Optimization of the poloxamer 407-conjugated gelatin to synthesize pH-sensitive nanocarriers for controlled paclitaxel delivery

Abstract

Chemotherapy is one of the most prevalent and efficacious treatments for a wide variety of cancers; however, chemotherapeutic agents have clinically limited applications due to their low water solubility and risk of side effects. Nanomedicine can help to easily deliver hydrophobic and hydrophilic agents for cancer treatment. Here, we describe a nanocarrier system that enables the sustainable and controllable release of hydrophobic anticancer drugs, Paclitaxel, based on poloxamer 407-conjugated gelatin (GeP) copolymers. The particle size, zeta potential, morphology, and thermal stability of the nanogels were characterized. The successful synthesis of nanogels was confirmed by analyzing their chemical components. Among the GePs at different amounts of poloxamer 407, a ratio of gelatin and poloxamer (Ge:P) at 1:15 for preparation resulted in the nanogels being positive in charge, spherical in shape, and 97.84 ± 2.94 nm in hydrodynamic diameter (Dh), with optimal drug-carrying efficacy. The in vitro drug release from nanogels was accelerated in the tumor microenvironment at pH 5.5 in comparison to pH 7.4, and the drug release kinetics from nanogels were due to Fickian diffusion. Finally, the cytotoxicity assays indicated that GePs were biocompatible nanocarriers without toxicity on both normal (VERO) and breast cancer cell (MCF-7) lines, which could improve the pharmacokinetics and pharmacodynamics of paclitaxel. Overall, these results revealed an optimal ratio (1:15) of Ge:P for the synthesis of pH-responsive hybrid nanogels for sufficient paclitaxel releasement to kill MCF-7 for effective cancer treatment.