PCL-b-P(MMA-co-DMAEMA)2 new triblock copolymer for novel pH-sensitive nanocapsules intended for drug delivery to tumors

Abstract

A novel poly(ε-caprolactone) (PCL) and poly [(methyl methacrylate)-co-(2-dimethylamino)ethyl methacrylate)2] block copolymer, PCL-b-P(MMA-co-DMAEMA)2, was synthesized using atom transfer radical polymerization to obtain pH-sensitive nanocapsules intended for drug delivery to solid tumors. The synthesis was performed using PCL:DMAEMA:MMA at two different molar proportions 0.2:10:1 and 0.7:33:1. Nanocapsules prepared using PCL-b-P(MMA-co-DMAEMA)2 proved sensitivity to pH, presenting z-average hydrodynamic diameters of 73 and 71nm at pH7.4, and 96 and 101nm at pH5.5, respectively, because of the decrease in the diffusion coefficient of the nanocapsules due to the increase in amine protonation forming ammonium at the surface. Zeta potential at pH7.2 was +23mV for batch 1 and +13mV for batch 2. In vitro cytotoxicity of the materials (solutions) and the nanocapsules (dispersed in water) was evaluated in a tumoral cell model (human breast adenocarcinoma cell line, MCF-7) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT). The homopolymers PDMAEMA and PMMA showed low cytotoxicity up to 0.60 and 0.44mmolL−1, respectively. After applying the nanoformulation, the cell viability was not affected for copolymer concentrations up to 340mgL−1. The results showed the new triblock copolymer is a promising material to be used in novel nanocapsule formulations intended for drug delivery to solid tumors.