载阿奇霉素-鼠李糖脂胶束制备工艺优化及性能表征

Preparation technology optimization and performance characterization of AZI-RHL micelles

采用薄膜水化法制备载阿奇霉素-鼠李糖脂(AZI-RHL)胶束,以包封率、载药量为评价指标,通过单因素试验和正交试验优化制备工艺,并考察其理化性质。制备载药胶束前先测定RHL水溶液的临界胶束浓度(CMC)。结果表明,RHL水溶液的CMC值约为0.25 mg/mL。优化后的最佳制备工艺条件为:RHL投料量100 mg,甲醇用量12 mL,搅拌时长20 min。在此条件下制备的AZI-RHL胶束呈球形,水动力学直径为136.3±68.5 nm,Zeta电位为-23.1±6.8 mV,包封率为80.34%±0.60%,载药量为19.42%±0.48%。红外光谱证明AZI包埋在胶束中。体外释放试验表明AZI-RHL胶束具有一定的缓释作用,其体外累计释放曲线符合Ritger-Peppas方程,释放药物以Fick扩散为主。综上所述,AZI-RHL胶束的制备工艺稳定可靠,胶束粒径小,且包封率、载药量高,是一种有潜力的新型制剂。

The azithromycin-rhamnolipid(AZI-RHL)micelles were prepared by thin film hydration method.Taking encapsulation efficiency and drug loading as evaluation indicators, the optimal preparation technology was obtained through single factor test and orthogonal test,and then the physical and chemical properties of AZI-RHL micelles were investigated. The critical micelle concentration(CMC) of RHL aqueous solution was determined before preparing the AZI-RHL micelles. The results showed that the CMC of RHL aqueous solution was about 0.25 mg/mL. The optimized preparation technology conditions were as follows: RHL dosage was 100 mg, methanol dosage was 12 mL, and the stirring time was 20 min. The AZI-RHL micelles prepared under the optimized preparation technology conditions were spherical when observed under transmission electron microscope(TEM), with a hydrodynamic diameter of 136.3±68.5 nm, a Zeta potential of-23.1±6.8 mV, an encapsulation efficiency of 80.34%±0.60%, and a drug loading of 19.42%±0.48%. Infrared spectroscopy revealed that AZI was embedded in micelles. The in vitro cumulative release test showed that AZI-RHL micelles had a certain sustained release effect compared with bulk drugs. The cumulative release curve of AZI-RHL micelles in vitro conformed to the Ritger-Peppas equation, and the release of drugs was dominated by Fick diffusion. To sum up the above, the preparation technology of AZI-RHL micelles was stable and reliable;the AZI-RHL micelles had small particle size, high encapsulation efficiency and high drug loading. AZIRHL micelles achieved synergistic delivery of RHL and AZI by means of formulations. RHL had good anti-biofilm properties, and in combination with AZI, AZI-RHL micelles can exhibit greater anti-biofilm potential. In addition,rhamnolipids, as small-molecule biosurfactants, had the characteristics of low toxicity and easy degradation compared with other types of surfactants. AZI-RHL micelles enriched the research on surfactant micelles as drug carriers, and provided a certain reference for the preparation of subsequent surfactant micelle drug delivery systems.