Home About us Contact
|
Home About us Contact | ||
|
|
||
PLGA
Terms modified by PLGA Selected AbstractsLong circulating nanoparticles of etoposide using PLGA-MPEG and PLGA-pluronic block copolymers: characterization, drug-release, blood-clearance, and biodistribution studiesDRUG DEVELOPMENT RESEARCH, Issue 4 2010Khushwant S. Yadav Abstract The anti-leukemic drug, etoposide (ETO), has variable oral bioavailability ranging from 24,74% with a short terminal half-life of 1.5,h i.v. necessitating continuous infusion for 24,34,h for the treatment of leukemia. In the present study, etoposide-loaded PLGA-based surface-modified nanoparticles (NPs) with long circulation were designed as an alternative to continuous i.v. administration. PLGA-mPEG and PLGA-PLURONIC copolymers were synthesised and used to prepared ETO-loaded NPs by high-pressure homogenization. The mean particle size of ETO-loaded PLGA-MPEG nanoparticles was 94.02±3.4,nm, with an Entrapment Efficiency (EE) of 71.2% and zeta potential value of ,6.9±1.3,mV. ETO-loaded PLGA-pluronic nanoparticles had a mean particle size of 148.0±2.1,nm, an EE of 73.12±2.7%, and zeta potential value of ,21.5±1.6,mV. In vitro release of the pure drug was complete within 4,h, but was sustained up to 7 days from PLGA-mPEG nanoparticles and for 5 days from PLGA-pluronic nanoparticles. Release was first order and followed non-Fickian diffusion kinetics in both instances. ETO and ETO-loaded PLGA nanoparticles labeled with 99mTc were used in blood clearance studies in rats where the two coated NPs, 99mTc- ETO-PLGA-PLU NP and 99mTc- ETO-PLGA-mPEG NP, were found to be available in higher concentrations in the circulation as compared to the pure drug. Biodistribution studies in mice showed that ETO-loaded PLGA-MPEG NP and PLGA-PLURONIC NP had reduced uptake by the RES due to their steric barrier properties and were present in the circulation for a longer time. Moreover, the NPs had greater uptake in bone and brain where concentration of the free drug, ETO, was negligible. Drug delivered from these NPs could result in a single i.v. injection that would release the drug for a number of days, which would be potentially beneficial and in better control of leukemia therapy. Drug Dev Res 71: 228,239, 2010. © 2010 Wiley-Liss, Inc. [source] Antibiotic-Loaded PLGA Nanofibers for Wound Healing Applications,ADVANCED ENGINEERING MATERIALS, Issue 4 2010David A. Soscia Incorporating antibiotics into biocompatible nanoscale non-woven fibrous mats could provide utility for wound healing applications and for incorporation into wound dressing materials. In this study, the antibiotic chloramphenicol (Cm) was incorporated into electrospun poly(lactic-co-glycolic acid) (PLGA) nanofibers, which were then tested for inhibition of bacterial growth for multiple bacterial species (Escherichia coli, Staphylococcus aureus, Bacillus cereus, Salmonella typhimurium, and Pseudomonas aeruginosa). In addition, the cytotoxicity of Cm-PLGA nanofibers was examined for two types of mammalian cells including mouse embryonic stem cells and fibroblasts. Electrospun PLGA nanofibers containing Cm were able to reduce bacterial growth on solid agar plates for all species except for P. aeruginosa. In liquid culture, Cm-loaded nanofibers inhibited growth for E. coli, B. cereus and S. typhimurium by 93% or greater, while P. aeruginosa and S. aureus growth was inhibited by 42% and 56%, respectively. Cm-loaded nanofibers showed limited cytoxicity on fibroblasts and embryonic stem cells, with viability greater than 96% for all conditions tested. These results suggest that Cm can be successfully incorporated into electrospun nanofibers and that these fibers could be used for wound healing applications with minimal cytotoxicity to the surrounding tissue. [source] Neurite Outgrowth on Nanocomposite Scaffolds Synthesized from PLGA and Carboxylated Carbon Nanotubes,ADVANCED ENGINEERING MATERIALS, Issue 12 2009Hyun Jung Lee Abstract Carbon nanotubes (CNTs) have been suggested as suitable materials for biomedical applications, especially in the neural area. It is essential not only to investigate the biocompatibility of CNTs with the neural system but also to determine proper methods for applying CNTs to neuronal growth. This work represents the first application of CNTs by electrospun poly(D,L -lactic-co-glycolic acid) (PLGA) scaffolds for a neural system. We synthesized electrospun nanocomposites of PLGA and single-walled carbon nanotubes functionalized by carboxylic acid groups (c- SWNTs), and investigated neurite outgrowth from SH-SY5Y cells on these nanocomposites as compared to that on fibrous PLGA alone. Cells on our PLGA/c -SWNT nanocomposite showed significantly enhanced mitochondrial function and neurite outgrowth compared to cells on PLGA alone. We concluded that c -SWNTs incorporated into fibrous PLGA scaffolds exerted a positive role on the health of neural cells. [source] Stem Cell Aligned Growth Induced by CeO2 Nanoparticles in PLGA Scaffolds with Improved Bioactivity for Regenerative MedicineADVANCED FUNCTIONAL MATERIALS, Issue 10 2010Corrado Mandoli Abstract Hybrid 2D polymeric,ceramic biosupports are fabricated by mixing a nanostructured CeO2 powder with 85:15 poly(D,L -lactic- co -glycolic acid) (PLGA)/dichloromethane solutions at specific concentrations, followed by solvent casting onto pre-patterned molds. The mold patterning allows the orientation of ceramic nanoparticles into parallel lines within the composite scaffold. The ability of the produced films to host and address cell growth is evaluated after 1, 3, and 6 days of culturing with murine derived cardiac and mesenchymal stem cells (CSCs and MSCs), and compared with PLGA films without ceramics and loaded with nanostructured TiO2. Aligned cell growth is observed only for scaffolds that incorporate oriented ceramic nanoparticles, attributed to the nanoceramic ability to modulate the roughness pitch, thus improving cell sensitivity towards the host surface features. Better CSC and MSC proliferative activity is observed for CeO2 composites with respect to either TiO2 -added or unfilled PLGA films. This evidence may be related to the nanostructured CeO2 antioxidative properties. [source] Nanofibrous Patches for