pH-Responsive Vesicle Formation by PEGylated Cholesterol Derivatives: Physicochemical Characterization, Stability, Encapsulation, and Release Study

PEGylated vesicles are known to serve as blood-persistent drug-delivery systems (DDSs) with potential applications in intravenous drug administration. pH-responsive PEGylated vesicles are also among the most promising stimuli-responsive carriers for drug delivery and controlled release for cancer chemotherapy. Herein, we report design and synthesis of two novel pH-responsive amphiphiles by coupling a cholesterol (Chol) and poly(ethylene glycol) chain with l-cysteine amino acid through hydrolysable linkages. The objective of this work is to physicochemically characterize the nanoaggregates of the amphiphiles under different experimental conditions. We have demonstrated spontaneous vesicle formation by the amphiphiles in water using various spectroscopic, calorimetric, and microscopic techniques. The size of vesicles was observed to increase on reduction of solution pH and increase in amphiphile concentration. The vesicles were found to be sufficiently stable under physiological conditions and were shown to be able to encapsulate not only hydrophilic dyes in their aqueous core but also hydrophobic guest molecules in the bilayer membrane constituted by the Chol units. These nanosized vesicles exhibit pH-triggered release of encapsulated dye molecules in acidic pH. Thus, these spontaneously formed stable vesicles might hold potential as biocompatible DDSs in cancer chemotherapy.