Amount Of PLGA Research Articles

In vivo evaluation of different formulation strategies for sustained release injectables of a poorly soluble HIV protease inhibitor

At present no scientific rationale exists for selecting a particular enabling strategy to formulate a poorly water-soluble drug, although this is crucial as it will influence the in vivo performance of the resulting formulation. This study provides an insight into this complicated decision making process for a poorly soluble human immunodeficiency virus (HIV) protease inhibitor based upon in vivo test results. A formulation strategy based on the molecular dispersion of this active pharmaceutical ingredient (API) into a biphasic matrix consisting of water-insoluble poly(lactic-co-glycolic acid) (PLGA) and water-soluble polyvinylpyrrolidone (PVP) was evaluated. The long-term in vivo performance of this strategy was compared to that of other solubility enhancing approaches by evaluating exposure of the API in male Beagle dogs. Solid dispersions, based on a PLGA/PVP matrix, were compared to solid dispersions in a pure PLGA matrix. Additionally these solid dispersion strategies were compared to the strategy of particle size reduction by means of an API microsuspension. The in vivo performance of the various formulations over a period of 28days after intramuscular injection was evaluated by the observed initial burst release, plasma concentration-time profiles, time at which maximum plasma levels were reached and the estimated bioavailability. Compared to the other formulation strategies assessed, it was concluded that the addition of PVP in a PLGA matrix resulted in vivo in a more sustained release as well as a higher amount of drug released from the polymeric matrix. This was explained based on the structure of these binary PLGA/PVP matrices where the pore network originating from rapidly dissolving PVP plays a key role. Moreover, the results suggest that the API release from this type of formulation could be delayed by increasing the amount of PLGA in the formulation.

Miscibility, Thermal and Mechanical Properties of Poly(para-dioxanone)/Poly(lactic-co-glycolic acid) Blends

A series of biodegradable polymers was prepared by solution co-precipitation of poly(para-dioxanone) (PPDO) and poly(lactic-co-glycolic acid) (PLGA) in various blend ratios. Samples were compression-molded into bars using a platen vulcanizing press. The miscibility, thermal and mechanical properties of the materials were investigated using differential scanning calorimetry (DSC), polarized optical microscopy, and scanning electron microscopy (SEM). Dynamic contact angle was used to characterize the water wettability of PLGA/PPDO blends. The mechanical properties of blends and pure polymers were measured by tensile tests. The position of the glass transition temperatures (Tg) was dependent upon composition. When 10 % PLGA was added into PPDO, the DSC curve revealed only one Tg (−7.35 °C) which was located between the Tg values of PPDO and PLGA. When 20 % PLGA was added into the blend, two independent Tg values for PPDO/PLGA blends were observed, and such characteristics improved further upon addition of 30 % PLGA. SEM images of fractured surfaces displayed evidence of the morphology of PPDO/PLGA blends that were consistent with the DSC results. Hence, a relationship was found between homogeneity and the contents of PLGA in the blend. The compatibility of the blends increased with addition of small amounts of PLGA, followed by a leveling-off at higher content.

New Coating Method for Sustained Drug Release: Surface Modification of ePTFE Grafts by inner coating PLGA

Division of Nephrology, Samsung Medical Center, Sungkyunkwan University of School of Medicine, Seoul 135-710, KoreaReceived December 24, 2013, Accepted January 6, 2014Expanded polytetrafluoroethylene (ePTFE) grafts have been used as vascular access for many patientssuffering from end stage renal disease. However, the vascular graft can cause significant clinical problems suchas stenosis or thrombosis. For this reason, many studies have been performed to make drug eluting graft, butinitial burst is major problem in almost drug eluting systems. Therefore we used biodegradable polymer toreduce initial burst and make sustained drug delivery. The ePTFE grafts were dipped into a paclitaxel-dissolvedsolution and then PLGA-dissolved solution was passed through the lumen of ePTFE. We analyzed whether thedose of paclitaxel is enough and the loading amount of PLGA on ePTFE graft increases according to the coatingsolution’s concentration. Scanning electron microscope (SEM) images of various concentration of PLGAshowed that the porous surface of graft was more packed with PLGA by tetrahydrofuran solution dissolvedPLGA. In addition, in vitro release profiles of Ptx-PLGA graft demonstrated that early burst was graduallydecreased as increasing the concentration of PLGA. These results suggest that PLGA coating of Ptx loadedgraft can retard drug release, it is useful tool to control drug release of medical devices.Key Words : Hemodialysis, Vascular access, ePTFE graft, Paclitaxel, Biodegradable polymerIntroductionMany patients suffering from end stage renal diseaseusually receive hemodialysis three times a week. To performthe hemodialysis, the secure of vascular access is important.Most common forms of vascular access are the nativearteriovenous fistulas (AVF) and arteriovenous graft (AVG)using expanded polytetrafluoroethylene (ePTFE) graft.

