The effect of different grades of PLGA on characteristics of microspheres encapsulated with cyclosporine A

The aim of this study was to evaluate the effect of different grades of poly D, L lactide-co-glycolide (PLGA) on the properties of microspheres encapsulated with Cyclosporine A (CyA). Microspheres were prepared by solvent evaporation method using three grades of PLGA. Various characteristics of microspheres such as morphology, size distribution, encapsulation efficiency and release profile were evaluated. Complementary studies were also carried out by Infrared (IR) spectroscopy and Differential scanning calorimetry (DSC) to evaluate possible drug-polymer interactions. Scanning electron microscopy (SEM) studies showed microspheres as spherical particles with CyA deposited as islands on the surface of spheres. Particle size range was 1-25 microm for microspheres made of PLGA (50:50) which showed the minimum size. Encapsulation efficiency was found to vary from 75% to 92% in various formulations. The profile of release was biphasic, showing an initial rapid phase followed by a continuous and slower rate thereafter. Microspheres made of grades 50:50 and 85:15 showed the highest and lowest amount of drug release, respectively. IR spectra for drug, polymer and microspheres did not indicate any chemical interaction between the components of microsphere and DSC thermograms revealed that CyA was present in its amorphous state within microspheres. In conclusion, the effect of polymer characteristics should be considered in microsphere formulations. In this study, suitable microspheres especially with PLGA (50:50) were prepared which allow the controlled release of CyA over a prolonged period of time.     

Formulation, characterization, and evaluation of ketorolac tromethamine-loaded biodegradable microspheres

Ketorolac tromethamine has to be given every 6 hr intramuscularly in patients for acute pain, so to avoid frequent dosing and patient inconvenience we found it to be a suitable candidate for parenteral controlled delivery by biodegradable microspheres for the present study. Ketorolac tromethamine-loaded microspheres were prepared by o/w emulsion solvent evaporation technique using different polymers: polycaprolactone, poly lactic-co-glycolic acid (PLGA 65/35), and poly lactic-co-glycolic acid (PLGA 85/15). To tailor the release profile of drug for several days, blends of PLGA 65/35 and PLGA 85/15 were prepared with polycaprolactone (PCL) in different ratios. The results revealed that microspheres made with 1:3 (PLGA65/35: PCL) blend released 97% of the drug in 5 days as compared with 97% in 30 days in with pure PLGA65/35 microspheres. Microspheres made with 1:1 (PLGA65/35:PCL) and 3:1 (PLGA65/35:PCL released 98% of the drug in 30 days. In microspheres made with 1:3 (PLGA85/15:PCL), almost the entire drug was released in a week whereas in batches made with pure PLGA85/15 and 3:1 (PLGA 85/15:PCL) more than 80% of the drug was released in 60 days as compared with 96% in 60 days in 1:1 (PLGA85/15:PCL). Higher encapsulation efficiency was obtained with microspheres made with pure PLGA 65/35. These formulations were characterized for particle size analysis by Malvern mastersizer that revealed particle size in range of 12-15 micron and 12-22 micron for microspheres made with polymer blends of PLGA 65/35:PCL and PLGA85/15:PCL, respectively. In with pure PLGA65/35 and PLGA85/15, particle size was 28 micron and 8 micron, respectively. Surface topography was studied by scanning electron microscopy that revealed a spherical shape of microspheres. From our study it we concluded that with careful selection of different polymers and their combinations, we can tailor the release of ketorolac tromethamine for long periods.     

Formulation,Characterization, and Evaluation of Ketorolac Tromethamine-Loaded Biodegradable Microspheres

