Jean-Louis; Aoike, Kan; Sunamura, Michinari; Urabe, Tetsuro; Mottl, Michael J.; Takai, Ken

2013-01-01

During the Integrated Ocean Drilling Program (IODP) Expedition 331 at the Iheya North hydrothermal system in the Mid-Okinawa Trough by the D/V Chikyu, we conducted microbiological contamination tests of the drilling and coring operations. The contamination from the drilling mud fluids was assessed using both perfluorocarbon tracers (PFT) and fluorescent microsphere beads. PFT infiltration was detected from the periphery of almost all whole round cores (WRCs). By contrast, fluorescent microspheres were not detected in hydrothermally active core samples, possibly due to thermal decomposition of the microspheres under high-temperature conditions. Microbial contamination from drilling mud fluids to the core interior subsamples was further characterized by molecular-based evaluation. The microbial 16S rRNA gene phylotype compositions in the drilling mud fluids were mainly composed of sequences of Beta- and Gammaproteobacteria, and Bacteroidetes and not archaeal sequences. The phylotypes that displayed more than 97% similarity to the sequences obtained from the drilling mud fluids were defined as possible contaminants in this study and were detected as minor components of the bacterial phylotype compositions in 13 of 37 core samples. The degree of microbiological contamination was consistent with that determined by the PFT and/or microsphere assessments. This study suggests a constructive approach for evaluation and eliminating microbial contamination during riser-less drilling and coring operations by the D/V Chikyu. PMID:24265628

The first microbiological contamination assessment by deep-sea drilling and coring by the D/V Chikyu at the Iheya North hydrothermal field in the Mid-Okinawa Trough (IODP Expedition 331).

PubMed

Yanagawa, Katsunori; Nunoura, Takuro; McAllister, Sean M; Hirai, Miho; Breuker, Anja; Brandt, Leah; House, Christopher H; Moyer, Craig L; Birrien, Jean-Louis; Aoike, Kan; Sunamura, Michinari; Urabe, Tetsuro; Mottl, Michael J; Takai, Ken

2013-01-01

During the Integrated Ocean Drilling Program (IODP) Expedition 331 at the Iheya North hydrothermal system in the Mid-Okinawa Trough by the D/V Chikyu, we conducted microbiological contamination tests of the drilling and coring operations. The contamination from the drilling mud fluids was assessed using both perfluorocarbon tracers (PFT) and fluorescent microsphere beads. PFT infiltration was detected from the periphery of almost all whole round cores (WRCs). By contrast, fluorescent microspheres were not detected in hydrothermally active core samples, possibly due to thermal decomposition of the microspheres under high-temperature conditions. Microbial contamination from drilling mud fluids to the core interior subsamples was further characterized by molecular-based evaluation. The microbial 16S rRNA gene phylotype compositions in the drilling mud fluids were mainly composed of sequences of Beta- and Gammaproteobacteria, and Bacteroidetes and not archaeal sequences. The phylotypes that displayed more than 97% similarity to the sequences obtained from the drilling mud fluids were defined as possible contaminants in this study and were detected as minor components of the bacterial phylotype compositions in 13 of 37 core samples. The degree of microbiological contamination was consistent with that determined by the PFT and/or microsphere assessments. This study suggests a constructive approach for evaluation and eliminating microbial contamination during riser-less drilling and coring operations by the D/V Chikyu.

Computational Intelligence Modeling of the Macromolecules Release from PLGA Microspheres-Focus on Feature Selection.

PubMed

Zawbaa, Hossam M; Szlȩk, Jakub; Grosan, Crina; Jachowicz, Renata; Mendyk, Aleksander

2016-01-01

Poly-lactide-co-glycolide (PLGA) is a copolymer of lactic and glycolic acid. Drug release from PLGA microspheres depends not only on polymer properties but also on drug type, particle size, morphology of microspheres, release conditions, etc. Selecting a subset of relevant properties for PLGA is a challenging machine learning task as there are over three hundred features to consider. In this work, we formulate the selection of critical attributes for PLGA as a multiobjective optimization problem with the aim of minimizing the error of predicting the dissolution profile while reducing the number of attributes selected. Four bio-inspired optimization algorithms: antlion optimization, binary version of antlion optimization, grey wolf optimization, and social spider optimization are used to select the optimal feature set for predicting the dissolution profile of PLGA. Besides these, LASSO algorithm is also used for comparisons. Selection of crucial variables is performed under the assumption that both predictability and model simplicity are of equal importance to the final result. During the feature selection process, a set of input variables is employed to find minimum generalization error across different predictive models and their settings/architectures. The methodology is evaluated using predictive modeling for which various tools are chosen, such as Cubist, random forests, artificial neural networks (monotonic MLP, deep learning MLP), multivariate adaptive regression splines, classification and regression tree, and hybrid systems of fuzzy logic and evolutionary computations (fugeR). The experimental results are compared with the results reported by Szlȩk. We obtain a normalized root mean square error (NRMSE) of 15.97% versus 15.4%, and the number of selected input features is smaller, nine versus eleven.

In Vivo Efficacy of an Injectable Microsphere-Hydrogel Ocular Drug Delivery System.

