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目的以天然海洋多糖聚甘露糖醛酸(PM)为原料,制备1种生物相容、生物可降解纳米材料,以难溶性药物他克莫司(FK506)为模型药物制备载药胶束,并对其体外释药特性进行考察。方法以油胺为疏水端,与PM通过酰胺反应制备纳米材料,利用FT-IR、1 H-NMR对其结构进行表征。通过超声乳化法制备FK506胶束,利用原子力显微镜与马尔文激光粒度仪分析载药胶束的形态、粒径及zeta-电位。利用高效液相色谱法测定FK506胶束的载药量和包封率。采用体外透析法分析FK506胶束的体外释放特性。结果油胺与PM等摩尔比投料反应的枝接率为56.8%,FK506胶束外形为球状且分散均匀,粒径大小在100~150nm,zeta-电位为-50mV,多分散系数<0.2,载药量和包封率分别为(17.6±0.21)%和(97.7±1.19)%。体外释药分为2个阶段,前12h释放较快,释放药物的(64.5±5.8)%,后一阶段药物释放较慢,至48h时可释放药物(89.2±6.9)%。结论成功制备生物可降解的PM纳米材料,以其为载体制得的FK506胶束可以提高FK506的溶解性,在体外具有明显的缓释特征,PM纳米材料具有良好的应用前景。
OBJECTIVE To prepare one kind of biocompatible and biodegradable nanomaterials from natural marine polysaccharide polymannuronic acid (PM) and prepare the drug-loaded micelles with the model drug FK506 In vitro release characteristics were investigated. Methods Olefin was used as the hydrophobic end to prepare nanomaterials by amidation reaction with PM. The structure of the nanomaterials was characterized by FT-IR and 1 H-NMR. FK506 micelles were prepared by ultrasonic emulsification. Morphology, particle size and zeta-potential of drug-loaded micelles were analyzed by atomic force microscopy and Malvern laser particle sizer. The drug loading and entrapment efficiency of FK506 micelles were determined by high performance liquid chromatography. In vitro dialysis assay FK506 micelles in vitro release characteristics. Results The coupling ratio of oleylamine to PM was 56.8%. The shape of FK506 micelles was spherical and uniformly dispersed. The particle size was 100-150 nm, zeta-potential was -50 mV, polydispersity <0.2, The dose and entrapment efficiency were (17.6 ± 0.21)% and (97.7 ± 1.19)%, respectively. In vitro release was divided into two stages, the first 12h release faster, the release of drugs (64.5 ± 5.8)%, the latter phase of drug release slower, to 48h release of drugs (89.2 ± 6.9)%. Conclusion The successful preparation of biodegradable PM nanomaterials with FK506 micelles can improve the solubility of FK506 and have obvious sustained-release characteristics in vitro. PM nanomaterials have good application prospects.