生物降解聚酯包埋利福平缓释微球的制备及释放行为

以生物可降解乙交酯和丙交酯的无规共聚物(PLGA)为载体,将抗结核病药利福平溶解于PLGA的有机溶液中,采用通常乳化-溶剂挥发方法制备了药物缓释微球.研究了影响微球制备的工艺条件.用电子显微镜观察了微球及降解后的表面形态,测定了微球粒径及载药量,评价了载药微球的体外释放行为.结果表明,以质量分数为1%的明胶为稳定剂,制备的微球形态完整,粒径范围为10～30μm,微球中利福平的平均质量分数为24.3%.体外释药时间可以通过高分子的降解速率来调控,本实验的释药时间可以在42～84d之间调控,药物缓释达到了理想的零级动力学释放.因此,利福平PLGA微球具有显著的长效、恒量药物缓释作用.     

以PHBV-PLGA为载体的硫酸庆大霉素缓释微球

以生物可降解聚羟基丁酸酯和羟基戊酸酯的共聚物(PHBV)、乙交酯和丙交酯的无规共聚物(PLGA)两种高分子作为壁材,采用复乳溶剂挥发法,制备了包裹硫酸庆大霉素(GS)的载药微球。在扫描电镜下观察到所得微球表面呈多孔状,为球形或椭圆形,粒径在20~80μm。分析结果表明,包封率在60%以上,在体外16~20 d内药物全部释放,90 d微球体外降解50%左右。     

可降解聚乙交酯-丙交酯缓释微球用于甲状旁腺相关肽的持续释放

采用水包油包水(W1/O/W2)复乳溶剂挥发法制备了包载甲状旁腺激素相关肽(PTHrP)的聚乙交酯-丙交酯(PLGA)微球,通过核磁,红外,GPC,扫描电子显微镜等观察PLGA载药微球的结构,表明载药微球具有良好的球形结构,其平均粒径约为8μm.而体外模拟释放表明,此PLGA载药微球能实现PTHrP1-34长达25天的持续释放.并通过MTT法、碱性磷酸酶活性测定等检测负载PTHrP1-34的PLGA微球缓释系统对小鼠成骨细胞MC3T3-E1增殖及分化的影响,结果表明PTHrP1-34浓度为1×10-9mol/L时对MC3T3-E1增殖促进效应最大,且随着药物作用时间的延长,缓释系统促进细胞增殖、分化的作用越明显.     

聚(L-谷氨酸)微球的制备及其口服药物控释研究

通过正己胺引发γ-苯甲基-L-谷氨酸酯-N-内羧酸酐(BLG-NCA)开环聚合制备聚(γ-苯甲基-L-谷氨酸酯)(PBLG), 并进一步脱掉苯甲基保护得到聚(L-谷氨酸)(PLG). 以利福平为模型药物, 通过油包油(O/O)无水乳液法制备了PLG载药微球. 扫描电子显微镜检测表明该载药微球具有良好的球形形貌且粒径分布较均一, 粒径大小约为9.0 μm. 体外释放实验表明该载药微球对利福平的释放具有明显的pH敏感性, 在模拟胃液中较少释放利福平, 而在模拟肠液中较快并大量释放利福平, 符合口服药物载体释放性能的要求, 可用于口服药物的定位肠溶性载体. 此外, 噻唑蓝实验表明该微球具有良好的生物相容性.     

壳聚糖修饰PLGA阳离子型纳米微球的制备与表征

采用单乳化-溶剂(O/W)挥发技术制备表面带正电荷的壳聚糖(CHS)修饰聚乙/丙交酯(PLGA)纳米微球(PLGA/CHS), 通过正交试验优化了纳米微球的制备条件. 结果表明, 微球粒径可控制在150～200 nm内, 在pH=4时, 纳米微球表面电位最高为55 mV. 影响微球粒径的主要因素是聚合物的浓度, CHS的分子量和浓度以及介质的pH值对微球表面电位也有明显影响. 制备粒径较小而表面电位较高的PLGA/CHS纳米微球条件为: ρ(CHS)=3 mg/mL, ρ(PLGA)=10 mg/mL, Vo/Va=1/4. SEM图像显示经CHS修饰的PLGA的纳米微球形状规整, 荧光显微观察和XPS分析结果证实CHS包覆于微球表面.     