Ketorolac tromethamine has to be given every 6 hr intramuscularly in patients for acute pain, so to avoid frequent dosing and patient inconvenience we found it to be a suitable candidate for parenteral controlled delivery by biodegradable microspheres for the present study. Ketorolac tromethamine-loaded microspheres were prepared by o/w emulsion solvent evaporation technique using different polymers: polycaprolactone, poly lactic-co-glycolic acid (PLGA 65/35), and poly lactic-co-glycolic acid (PLGA 85/15). To tailor the release profile of drug for several days, blends of PLGA 65/35 andPLGA85/15 were prepared with polycaprolactone (PCL) in different ratios. The results revealed that microspheres made with 1:3 (PLGA65/35: PCL) blend released 97% of the drug in 5 days as compared with 97% in 30 days in with pure PLGA65/35 microspheres. Microspheres made with 1:1 (PLGA65/35:PCL) and 3:1 (PLGA65/35:PCL released 98% of the drug in 30 days. In microspheres made with 1:3 (PLGA85/15:PCL), almost the entire drug was released in a week whereas in batches made with pure PLGA85/15 and 3:1 (PLGA 85/15:PCL) more than 80% of the drug was released in 60 days as compared with 96% in 60 days in 1:1 (PLGA85/15:PCL). Higher encapsulation efficiency was obtained with microspheres made with pure PLGA 65/35. These formulations were characterized for particle size analysis by Malvern mastersizer that revealed particle size in range of 12–15 micron and 12–22 micron for microspheres made with polymer blends of PLGA 65/35:PCL and PLGA85/15:PCL, respectively. In with pure PLGA65/35 and PLGA85/15, particle size was 28 micron and 8 micron, respectively. Surface topography was studied by scanning electron microscopy that revealed a spherical shape of microspheres. From our study it we concluded that with careful selection of different polymers and their combinations, we can tailor the release of ketorolac tromethamine for long periods.     

Effect of Polymer Blending on the Release of Ganciclovir from PLGA Microspheres

Purpose The aim of the study is to investigate the effect of polymer blending on entrapment and release of ganciclovir (GCV) from poly(d,l-lactide-co-glycolide) (PLGA) microspheres using a set of empirical equations. Methods Two grades of PLGA, PLGA 7525 [d,l-lactide:glycolide(75:25), MW 90,000–126,000 Da] and Resomer RG 502H [d,l-lactide:glycolide(50:50), MW 8000 Da], were employed in the preparation of PLGA microspheres. Five sets of microsphere batches were prepared with two pure polymers and their 1:3, 1:1, and 3:1 blends. Drug entrapment, surface morphology, particle size analysis, drug release, and differential scanning calorimetric studies were performed. In vitro drug-release data were fitted to a set of empirical sigmoidal equations by nonlinear regression analysis that could effectively predict various parameters that characterize both diffusion and degradation cum diffusion-controlled release phases of GCV. Results Entrapment efficiencies of GCV ranged from 47 to 73%. Higher amounts of GCV were entrapped in polymer blend microspheres relative to individual polymers. Triphasic GCV release profiles were observed, which consisted of both diffusion and degradation cum diffusion-controlled phases. In vitro GCV release was shortest for Resomer RG 502H microsphere (10 days) and longest for PLGA 7525 microspheres (90 days). Upon blending, the duration of release gradually decreased as the content of Resomer RG 502H in the matrix was raised. Equations effectively estimated the drug-release rate constants during both the phases with high R² values (>0.990). GCV release was slower from the blend microsphere during the initial diffusion phase. Majority of entrapped drug (70–95%) was released during the matrix degradation cum diffusion phase. Conclusions Drug entrapment and release parameters estimated by the equations indicate more efficient matrix packing between PLGA 7525 and Resomer RG 502H in polymer-blended microspheres. The overall duration of drug release diminishes with rising content of Resomer RG 502H in the matrix. Differential scanning calorimetry studies indicate stronger binding between the polymers in the PLGA 7525/Resomer RG 502H∷ 3:1 blend. Polymer blending can effectively alter drug-release rates of controlled delivery systems in the absence of any additives.     