Physicochemical features and transfection properties of chitosan/poloxamer 188/poly(D,L-lactide-co-glycolide) nanoplexes.

The aim of this study was the evaluation of the effects of two emulsifiers on the physicochemical and technological properties of low molecular weight chitosan/poly (D,L-lactide-co-glycolide) (PLGA) nanoplexes and their transfection efficiency. Nanospheres were prepared using the nanoprecipitation method of the preformed polymer. The mean diameter and surface charge of the nanospheres were investigated by photocorrelation spectroscopy. The degree of binding of the plasmid with the nanoplexes was qualitatively and quantitatively determined. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) testing was performed using HeLa, RPMI8226, and SKMM1 cell lines. Flow cytometry and confocal laser scanning microscopy were used to determine the degree of cellular transfection and internalization of the nanoplexes into cells, respectively. The nanoplexes had a positive zeta potential, and low amounts of PLGA and poloxamer 188 showed a mean colloidal size of ~200 nm with a polydispersity index of ~0.14. The nanoplexes had suitable entrapment efficiency (80%). In vitro experiments showed that the colloidal nanodevices did not induce significant cytotoxicity. The nanoplexes investigated in this study could represent efficient and useful nonviral devices for gene delivery. Use of low amounts of PLGA and poloxamer 188 enabled development of a nanosphere able to transfect cells efficiently. These nanosystems are a helpful platform for delivery of genetic material while preserving therapeutic efficacy.

Effects of PLGA reinforcement methods on the mechanical property of carbonate apatite foam.

The purpose of this study was to improve the mechanical property of brittle carbonate apatite (CO3Ap) foam aimed as bone substitute material by reinforcement with poly(DL-lactide-co-glycolide) (PLGA). The CO3Ap foam was reinforced with PLGA by immersion and vacuum infiltration methods. Compressive strength of CO3Ap foam (12.0±4.9 kPa) increased after PLGA reinforcement by immersion (187.6±57.6 kPa) or vacuum infiltration (407.0±111.4 kPa). Scanning electron microscopic (SEM) observation showed a gapless PLGA and CO3Ap foam interface and larger amount of PLGA inside the hollow space of the strut when vacuum infiltration method was employed. In contrast a gap was observed at the PLGA and CO3Ap foam interface and less amount of PLGA inside the hollow space of the strut when immersion method was employed. Strong PLGA-CO3Ap foam interface and larger amount of PLGA inside the hollow space of the strut is therefore the key to higher mechanical property obtained for CO3Ap foam when vacuum infiltration was employed for PLGA reinforcement.

Poly(l-glutamic acid)/chitosan polyelectrolyte complex porous microspheres as cell microcarriers for cartilage regeneration

In this study a novel kind of porous poly(l-glutamic acid) (PLGA)/chitosan polyelectrolyte complex (PEC) microsphere was developed through electrostatic interaction between PLGA and chitosan. By adjusting the formula parameters chitosan microspheres with an average pore size of 47.5±5.4μm were first developed at a concentration of 2wt.% and freeze temperature of −20°C. For self-assembly of the PEC microspheres porous chitosan microspheres were then incubated in PLGA solution at 37°C. Due to electrostatic interaction a large amount of PLGA (110.3μgmg−1) was homogeneously absorbed within the chitosan microspheres. The developed PEC microspheres retained their original size, pore diameters and interconnected porous structure. Fourier transform infrared spectroscopy, thermal gravimetric analysis and zeta potential analysis revealed that the PEC microspheres were successfully prepared through electrostatic interaction. Compared with microspheres fabricated from chitosan, the porous PEC microspheres were shown to efficiently promote chondrocyte attachment and proliferation. After injection subcutaneously for 8weeks PEC microspheres loaded with chondrocytes were found to produce significant more cartilaginous matrix than chitosan microspheres. These results indicate that these novel fabricated porous PLGA/chitosan PEC microspheres could be used as injectable cell carriers for cartilage tissue engineering.