肾上腺髓质素微球复合PLGA/纳米羟基磷灰石支架材料的制备及生物活性评价

利用离子乳化交联法制备了负载肾上腺髓质素的壳聚糖微球,应用热致相分离法制备了乳酸和乙醇酸共聚物/纳米羟基磷灰石(PLGA/nHA)支架材料并在其中包覆载药微球.通过扫描电子显微镜、体外释放行为、材料溶血行为、碱性磷酸酶(ALP)活性的测定、支架材料表面细胞荧光染色和MTT[3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐]比色法等手段综合评价载药支架材料的性能及生物活性.结果表明,微球直径均匀,载药支架孔径大小合适并相互穿通.支架材料的溶血率小于5%,符合医用材料的溶血实验要求.载药支架及支架材料本身对成骨细胞及血管内皮细胞的增殖以及成骨细胞的分化均有一定的促进作用.     

肾上腺髓质素微球复合PLGA/纳米轻基磷灰石支架材料的制备及生物活性评价

利用离子乳化交联法制备了负载肾上腺髓质素的壳聚糖微球,应用热致相分离法制备了乳酸和乙醇酸共聚物/纳米羟基磷灰石(PLGA/nHA)支架材料并在其中包覆载药微球.通过扫描电子显微镜、体外释放行为、材料溶血行为、碱性磷酸酶(ALP)活性的测定、支架材料表面细胞荧光染色和MTT[3-(4,5-二甲基噻唑-2)-2,5-二苯基...     

壳交联pH响应型PLGA载药微球的制备与研究

首先采用一次乳化法制备出PLGA[聚(乳酸-羟基乙酸)]纳米微球,并通过静电吸附将阳离子聚合物壳聚糖修饰到PLGA微球表面,然后以香草醛为交联剂对壳聚糖进行化学交联,得到一种壳交联的p H响应型纳米微球(PCV),微球粒径为(277.60±38.01)nm,表面电位为(21.60±4.51)m V.微球稳定性评价结果显示微球在24 h内粒径变化较小;流式细胞仪检测显示细胞对PCV微球的摄取量比未经修饰的PLGA微球的摄取量高;空白微球细胞毒性实验表明在空白微球浓度小于80μg/m L时细胞的存活率达93.24%.以多西他赛(DTX)为模型药物进行包载,该纳米微球DTX的载药率为7.48%,包封率为34.98%;体外药物释放实验显示,该微球在p H=5.0环境下孵育90 h的药物积累释放率达58.66%,而在p H=7.4的环境下的药物积累释放率为50.63%;此外,载DTX微球毒性试验结果表明该载药微球对A549肺癌细胞有较强的杀伤作用,其IC50值可达0.0009μg/m L.     

载有胰岛素的可生物降解微球的制备与表征

用乙交酯与丙交酯的无规共聚物(PLGA)和聚乙二醇单甲醚-聚丙交酯两嵌段共聚物(MPEG-PLA)的合金作为囊材料,包裹胰岛素固体粉末,包裹率分析表明,固体粉末法对胰岛素的包裹率高于双乳液法.所得微球球形很好,尺寸在1～3μm范围,剖面具有核壳结构,胰岛素以晶粒的形式包裹在高分子壳层中.两种高分子在凝聚过程中发生相分离,在壳层中有分层现象.测定微球的体外释放行为,由聚合物合金制备的微球的暴释现象得到了缓解,两种聚合物的配比不同,其暴释缓解的程度也不一样.     

咖啡因对聚[碳酸(亚丙酯-co-γ-丁内酯)酯]降解性能的影响

对碱性药物与新型脂肪族聚碳酸酯———聚[碳酸(亚丙酯-co-γ-丁内酯)酯]之间的相互影响进行了研究和讨论。通过O/W单相乳化-溶剂挥发法制备了不同咖啡因含量的聚[碳酸(亚丙酯-co-γ-丁内酯)酯]载咖啡因微球。研究发现,不同的咖啡因含量影响其在聚合物中的存在状态、聚合物降解行为以及微球释药特征,但它们之间并不是简单的正比关系。咖啡因在聚合物降解过程中起着碱催化的作用。     

Controlled release of dexamethasone from porous PLGA scaffolds under cyclic loading

Poly(L-lactide)-b-poly(ethylene glycol)(PLLA-PEG) microspheres containing dexamethasone(Dex) have been fabricated using a spray-drying technique.Porous poly(lactic-co-glycolic acid)(PLGA) scaffolds were prepared using a method combining thermally induced phase separation and porogen leaching.A post-seeding technique was used to immobilize Dex-containing PLLA-PEG microspheres on porous PLGA scaffolds,and drug-containing microspheres-scaffolds(MS-S) were obtained.Simple Dex-containing scaffolds(D-S) were also...     

