Development of polymer-lipid hybrid nanoparticles for anticancer drug delivery

Abstract

The challenge of conventional cancer treatment is the side effects caused by the chemotherapeutic drugs. To prevent these side effects, nanocarrier systems can be designed to have functions of controlled and selective drug release. Among these systems, core-shell structured hybrid nanoparticles have been drawing attention in the last decades because of their multifunctional structures. The major limitations of these nanocarrier systems are the toxicity related to synthetic surfactants as well as undesired leakage of highly toxic drugs. In this study, a unique nanocarrier sys tem was designed using natural materials for controlled delivery of an anticancer drug. This system contains a biopolymeric shell and a lipid core which could be used to encapsulate lipophilic anticancer drugs. Bovine Serum Albumin (BSA) and Dextran in different molecular weights were covalently conjugated via Maillard reaction to pro duce shell and used to stabilize lipid core by miniemulsion/solvent evaporation method. The shell of the nanoparticle could prevent undesired drug leakage from the core and provide enzyme-sensitive drug release thanks to its protein structure. Shell properties such as concentration of the Maillard conjugate, protein-polysaccharide molar ratio, and polysaccharide molecular weight were systematically investigated to reach opti mum nanoparticle features that are size which can enable passive targeting through enhanced permeability and retention (EPR) effect, narrow size distribution, and high stability. Furthermore, zeta potential analysis was performed to evaluate surface charge of the nanoparticles in physiological (pH 7.4) and early endosomal (pH 6.5) mimicking environment. This study can bring new perspectives to the hybrid nanoparticles and has a potential to be a new delivery platform for lipophilic anticancer drugs.|Keywords : Drug Delivery Systems, Hybrid Nanoparticles, Protein-Polysaccharide Complexes.