Controlled delivery of testosterone from smart polymer solution based systems: in vitro evaluation.
Controlled delivery of testosterone from smart polymer solution based systems: in vitro evaluation.
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DOI：
10.1016/j.ijpharm.2005.02.023
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发表时间：
2005-05
影响因子：
5.8
通讯作者：
Sibao Chen;Jagdish Singh
中科院分区：
文献类型：
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作者：
Sibao Chen;Jagdish Singh
本研究的目的是开发基于注射聚合物溶液的睾酮（TSN）控释系统，使用相敏和热敏聚合物。采用聚丙交酯（PLA）和苯甲酸苄酯（BB）、苯甲醇（BA）混合溶剂组成相敏聚合物传递体系。考察了溶剂体系和载药量对TSN体外释放的影响。在热敏性聚合物递送体系中，研究了一系列低分子量的聚（丙交酯-共乙二醇酯）-聚（乙二醇）-聚（丙交酯-共乙二醇酯）（PLGA-PEG-PLGA）三嵌段共聚物（LA/GA, 2.0-3.5），以控制TSN的释放。考察了不同嵌段长度共聚物1-4对TSN体外释放的影响。体外释放介质为含0.5% （w/v）吐温-80的磷酸盐缓冲盐水（pH 7.4）。采用高效液相色谱法测定TSN的释放量。在相敏和热敏两种聚合物给药体系中，TSN均有可控（零级）的体外释放。溶剂体系中添加15%的BA （v/v）比不添加BA的溶剂（0.27±0.00mg/d）显著提高了相敏给药体系中TSN的释放率（0.33±0.01mg/ml） （p<0.05）。增加载药量也增加了释药速率。在热敏性聚合物递送体系中，增加共聚物的疏水PLGA嵌段长度显著（p<0.05）降低了TSN的释放率。本研究结果表明，相敏聚合物和热敏聚合物适合于开发可注射的TSN植入物缓释系统。
The objective of this research is to develop injectable polymers solution based controlled release delivery systems for testosterone (TSN), using phase sensitive and thermosensitive polymers. A combination of poly(lactide) (PLA) and solvents mixture of benzyl benzoate (BB) and benzyl alcohol (BA) was used in the phase sensitive polymer delivery system. The effects of solvents system and drug loading on the in vitro TSN release were evaluated. In the case of thermosensitive polymer delivery systems, a series of low-molecular-weight poly(lactide-co-glycolide)–poly(ethylene glycol)–poly(lactide-co-glycolide) (PLGA–PEG–PLGA) triblock copolymers with varying ratio of lactide/glycolide (LA/GA, 2.0–3.5) were studied to control the release of TSN. The effects of varying block length of copolymers 1–4 on the in vitro TSN release were evaluated. Phosphate buffer saline (pH 7.4) containing 0.5% (w/v) Tween-80 was used as in vitro release medium. The amount of the released TSN was determined by an HPLC method. A controlled (zero-order) in vitro release of TSN was observed from both the phase sensitive and thermosensitive polymer delivery systems. Addition of BA (15%, v/v) in solvents system significantly (p<0.05) increased the release rate of TSN (0.33±0.01mg/ml) from phase sensitive delivery system in comparison to solvent without BA (0.27±0.00mg/day). Increasing drug loading also increased release rate. In the case of thermosensitive polymer delivery system, increasing the hydrophobic PLGA block length of copolymers significantly (p<0.05) decreased the release rate of TSN. It is evident from this study that the phase sensitive and thermosensitive polymers are suitable for developing prolong-release injectable implant delivery systems for TSN.