装载于PLGA中的5-氟尿嘧啶缓释微球的制备及其体外释放的研究

目的：研究装载于不同分子量的PLGA中的5-氟尿嘧啶微球的制备方法及其在体外条件下的缓释行为。方法：以水包油包固复乳法将5-氟尿嘧啶包裹在高分子聚乳酸-聚羟基乙酸共聚物（PLGA）中,形成缓释微球,考察其大小,外观,包封率等理化性质,以紫外分光光度法为检测方法研究其体外释放行为。结果：经扫描电子显微镜观察,所制备的微球形态完整,大小较均匀。具有一定得包封率和载药量,体外释放研究表明其处方1和处方2的缓释时间为8天和23天。结论：以水包油包固复乳法制备的PLGA 5-氟尿嘧啶微球能够达到缓释的目的。     

装载于PLGA中的5-氟尿嘧啶缓释微球的制备及其体外释放的研究

目的:研究装载于不同分子量的PLGA中的5-氟尿嘧啶微球的制备方法及其在体外条件下的缓释行为。方法:以水包油包固复乳法将5-氟尿嘧啶包裹在高分子聚乳酸-聚羟基乙酸共聚物(PLGA)中,形成缓释微球,考察其大小,外观,包封率等理化性质,以紫外分光光度法为检测方法研究其体外释放行为。结果:经扫描电子显微镜观察,所制备的微球形态完整,大小较均匀。具有一定得包封率和载药量,体外释放研究表明其处方1和处方2的缓释时间为8天和23天。结论:以水包油包固复乳法制备的PLGA 5-氟尿嘧啶微球能够达到缓释的目的。     

氢氧化镁调控BSA-PLGA微球体外释放的研究

目的:探索氢氧化镁对BSA微球体外释放的影响,优化BSA微球的制备工艺。方法:通过水包油包固复乳法制备BSA-PLGA微球。先将BSA与葡聚糖制备成玻璃体颗粒,再将玻璃体颗粒与氢氧化镁包裹进PLGA中,制备成缓释微球。在扫描电镜下观察其形态。然后用Micro BCA法测定其包封率和载药量,并考察其体外释放行为。结果:所制得的微球粒径约60μm,呈较好的球形。添加氢氧化镁后,BSA微球的包封率和载药量都有显著提高。不同含量的氢氧化镁对BSA微球的包封率和载药量影响也不同。在体外释放过程中,载有氢氧化镁的微球14天累积释放量为(85.10±2.67)%,而对照组不到80%。结论:通过调整氢氧化镁的量,可以制得形态完整,大小均匀,突释较小的BSA微球。     

PLGA微球复合明胶组织工程支架缓释蛋白药物的研究

目的：研究PLGA微球复合明胶支架对蛋白药物的释放影响。方法：将模型蛋白BSA通过复乳法制备成缓释PLGA微球,然后将微球埋置于明胶支架中,形成担载蛋白的PLGA微球复合明胶组织工程支架。考察复合支架体外蛋白释放行为,并用MicroBCA法定量测定释放的BSA量,采用β-半乳糖苷酶催化ONPG的方法检测制备前后蛋白的活性,并与不含PLGA微球直接担载蛋白的支架做对照。结果：PLGA微球复合支架蛋白的包封率能达到73．2％,其中第一天释放20％,对蛋白活性的保持达到70％以上。结论：微球复合明胶支架可以改善一般组织工程支架蛋白药物的突释,提高蛋白药物在制剂,贮存,释放过程中的稳定性。     

一种白细胞介素-2缓释微球制备新方法及体外表征

目的：开发一种白细胞介素-2（m-2）长效缓释微球剂型。方法：采用S／O／W法制备了白介素-2因子多糖微粒的PLGA微球,考察了微球的表面形态、粒径分布等,并且运用ELISA方法考察了微球的体外释放效果。结果：本方法制备的白介素-2因子微球光滑圆整,粒径分布较均匀,体外缓释达32天,累积释放率近90％。结论：本方法制备的白介素-2因子微球,不仅具有有效地保护IL-2蛋白活性,同时实现长效缓释的目标,是一种可行的蛋白缓释方案。     

粒细胞-巨噬细胞集落刺激因子微球制剂的体外释放研究

目的：开发一种粒细胞-巨噬细胞集落刺激因子（GM—CSF）长效缓释微球剂型。方法：采用S／O／hO法制备了包裹粒细胞一巨噬细胞集落刺激因子多糖玻璃体颗粒的PLGA微球,考察了微球的表面形态、粒径分布等,并且运用ELISA方法考察了微球的体外释放效果。结果：本方法制备的粒细胞-巨噬细胞集落刺激因子微球光滑圆整,粒径分布均匀,体外可以缓释达32天,累积释放率接近90％。结论：本方法制备的粒细胞-巨噬细胞集落刺激因子微球能有效地保护蛋白活性,同时实现长效缓释的目标,是一种可行的蛋白缓释方案。     