Influence of PLGA concentrations on structural and mechanical properties of carbonate apatite foam

Reinforcement with bioresorbable polymer such as PLGA is one of the useful ways to improve the mechanical property of brittle carbonate apatite (CO3Ap) foam. In the present study, CO3Ap foam was reinforced with various concentrations of PLGA solution (5, 10, 15 and 20 wt%) using vacuum infiltration method and its influence on structure, porosity and mechanical property was investigated. It was found that the amount of PLGA inside the hollow space of the CO3Ap foam strut increased with the concentration of PLGA. Porosity likewise was significantly (p<0.05) reduced from 94% (CO3Ap foam without PLGA) down to 82% (CO3Ap foam reinforced with 20 wt% PLGA). Compressive strength of CO3Ap foam significantly (p<0.05) increased from 0.02 MPa (CO3Ap foam without PLGA) up to 1.5 MPa (CO3Ap foam reinforced with 20 wt% PLGA).

Synthesis and encapsulation of magnetite nanoparticles in PLGA: effect of amount of PLGA on characteristics of encapsulated nanoparticles

Oleic acid-coated superparamagnetic iron oxide nanoparticles (Fe3O4) encapsulated within poly(d,l-lactide-co-glycolide) (PLGA) particles were prepared by the w/o/w emulsion technique using poly(vinyl alcohol) as a dispersant. The concentration of PLGA in the oil phase was varied (5, 15, 30, 45, and 60 mg/ml) at constant magnetite concentration in the oil phase (5 mg/ml) to study the properties of composite Fe3O4–PLGA nanoparticles. Even though PLGA concentration varied widely in the oil phase, the weight percent of 7–16 nm diameter magnetite in the particles varied only from 56 to 62 % (23–28 vol.%). The obtained composite nanoparticles were essentially spherical with magnetite spatially uniformly dispersed in individual PLGA particles, as measured by transmission electron microscopy (TEM). Also, the magnetite concentration in each particle did not vary widely as determined qualitatively via microscopy. Hydrodynamic diameters of the composite nanoparticles as measured by dynamic light scattering increased by approximately 10 % with added magnetite, with a smaller relative increase in diameter measured by TEM. The zeta potential of the particles was about −26 mV, independent of Fe3O4 loading. Relatively high saturation magnetizations (36–45 emu/g) were measured for these highly loaded particles, with the latter value only 7 emu/g lower than the value measured for the oleic acid-coated particles alone.

Improved Cardiomyocyte Functions of Carbon Nanofiber Cardiac Patches

ABSTRACTThe objective of the present in vitro research was to determine cardiomyocyte functions on poly-lactic-co-glycolic acid (50:50 (PLA:PGA); PLGA) with greater amounts of carbon nanofibers (CNFs) using an in vitro electrical stimulation system for myocardial tissue engineering applications. The addition of CNFs can increase the conductivity and strength of pure PLGA. For this reason, different PLGA: CNF ratios (100:0, 75:25, 50:50, 25:75, 0:100 wt%) were created where conductivity and cytocompatibility properties under electrical stimulation with human cardiomyocytes were determined. Results showed that PLGA:CNF materials were conductive and that conductivity increased with greater amounts of PLGA added, from 0 S.m-1 for 100:0 wt% (pure PLGA) to 6.5x10-3 S.m-1 for 0:100 wt% (pure CNFs) materials. Furthermore, results indicated that cardiomyocyte cell density increased with continuous electrical stimulation (rectangular, 2 nm, 5 V/cm, 1 Hz) after 1, 3, and 5 days as well as a slight increase in Troponin I excretion compared to non-electrically stimulated normal cardiomyocyte cell functions. This study, thus, provides an alternative conductive scaffold using nanotechnology which should be further explored for numerous cardiovascular applications.