Paclitaxel-loaded polyester nanoparticles prepared by spray-drying technology: in vitro bioactivity evaluation

Paclitaxel (PTX), an antimicrotubular agent used in the treatment of ovarian and breast cancer, was encapsulated in nanoparticles (NPs) of poly(lactide-co-glycolide) (PLGA) and poly(ε-caprolactone) (PCL) polymers using the spray-drying technique. Morphology, size distribution, drug encapsulation efficiency, thermal degradation and drug release were characterized. MCF7 cells were employed to evaluate the efficacy of the systems on cell cycle and cytotoxicity. The particle size was in the range 0.8-1?μm. The incorporation efficiency of PTX was more than 80% in all NPs obtained. In?vitro drug release took place during 35 days, and drug release rates were in the order PCL?>?PLGA 50:50?>?PLGA 75:25. Unloaded NPs showed to be cytocompatible at MCF7 cells. PTX-loaded NPs demonstrated the release of the drug block cells in the G2/M phase. All PTX-loaded formulations showed their efficacy in killing MCF7 cells, mainly PTX-loaded PLGA 50:50 and PLGA 75:25 that cause a decrease in cell viability lower than 20%.     

Diphtheria and tetanus toxoid microencapsulation into conventional and end-group alkylated PLA/PLGAs.

The feasibility of biodegradable polyester microspheres (MS) for single injection vaccines will greatly depend on the toxoid stability within the MS exposed to in vivo conditions. This study examined the effects of polymer type and co-encapsulated additives on diphtheria (Dtxd) and tetanus (Ttxd) toxoid entrapment and stability. The co-encapsulated stabilizers influenced significantly the entrapment of Dtxd and Ttxd in PLA/PLGA MS. Typically, 5% BSA or trehalose decreased the amount of Dtxd entrapped in spray-dried MS, whereas BSA increased the entrapment in coacervated MS. Further, the entrapment of Dtxd decreased as a function of polymer hydrophobicity in spray-dried MS. Without additives, approx. 64, 43 and 16% entrapment efficiency of ELISA-reactive antigen was obtained for 14-17 kDa PLGA 50:50, PLGA 75:25 and PLA, respectively. The novel end-group stearylated 1-PLAs were only processed by coacervation. Satisfactory entrapment of 30-60% Dtxd was obtained. Here, albumin was a prerequisite for toxoid encapsulation, as BSA-free formulations produced strong toxoid precipitation. Furthermore, protein burst release increased with the more hydrophobic polymers, with Dtxd, Ttxd and the co-encapsulated BSA following a similar pattern and magnitude. This investigation also revealed that the method of protein extraction from the microspheres (O/W-partition or polymer hydrolysis) as well as the analytical methods (HPLC or ELISA) strongly influenced the determined amount of encapsulated toxoid and BSA. In conclusion, the study revealed the complexity of antigen microencapsulation when using different preparation and analytical techniques, as well as different types of materials.     

Paclitaxel-loaded polyester nanoparticles prepared by spray-drying technology: in vitro bioactivity evaluation

Paclitaxel (PTX), an antimicrotubular agent used in the treatment of ovarian and breast cancer, was encapsulated in nanoparticles (NPs) of poly(lactide-co-glycolide) (PLGA) and poly(ε-caprolactone) (PCL) polymers using the spray-drying technique. Morphology, size distribution, drug encapsulation efficiency, thermal degradation and drug release were characterized. MCF7 cells were employed to evaluate the efficacy of the systems on cell cycle and cytotoxicity. The particle size was in the range 0.8–1?µm. The incorporation efficiency of PTX was more than 80% in all NPs obtained. In vitro drug release took place during 35 days, and drug release rates were in the order PCL?>?PLGA 50:50?>?PLGA 75:25. Unloaded NPs showed to be cytocompatible at MCF7 cells. PTX-loaded NPs demonstrated the release of the drug block cells in the G2/M phase. All PTX-loaded formulations showed their efficacy in killing MCF7 cells, mainly PTX-loaded PLGA 50:50 and PLGA 75:25 that cause a decrease in cell viability lower than 20%.     

