使用具有叔胺支化单元的新型双头杂化脂质的喜树碱自微乳给药系统。
Self-microemulsifying drug delivery system for camptothecin using new bicephalous heterolipid with tertiary-amine as branching element.
机构信息
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai 400019, India.
Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai 400019, India.
出版信息
Int J Pharm. 2018 Apr 25;541(1-2):48-55. doi: 10.1016/j.ijpharm.2018.02.030. Epub 2018 Feb 17.
Camptothecin (CPT) has a potent and broad-spectrum anti-tumor activity but its clinical use is limited due to its poor water solubility, stability at physiological conditions and toxicity. The aim of our study was to evaluate bicephalous heterolipid E1E for enhancing the solubility and stability of CPT through the development of a self-microemulsifying drug delivery system (SMEDDS). The solubility of CPT in heterolipid E1E was found to be 82 and 5.86 folds higher than oleic acid and ethyl oleate respectively. Molecular dynamic simulation (MDS) studies revealed that stability of hydrogen bonding between CPT with E1E contributed to solubility enhancement of CPT. SMEDDS of CPT with heterolipid E1E as an oil phase was prepared and evaluated for drug loading, droplet size, morphology, thermodynamic and long-term stability studies as per ICH guidelines. The product, CPT-SMEDDS Fc showed 1.75 mg CPT loading per 1 g of SMEDDS having a droplet size of 20.93 ± 0.41 nm. CPT-SMEDDS Fc was found to be stable, equipotent as compared to doxorubicin and had low toxicity in HeLa, MCF-7, and HL-60 cell lines. These results signify that the delivery system, CPT-SMEDDS Fc could be a very good candidate to be considered for preclinical and clinical investigations.
喜树碱（CPT）具有强大而广谱的抗肿瘤活性，但由于其水溶性差、生理条件下稳定性差和毒性，其临床应用受到限制。我们的研究目的是通过开发自微乳药物传递系统（SMEDDS）来评估双叉异质脂 E1E 以提高 CPT 的溶解度和稳定性。CPT 在异质脂 E1E 中的溶解度分别比油酸和油酸乙酯高 82 倍和 5.86 倍。分子动力学模拟（MDS）研究表明，CPT 与 E1E 之间氢键的稳定性有助于 CPT 溶解度的提高。根据 ICH 指南，用异质脂 E1E 作为油相制备并评价了 CPT 的 SMEDDS 的载药量、粒径、形态、热力学和长期稳定性研究。产品 CPT-SMEDDS Fc 每 1g SMEDDS 可负载 1.75mg CPT，粒径为 20.93±0.41nm。CPT-SMEDDS Fc 被发现是稳定的，与多柔比星相比具有同等效力，并且在 HeLa、MCF-7 和 HL-60 细胞系中具有低毒性。这些结果表明，该传递系统 CPT-SMEDDS Fc 可能是一个非常好的候选者，可以考虑进行临床前和临床研究。
Zotero 插件