Spinal Cord RegenerationADVANCED FUNCTIONAL MATERIALS, Issue 9 2010Yiqian Zhu Abstract The difficulty in spinal cord regeneration is related to the inhibitory factors for axon growth and the lack of appropriate axon guidance in the lesion region. Here scaffolds are developed with aligned nanofibers for nerve guidance and drug delivery in the spinal cord. Blended polymers including poly(L -lactic acid) (PLLA) and poly(lactide- co -glycolide) (PLGA) are used to electrospin nanofibrous scaffolds with a two-layer structure: aligned nanofibers in the inner layer and random nanofibers in the outer layer. Rolipram, a small molecule that can enhance cAMP (cyclic adenosine monophosphate) activity in neurons and suppress inflammatory responses, is immobilized onto nanofibers. To test the therapeutic effects of nanofibrous scaffolds, the nanofibrous scaffolds loaded with rolipram are used to bridge the hemisection lesion in 8-week old athymic rats. The scaffolds with rolipram increase axon growth through the scaffolds and in the lesion, promote angiogenesis through the scaffold, and decrease the population of astrocytes and chondroitin sulfate proteoglycans in the lesion. Locomotor scale rating analysis shows that the scaffolds with rolipram significantly improved hindlimb function after 3 weeks. This study demonstrates that nanofibrous scaffolds offer a valuable platform for drug delivery for spinal cord regeneration. [source] Generic Strategy of Preparing Fluorescent Conjugated-Polymer-Loaded Poly(DL -lactide- co -Glycolide) Nanoparticles for Targeted Cell ImagingADVANCED FUNCTIONAL MATERIALS, Issue 22 2009Kai Li Abstract A general strategy for the preparation of highly fluorescent poly(DL-lactide- co -glycolide) (PLGA) nanoparticles (NPs) loaded with conjugated polymers (CPs) is reported. The process involves encapsulation of organic-soluble CPs with PLGA using a modified solvent extraction/evaporation technique. The obtained NPs are stable in aqueous media with biocompatible and functionalizable surfaces. In addition, fluorescent properties of the CP-loaded PLGA NPs (CPL NPs) could be fine-tuned by loading different types of CPs into the PLGA matrix. Four types of CPL NPs are prepared with a volume-average hydrodynamic diameter ranging from 243 to 272,nm. The application of CPL NPs for bio-imaging is demonstrated through incubation with MCF-7 breast cancer cells. Confocal laser scanning microscopy studies reveal that the CPL NPs are internalized in cytoplasm around the nuclei with intense fluorescence. After conjugation with folic acid, cellular uptake of the surface-functionalized CPL NPs is greatly enhanced via receptor-mediated endocytosis by MCF-7 breast cancer cells, as compared to that for NIH/3T3 fibroblast cells, which indicates a selective targeting effect of the folate-functionalized CPL NPs in cellular imaging. The merits of CPL NPs, such as low cytotoxicity, high fluorescence, good photostability, and feasible surface functionalization, will inspire extensive study of CPL NPs as a new generation of probes for specific biological imaging and detection. [source] Fabrication of Microbeads with a Controllable Hollow Interior and Porous Wall Using a Capillary Fluidic DeviceADVANCED FUNCTIONAL MATERIALS, Issue 18 2009Sung-Wook Choi Abstract Poly(D,L -lactide-co-glycolide) (PLGA) microbeads with a hollow interior and porous wall are prepared using a simple fluidic device fabricated with PVC tubes, glass capillaries, and a needle. Using the fluidic device with three flow channels, uniform water-in-oil-in-water (W-O-W) emulsions with a single inner water droplet can be achieved with controllable dimensions by varying the flow rate of each phase. The resultant W-O-W emulsions evolve into PLGA microbeads with a hollow interior and porous wall after the organic solvent in the middle oil phase evaporates. Two approaches are employed for developing a porous structure in the wall: emulsion templating and fast solvent evaporation. For emulsion templating, a homogenized, water-in-oil (W/O) emulsion is introduced as the middle phase instead of the pure oil phase. Low-molecular-weight fluorescein isothiocyanate (FITC) and high-molecular-weight fluorescein isothiocyanate,dextran conjugate (FITC,DEX) is added to the inner water phase to elucidate both the pore size and their interconnectivity in the wall of the microbeads. From optical fluorescence microscopy and scanning electron microscopy images, it is confirmed that the emulsion-templated microbeads (W-W/O-W) have larger and better interconnected pores than the W-O-W microbeads. These microstructured microbeads can potentially be employed for cell encapsulation and tissue engineering, as well as protection of active agents. [source] Magnetic-Field-Assisted Electrospinning of Aligned Straight and Wavy Polymeric NanofibersADVANCED MATERIALS, Issue 22 2010Yaqing Liu Aligned straight and wavy fibers of biodegradable poly(D,L-lactic- co -glycolic acid) (PLGA) are fabricated using a magnetic-field-assisted electrospinning method. PLGA fibrous matrices prepared by this method can guide the growth of pluripotent murine mesenchymal stem cells. While the stem cells on the randomly oriented fibers adapt pseudo-sphere-like shape, those on aligned fibers exhibit elongated morphology along the long axes (see figure). [source] Biodegradable Xylitol-Based Polymers,ADVANCED MATERIALS, Issue 10 2008Joost P. Bruggeman Synthetic polymers composed of metabolites endogenous to the mammalian organism are designed. The design is based on the monomer xylitol, which possesses a wide range of physical properties that are biologically relevant. Xylitol-based hydrogels and elastomers are biocompatible in vitro and in vivo, compared to the prevalent synthetic polymer poly(L-lactic- co - glycolic acid) (PLGA). It furthermore provides a platform to tune mechanical properties, degradation profiles, and cell attachment. [source] Sustained delivery and efficacy of polymeric nanoparticles containing osteopontin and bone sialoprotein antisenses in rats with breast cancer bone metastasisINTERNATIONAL JOURNAL OF CANCER, Issue 7 2010Victoria Elazar Abstract Poor prognosis in mammary carcinoma is associated with a certain expression profile of a defined