School of Biological Science and Technology, University of Jinan, No. 336 West Road of Nanxinzhuang, Jinan, 250022, Shandong, People's Republic of China.
School of Basic Medical Sciences, Dali University, Dali, 671000, Yunnan, People's Republic of China.
AAPS PharmSciTech. 2018 Jul;19(5):2041-2047. doi: 10.1208/s12249-018-1009-0. Epub 2018 Apr 19.
Macrolide antibiotics are lipophilic drugs with some limitations including low solubility, limited cellular permeation, patients discomfort, etc. With amphiphilic methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (MPEG-PCL) copolymer and azithromycin (AZT) as drug carrier and model drug, AZT-loaded micelles were prepared via thin-membrane hydration method in order to overcome these limitations. Encapsulation efficiency of AZT-loaded micelles was 94.40% with good storage stability for 28 days, and AZT's water solubility was enhanced to 944 μg/mL. Fourier transform infrared spectrum and x-ray diffraction analysis indicated that AZT was enveloped into the micelles in amorphous form due to its interaction with the copolymer. AZT's in vitro release from the AZT-loaded micelles demonstrated a slow and continuous behavior when compared with raw AZT. The release dynamics was accorded with Weibull equation, meaning that release amount of AZT lowered with time and was proportional to remaining amount of drug in the AZT-loaded micelles. Korsmeyer-Peppas fitting result suggested that drug release process was a classical Fickian diffusion-controlled manner. With Staphylococcus aureus as bacterial strain, antibacterial activity of the AZT-loaded micelles displayed was comparable with raw AZT. In conclusion, MPEG-PCL should be a promising carrier for macrolide antibiotic delivery in treatment of bacterial infections.
大环内酯类抗生素是亲脂性药物，具有一些局限性，包括低溶解度、有限的细胞渗透、患者不适等。以两亲性甲氧基聚（乙二醇）-b-聚（ε-己内酯）（MPEG-PCL）共聚物和阿奇霉素（AZT）为药物载体和模型药物，通过薄膜水化法制备载 AZT 胶束，以克服这些局限性。载 AZT 胶束的包封效率为 94.40%，在 28 天内具有良好的储存稳定性，AZT 的水溶性提高到 944μg/mL。傅里叶变换红外光谱和 X 射线衍射分析表明，由于与共聚物的相互作用，AZT 以无定形形式包裹在胶束中。与原料药相比，载 AZT 胶束中 AZT 的体外释放呈现缓慢连续的行为。释放动力学符合 Weibull 方程，意味着 AZT 的释放量随时间降低，与载 AZT 胶束中药物的剩余量成正比。Korsmeyer-Peppas 拟合结果表明，药物释放过程是一种经典的菲克扩散控制方式。以金黄色葡萄球菌为细菌株，载 AZT 胶束的抗菌活性与原料药相当。综上所述，MPEG-PCL 有望成为治疗细菌感染大环内酯类抗生素递送的理想载体。
