Preparation and in vitro properties of N-succinylchitosan- or carboxymethylchitin-mitomycin C conjugate microparticles with specified size
Preparation and in vitro properties of N-succinylchitosan- or carboxymethylchitin-mitomycin C conjugate microparticles with specified size
复制标题
DOI：
10.1081/ddc-100107322
复制
发表时间：
2001-01-01
影响因子：
3.4
通讯作者：
Machida, Y
中科院分区：
文献类型：
--
作者：
Onishi, H;Takahashi, H;Machida, Y
N-琥珀酰-壳聚糖（Sue）或6-O-羧甲基甲壳素（CM）与丝裂霉素C（MMC）的交联缀合物微粒的制备，其显示出足够的尺寸用于肝靶向（0.2-3 μ m），尝试通过水溶性碳二亚胺（EDC）偶联和乳化技术的组合。对于Suc，可以容易地获得直径小于几微米的微粒，而制备相同直径的CM微粒（CM-MP）不一定容易。首先，比较CM-MP的制备条件，并且一些条件得到直径小于几微米的CM-MP。对于CM-MMC缀合物微粒，在使用低分子量的CM（CML）乳化后加入EDC的方法得到了平均直径为0.97 μ M的更合适的微粒（CML-MP-MMC）。Suc-MMC共轭微粒足以肝靶向可以通过添加EDC之前和之后乳化，特别是，具有0.45 μ m的平均直径的共轭微粒（Suc-MP-MMC）的衍生通过添加EDC之前乳化。Suc-MP-MMC的药物含量高于CML-MP-MMC。CML-MP-MMC和Suc-MP-MMC的50%药物释放时间分别为2.87 h和42.1 h。
The preparation of cross-linked conjugate microparticles of N-succinyl-chitosan (Sue) or 6-O-carboxymethylchitin (CM) with mitomycin C (MMC), which showed an adequate size for liver targeting (0.2-3 mum), was attempted by a combination of water-soluble carbodiimide (EDC) coupling and emulsification technique. As for Suc, microparticles with a diameter less than a few micrometers could be obtained easily, while the preparation of CM microparticles (CM-MPs) of the same diameter was not necessarily easy. First, preparation conditions were compared for CM-MPs, and some conditions gave CM-MPs with a diameter less than a few micrometers. As to CM-MMC conjugate microparticles, the method by addition of EDC after emulsification using CM with low molecular weight (CML) gave more appropriate microparticles with a mean diameter of 0.97 muM (CML-MP-MMC). Suc-MMC conjugate microparticles adequate for liver targeting could be produced by the addition of EDC both before and after emulsification; especially, the conjugate microparticles with a mean diameter of 0.45 mum (Suc-MP-MMC) were derived by the addition of EDC before emulsification. Suc-MP-MMC exhibited a higher drug content than CML-MP-MMC. CML-MP-MMC and Suc-MP-MMC exhibited 50% drug release times of 2.87 h and 42.1 h, respectively.