set of genes including osteopontin and bone sialoprotein. Efficient and specific delivery of antisenses (AS) and a protection of the sequences from degradation are the crucial conditions for AS therapeutic efficiency. We hypothesized that effective and safe AS delivery direceted against these genes could be achieved by polymeric nanoparticles (NP) fabricated from a biocompatible polymer. Due to their nano-size range and small negative charge, AS-NP can overcome the absorption barrier offering increased resistance to nuclease degradation, sustained duration of AS administration, and consequently, prolonged antisense action. The ASs designed against OPN and BSP-II were successfully encapsulated in NP composed of the biodegradable and biocompatible polylactide- co -glycolide polymer (PLGA), exhibiting sustained release and stability of the ASs. The therapeutic efficacy of the AS-NP delivery system was examined in vitro, and in a breast cancer bone metastasis animal model of MDA-MB-231 human breast cancer cells in nude rats. Treatment with OPN-AS or BSP-AS loaded NP in comparison with osmotic mini-pumps (locoregional injection and SC implants, respectively) resulted in a significant decrease in both, tumor bone metastasis incidence and in the size of the lesions in rats with metastases. Despite its smaller dose, AS-NP exhibited a better therapeutic efficacy than osmotic mini-pumps in terms of lesion ratio at later time periods (8,12 weeks). It may be concluded that AS delivery by NP is a promising therapeutic modality providing stability of the encapsulated AS and a sustained release. [source] Technological strategies to improve photostability of a sunscreen agentINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 2 2006P. Perugini Due to the reduction of the ozone layer, there is an increasing need of effective UV protection systems with minimized side-effects. Trans-2-ethylhexyl- p -methoxycinnamate (trans -EHMC) represents one of the most widely used sunscreen compound. Several studies demonstrated that trans -EHMC is unstable following UV irradiation both in solution and in emulsion formulations. Moreover, various reports of photocontact sensitization induced by trans -EHMC have appeared in the literature. Consequently, in order to ensure adequate efficacy and safety for this sunscreen agent, there is a need for new carrier systems to enhance trans -EHMC photostability. In the present study the photostability of the filter in different formulation types (emulsion,gel, gel and emulsion) with various ingredients is evaluated. In addition, nanoparticles based on poly- D,L -lactide-co-glycolide (PLGA) as carrier for trans -EHMC are investigated. The influence of nanoparticle matrix on the photochemical stability of the sunscreen agent is also presented. The results obtained demonstrated that PLGA nanoparticles are effective in reducing the light-induced degradation of the sunscreen agent. Moreover, the choice of formulation type and the excipients used play an important role in order to obtain a stable cosmetic product containing trans -EHMC. [source] Effects of ethyl benzoate on performance, morphology, and erosion of PLGA implants formed in situADVANCES IN POLYMER TECHNOLOGY, Issue 1 2008R. Astaneh Abstract An in situ forming implant (ISFI) is a novel drug delivery system used for protein and peptide delivery, especially for cancer treatment. An ISFI based on 33% (w/w) poly(D,L -lactide- co -glycolide)(PLGA; 50:50)/3% (w/w) leuprolide acetate (LA)/64% (w/w) N -methyl-2-pyrrolidone (NMP) was prepared for this study. After injection of the final formulation, which is a viscous liquid to an aqueous medium, it deforms to become a semisolid or solid matrix. The performance of this matrix was investigated on the basis of peptide release from it. Erosion and morphology of ISFI were also studied. The effects of adding 12.8% (w/w) ethyl benzoate (EB) as a rate-modifying agent on performance, erosion, and morphology of ISFI were assessed. The implant containing EB showed very low burst release (5.53% ± 0.82%) and the morphology turns to closed pore-like structures. After adding EB, the morphology turns to closed pore-like structures. This type of morphology has very close relation to the performance of the implant as well. Finally, the effect of EB on performance, erosion, and morphology is explained by means of solvent,nonsolvent affinity, water permeation, and the rate of phase inversion. © 2008 Wiley Periodicals, Inc. Adv Polym Techn 27:17,26, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/adv.20114 [source] Microencapsulation of doxycycline into poly(lactide- co -glycolide) by spray drying technique: Effect of polymer molecular weight on process parametersJOURNAL OF APPLIED POLYMER SCIENCE, Issue 6 2008Pradip Patel Abstract Poly(lactide- co -glycolide) (PLGA) polymers with three different molecular weights were prepared, and microparticles were produced by spray drying and water-in-oil-water (w/o/w) double emulsion techniques to encapsulate 86% of doxycycline (DXY), an antibiotic drug, for the use of periodontitis. Placebo and drug-loaded microspheres and pristine DXY were analyzed by Fourier transform infrared spectroscopy, which indicated no chemical interactions between DXY and PLGA. X-ray diffraction of drug-loaded microspheres confirmed the molecular level dispersion of DXY in PLGA. Scanning electron microscopy confirmed spherical nature and smooth surfaces of the microspheres. Mean particle size as measured by laser light scattering technique ranged between 10 and 25 ,m. In vitro release of DXY performed in 7.4 pH media continued up to 72 h and depended on molecular weight of PLGA and extent of DXY loading. Antimicrobial studies performed on one formulation and placebo microspheres suggested that drug concentrations during in vitro release are above the minimum inhibitory concentration (MIC) for Staphylococcus aureus growth. Overall, the release studies depended on the molecular weight of PLGA, extent of drug loading, and the method used to prepare microspheres. Statistical analyses of release data performed using the analysis of variance (ANOVA) method agreed well with experimental observations. