Phase-sensitive polymer-based controlled delivery systems of leuprolide acetate: in vitro release, biocompatibility, and in vivo absorption in rabbits.
Phase-sensitive polymer-based controlled delivery systems of leuprolide acetate: in vitro release, biocompatibility, and in vivo absorption in rabbits.
复制标题
基于相敏聚合物的醋酸亮丙瑞林控释系统：体外释放、生物相容性和兔子体内吸收。
DOI：
10.1016/j.ijpharm.2006.07.051
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发表时间：
2007
影响因子：
5.8
通讯作者：
Singh,Jagdish
中科院分区：
文献类型：
--
作者：
Singh,Somnath;Singh,Jagdish
醋酸亮丙瑞林（LA）是促性腺激素释放激素的合成类似物。只有当其在血液中的期望浓度维持较长时间时，它才能有效治疗前列腺癌。因此，本研究的目的是研究LA从相敏聚合物递送系统的体外释放、生物相容性和体内吸收，所述相敏聚合物递送系统能够以受控速率较长时间递送LA。通过将dl-聚乳酸（dl-PLA）溶解在有机溶剂苯甲酸苄酯（BB）和苯甲醇（BA）的混合物中来制备相敏制剂。通过均质化将LA掺入聚合物溶液中。在包含于小瓶中的15 ml释放介质中研究体外释放，所述小瓶在往复振荡水浴中维持在37°C。通过稳定性指示HPLC方法分析释放样品中的LA量。通过体外3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四氮唑（MTT）测定研究聚合物制剂的生物相容性。在兔体内研究了LA从递送系统的吸收。通过市售免疫测定试剂盒分析血液样品的LA和睾酮含量。体外释放研究表明，从溶剂混合物中含有更大比例的BA（亲水部分）的制剂中释放的LA更大。体外生物相容性研究显示，在用聚合物浸提液稀释的生长培养基中，细胞活力显著高于对照组（p<0.05）。LA在家兔体内的吸收及其对睾酮水平的影响表明，LA的持续血浆水平长达12周，从第14天开始直到90天，将睾酮血浆浓度抑制到去势水平。因此，LA的相敏聚合物递送系统是生物相容的，并且在体外和体内以受控速率递送LA以将睾酮血浆浓度保持在去势水平长达3个月。
Leuprolide acetate (LA) is a synthetic analog of gonadotropin releasing hormone. It is effective in prostrate cancer treatment only when its desired concentration in blood is maintained for longer duration. Therefore, the purpose of this study was to investigate the in vitro release, biocompatibility, and in vivo absorption of LA from phase-sensitive polymer delivery systems capable of delivering it at a controlled rate for longer duration. Phase-sensitive formulations were prepared by dissolving dl-polylactic acid (dl-PLA) in a mixture of organic solvents, benzyl benzoate (BB) and benzyl alcohol (BA). LA was incorporated into the polymer solution by homogenization. In vitro release was studied into 15ml of releasing media contained in a vial which was maintained at 37°C in a reciprocal shaking water bath. The amount of LA in the released samples was analyzed by stability indicating HPLC method. The biocompatibility of polymer formulations was investigated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vivo absorption of LA from delivery systems was studied in rabbits. Blood samples were analyzed for LA and testosterone contents by commercially available immunoassay kits. In vitro release studies showed a greater release of LA from formulations containing a greater proportion of BA (hydrophilic fraction) in the solvent mixture. In vitro biocompatibility study showed significantly (p<0.05) higher cell viability in growth media diluted with polymer extract than the control. In vivo absorption of LA and its effect on testosterone level in rabbits from the delivery system showed a sustained plasma level of LA up to 12 weeks which suppressed the testosterone plasma concentration to castration level beginning from 14th day until 90 days. Thus, phase-sensitive polymer delivery systems of LA were biocompatible and delivered LA at a controlled rate both in vitro and in vivo to keep testosterone plasma concentration at a castration level up to 3 months.