In vitro and in vivo characterization of a novel biocompatible polymer-lipid implant system for the sustained delivery of paclitaxel
In vitro and in vivo characterization of a novel biocompatible polymer-lipid implant system for the sustained delivery of paclitaxel
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DOI：
10.1016/j.jconrel.2005.02.008
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发表时间：
2005-05-05
影响因子：
10.8
通讯作者：
Piquette-Miller, M
中科院分区：
文献类型：
--
作者：
Ho, EA;Vassileva, V;Piquette-Miller, M
最近，开发了一种新型基于壳聚糖的可植入制剂（壳聚糖-ePC），可提供紫杉醇（PTX）的受控局部释放，用于治疗卵巢肿瘤。因此，本研究的目的是在人卵巢 SKOV-3 细胞中体外评估该递送系统，并在腹膜内植入无药或 C-14-PTX-壳聚糖-PC 膜的小鼠体内评估该递送系统。在体外，C-14-PTX-壳聚糖-ePC 植入物 (10 mg) 在 5 天内提供 0.92 +/- 0.03 pg/天 PTX 的零级恒定释放。释放的 PTX 保留了剂量依赖性活性；有效抑制 SKOV-3 增殖，释放的 PTX 的 ED50 为 211 ng/ml。无药植入物不会影响 SKOV-3 细胞的细胞活力或细胞形态。在植入 C-14-PTX-壳聚糖-ePC 膜的小鼠体内，两周内也观察到 PTX 持续零级释放。 PTX 体外和体内释放之间的相关性非常显着 (R-2 = 0.975)。 2-4周后，植入壳聚糖-ePC的小鼠没有表现出任何封装、炎症或感染的迹象。总体而言，我们的体外和体内结果证明了新型壳聚糖-ePC 薄膜的零级药物释放和生物相容性。这表明壳聚糖-ePC 植入物在持续局部递送抗肿瘤药物方面具有潜在的用途。 (c) 2005 Elsevier B.V. 保留所有权利。
Recently, a novel chitosan-based implantable formulation (chitosan-ePC) was developed to provide controlled, local release of paclitaxel (PTX) for the treatment of ovarian tumors. Hence, the objective of this study was to evaluate this delivery system in vitro in human ovarian SKOV-3 cells and in vivo in mice with intraperitoneal implants of drug-free or C-14-PTX-chitosane-PC films. In vitro, C-14-PTX-chitosan-ePC implants (10 mg) provided zero-order constant release of 0.92 +/- 0.03 pg/day PTX over 5 days. Released PTX retained dose-dependent activity; effectively inhibiting SKOV-3 proliferation with an ED50 of 211 ng/ml of released PTX. Drug-free implants did not affect cell viability or cell morphology of SKOV-3 cells. A sustained, zero-order release of PTX was also seen in vivo over a 2 week period in mice implanted with C-14-PTX-chitosan-ePC films. Correlations between the in vitro and in vivo release of PTX was highly significant (R-2 = 0.975). After 2-4 weeks, mice with chitosan-ePC implants did not demonstrate any signs of encapsulation, inflammation or infection. Overall, our in vitro and in vivo results demonstrated zero-order drug release and biocompatibility of the novel chitosan-ePC film. This indicates potential usefulness of chitosan-ePC implants in the sustained and local delivery of anti-neoplastic agents. (c) 2005 Elsevier B.V. All rights reserved.