A new approach to the in vivo and in vitro investigation of drug release from locoregionally delivered microspheres
A new approach to the in vivo and in vitro investigation of drug release from locoregionally delivered microspheres
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DOI：
10.1016/j.jconrel.2004.08.004
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发表时间：
2004-11-05
影响因子：
10.8
通讯作者：
Wu, XY
中科院分区：
文献类型：
--
作者：
Cheung, RY;Kuba, R;Wu, XY
本工作的目的是测定葡聚糖微球(MS)局部给药的阿霉素(Dox)的体内释放曲线，并建立一种预测MS体内药物释放(IVIVC)的方法。为了测定体内Dox的释放，将载药的MS植入中空纤维(HF)，并植入C3H小鼠的皮下。植入后不同时间取材，从HF中去除MS，用紫外/可见(UV/Vis)分光光度法测定剩余Dox的量。各种体外系统被设计并研究其连接体内和体外释放曲线的能力，包括具有以不同流速连续流动的释放介质的开放系统(例如柱)和使用不同释放介质和条件的封闭式系统(例如试管)。所研究的三种体外释放系统、柱系统和浸泡在缓冲液或生长介质中的HF从MS中释放Dox的动力学曲线与体内释放曲线高度相关(r(2)>；0.9)。这种线性和非线性的关系表明，可以使用专门设计的释放系统来开发用于从区域内递送的MS释放Dox的A级IVIVC模型。(C)2004爱思唯尔B.V.保留所有权利。
The purpose of this work was to determine the in vivo release profile of doxorubicin (Dox) delivered locoregionally by dextran-based microspheres (MS) and to develop an in vitro method for predicting in vivo drug release from MS- in vitro-in vivo correlation (IVIVC). For the determination of in vivo Dox release, drug-loaded MS were placed into hollow fibers (HF) and implanted subcutaneously into C3H mice. Samples were retrieved at various times following implantation, MS removed from HF, and the amount of Dox remaining determined via ultraviolet/visible (UV/Vis) spectrophotometry. Various in vitro systems were designed and investigated for their ability to link in vivo and in vitro release profiles, including an open system (e.g. a column) with continuous flow of release medium at different flow rates and closed systems (e.g. a cuvette) using different release media and conditions. About 34% of loaded Dox was released from MS in vivo at 48 h. Only an incremental release was observed over the ensuing 72 h. The release kinetics of Dox from MS using three of the investigated in vitro systems, column system and HF immersed in a buffer solution or growth medium gave release profiles that were highly correlated with the in vivo release profile (r(2)>0.9). The relationships, both linear and non-linear, suggest that Level A IVIVC models can be developed for Dox release from locoregionally delivered MS using specially designed release systems. (C) 2004 Elsevier B.V. All rights reserved.