降钙素葡聚糖颗粒缓释微球的研究

目的：降钙素（一个由32个氨基酸组成的多肽）是治疗骨质疏松的首选药之一。降钙索的劣势是其半衰期过短,需要一天一次注射给药,本实验旨在制备突释小,药物释放浓度稳定的降钙素微球制剂。方法：制备降钙素羧酸葡聚糖颗粒和降钙素硫酸葡聚糖颗粒组合物,分别将其包裹于PLGA微球内,制备成降钙素组合微球,采用C18反相色谱柱研究药物的包封率和体外释放行为。结果：所制得的降钙素葡聚糖颗粒缓释微球体外释放一个月,释放曲线比较完美,接近零级释放。结论：本研究制得的降钙素葡聚糖颗粒缓释组合微球能实现理想的体外缓释效果,为后期药动学实验提供基础。     

干扰素α缓释微球的制备及体外释放研究

目的:开发一种有效地长效缓释干扰素α微球制剂。方法:利用S/O/W乳剂-挥发法制备了包裹干扰素α多糖颗粒的PLAG微球,对其外观形态进行了考察,并用ELISA方法考察了微球体外释放效果。结果:制备的干扰素α微球圆整光滑,粒径均匀;经24天体外释放,累计释放率达到80%以上。结论:通过包封包裹干扰素α的多糖颗粒进PLGA微球,有效地保护了干扰素α在微球中的活性,实现了长效缓释,是一种可行的缓释方案。     

左旋多巴甲酯缓释微球的研究

目的：由于长期服用左旋多巴治疗帕金森病,其药物浓度波动刺激易引起异动症,本实验旨在制备突释小,药物释放浓度稳定的左旋多巴甲酯微球制剂。方法：将左旋多巴甲酯用复乳法包裹于PLGA微球内,采用C18反相色谱研究药物包封率和体外释放行为。结果：通过调节药物浓度和不同高分子组合筛选出突释小,包封率高且缓慢释放的处方。结论：左旋多巴甲酯包裹于PLGA能实现理想的缓释效果,降低药物浓度波动,为后期药效学实验提供基础。     

包封不对称膜高分子囊泡对PLGA微球中蛋白释放行为的改善作用

目的:研究含蛋白的不对称膜高分子囊泡包封进PLGA微球后对其体外释放动力学的改善作用.方法:将包封有BSA蛋白的不对称膜高分子囊泡采用S/O/W法包裹进PLGA微球中,制备复合微球,对微球表征后,以包封葡聚糖颗粒的微球做对照品,于37℃测定微球的体外释放,比较两者的释放曲线,考察不对称膜高分子囊泡时微球中蛋白释放的改善作用.结果:①经扫描电镜(SEM)观察,包裹高分子囊泡的复合微球形态圆整,表面光滑,平均粒径为75.20μm,粒径较为均匀,复合微球制备成功.②比较复合微球和对照微球的释放曲线,发现对照微球有较小的突释,而复合微球的几乎没有突释效应.结论:不对称膜高分子囊泡包封进PLGA微球后可以很好的改善蛋白的释放行为,获得更为理想的释放曲线.     

一种白细胞介素 -12 缓释微球制备及体外表征

目的:开发一种白细胞介素-12(IL-12)长效缓释微球剂型。方法:采用水包油-油包固(S/O/W)法制备了白介素-12因子多糖微粒的聚乳酸-聚羟基乙酸共聚物(PLGA-PLA)微球,研究了微球的表面形态和粒径大小,并且运用ELISA方法考察了微球的体外释放效果和免疫活性。结果:本方法制备的白介素-12因子微球光滑圆整,体外缓释达45天,累积释放率近90%。结论:本方法制备的白介素-12因子微球,不仅具有有效地保护IL-12蛋白活性,同时实现长效缓释的目标,是一种可行的IL-12缓释方案。     

担载b-FGF的PLGA微球复合明胶支架的体外释放研究

目的:研究担载碱性成纤维细胞生长因子(b-FGF)微球复合明胶支架的外形特征、孔径、孔隙率及体外释放动力学,以期构建具有缓释功能、高孔隙率的担载细胞因子的新型复合明胶支架。方法:本文利用冷冻相分离法和S/O/W法先将b-FGF水溶液包裹于PLGA微球中,然后埋置于明胶溶液中制备为多孔复合明胶支架。分别对微球的形态和复合明胶支架的基本形态、孔径、孔隙率进行表征,通过Elisa法测定b-FGF在复合明胶支架中的体外释放行为。结果:制备成形态良好的三维复合明胶支架,其孔隙率为82.90%±1.45%,孔径范围为150~300μm,复合明胶支架中b-FGF在体外缓慢释放20余天。结论:担载蛋白微球复合明胶支架不仅满足组织工程支架的要求,还能有效缓释细胞因子,为细胞和组织生长提供良好的微环境,为进一步应用于组织工程领域提供了可能。     