利培酮长效注射微球的制备及体外释放的研究

目的：制备利培酮长效注射微球并考察其体外释放行为。方法：使用乳酸-羟基乙酸共聚物（PLGA）为材料,采用乳化-溶剂挥发法制备利培酮微球,观察微球的形态及粒径,测定微球的载药量和包封率,考察微球的体外释放情况。结果：利培酮微球表面圆整,粒径集中在40～80μm之间。微球的包封率较高,达到80％以上,以低分子量PLGA（50：50）制备的微球,体外突释很高达到40％以上;以高分子量PLGA（75：25）制备的微球,在高载药量时突释较小,可持续释放达3周以上。结论：以高分子量PLGA制备的高载药量的利培酮微球,体外突释较小可缓释达3周以上。     

氟维司群PLA-block-mPEG微球在大鼠体内的药动学研究

分别以嵌段共聚物(聚乳酸-单甲氧基聚乙二醇,分子量比为40 000:2 000)和非嵌段共聚物(聚乳酸-聚羟乙酸,分子量均为40 000,摩尔比分别为75:25、50:50)作为载体材料,采用乳化-液中干燥法制备包载氟维司群的微球.大鼠单剂量(50 mg/kg)皮下注射3种氟维司群微球,采用LC-MS/MS法测定血药浓度,计算药动学参数.结果表明,使用嵌段共聚物制备的微球,药-时曲线较平稳,释放效果较好.     

PLGA微球的制备及其用于脉冲给药的初步研究

目的：制备聚乳酸-羟基乙酸共聚物（PLGA）微球,并考察其用于脉冲式释药系统的可行性。方法：以牛血清白蛋白（BSA）为模型药物,用S/O/W（Solid-in-oil-in-water）法和S/O/O（Solid-in-oil-in-oil）法制备PLGA（75：25）和PLGA（50：50）微球,比较2种方法制备的微球的表面形态、包封率及载药量等,并考察2种微球的体外释放行为。结果：S/O/W法和S/O/O法制备的微球均圆整、无粘连、形态良好,但S/O/W法制备的微球表面较为平整,而S/O/O法表面均匀分布有较大的凹陷。S/O/W法制备的PLGA（75：25）和PLGA（50：50）微球包封率分别为（60.15±5.95）%、（49.50±3.69）%,载药量分别为（2.56±0.25）%、（2.10±0.16）%,10h内药物释放均为10%左右,而后随着聚合物的降解药物的释放量突然增加;S/O/O法所制微球包封率分别为（84.36±1.11）%、（77.94±1.42）%,载药量分别为（3.58±0.05）%、（3.31±0.06）%,24h内药物释放均可达50%左右,而后呈现较为平稳的释放行为。S/O/O法制备的微球包封率及载药量均较S/O/W法高;S/O/W法制备的PLGA微球药物释放呈现一定的脉冲行为,其中PLGA（75：25）微球体外释放行为受微球粒径的影响较大。结论：S/O/W法制备的PLGA微球具有一定的脉冲式释药效果,微球的粒径最好控制在120μm以下。     

Solvent, emulsifier and drug concentration factors in poly(D,L-lactic acid) microspheres containing hexamethylmelamine.

Biodegradable poly(D,L-lactic acid) (PLA) microspheres containing hexamethylmelamine (HMM) were developed for potential use in chemoembolization and intraperitoneal implantation. The emulsion-solvent-evaporation/extraction method was used to prepare 15 formulations with different drug/polymer ratios, solvent compositions and emulsifer concentrations in the continuous aqueous phase. A central composite experimental design was used, with five levels of the three different factors. All formulations resulted in the formation of discrete matrix microspheres containing crystalline drug. The mean particle sizes of the microsphere formulations ranged from 62-348 microm and the effect of the independent variables on microsphere size was satisfactorily predicted using response surface methodology. For theoretical drug loads of 5-40%, efficiency of entrapment ranged from 75-107% and porosities of the microspheres were between 0-6.5%. The rate of drug release from the microspheres depended on drug loading and particle size. Microspheres with 22.5% or greater theoretical drug content released drug rapidly, with almost complete release occurring in 70 h or less. Formulations with drug loading of 5% and 9.57%, however, released drug very slowly, with less than 50% released in 40 days. Release kinetics of narrow sieve cuts of microspheres with high drug load (35.4%) followed square root of time profiles.     