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source] In vitro release of complexed pDNA from biodegradable polymer filmsJOURNAL OF APPLIED POLYMER SCIENCE, Issue 1 2008Y. Ramgopal Abstract The controlled delivery of low-molecular weight drugs and proteins from biodegradable polymers has received considerable attention. However, controlled release studies of pDNA from such polymers have not been reported to date. In this study, a plasmid DNA was complexed with the cationic polymer called polyethylenimine (PEI). This gene vector has been shown to be very effective in transfecting cells. The complexed DNA were then incorporated into different types of poly-lactic- co -glycolic acid (PLGA) film; PLGA 53/47 (Mw 90 kDa), 50/50 (Mw 11 kDa, end group is lauryl ester) and 75/25 (Mw 120 kDa). Their release profiles from a buffer solution were studied. An initial (small) burst release of PEI-DNA from film was observed in PLGA 53/47 and 50/50, followed by a plateau phase and finally a rapid erosion-controlled release. For PLGA 50/50, the rapid release started after 14 days; erosion-controlled release for PLGA 53/47 started after 9 days; for PLGA 75/25, the release rate was governed by an initial burst release (10%) followed by a slow release controlled by diffusion. No obvious erosion-controlled release rate was observed for this polymer up to 27 days. Thus, the controlled release of complexed DNA follows the general features exhibited by lower- Mw drugs. This is of significance in designing gene vector matrices that offer the promise of more lasting gene therapy compared with particulate formulations. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008 [source] Tissue-engineered tear secretory system: Functional lacrimal gland acinar cells cultured on matrix protein-coated substrataJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2007Shivaram Selvam Abstract Dry eye is a general term that refers to a myriad of ophthalmic disorders resulting in the inadequate wetting of the corneal surface by the tear film. Dry eyes are typically treated by the application of artificial tears. However, patients with lacrimal insufficiencies such as Stevens-Johnson syndrome, chemical and thermal injuries, or ocular cicatricial pemphigoid have very limited options because of the short duration and action of lubricating agents. As a therapeutic strategy, we are working to develop a bioengineered tear secretory system for such patients. This article describes the growth and physiological properties of purified rabbit lacrimal gland acinar cells (pLGACs) on several matrix protein-coated polymers such as silicone, collagen I, copolymers of poly- D,L -lactide- co -glycolide (PLGA; 85:15 and 50:50), poly- L -lactic acid (PLLA), and Thermanox® plastic cell culture coverslips. Monolayers of acinar cells were established on all of the polymeric substrata. An assay of ,-hexosaminidase activity in the supernatant medium showed significant increases in protein secretion, following stimulation with 100 ,M carbachol on matrix protein-coated and uncoated polymers such as silicone, PLGA 85:15, and PLLA. Our study demonstrates that PLLA supported the morphological and physiological properties of purified rabbit lacrimal gland epithelial cells more successfully than the others. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007 [source] Ciprofloxacin-releasing bioabsorbable polymer is superior to titanium in preventing Staphylococcus epidermidis attachment and biofilm formation in vitroJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2006Sanna-Mari Niemelä Abstract Antibiotic coating systems have been successfully used to prevent bacterial attachment and biofilm formation. Our purpose was to evaluate whether bioabsorbable polylactide-co-glycolide (PLGA) 80/20 on its own, and PLGA together with ciprofloxacin (PLGA+C) have any advantages over titanium in preventing Staphylococcus epidermidis attachment and biofilm formation in vitro. Cylindrical specimens of titanium, PLGA, and PLGA+C in triplicate were examined for S. epidermidis ATCC 35989 attachment and biofilm formation after incubation with a bacterial suspension of about 105 cfu/mL for 1, 3, 7, 14, and 21 days, using scanning electron microscopy. Growth inhibition properties of PLGA and PLGA+C cylinders were tested on agar plates. On days 1, 3, and 21, no bacterial attachment was seen in 19.5, 9.2, and 41.4% of the titanium specimens; in 18.4, 28.7, and 34.5% of the PLGA specimens; and in 57.5, 62.1, and 57.5% of the PLGA+C specimens, respectively. During the whole study period, no biofilm was observed on 74,93% of the titanium specimens, 58,78% of the PLGA specimens, and 93,100% of the PLGA+C specimens. PLGA+C showed clear bacterial growth inhibition on agar plates, while PLGA and titanium did not show any inhibition. PLGA+C bioabsorbable material was superior to titanium in preventing bacterial attachment and biofilm formation and may have clinical applicability, for example, in prevention of infection in trauma surgery or in the treatment of chronic osteomyelitis. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006 [source] Periodontal wound healing/regeneration following the application of rhGDF-5 in a , -TCP/PLGA carrier in critical-size supra-alveolar periodontal defects in dogsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 7 2010David H. Kwon Kwon DH, Bisch FC, Herold RW, Pompe C, Bastone P, Rodriguez NA, Susin C, Wikesjö UM. Periodontal wound healing/regeneration following application of rhGDF-5 in a , -TCP/PLGA carrier in critical-size supra-alveolar periodontal defects in dogs. J Clin Periodontol 2010; 37: 667,674. doi: 10.1111/j.1600-051X.2010.01569.x. Abstract Aim: The objective of this study was to evaluate the effect of a novel recombinant human GDF-5 (rhGDF-5) construct intended for onlay and inlay indications on periodontal wound healing/regeneration. Methods: Contralateral, surgically created, critical-size, 6-mm, supra-alveolar periodontal defects in five adult Hound Labrador mongrel dogs received rhGDF-5 coated onto , -tricalcium phosphate (, -TCP) particles and immersed in a bioresorbable poly(lactic- co -glycolic acid) (PLGA) composite or the , -TCP/PLGA carrier alone (control). The rhGDF-5 and control constructs were moulded around