Formulation and Optimization of Mucoadhesive Nanodrug Delivery System of Acyclovir

Acyclovir is an antiviral drug used for the treatment of herpes simplex virus infections, with an oral bioavailability of only 10–20% [limiting absorption in gastrointestinal tract to duodenum and jejunum] and half-life of about 3 h, and is soluble only at acidic pH (pKa 2.27). Mucoadhesive polymeric nanodrug delivery systems of acyclovir have been designed and optimized using 23 full factorial design. Poly (lactic-co-glycolic acid) (PLGA) (50:50) was used as the polymer along with polycarbophil (Noveon AA-1) as the mucoadhesive polymer and pluronic F68 as the stabilizer. From the preliminary trials, the constraints for independent variables X1 (amount of PLGA), X2 (amount of pluronic F68) and X3 (amount of polycarbophil) have been fixed. The dependent variables that were selected for study were particle size (Y1), % drug entrapment (Y2) and % drug release in 12 h (Y3). The derived polynomial equations were verified by check point formulation. The application of factorial design gave a statistically systematic approach for the formulation and optimization of nanoparticles with the desired particle size, % drug release and high entrapment efficiency. Drug: Polymer ratio and concentration of stabilizer were found to influence the particle size and entrapment efficiency of acyclovir-loaded PLGA nanoparticles. The release was found to follow Fickian as well as non-Fickian diffusion mechanism with zero-order drug release for all batches. In vitro intestinal mucoadhesion of nanoparticles increased with increasing concentration of polycarbophil. These preliminary results indicate that acyclovir-loaded mucoadhesive PLGA nanoparticles could be effective in sustaining drug release for a prolonged period.

Biodegradable Microcapsules: Optimization of Formulation Using Factorial Design

Biodegradable microcapsules of zidovudine (AZT) were prepared using a solvent evaporation technique. The experimental protocol was based on a 4 times 3 factorial design. The effect of volatile organic solvent was examined at four levels: 100/0, 90/10, 80/20, and 70/30 mixtures of dichloromethane with methanol. Poly(lactide/glycolide) copolymer (PLGA 50:50) was used at three levels: 50, 100, and 200 mg mL−1 The efficiency of encapsulation significantly increased with increasing polymer concentration. The four levels of the organic solvent showed no significant effect on the encapsulation. A comparison of the SEM photographs of the twelve batches of the microcapsules showed that the formation of surface pinholes could be avoided by increasing the concentration of the polymer. Higher methanol concentrations (>10%) in the dichloromethane/methanol mixture also significantly changed the surface morphology. No significant rank order correlation was observed between the median particle sizes of the different batches of the microcapsules and the organic solvent or the amount of PLGA. The median particle sizes were between 33 and 193 μm. Particle size ranges were between 0.5 and 600 μm. The initial drug release was between 15 and 50% during the first day with a sustained release observed up to 60 days.

Poly Lactic-Co-Glycolic Acid Carbon Nanofiber Composite for Enhancing Cardiomyocyte Function

ABSTRACTThe objective of the present in vitro research was to determine cardiomyocyte function on poly lactic-co-glycolic acid (50:50 (PLA:PGA); PLGA) with greater amounts of carbon nanofibers (CNFs) and variations in CNF size, for myocardial tissue engineering applications. The addition of CNFs would increase conductivity and strength of pure PLGA. For this reason, different PLGA: CNF ratios (100:0, 75:25, 50:50, 25:75, 0:100 wt.%) were created and conductivity and cytocompatibility properties with human cardiomyocytes were determined. Results showed that PLGA:CNF materials were conductive and that conductivity increased with greater amounts of PLGA added, from 0 S.m-1 for 100:0 wt.% (pure PLGA) to 5.5x10-3 S.m-1 for 0:100 wt.% (pure CNFs) material. Furthermore, results indicated that cardiomyocyte density increased with greater amounts of CNFs of 200nm in diameter in PLGA (up to 25:75 wt.% , PLGA:CNFs). This study, thus, provided an alternative conductive scaffold using nanotechnology which should be further explored for cardiovascular applications.