5-Fluorouracil plasma levels and biodegradation of subcutaneously injected drug-loaded microspheres prepared by spray-drying poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) polymers

Microspheres (MS) of 5-fluorouracil-loaded poly(D,L-lactide) (PLA), poly(D,L-lactide-co-glycolide) 75/25 (PLGA 75/25) and poly(D,L-lactide-co-glycolide) 50/50 (PLGA 50/50) prepared by the spray-drying technique were subcutaneously injected in the back of Wistar rats in order to evaluate the 5-fluorouracil (5-FU) release and the biodegradation characteristics. Determination of plasma 5-FU concentration by HPLC with analysis of data using a non-compartmental model showed drug in plasma between 9 and 14 days after administration of drug-loaded PLGA 50/50 or PLA and PLGA 75/25 microspheres, respectively, with a maximum drug concentration of 2.4+/-0.2microg/mL at 24h (5-FU-loaded PLGA 50/50 MS), 2.5+/-0.1microg/mL at 48h (5-FU-loaded PLGA 75/25 MS), and 2.3+/-0.1microg/mL at 24h (5-FU-loaded PLA MS). Pharmacokinetically, a significant increase of AUC (up to 50 times) and MRT (up to 196 times) of 5-FU with regard to the administration of the drug in solution was observed. Scanning electron microscopy and histological studies indicated that a small fibrous capsule was observed around the microspheres in the site of injection. One month after the injection of PLGA 50/50 MS and 2 months after the injection of PLGA 75/25 and PLA MS, masses of polymers, instead of single microspheres, were observed. Close to them, macrophagic cells were present, and blood vessels were observed in the connective tissue. Total absence of fibrous capsule and injected microspheres was observed after 2 (for PLGA 50/50 MS) or 3 (PLGA 75/25 and PLA MS) months.     

Preparation and characterization of poly(D,L-lactic-co-glycolic Acid) microspheres containing flurbiprofen sodium

This study aimed to prepare biodegradable microspheres containing flurbiprofen sodium, a nonsteroidal anti-inflammatory drug (NSAID), as the drug delivery system to the periodontal pocket. Microspheres were prepared from biodegradable copolymers of poly (D,L-lactic-co-glycolic acid) (PLGA) using solvent evaporation method. The effects of the different copolymers and amounts of polyvinyl alcohol (PVA) as a dispersing agent on characteristics of the microspheres were evaluated. Although there was no correlation between microsphere size and amount of PVA, an optimum PVA concentration was essential to achieve narrower size distributions of microspheres. As the concentration of PVA increased, the drug loading of the microspheres increased. The effect of PVA on drug loading was found to be statistically significant for those microspheres prepared from PLGA 50:50 (p < 0.05). Regarding copolymer composition, PLGA 85:15 provided higher drug loading into the microspheres than PLGA 50:50 (p < 0.05). The recoveries of microspheres (60-80%) were affected neither by different PVA concentrations nor by copolymer compositions (p > 0.05). According to the first-order release rate constants of the microspheres, the microspheres of PLGA 50:50 released the drug at the highest rate consistently, with the highest hydrophilicity of this copolymer.     

Preparation and characterization of hCG-loaded polylactide or poly(lactide-co-glycolide) microspheres using a modified water-in-oil-in-water (w/o/w) emulsion solvent evaporation technique

A modified w/o/w emulsion solvent evaporation technique was adopted to prepare human Chorionic Gonadotropin (hCG)-loaded polylactide (PLA) or poly(lactide-co-glycolide) (PLGA) microspheres. The effects of preparative parameters, such as stirring rate, polymer MW and concentration, and the composition of both the inner aqueous phase and oil phase etc., on hCG entrapment efficiency and microsphere characteristics were investigated. It was found that by adding 20% glycerol into the inner aqueous phase and 40% acetone into the oil phase, smooth microspheres 1mum in diameter could be produced with high hCG entrapment efficiency (&gt;90%). In vitro release test showed a burst release of hCG from PLGA (75:25) microspheres, followed by sustained release of 55% hCG over 2 months. The initial hCG burst from PLGA microspheres increased with the glycerol concentration in the inner aqueous phase, but decreased to a low value (ca. 20%) with the addition of acetone into the oil phase, which could beattributed to the associated changes in surface morphology of the microspheres. In vivo experiments demonstrated that a single shot of hCG-loaded PLGA microspheres could produce a comparable antibody response with the inoculation of free hCG four times.     