the teeth and allowed to set. The gingival flaps were then advanced; flap margins were adapted 3,4 mm coronal to the teeth and sutured. The animals were euthanized at 8 weeks post-surgery when block biopsies were collected for histometric analysis. Results: Healing was generally uneventful. A few sites exhibited minor exposures. Three control sites and one rhGDF-5 site (in separate animals) experienced more extensive wound dehiscencies. The rhGDF-5 and control constructs were easy to apply and exhibited adequate structural integrity to support the mucoperiosteal flaps in this challenging onlay model. Limited residual , -TCP particles were observed at 8 weeks for both rhGDF-5/, -TCP/PLGA and , -TCP/PLGA control sites. The rhGDF-5/, -TCP/PLGA sites showed significantly greater cementum (2.34 ± 0.44 versus 1.13 ± 0.25 mm, p=0.02) and bone (2.92 ± 0.66 versus 1.21 ± 0.30 mm, p=0.02) formation compared with the carrier control. Limited ankylosis was observed in four of five rhGDF-5/, -TCP/PLGA sites but not in control sites. Conclusions: Within the limitations of this study, the results suggest that rhGDF-5 is a promising candidate technology in support of periodontal wound healing/regeneration. Carrier and rhGDF-5 dose optimization are necessary before further advancement of the technology towards clinical evaluation. [source] Feasibility study of aerosolized prostaglandin E1 microspheres as a noninvasive therapy for pulmonary arterial hypertensionJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2010Vivek Gupta Abstract This study was designed to test the feasibility of polymeric microspheres as an inhalable carrier for prostaglandin E1 (PGE1) for treatment of pulmonary arterial hypertension. Poly(lactic- co -glycolic acid) (PLGA) microspheres were prepared by a double emulsion,solvent evaporation method. Six different microspheric formulations were prepared using two different blends of PLGA (50:50 and 85:15) and varying concentrations of polyvinyl alcohol (PVA) in the external aqueous phase (EAP). The particles were characterized for morphology, size, aerodynamic diameter, entrapment efficiency, release patterns, and metabolic stability. Pulmonary absorption was studied in a rat model, and safety of the formulations was evaluated by measuring cytotoxicity in Calu-3 cells and assessing injury markers in bronchoalveolar lavage (BAL) fluid. Both actual particle size and aerodynamic diameter of the formulations decreased with increasing PVA concentration. The mass median aerodynamic diameter of the particles was within the respirable range. Entrapment efficiency increased with increasing PVA concentration; PLGA 85:15 showed better entrapment due to hydrophobic interactions with the drug. Compared to intravenously administered PGE1, microspheres prepared with PLGA 85:15 produced a 160-fold increase in the half-life of PGE1 following pulmonary administration. Although plain PGE1 showed rapid degradation in rat lung homogenate, PGE1 entrapped in the particles remained intact for about 8,h. Optimized formulations were demonstrated to be safe, based on analysis of cytotoxicity and lung-injury markers in BAL fluid. Overall, the data suggest that microspheric PGE1 formulations have the potential to be used as a noninvasive and controlled-release alternative to the current medications used for treatment of pulmonary arterial hypertension that are administered by continuous infusion or require multiple inhalations. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1774,1789, 2010 [source] Fabrication, characterization and in vitro evaluation of poly(D,L -lactide- co -glycolide) microparticles loaded with polyamidoamine,plasmid DNA dendriplexes for applications in nonviral gene deliveryJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2010Janjira Intra Abstract We report, for the first time, on the preparation, characterization and in vitro testing of poly(D,L -lactide- co -glycolide) (PLGA) microparticles loaded with polyamidoamine (PAMAM),plasmid DNA (pDNA) dendriplexes. Loading of pDNA into the PLGA microparticles increased by 150% when pDNA was first complexed with PAMAM dendrimers relative to loading of pDNA alone. Scanning electron microscopy (SEM) showed that the presence of PAMAM dendrimers in the PLGA microparticles created porous features and indentations on the surface of the microparticles. Loading PLGA microparticles with PAMAM,pDNA dendriplexes lowered the average PLGA microparticle size and changed the surface charge of the microparticles from negative to positive when compared to PLGA microparticles loaded with pDNA alone. The zetapotential and buffering capacity of the microparticles increased as the generation of the PAMAM dendrimer loaded in the PLGA microparticles increased. Gel electrophoresis assays showed that all the PLGA microparticle formulations were able to entrap the pDNA within the PLGA matrix. There was no significant difference in the cytotoxicity of PLGA microparticles loaded with PAMAM,pDNA dendriplexes when compared to PLGA microparticles loaded with pDNA alone. Furthermore, and in contrast to PAMAM dendrimers alone, the generation of the PAMAM dendrimer loaded in the PLGA microparticles had no significant impact on cytotoxicity or transfection efficiencies in human embryonic kidney (HEK293) or Monkey African green kidney fibroblast-like (COS7) cells. The transfection efficiency of PLGA microparticles loaded with generation 3 (G3) PAMAM,pDNA dendriplexes was significantly higher than PLGA microparticles loaded with pDNA alone in HEK293 and COS7 cells. PLGA microparticles loaded with G3 PAMAM,pDNA dendriplexes generated equivalent transfection efficiencies as (G3 to G6) PAMAM,pDNA dendriplexes alone in COS7 cells when the transfection was carried out in serum containing media. The delivery system developed in this report has low toxicity, high pDNA loading efficiencies and high transfection efficiencies that are not reduced in the presence of serum. A delivery system with these characteristics is expected to have significant potential for translational applications. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:368,384, 2010 [source] Lung-specific delivery of paclitaxel by chitosan-modified PLGA nanoparticles via transient formation of microaggregatesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2009Rui Yang Abstract Chitosan-modified paclitaxel-loaded poly lactic- co -glycolic acid (PLGA) nanoparticles with a mean diameter of 200,300 nm in distilled water were prepared by a solvent evaporation method. The mean diameter increased dramatically in contact with the mouse (CDF1) plasma, as a function of chitosan concentration in the modification solution (e.g., 2670.5 nm for 0.7% chitosan-modified nanoparticles, NP3), but reverted to almost its original size (i.e., 350.7 nm for NP3) following 5 min of gentle agitation. The zeta potential of PLGA nanoparticles was changed to positive by the chitosan modification. The in vitro uptake into, and cytotoxicity of the nanoparticles against, a lung cancer cell line (A549) were significantly increased by the modification. Most importantly, a lung-specific increase in the distribution index of paclitaxel (i.e., AUClung/AUCplasma) was observed for chitosan-modified nanoparticles (e.g., 99.9 for NP3 vs. 5.4 for TaxolÔ) when nanoparticles were administered to lung-metastasized mice via the tail vein at a paclitaxel dose of 10 mg/kg. Transient formation of aggregates in the blood stream followed by enhanced trapping in the lung capillaries, and electrical interaction-mediated enhanced uptake across the endothelial cells of the lung tumor capillary appear to be responsible for the lung-tumor-specific distribution of the chitosan modified nanoparticles. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:970,984, 2009 [source] Chemical degradation of peptides and proteins in PLGA: A review of reactions and mechanismsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2008M.L. Houchin Abstract Biodegradable poly(lactide-co-glycolide) (PLGA) polymers have been studied extensively for the controlled release of peptide and protein drugs. In addition to polymer biodegradation, chemical degradation of the incorporated peptide/protein has also been reported in PLGA devices, and the role of the polymer in promoting these reactions has been debated. This review summarizes the peptide/protein chemical degradation reactions that have been reported in PLGA systems and their mechanisms. Reported methods for stabilizing peptides and proteins in PLGA devices are also discussed. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:2395,2404, 2008 [source] Solid-state solubility influences encapsulation and release of hydrophobic drugs from PLGA/PLA nanoparticlesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2004Jayanth Panyam Abstract Biodegradable nanoparticles formulated from poly(D,L -lactide- co -glycolide) (PLGA) and polylactide (PLA) polymers are being extensively investigated for various drug delivery applications. In this study, we hypothesize that the solid-state solubility of hydrophobic drugs in polymers could influence their encapsulation and release from nanoparticles. Dexamethasone and flutamide were used as model hydrophobic drugs. A simple, semiquantitative method based on drug,polymer phase separation was developed to determine the solid-state drug,polymer solubility. Nanoparticles using PLGA/PLA polymers were formulated using an emulsion,solvent evaporation technique, and were characterized for size, drug loading, and in vitro release. X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) were used to determine the physical state of the encapsulated drug. Results demonstrated that the solid-state drug,polymer solubility depends on the polymer composition, molecular weight, and end-functional groups (ester or carboxyl) in polymer chains. Higher solid-state drug,polymer solubility resulted in higher drug encapsulation in nanoparticles, but followed an inverse correlation with the percent cumulative drug released. The XRD and DSC analyses demonstrated that the drug encapsulated in nanoparticles was present in the form of a molecular dispersion (dissolved state) in the polymer, whereas in microparticles, the drug was present in both molecular dispersion and crystalline forms. In conclusion, the solid-state drug,polymer solubility affects the nanoparticle characteristics, and thus could be used as an important preformulation parameter. © 2004 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 93:1804,1814, 2004 [source] Microparticulate formulations for the controlled release of interleukin-2JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2004Tommy T. Thomas Abstract Interleukin 2 (IL-2) is a pleotropic growth factor essential to immune system function. Current methods of administration are limited by the necessity of hospitalization as well as dose-limiting toxicities and side effects. There is also the issue of low therapeutic concentrations at the desired site of action; for instance, in the case of solid tumor treatment. Here we describe the design of controlled-release vehicles for the local administration of IL-2 based on single (SE) and double emulsion (DE) poly(lactic- co -glycolic acid) (PLGA) systems and a newly developed class of spray-dried lipid,protein,sugar systems composed of L -,-dipalmitoylphosphatidylcholine (DPPC) and 0.2% Eudragit E 100. All three systems demonstrated the release of therapeutic drug quantities. Totals of 2.0, 0.5, and 2.8 ,g of IL-2 (per mg of solid) were encapsulated in the SE, DE, and spray-dried formulations, respectively. The SE and DE released of 30 and 15% of the encapsulated protein, respectively, with delivery of biologically active IL-2 during the first 5 to 10 days. The lipid,protein,sugar-based system demonstrated extended sustained release of biologically active IL-2 for a period of 4 months. These systems provide a potential framework for long-term loco-regional immunotherapeutic treatment regimens. