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目的:以N-辛基-O,N-羟乙基壳聚糖(OGC)为载体材料,制备环孢素-壳聚糖胶束(CsA-OGC),并对其理化性质及其大鼠口服相对生物利用度进行研究。方法:以载药量和包封率为主要指标,对CsA-OGC的制备工艺进行优选,动态光散射法测定其粒径、Zeta电位,透射电镜观察其形态,并考察其稳定性。将市售制剂Neoral及CsA-OGC按7 mg·kg-1大鼠口服,HPLC法测定全血药物浓度,WinNonlin 5.1计算药动学参数。结果:透析法工艺为最佳制备工艺,载药量和包封率分别为29.5%和75.3%,粒径为185.2 nm,透射电镜照片表明载药胶束为规整球形结构,且具有良好的稀释稳定性。与市售制剂Ne-oral相比,CsA-OGC胶束口服给药在大鼠体内的Cmax和AUC均显著提高(P<0.05),相对生物利用度为137.0%。结论:OGC胶束具优越的载药性能,且对药物具有良好的促吸收效果,作为口服药物载体具有优良的应用前景。
OBJECTIVE: To prepare cyclosporin-chitosan micelles (CsA-OGC) with N-octyl-O, N-hydroxyethyl chitosan (OGC) as carrier material, Oral bioavailability was studied. Methods: The preparation method of CsA-OGC was optimized with the drug loading and entrapment efficiency as the main indexes. The particle size, zeta potential and transmission electron microscopy were used to observe the morphology and the stability of CsA-OGC. Pharmacokinetic parameters of Neoral and CsA-OGC were determined by oral administration of 7 mg · kg-1 rat serum and HPLC method. WinNonlin 5.1 was used to calculate pharmacokinetic parameters. Results: The dialysis process was the best preparation process. The drug loading and entrapment efficiency were 29.5% and 75.3%, respectively. The diameter of the drug-loaded micelles was 185.2 nm. The transmission electron micrographs showed that the drug-loaded micelles had a regular spherical structure with good dilution stability. Compared with the commercially available preparation Ne-oral, the Cmax and AUC of oral administration of CsA-OGC micelles were significantly increased (P <0.05), and the relative bioavailability was 137.0%. CONCLUSION: OGC micelles have excellent drug-loading properties and good absorption-promoting effect on the drugs. OGC micelles have excellent application prospect as an oral drug carrier.