Preparation and Properties of Nanosized Biodegradable Polymer Capsules

This article reports the preparation and properties of nanosized biodegradable polymer capsules synthesized using the electrocapillary emulsification method. The biodegradable polymers used were poly(ε-caprolactone) (PCL), which is a highly biodegradable and biocompatible polymer, and poly(lactide-co-glycolic acid) (PLGA). While the size of the capsules prepared using PCL alone was in the micrometer range, it decreased with an increase in the amount of PLGA added to PCL and eventually reached the nanometer level. When the electrocapillary emulsification applied potential was 2000 V, the sizes of the capsules (PCL:PLGA = 5:5) ranged from 50 to 80 nm. The percentage of glucose trapped in the PCL/PLGA nanocapsules was higher than 80% and the duration of glucose release from the nanocapsules was about two times longer than that from PCL capsules.

Design of semi-degradable hydrogels based on poly(vinyl alcohol) and poly(lactic-co-glycolic acid) for cartilage tissue engineering

Articular cartilage damage is a persistent challenge in biomaterials and tissue engineering. Poly(vinyl alcohol) (PVA) hydrogels have shown promise as implants, but their lack of integration with surrounding cartilage prevents their utility. We sought to combine the advantages of PVA hydrogels with poly(lactic-co-glycolic acid) (PLGA) scaffolds, which have been successful in facilitating the integration of neocartilage with surrounding tissue. Through a novel double-emulsion technique, PLGA microparticles and a high level of porosity were simultaneously incorporated into PVA hydrogels. The porosity, average pore size and swelling properties of the hydrogels were controlled by varying initial processing parameters, such as the relative amounts of PLGA and solvent. Average pore sizes were in the ranged 50-100 µm. The PLGA microparticles degraded within the hydrogels over time in aqueous conditions, resulting in increases in porosity and pore size. After 4 weeks in cell culture, immature cartilage tissue filled many of the pores of the hydrogels that initially contained PLGA, and proteoglycan production was proportional to the amount of PLGA. In contrast, there was little cell attachment and no proteoglycan production in control hydrogels without PLGA. The compressive moduli of the hydrogels were similar to that of healthy cartilage and increased over time from 0.05-0.1 to 0.3-0.7 MPa. The generation of a hybrid cartilage-hydrogel construct using this technique may finally allow the integration of PVA hydrogels with surrounding cartilage.

Preparation, evaluation and dissolution behaviors of water soluble drug loaded PLGA microspheres.

One of important drug delivery system is microencapsulation of bioactive agents using biodegradable polymers. Although a large number of studies, which utilizes PLGA have been performed, however, basic data and information upon drug release are in sufficient. Formulation of indomethacin sodium as microspheres using different percentages of PLGA by applying coacervation / phase separation and emulsification / solvent evaporation methods, were performed. The morphology, particle size and dissolution – release profile of the prepared microspheres have been studied. From both methods, it was noticed that the release of the drug is decreased as the amount of PLGA increased since it affects core: coat ratio. The microspheres prepared with low percentages of PLGA (not more than 20%) showed initial burst effect, which may suggest that erosion, is the major dissolution mechanism while diffusion might be the main mechanism for microspheres prepared with high percentages of PLGA. The shape of microspheres with &gt; 30% PLGA (by coacervation method) has limited sphericity and larger particles size in comparison to that prepared with emulsification / solvent evaporation methods. Therefore, indomethacin – loaded PLGA microspheres (using 50% polymer) prepared by the second method can be used in the formulation of prolonged duration injectable dosage form.

NEW DRUG DELIVERY SYSTEM OF DICLOFENAC SODIUM FOR ITS APPLICATION IN THERAPEUTIC EMBOLIZATION STRATEGY.