Study of types and mixture ratio of organic solvent used to dissolve polymers for preparation of drug-containing PLGA microspheres

The effects of the types and the ratios of various organic solvents used as a mixtures to dissolve poly (lactide-co-glycolide) (PLGA) by using a solvent evaporation method, a technique used to prepare polymer particles, were carefully studied in order to investigate their advantages in developing drug delivery system (DDS) formulations for the prepared microspheres. The particle size and drug loading efficiency of drug-containing PLGA microspheres were found to be dependent on the types of solvent used due to the interfacial tension between the organic solvent and water phase. The drug loading efficiency of monodisperse microspheres prepared by using a membrane emulsification technique employing organic solvents and high interfacial tension for dissolving the PLGA was increased in a controlled manner. The organic solvents with high interfacial tension in the water phase used for the preparation of polymer particles by means of the solvent evaporation method were found to be suitable in terms of improvement in the properties of DDS formulations.     

Enhanced gentamicin loading and release of PLGA and PLHMGA microspheres by varying the formulation parameters

The purpose of this study was to develop a suitable formulation for gentamicin sulfate (GS) that gives a sustained release of the drug. Therefore this drug was loaded into poly(D,L-lactide-co-glycolide) (PLGA) and poly(lactic-co-hydroxymethyl glycolic acid) (PLHMGA) microspheres. The effects of various formulation parameters (ethanol, surfactant, osmotic value of the external phase, polymer type and concentration) on particle characteristics (size, loading and release) were investigated. The GS loaded microspheres were prepared using a double emulsion evaporation technique. The results demonstrate that neither ethanol nor surfactants had beneficial effects on the drug loading efficiency (around 4-10%). However, an increase in buffer concentration (and thus osmotic pressure) of the external phase resulted in a substantial increase of GS-loading (from 10 to 28%). Further, an increase of concentration of PLGA in DCM from 10% to 15/20% caused a 4-time increase of the drug loading. The best formulation identified in this study had a loading efficiency of around 70% resulting in PLGA microspheres with a 6% (w/w) loading. The particles showed a burst release of the drug depending on their porosity, followed by a phase of 35 days where hardly any release occurred. The drug was then slowly released for around 25 days likely due to degradation of the microspheres. The drug loading efficiency of GS in PLHMGA was not significantly different from PLGA microspheres (64%). The release of GS from PLHMGA microspheres was faster than that of PLGA because the degradation rate of PLHMGA is more rapid than PLGA. This study shows that prolonged release of gentamicin can be obtained by loading this drug into microspheres made of biodegradable aliphatic polyesters.     

Biodegradable PLGA microspheres as a sustained release system for a new luteinizing hormone-releasing hormone (LHRH) antagonist

A sustained release poly(DL-lactide-co-glycolide) (PLGA) microsphere delivery system to treat prostate cancer for a luteinizing hormone-releasing hormone (LHRH) antagonists, LXT-101 was prepared and evaluated in the paper. LXT-101 microspheres were prepared from PLGA by three methods: (1) double-emulsion solvent extraction/evaporation technique, (2) single-emulsion solvent extraction/evaporation technique, and (3) S/O/O (solid-in-oil-in-oil) method. The microspheres were investigated on drug loading, particle size, surface morphology and in vitro release profiles. An accelerated release approach was also established in order to expedite the evaluation periods. The in vivo evaluation of the microspheres was made by monitoring testosterone levels after subcutaneous administration to rats. The LXT-101 PLGA microspheres showed smooth and round surfaces according to a scanning electron microscopic investigation, and average particle size of ca. 30 mum according to laser diffractometry. The drug encapsulation efficiency of microspheres was influenced by LA/GA ratio of PLGA, salt concentrations, solvent mixture and preparation methods. Moreover, LA/GA ratio of PLGA, different preparation methods and different peptide stabilizers affected in vitro release of drugs. In vivo study, the testosterone levels were suppressed to castration up to 42 d as for the 7.5 mg/kg dose. And in vivo performance of LXT-101 microspheres was dose-dependent. The weights of rat sexual organs decreased and histopathological appearance of testes had little changes after 4-month microspheres therapy. This also testified that LXT-101 sustained release microspheres could exert the efficacy to suppress the testosterone level to castration with little toxicity. In conclusion, the PLGA microspheres could be a well sustained release system for LXT-101.     