Preparation and characterization of hCG-loaded polylactide or poly(lactide-co-glycolide) microspheres using a modified water-in-oil-in-water (w/o/w) emulsion solvent evaporation technique

A modified w/o/w emulsion solvent evaporation technique was adopted to prepare human Chorionic Gonadotropin (hCG)-loaded polylactide (PLA) or poly(lactide-co-glycolide) (PLGA) microspheres. The effects of preparative parameters, such as stirring rate, polymer MW and concentration, and the composition of both the inner aqueous phase and oil phase etc., on hCG entrapment efficiency and microsphere characteristics were investigated. It was found that by adding 20% glycerol into the inner aqueous phase and 40% acetone into the oil phase, smooth microspheres approximately 1 microm in diameter could be produced with high hCG entrapment efficiency (>90%). In vitro release test showed a burst release of hCG from PLGA (75:25) microspheres, followed by sustained release of 55% hCG over 2 months. The initial hCG burst from PLGA microspheres increased with the glycerol concentration in the inner aqueous phase, but decreased to a low value (ca. 20%) with the addition of acetone into the oil phase, which could be attributed to the associated changes in surface morphology of the microspheres. In vivo experiments demonstrated that a single shot of hCG-loaded PLGA microspheres could produce a comparable antibody response with the inoculation of free hCG four times.     

Lappaconitine-loaded microspheres for parenteral sustained release: effects of formulation variables and in vitro characterization

Lappaconitine instead of its hydrobromide salts has been encapsulated in poly (lactide-co-glycolide) acid (PLGA) microspheres by the simple o/w emulsion solvent evaporation technique. The effects of several variables including emulsifier (polyvinyl alcohol, PVA) concentration, stirring speed, PLGA concentration and drug/polymer mass ratios on quality of microspheres have been investigated. The particle size and size distribution can be controlled by PVA concentration, stirring speed and PLGA concentration. The entrapment efficiency and the burst release of lappaconitine from drug-loaded microspheres were dominantly affected by the drug/polymer mass ratio and PVA concentration. The best parameters of formulation were 1.5% PVA, the PLGA concentration of 50 g/L, and the stirring speed of 800 rpm and drug/polymer of 1:5. The optimized formulation has a mean particle size of 19.3 +/- 0.93 microm, mean entrapment efficiency of 70.77 +/- 3.23% and mean drug loading of 11.45 +/- 0.47%. Based on the optimized parameters of formulation, the effects of oil/aqueous solubility partition ratio of drug on entrapment efficiency of drug-loaded microspheres prepared by o/w emulsion solvent evaporation were further studied. A good linear relation existed between the partition ratio and entrapment efficiency. The optimized microspheres were characterized by SEM, FT-IR, DSC and XRD. SEM shows spherical and smooth surface and uniform size distribution. The results of DSC, FT-IR study reveal no interaction between drug and polymer. The results of the XRD study indicate lappaconitine trapped in microsphere exists in form of an amorphous or disordered crystalline status in polymer matrix. The in vitro release models were evaluated with two different groups of drug-loaded microspheres including microspheres washed with distilled water and 0.01N HCL, respectively. The drug release profile of lappaconitine-loaded microspheres washed with distilled water agreed with zero order equation and that of the latter better agreed with first order equation.     

Development of biodegradable drug releasing polymeric cardiovascular stents and in vitro evaluation

Prednisolone acetate (PA) is insoluble in water and was chosen as a model drug for its anti-inflammatory/anti-proliferative functions. PA is incorporated into the film-based polymeric biodegradable stents to provide controlled local release of the drug during the mechanical support phase. Stent formulations were 3 mm in diameter with lengths of 150 mm. The polymer wall thickness was 145.0 +/- 4.0 microm for microsphere-containing PLGA 75 : 25 stents. The ATR-FTIR spectra showed biodegradable stent surfaces were free of drug and microspheres. Incorporation of PA into the stents increased the surface area when compared to empty and microsphere-incorporated stents. PA release from the stents containing chitosan microspheres was slower than the PA-only incorporated stents. The drug release from the stents coated with microsphere-containing PLGA 75 : 25 solutions was determined to be the slowest one (19.1% cumulative PA released in 32 days). The stents formulated with PLGA 75 : 25 polymers were considered to be more promising due to their suitable mechanical properties and controlled release of the drug.     