The perfectly spherical microspheres of the ion- exchange resins diethylaminoethyl – trisacryl (DEAE) had been successfully used for achieving mechanical occlusion of vascular lumen. In this study; diclofenac sodium is reversibly adsorbed onto DEAE microspheres (28.3 g drug / 100 g of microspheres). The dissolution profile showed rapid release of the drug from the loaded microspheres, and since this may lead to dramatic decrease in the drug before the microspheres. reaches the targeted site, therefore, microencapsulation of the drug loaded DEAE microspheres is carried out for the first time in this study using PLGA as a coating polymer and applying two different methods of microencapsulation. The results showed that increasing the amount of PLGA lead tomore retardation in the release of the drug through affecting core : coat ratio and the mechanism of drug release. It is also found that applying emulsification / solvent evaporation method with 60% w/w PLGA gave regular retarded release microcapsules with better sphericity, which may be easily injected by a catheter at the required site and offers a new drug delivery system and new application for diclofenac sodium in the promising strategy of using embolization particles with anti – inflammatory activity.

Preparation and in vitro characterization of amifostine biodegradable microcapsules

The purpose of this project was to develop sustained release microcapsules of amifostine. The microcapsules were prepared using solvent evaporation technique. The effect of several formulation variables on the characteristics of the microcapsules was studied. The formulation variables studied were drug loading, polymer (polylactide-co-glycolide) (PLGA) concentration, and the amount of gelatin in the initial aqueous phase. The drug loading was studied at three different levels (5, 10, and 25 mg); the PLGA concentration was studied at two levels (500 and 1000 mg); and the amount of gelatin used ranged from 2 to 14 mg. In general, the microcapsules were less than 155 μm in diameter with median size between 50 and 80 μm. While the use of higher amounts of PLGA significantly increased the median size of the microcapsules, using higher amounts of amifostine had no significant effect, irrespective of the amount of PLGA. The use of gelatin, within the range 2–14 mg, did not show any significant effect on the particle size distribution. Scanning electron microscopy (SEM) of the microcapsules revealed that all nine formulations yielded spherical particles. The use of 500 mg PLGA with 10 or 25 mg amifostine yielded microcapsules with porous surfaces. The surface pores, however, were not present in microcapsules prepared using 1000 mg PLGA. The efficiency of encapsulation decreased significantly from 63 to 24% when the amount of amifostine increased from 5 to 25 mg in the formulations using 500 mg PLGA. Similarly, the efficiency of encapsulation decreased from 87 to 23% when the amount of PLGA was doubled to 1000 mg. An increase in the amount of amifostine in the formulation using 500 mg PLGA also resulted in a significant increase in initial drug release (from 20 to 62%) within the first hour. These results were consistent with the porous morphology of these microcapsules. In general, all batches of microcapsules showed 24–96 h sustained drug release.

Preparation of poly( dl-lactide-co-glycolide) nanoparticles by modified spontaneous emulsification solvent diffusion method

Purpose: The objectives of this study were to establish a new preparation method for poly( dl-lactide-co-glycolide) (PLGA) nanoparticles by modifying the spontaneous emulsification solvent diffusion (SESD) method and to elucidate the mechanism of nanoparticle formation on the basis of the phase separation principle of PLGA and poly(vinyl alcohol) (PVA) in the preparation system. Methods: PLGA nanoparticles were prepared by the modified-SESD method using various solvent systems consisting of two water-miscible organic solvents, in which one solvent has more affinity to PLGA than to PVA and the other has more affinity to PVA than to PLGA. The yield, particle size, size distribution and PVA content of the PLGA nanoparticles were evaluated, and the phase separation behaviors of the polymers were elucidated. Results: The modified-SESD method provided a good yield of PLGA nanoparticles over a wide range of composition ratios in the binary mixture of organic solvents. Several process parameters, including the fed amount of PLGA, PLGA concentration and PVA concentration were examined to achieve the optimum preparation conditions. The discrete powder of PLGA nanoparticles was obtained by freeze-drying. No change in the PVA content of PLGA nanoparticles was observed even after several times of washing treatment by ultrafiltration, suggesting a strong surface adsorption. It was found that the appropriate selections of binary solvent mixtures and polymeric concentrations in both organic and aqueous phases could provide excellent yield and favorable physical properties of PLGA nanoparticles. Conclusion: The proposed modified-SESD method can be used to provide PLGA nanoparticles of satisfactory quality at an acceptable yield for industrial purposes.