Self-microemulsifying drug delivery system for camptothecin using new bicephalous heterolipid with tertiary-amine as branching element

Abstract

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.