Preparation, characterization and related in vivo release, safety and toxicity studies of long acting lanreotide microspheres.
Preparation, characterization and related in vivo release, safety and toxicity studies of long acting lanreotide microspheres.
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DOI：
10.1248/bpb.b110726
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发表时间：
2012-11
影响因子：
2
通讯作者：
Shuang Wang;Mingsheng Wu;Dan Li;Mingli Jiao;Lan Wang;Haifeng Zhang;Huaiyu Liu;Daifeng Wang;B. Han
中科院分区：
文献类型：
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作者：
Shuang Wang;Mingsheng Wu;Dan Li;Mingli Jiao;Lan Wang;Haifeng Zhang;Huaiyu Liu;Daifeng Wang;B. Han
本课题的目的是制备长效醋酸兰瑞肽聚乳酸-羟基乙酸共聚物（PLGA）微球，并对其体内外释放、安全性和毒理学进行研究。采用复乳溶剂挥发法制备了缓释期为5周的长效醋酸兰瑞肽PLGA微球。在大鼠、豚鼠、家兔和比格犬动物模型中进行了兰瑞肽微球的物理表征以及体内和体外释放、安全性、急性毒性和慢性毒性分析。复乳溶剂挥发法制备的醋酸兰瑞肽PLGA微球表面光滑、粒径均匀、载药量稳定。体内外实验表明，醋酸兰瑞肽PLGA微球可持续释放兰瑞肽5周。在豚鼠主动全身过敏试验、大鼠被动皮肤过敏试验、家兔溶血试验、家兔皮下给药后局部皮肤刺激试验和家兔肌肉刺激试验中，这些长效兰瑞肽微球的安全性良好。此外，在比格犬中以高达22 mg/kg的剂量给予醋酸兰瑞肽PLGA微球后，未观察到显著的急性毒性或慢性毒性。本研究制备的醋酸兰瑞肽PLGA微球在表观性质、结构稳定性以及体内外释药趋势等方面均表现出良好的特性。
The goal of this project was to prepare long-acting lanreotide acetate poly(lactic-co-glycolic acid) (PLGA) microspheres and to analyze the in vivo and in vitro release, safety and toxicology of these preparations. Long-acting lanreotide acetate PLGA microspheres that exhibited a 5-week slow-release period were prepared by a multiple-emulsion solvent evaporation method. Physical characterization, as well as the analysis of the in vivo and in vitro release, safety, acute toxicity and chronic toxicity of the lanreotide microspheres, were conducted in animal models in rats, guinea pigs, rabbits and beagle dogs. The lanreotide acetate PLGA microspheres prepared by multiple-emulsion solvent evaporation had smooth surfaces, uniform particle size and stable lanreotide loading. In vivo and in vitro experiments showed that the lanreotide acetate PLGA microspheres could continuously release lanreotide for 5 weeks. The safety of these long acting lanreotide microspheres was good in the following animal models: active systemic anaphylaxis test in guinea pigs, passive cutaneous anaphylaxis test in rats, hemolytic test in rabbits, local skin irritation test after subcutaneous administration in rabbits and muscle stimulation test in rabbits. Furthermore, no significant acute toxicity or chronic toxicity was observed after administration of lanreotide acetate PLGA microspheres in beagle dogs at dosages up to 22 mg/kg. The lanreotide acetate PLGA microspheres that were prepared in this study exhibited beneficial characteristics in apparent property and structural stability, as well as in release trends in vivo and in vitro.