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1100,1109, 2004 [source] Pharmaceutical and immunological evaluation of a single-shot hepatitis B vaccine formulated with PLGA microspheresJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2002Li Shi Abstract A single-shot Hepatitis B vaccine formulation using poly(d,l)-lactide-co-glycolide acid (PLGA) microspheres as a delivery system was examined using a variety of biophysical and biochemical techniques as well as immunological evaluation in C3H mice. PLGA microsphere encapsulation of the Hepatitis B surface antigen (HBsAg), a lipoprotein particle, resulted in good recoveries of protein mass, protein particle conformational integrity, and in vitro antigenicity. Some partial delipidation of the HBsAg, however, was observed. The loading and encapsulation efficiency of HBsAg into the PLGA microspheres were measured along with the morphology and size distribution of the vaccine-loaded PLGA microspheres. The in vitro release kinetics of HBsAg from the PLGA microspheres was evaluated and found to be affected by experimental conditions such as stirring rate. HBsAg showed enhanced storage stability at 37°C in the slightly acidic pH range reported to be found inside PLGA microspheres; thus, the antigen is relatively stable under conditions of temperature and pH that may mimic in vivo conditions. The immunogenicity of the microsphere formulations of HBsAg was compared with conventional aluminum adjuvant formulated HBsAg vaccine in C3H mice. Comparisons were made between aluminum formulations (one and two injections), PLGA microsphere formulations (single injection), and a mixture of aluminum and PLGA microsphere formulations (single injection). The nine-month serum antibody titers indicate that a single injection of a mixture of aluminum and PLGA-formulated HBsAg results in equal or better immune responses than two injections of aluminum-formulated HBsAg vaccine. Based on these invitro and in vivo studies, it is concluded that HBsAg can be successfully encapsulated and recovered from the PLGA microspheres and a mixture of aluminum-adjuvanted and PLGA-formulated HBsAg can auto-boost an immune response in manner comparable to multiple injections of an aluminum-formulated vaccine. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1019,1035, 2002 [source] Release mechanisms from gentamicin loaded poly(lactic- co -glycolic acid) (PLGA) microparticlesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2002Wolfgang Friess Abstract To provide local gentamicin delivery for 1 week based on a biodegradable system, poly(lactic- co -glycolic acid) (PLGA) microparticles were developed utilizing a 50/50 blend of Resomer® RG 502H, an uncapped variety of 13.5 kD, and Resomer® RG 503, an endcapped polymer of 36.2 kD. The liberation mechanism was investigated by analysis of morphological changes and thermal analysis focusing on the polymer glass transition temperature (Tg) and the mechanical properties. The release of gentamicin was related to a structural breakdown of the particles reaching a critical molecular weight. A Tg of <,37°C in the hydrated state was not indicative of collapse and agglomeration of the particles because the mechanical strength of the polymer structures in the rubbery state may still render sufficient support. As the gap between incubation temperature and Tg widened, the mechanical stability of the PLGA microparticles decreased and became decisive. Particles prepared with RG 502H show a lower ability to bear mechanical stress than RG 503 and 50/50 RG 502H/RG 503 microparticles. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91: 845,855, 2002 [source] Preparation of polylactide-co-glycolide and chitosan hybrid microcapsules of amifostine using coaxial ultrasonic atomizer with solvent evaporationJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 3 2008Sarala Pamujula The objective of this study was to evaluate the effect of various processing and formulation factors on the characteristics of amifostine hybrid microcapsules. Amifostine-loaded hybrid microcapsules were prepared using PLGA and chitosan. In short, amifostine powder was dissolved in de-aerated water with or without chitosan. The amifostine solution was later emulsified into PLGA solution in dichloromethane containing phosphatidylcholine. The resultant emulsion was fed through the inner capillary of a coaxial ultrasonic atomizer. The liquid fed through the coaxial outer capillary was either water or chitosan solution. The atomized droplets were collected into PVA solution and the droplets formed microcapsules immediately. The hybrid microcapsules prepared with chitosan solution only as an outer layer liquid showed the maximum efficiency of encapsulation (30%). The median sizes of all three formulations were 33,44 ,m. These formulations with chitosan showed positive zeta-potential and sustained drug release with 13,45% amifostine released in 24 h. When chitosan was incorporated into inner as well as outer liquid layers, the drug release increased significantly, 45% (compared with other formulations) released in 24 h and almost 100% released in 11 days. Hybrid microcapsules of amifostine showed moderately high efficiency of encapsulation. The cationic charge (due to the presence of chitosan) of these particles is expected to favour oral absorption and thus overall bioavailability of orally administered amifostine. [source] Pharmacokinetic characterization of 14C-vascular endothelial growth factor controlled release microspheres using a rat modelJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2002Tae-Kyoung Kim The objectives of this study were to characterize the pharmacokinetics of vascular endothelial growth factor (VEGF) in poly(lactic-co-glycolic) acid (PLGA) microspheres using a rat model, and to develop a pharmacokinetic model for this controlled release formulation. 