Chung Tze-Wen, Yang Min-Chia, Tsai Wei-Jean
Department of Chemical Engineering, National Yunlin University of Science and Technology, Yunlin 640, Taiwan, ROC.
Int J Pharm. 2006 Mar 27;311(1-2):122-9. doi: 10.1016/j.ijpharm.2005.12.038. Epub 2006 Jan 30.
A depot drug delivery system, fibrin encapsulated liposome-in-chitosan matrix (FLCM), has been developed to deliver a water-soluble drug which is configured by a porous chitosan matrix containing a bovine fibrin network encapsulated different surface properties of liposomes. Quinacrine (QR), a water-soluble, low-molecular weight fluorescent marker, is used as a model drug to evaluate the delivery characteristics of the system. The SEM photographs show that the fibrin network adheres to the surfaces and pores of the chitosan matrix of a FLCM system. The QR release periods of the FLCM are sustained for about four times longer than those of QR encapsulated into the liposomes. However, the QR release periods and profiles of the FLCM are influenced by the surface properties of liposomes. The release of QR from FLCM is sustained for 9 days for neutral liposomes and only 5 days for PEG modified liposomes (PEG-liposome). After crosslinking the fibrin network of the FLCM with 0.5% of glutaldehyde, the release of QR is further sustained for 17 days with good linear profiles (e.g., 13 days) and with 50% of reduced burst release compared with those of without crosslinking, indicating that the stability of the fibrin network plays an important role on QR release of the system. More interestingly, the release periods and profiles of QR of the FLCM system are highly similar to those of Tirofiban, low-molecular weight of a water-soluble clinical cardiovascular drug, although the study has been done by human platelet poor plasma instead of bovine fibrinogen as a source of fibrin network. It suggests that the QR is a suitable model for investigating the drug delivery behaviors for water-soluble, low-molecular weight drugs of the FLCM. In conclusion, with QR as a model drug, FLCM with crosslinked fibrin network can effectively sustain the release of QR for 17 days but the release profiles are influenced by the surface properties of encapsulated liposomes. This study suggests that FLCM may have the potential as a depot drug delivery system for water-soluble drugs.
一种长效药物递送系统——纤维蛋白包裹的壳聚糖基质脂质体（FLCM）已被开发用于递送水溶性药物，它由含有包裹不同表面性质脂质体的牛纤维蛋白网络的多孔壳聚糖基质构成。喹吖因（QR）是一种水溶性低分子量荧光标记物，用作模型药物来评估该系统的递送特性。扫描电子显微镜照片显示，纤维蛋白网络附着在FLCM系统壳聚糖基质的表面和孔隙上。FLCM中QR的释放期比包封在脂质体中的QR长约四倍。然而，FLCM的QR释放期和释放曲线受脂质体表面性质的影响。中性脂质体的FLCM中QR释放持续9天，而聚乙二醇修饰脂质体（PEG - 脂质体）仅持续5天。用0.5%的戊二醛交联FLCM的纤维蛋白网络后，QR的释放进一步持续17天，具有良好的线性曲线（如13天），与未交联相比，突释减少50%，这表明纤维蛋白网络的稳定性对该系统中QR的释放起重要作用。更有趣的是，尽管该研究是用人贫血小板血浆而非牛纤维蛋白原作为纤维蛋白网络的来源，但FLCM系统中QR的释放期和释放曲线与临床水溶性心血管药物替罗非班的高度相似。这表明QR是研究FLCM中水溶性低分子量药物递送行为的合适模型。总之，以QR为模型药物，具有交联纤维蛋白网络的FLCM能有效持续释放QR达17天，但释放曲线受包封脂质体表面性质的影响。这项研究表明FLCM可能有作为水溶性药物长效递送系统的潜力。
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