PubMed

Osswald, Christian R; Guthrie, Micah J; Avila, Abigail; Valio, Joseph A; Mieler, William F; Kang-Mieler, Jennifer J

2017-09-01

Demonstrate in vivo that controlled and extended release of a low dose of anti-vascular endothelial growth factor (anti-VEGF) from a microsphere-hydrogel drug delivery system (DDS) has a therapeutic effect in a laser-induced rat model of choroidal neovascularization (CNV). Anti-VEGF (ranibizumab or aflibercept) was loaded into poly(lactic-co-glycolic acid) microspheres that were then suspended within an injectable poly(N-isopropylacrylamide)-based thermo-responsive hydrogel DDS.The DDS was shown previously to release bioactive anti-VEGF for ~200 days. CNV was induced using an Ar-green laser. The four experimental groups were as follows: (i) non-treated, (ii) drug-free DDS, (iii) anti-VEGF-loaded DDS, and (iv) bolus injection of anti-VEGF. CNV lesion areas were measured based on fluorescein angiograms and quantified using a multi-Otsu thresholding technique. Intraocular pressure (IOP) and dark-adapted electroretinogram (ERG) were also obtained pre- and post-treatment (1, 2, 4, 8, and 12 weeks). The anti-VEGF-loaded DDS group had significantly smaller (60%) CNV lesion areas than non-treated animals throughout the study. A small transient increase in IOP was seen immediately after injection; however, all IOP measurements at all time points were within the normal range. There were no significant changes in ERG maximal response compared to pre-treatment measurements for the drug-loaded DDS, which suggests no adverse effects on retinal cellular function. The current study demonstrates that the DDS can effectively decrease laser-induced CNV lesions in a murine model. Controlled and extended release from our DDS achieved greater treatment efficacy using an order of magnitude less drug than what is required with bolus administration. This suggests that our DDS may provide a significant advantage in the treatment of posterior segment eye diseases.

Visible-light photocatalytic activity of graphene oxide-wrapped Bi2WO6 hierarchical microspheres

NASA Astrophysics Data System (ADS)

Zhai, Jiali; Yu, Hongwen; Li, Haiyan; Sun, Lei; Zhang, Kexin; Yang, Hongjun

2015-07-01

A facile approach of fabricating homogeneous graphene oxide (GO)-wrapped Bi2WO6 microspheres (GO/Bi2WO6) is developed. The transmission electron microscopy (TEM) results show that a heterojunction interface between GO and Bi2WO6. The UV-vis diffuse reflection spectra (DRS) reveal that the as-prepared GO/Bi2WO6 composites own more intensive absorption in the visible light range compared with pure Bi2WO6. These characteristic structural and optical properties endow GO/Bi2WO6 composites with enhanced photocatalytic activity. The enhanced photocatalytic activity of the GO/Bi2WO6 is attributed predominantly to the synergetic effect between GO and Bi2WO6, causing rapid generation and separation of photo-generated charge carriers.

Molecular modeling and cytotoxicity of diffractaic acid: HP-β-CD inclusion complex encapsulated in microspheres.

PubMed

Silva, Camilla V N S; Barbosa, Jéssica A P; Ferraz, Milena S; Silva, Nicácio H; Honda, Neli K; Rabello, Marcelo M; Hernandes, Marcelo Z; Bezerra, Beatriz P; Cavalcanti, Isabella M F; Ayala, Alejandro P; Santos, Noemia P S; Santos-Magalhães, Nereide S

2016-11-01

In this pioneer study, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was used to improve the solubility of the diffractaic acid (DA) via inclusion complex (DA:HP-β-CD). Subsequently, DA:HP-β-CD was incorporated into poly-ε-caprolactone (PCL) microspheres (DA:HP-β-CD-MS). Microspheres containing DA (DA-MS) or DA:HP-β-CD (DA:HP-β-CD-MS) were prepared using the multiple W/O/W emulsion-solvent evaporation technique. The phase-solubility diagram of DA in HP-β-CD (10-50mM) showed an A L type curve with a stability constant K 1:1 =821M -1 . 1 H NMR, FTIR, X-ray diffraction and thermal analysis showed changes in the molecular environment of DA in DA:HP-β-CD. The molecular modeling approach suggests a guest-host complex formation between the carboxylic moiety of both DA and the host (HP-β-CD). The mean particle size of the microspheres were ∅ DA-MS =5.23±1.65μm and ∅ DA:HP-β-CD-MS =4.11±1.39μm, respectively. The zeta potential values of the microspheres were ζ DA-MS =-7.85±0.32mV and ζ DA:HP-β-CD-MS =-6.93±0.46mV. Moreover, the encapsulation of DA:HP-β-CD into microspheres resulted in a more slower release (k 2 =0.042±0.001; r 2 =0.996) when compared with DA-MS (k 2 =0.183±0.005; r 2 =0.996). The encapsulation of DA or DA:HP-β-CD into microspheres reduced the cytotoxicity of DA (IC 50 =43.29μM) against Vero cells (IC 50 of DA-MS=108.48μM and IC 50 of DA:HP-β-CD-MS=142.63μM). Copyright © 2016 Elsevier B.V. All rights reserved.