14C-VEGF was encapsulated using a solid-in-oil-in-water emulsification method. The microspheres were administered subcutaneously to rats and the pharmacokinetic parameters were compared with those of protein solutions. Intravenous administration of protein solutions resulted in short half-lives and subcutaneous administration resulted in rapid clearance from the subcutaneous tissue, with high plasma concentrations as expressed by rapid absorption and elimination. The subcutaneous administration of the VEGF microspheres produced low plasma concentrations and high subcutaneous concentrations over a period of 7 weeks. The area under the curve (AUC), the time required to achieve the maximum concentration (tmax), the maximum concentration (Cmax) in blood samples and the elimination rate constant (kel) values at the subcutaneous tissue site were selected to compare the pharmacokinetic characterization of VEGF microspheres with that of protein solutions. The in-vivo release profiles of the proteins were slower than the in-vitro release profiles and they followed the same trend as the in-vitro and in-vivo PLGA degradation rates. The PLGA microsphere degradation was the determinant step for VEGF release from the microspheres and its absorption at the subcutaneous site. Microspheres appear to be an attractive system for the localized rate-controlled delivery of VEGF. 14C-Methylation via reductive alkylation of VEGF did not affect its mitogenic activity, however approximately 25% activity was lost following release from PLGA microspheres. This loss of activity may be due to degradation in an acidic environment as a result of PLGA degradation. [source] Comparison of micelles formed by amphiphilic star block copolymers prepared in the presence of a nonmetallic monomer activatorJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 6 2008Hoon Hyun Abstract In this article, we describe the synthesis of PEG- b -polyester star block copolymers via ring-opening polymerization (ROP) of ester monomers initiated at the hydroxyl end group of the core poly(ethylene glycol) (PEG) using HCl Et2O as a monomer activator. The ROP of ,-caprolactone (CL), trimethylene carbonate (TMC), or 1,4-dioxan-2-one (DO) was performed to synthesize PEG- b -polyester star block copolymers with one, two, four, and eight arms. The PEG- b -polyester star block copolymers were obtained in quantitative yield, had molecular weights close to the theoretical values calculated from the molar ratio of ester monomers to PEG, and exhibited monomodal GPC curves. The crystallinity of the PEG- b -polyester star block copolymers was determined by differential scanning calorimetry and X-ray diffraction. Copolymers with a higher arm number had a higher tendency toward crystallization. The crystallinity of the PEG- b -polyester star block copolymers also depended on the nature of the polyester block. The CMCs of the PEG- b -PCL star block copolymers, determined from fluorescence measurements, increased with increasing arm number. The CMCs of the four-arm star block copolymers with different polyester segments increased in the order 4a-PEG- b -PCL < 4a-PEG- b -PDO < 4a-PEG- b -PLGA < 4a-PEG- b -PTMC, suggesting a relationship between CMC and star block copolymer crystallinity. The partition equilibrium constant, Kv, which is an indicator of the hydrophobicity of the micelles of the PEG-polyester star block copolymers in aqueous media, increased with decreasing arm number and increasing crystallinity. A key aspect of the present work is that we successfully prepared PEG- b -polyester star block copolymers by a metal-free method. Thus, unlike copolymers synthesized by ROP using a metal as the monomer activator, our copolymers do not contain traces of metals and hence are more suitable for biomedical applications. Moreover, we confirmed that the PEG- b -polyester star block copolymers form micelles and hence may be potential hydrophobic drug delivery vehicles. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 2084,2096, 2008 [source] Electrospun, Biofunctionalized Fibers as Tailored in vitro Substrates for Keratinocyte Cell CultureMACROMOLECULAR BIOSCIENCE, Issue 9 2010Dirk Grafahrend Abstract Cell adhesion preventing fiber surfaces were tailored differently with bioactive peptides (a fibronectin fragment (GRGDS), a collagen IV fragment (GEFYFDLRLKGDK) and a combination of both) to provide an artificial extracellular matrix as a substrate for HaCaT keratinocyte cell culture. Therefore, a polymer blend containing a six-arm star-shaped statistical copolymer of ethylene oxide and propylene oxide in the ratio 80:20 (NCO- sP[EO- co -PO]) and poly-[D,L -(lactide- co -glycolide)] (PLGA) was electrospun. The resulting fibers were biofunctionalized and investigated as in vitro substrates using the HaCaT kerationcyte cell line. Appropriate surface chemistry on these electrospun fibers proved to prevent adhesion of keratinocytes, while additional immobilization of certain peptide sequences induced cell adhesion. These specific fibers enable investigation of immobilized active molecules and the subsequent cellular response to the scaffold. HaCaT keratinocytes were found to selectively adhere to those fibers modified with either collagen IV segment GEFYFDLRLKGDK or a mixture of the two peptide sequences GEFYFDLRLKGDK and GRGDS (1:1). However, the synergistic effects of both (the fibronectin fragment and the collagen IV fragment) seem to significantly increase the numbers of adherent keratinocytes. [source] Evaluating the In Vitro and In Vivo Efficacy of Nano-Structured Polymers for Bladder Tissue Replacement ApplicationsMACROMOLECULAR BIOSCIENCE, Issue 5 2007Megan Pattison Abstract Bladder cancers requiring radical cystectomy, along with congenital and acquired disorders which result in obstruction of the bladder, necessitate surgical measures (including augmentation); such diagnoses bring a clinical need for effective bladder replacement implant designs. Many recent approaches for the design of soft tissue replacement materials have relied on the use of synthetic polymeric substances; unfortunately, the optimal soft tissue implant material is yet to be found. This may, in part, be because current polymeric formulations fail to sufficiently biomimic the neighboring bladder tissue. This study took a brand new approach in designing the next generation of tissue-engineered bladder constructs through the use of nanotechnology, or materials with nanometer (less than 100 nm) surface features. Results provided evidence that nano-structured polymeric scaffolds (specifically, PLGA and PU) created using chemical etching techniques are capable of enhancing the human bladder smooth muscle cell adhesion, proliferation, and the production of extracellular matrix (ECM) proteins. Preliminary in vivo results also speak to the usefulness of such nano-structured materials. In combination, these findings suggest that nano-dimensional PLGA and PU scaffolds are promising replacement materials for the human bladder wall. [source] | |||||||||||||||||||||||||||||||