Development of biodegradable drug releasing polymeric cardiovascular stents and in vitro evaluation

Prednisolone acetate (PA) is insoluble in water and was chosen as a model drug for its anti-inflammatory/anti-proliferative functions. PA is incorporated into the film-based polymeric biodegradable stents to provide controlled local release of the drug during the mechanical support phase. Stent formulations were 3 mm in diameter with lengths of 150 mm. The polymer wall thickness was 145.0 ± 4.0 µm for microsphere-containing PLGA 75 : 25 stents. The ATR-FTIR spectra showed biodegradable stent surfaces were free of drug and microspheres. Incorporation of PA into the stents increased the surface area when compared to empty and microsphere-incorporated stents. PA release from the stents containing chitosan microspheres was slower than the PA-only incorporated stents. The drug release from the stents coated with microsphere-containing PLGA 75 : 25 solutions was determined to be the slowest one (19.1% cumulative PA released in 32 days). The stents formulated with PLGA 75 : 25 polymers were considered to be more promising due to their suitable mechanical properties and controlled release of the drug.     

长春西汀聚乳酸-聚乙醇酸缓释微球的研制

目的:制备长春西汀聚乳酸-聚乙醇酸(PLGA)缓释微球,并研究其药剂学性质。方法:采用改良O/W乳化-溶剂挥发法制备微球,以PLGA浓度、理论载药量、有机相与分散介质的比例和分散介质中明胶的浓度为4因素,每个因素选定3个水平,按L9(34)的正交设计方案,以载药量、包封率和粒径分布为指标,优化处方。用扫描电镜观察微球的形态,用光学显微镜观察并计算微球的粒径分布,用差示扫描量热(DSC)法研究药物在载体中的分散状态,用紫外分光光度法检测微球中长春西汀含量并计算载药量和包封率,用动态透析释药法进行微球的体外释放研究。结果:最佳处方为PLGA浓度16%,理论载药量20%,有机相与分散介质的比例1:10,分散介质中明胶的浓度1%;制备的长春西汀PLGA缓释微球的形态圆整、光滑,粒径分布均匀,平均粒径为(10.0±0.18)μm(n=500),DSC法分析药物确已被包裹于微球中,载药量为(18.46±0.26)%,包封率为(91.30±0.98)%(n=3),24h累积释药率约为18%。结论:长春西汀PLGA缓释微球制备工艺稳定,质量符合药剂学要求,缓释性好。     

Ketotifen-loaded microspheres prepared by spray-drying poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) polymers: characterization and in vivo evaluation

Ketotifen (KT) was encapsulated into poly(D,L-lactide) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA 50/50) by spray-drying to investigate the use of biodegradable drug-loaded microspheres as delivery systems in the intraperitoneal cavity. Ketotifen stability was evaluated by HPLC, and degradation was not observed. Drug entrapment efficiency was 74 +/- 7% (82 +/- 8 microg KT/mg for PLA) and 81 +/- 6% (90 +/- 7 microg KT/mg for PLGA 50/50). PLA microspheres released ketotifen (57% of encapsulated KT) in 350 h at two release rates (221 microg/h, 15 min to 2 h; 1.13 microg/h, 5-350 h). A quicker release of ketotifen took place from PLGA 50/50 microspheres (67.4% of encapsulated KT) in 50 h (322 microg/h, 15 min to 2 h; 16.18 microg/h, 5-50 h). After intraperitoneal administration (10 mg KT/kg b.w.), microsphere aggregations were detected in adipose tissue. Ketotifen concentration was determined in plasma by HPLC. The drug released from PLA and PLGA 50/50 microspheres was detected at 384 and 336 h, respectively. Noncompartmental analysis was performed to determine pharmacokinetic parameters. The inclusion of ketotifen in PLGA and PLA microspheres resulted in significant changes in the plasma disposition of the drug. Overall, these ketotifen-loaded microspheres yielded an intraperitoneal drug release that may be suitable for use as delivery systems in the treatment of inflammatory response in portal hypertension.