Sustained local delivery of insulin for potential improvement of peri-implant bone formation in diabetes

Dental implantation is an effective standard treatment modality to restore missing teeth and maxillofacial defects. However, in diabetics there is an increased risk for implant failure due to impaired peri-implant osseous healing. Early topical insulin treatment was recently shown to normalize diabetic bone healing by rectifying impairments in osteoblastic activities. In this study, insulin/poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared by a double-emulsion solvent evaporation method. Microspheres were then incorporated in fibrin gel to develop a local drug delivery system for diabetic patients requiring implant treatment. In vitro release of insulin from fibrin gel loaded with these microspheres was assessed, and sustained prolonged insulin release over 21 days ascertained. To assess the bioactivity of released insulin and determine whether slow release might improve impaired diabetic bone formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), alkaline phosphatase (ALP) activity, mineralized nodule formation, and ELISA (enzyme-linked immunosorbent assay) assays were performed. The insulin released from the drug delivery system stimulated cell growth in previously inhibited cells, and ameliorated the impaired bone-forming ability of human MG-63 cells under high glucose conditions. Fibrin gel loaded with insulin/PLGA microspheres shows potential for improving peri-implant bone formation in diabetic patients.     

Controlled Release of Dutasteride from Biodegradable Microspheres: In Vitro and In Vivo Studies

The aim of the present work was to study the in vitro/in vivo characteristics of dutasteride loaded biodegradable microspheres designed for sustained release of dutasteride over four weeks. An O/W emulsion-solvent evaporation method was used to incorporate dutasteride, which is of interest in the treatment of benign prostatic hyperplasia (BPH), into poly(lactide-co-glycolide) (PLGA). A response surface method (RSM) with central composite design (CCD) was employed to optimize the formulation variables. A prolonged in vitro drug release profile was observed, with a complete release of the entrapped drug within 28 days. The pharmacokinetics study showed sustained plasma drug concentration-time profile of dutasteride loaded microspheres after subcutaneous injection into rats. The in vitro drug release in rats correlated well with the in vivo pharmacokinetics profile. The pharmacodynamics evaluated by determination of the BPH inhibition in the rat models also showed a prolonged pharmacological response. These results suggest the potential use of dutasteride loaded biodegradable microspheres for the management of BPH over long periods.     

包裹于PLGA微球中用于蛋白控释的多糖纳米颗粒

目的:研究包裹在PLGA微球中的多糖纳米颗粒在保护蛋白稳定性和改善药物体外释放行为方面的作用。方法:将模型药物BSA用低温诱导相分离方法担载于多糖纳米颗粒之中,后将其用水包油包固复乳法包裹于PLGA微球内。应用体积排阻色谱(SEC-HPLC)和红外色谱(FTIR)表征蛋白的稳定性,而且也研究了样品的体外释放行为。结果:这种方法能够很好的保护蛋白的稳定性,保持蛋白结构在制备过程中不会改变,而且改善了体外释放行为,减少了突释。结论:多糖纳米颗粒结合PLGA微球能够提供一种有效的解决蛋白控释的途径。     

Design of Methylprednisolone Biodegradable Microspheres Intended for Intra-articular Administration

This study aimed to design methyprednisolone (MP)-loaded poly(d,l lactide-co-glycolide) (PLGA) microspheres (MS) intended for intra-articular administration. MP was encapsulated in four different types of PLGA by using an S/O/W technique. The effects of β-irradiation at the dose of 25 kGy were evaluated on the chemical and physicochemical properties of MS and the drug release profiles. The S/O/W technique with hydroxypropylmethylcellulose (HPMC) as surfactant allowed obtaining MS in the tolerability size (7–50 μm) for intra-articular administration. The MP encapsulation efficiency ranged 56–60%. HPMC traces were evidenced in the loaded and placebo MS by attenuated total reflectance Fourier transform infrared spectroscopy. MS made of the capped PLGA DL5050 2M (MS 2M) and uncapped PLGA DL5050 3A (MS 3A) prolonged the release of MP over a 2- to 3-month period with a triphasic (burst release–dormant period–second release pulse) and biphasic release pattern, respectively. The β-irradiation did not significantly alter the morphology, chemical, and physicochemical properties of MS. The only variation was evidenced in the drug release for MS 2M in term of shorting of the dormant period. The minimal variations in the properties of irradiated PLGA MS, which are in disagreement with literature data, may be attributed to a radioprotecting effect exerted by HPMC.