壳多糖庆大霉素缓释药体内动力学研究

Experimental study of in vivo release test of gentamicin loaded chitosan drug delivery system

目的：研究壳多糖（几丁质）庆大霉素缓释药体内动力学行为，为其临床应用提供理论依据。方法：将缓释药棒植入兔胫骨干骺端，监测术后不同时间血药浓度、血尿素氮（ＢＵＮ）和肌酐（Ｃｒ）值，局部骨组织和血肿中庆大霉素浓度。结果：血药浓度峰值（０．９２μｇ／ｍｌ）在２４ｈ出现，维持时间为３周。术后血ＢＵＮ和Ｃｒ值无增加。术后第１天离药棒０．５ｃｍ处的血肿、１ｃｍ处的皮质骨和松质骨中庆大霉素浓度分别为：６２．００，４０．３８，２９．７８μｇ／ｇ，其后下降；第１０周时，庆大霉素浓度仍为金葡菌最小抑菌浓度数倍以上。结论：壳多糖庆大霉素缓释药具有良好体内缓释作用，有望为临床治疗骨感染提供一种无需二期取出的简便而有效的方法。

Objective:To study an in vivo release test for a biodegradable drug delivery system (DDS)of gentamicin loaded chitosan bar with the purpose of giving further data for its clinical application. Methods: One DDS bar was inserted into the proximal portion of tibia in a rabbit. Serum, bone and haematoma concentrations of gentamicin as well as blood urea nitrogen (BUN) and serum creatinine (Cr) were observed after implantation at different time. Results: Serum gentamicin concentration reached its peak level (0.92 μg/ml) at 24 h after implantation and lasted for 3 weeks. No increase in the concentration of BUN and Cr was observed after implantation. The gentamicin concentration of test material l cm apart from bar exceeded 40.38 μg/g in cortical bone, 29.78 μg/g in cancellous bone and 62.0 μg/g in haematoma (0.5 cm apart from bar)respectively at the first day. It fell by this time. In all the bone tissue around the bar, the gentamicin concentration was many times higher than MIC of S.aureus, and maintained untill 10 weeks. Conclusion: The gentamicin loaded chitosan bar is a good DDS with sustained antibiotic effect in vivo. It might be a clinical useful and simple method for the treatment of bone infection without a second operation for removal of the carrier.