Preparation of PLGA microspheres with different porous morphologies

Poly(D,L-lactide-co-glycolide)(PLGA) microspheres were prepared by emulsion solvent evaporation method. The influences of inner aqueous phase, organic solvent, PLGA concentration on the morphology of microspheres were studied. The results showed that addition of porogen or surfactants to the inner aqueous phase, types of organic solvents and polymer concentration affected greatly the microsphere morphology. When dichloromethane was adopted as organic solvent, microspheres with porous structure were produced. When ethyl acetate served as organic solvent, two different morphologies were obtained. One was hollow microspheres with thin porous shell under a lower PLGA concentration, another was erythrocyte-like microspheres under a higher PLGA concentration. Three types of microspheres including porous, hollow core with thin porous shell(denoted by hollow in brief) and solid structures were finally selected for in vitro drug release tests. Bovine serum albumin(BSA) was chosen as model drug and encapsulated within the microspheres. The BSA encapsulation efficiency of porous, hollow and solid microspheres was respectively 90.4%, 79.8% and 0. And the ultimate accumulative release was respectively 74.5%, 58.9% and 0. The release rate of porous microspheres was much slower than that of hollow microspheres. The experiment results indicated that microspheres with different porous structures showed great potentials in controlling drug release behavior.     

PLGA/TiO2纳米药物缓释载体的研究

首先利用硅烷偶联剂(KH550)对纳米二氧化钛表面进行预处理,得到氨基改性的二氧化钛,然后与带有高活性端基的丙交酯-乙交酯共聚物(PLGA)反应,制备纳米药物缓释载体PLGA/TiO2有机-无机杂化材料.通过核磁(1H-NMR)、傅里叶变换红外光谱仪(FTIR)、热重分析(TGA)、扫描电子显微镜(SEM)、透射电子显...     

Development of biodegradable co-poly( -lactic/glycolic acid) microspheres for the controlled release of 5-FU by the spray drying method

The water-soluble anti-cancer drug, 5-fluorouracil (5-fluoro-2,4-pyrimidinedione) (5-FU) is encapsulated into biodegradable co-poly ( -lactic/glycolic acid) (PLGA) using the spray drying method for the development of long-lasting controlled release systems. In this study, the effects of both polymeric composition and technological parameters on release profiles of 5-FU were investigated. The degradation of various microspheres was also investigated. The mixture of dichloromethane/chloroform/methanol (1:1:2 v/v) instead of dichloromethane/chloroform (1:1 v/v) resulted in the modification of morphology, while the physical structure of the microsphere varied from a porous PLGA microsphere to a dense PLGA microsphere. The results show that the average diameter was 2 μm and the anti-cancer drug loading of microspheres approached approximately 8% (w/w). In addition, the lactide/glycolide ratio of the polymer is an important parameter for controlling the release profile of the entrapped anticancer drug. Our results indicate that the mixture solvent using the spray drying method was more efficient than emulsification solvent diffusion.     

Effect of polyethylene glycol on preparation of rifampicin-loaded PLGA microspheres with membrane emulsification technique

Monodisperse poly(lactide-co-glycolide) (PLGA) microspheres containing rifampicin (RFP), anti-tubercle drug, as hydrophobic model drug were prepared by solvent evaporation method with a membrane emulsification technique using Shirasu Porous Glass (SPG) membranes. Five kinds of rifampicin-loaded PLGA (RFP/PLGA) microspheres with different sizes were prepared by changing pore size of the membranes. Effect of polyethylene glycol (PEG) added to polyvinyl alcohol (PVA) solution (continuous phase) upon the monodispersity of microspheres was studied. PEG was used as a stabilizer for microspheres dispersing in PVA solution. The most suitable molecular weight of PEG as a stabilizer was 20,000. RFP/PLGA microspheres prepared with PEG20000 were apparently more uniform than those prepared without PEG. The yield of RFP/PLGA microspheres was 100%. The initial burst observed in the release of RFP from RFP/PLGA microspheres was suppressed by the addition of PEG.     

Preparation and properties of monodispersed rifampicin-loaded poly(lactide-co-glycolide) microspheres

Monodispersed rifampicin (RFP)-loaded poly(lactide-co-glycolide) (PLGA) microspheres were prepared by a solvent evaporation method. In order to control the sizes of the microspheres, a membrane emulsification technique using Shirasu porous glass (SPG) membranes was applied. RFP/PLGA microspheres with the average diameters of 1.3, 2.2, 5.2, and 9.0 microm were obtained. They were relatively monodisperse and the values of the coefficient of variation (CV) for the size distributions of the microspheres were in the range between 7.0 and 16.0%. The loading efficiency of RFP was in the range between 50.3 and 67.4% independent of the microsphere size. The release ratio of RFP from RFP/PLGA microspheres was measured in pH 7.4 PBS at 37 degrees C. From RFP/PLGA microspheres with average diameters of 1.3 and 2.2 microm, almost 60% of RFP loaded in the microspheres was released in the initial day and the release was terminated almost within 10 days. On the other hand, from those with average diameters of 5.2, and 9.0 microm, the release of RFP was observed even 20 days after the release started.