Exploring fatty acid-amino acid conjugate for the development of self-assembling, pH-sensitive vesicles for targeted anticancer drug delivery

Abstract A novel, pH-sensitive ‘fatty acid-amino acid conjugate’ (L-arginine oleoyl acid amide) was synthesized. The conjugate was evaluated for its suitability as a carrier in the development of a biocompatible and pH-responsive vesicular system for tumor-targeted delivery of pazopanib hydrochloride (PHC). Prepared vesicles exhibited high drug encapsulation efficiency (83.3 %) and a pH-dependent phase transition at the acidic pH of the tumor microenvironment. Formulated vesicles showed a high rate of PHC release in the acidic media (pH 5 > 6.8 > 7.4) similar to the pH of the tumor site, indicating more accurate and selective drug delivery. The vesicles showed a PHC concentration-dependent effect on the viability of ACHN/A498 human renal cancer cells and significantly high intracellular uptake of PHC (83.07 %). Therefore, the developed pH-activated vesicular drug delivery system with predetermined fatty acid-amino acid composition in conjugate could serve as a promising controlled and targeted delivery approach for PHC and other anticancer drugs.