Bioresponsive nanohydrogels based on HEAA and NIPA for poorly soluble drugs delivery

Environmentally sensitive hydrogels have gained considerable attention in recent years as one of the most promising drug delivery systems. In the present study, two new formulations of pH and temperature stimuli-responsive nanogels (NGs) based on poly-N-isopropylacrylamide (NIPA), N-hydroxyethyl acrylamide (HEAA) and tert-butyl 2-acrylamidoethyl carbamate (2AAECM) were synthesized and evaluated for passive targeting of paclitaxel (PTX). Nanogels were prepared by microemulsion polymerization method using N-methylenebis(acrylamide) (NMBA) as crosslinking agent. TEM images and DLS results showed nanosized spherical hydrogels. FTIR spectra confirmed the synthesis of nanogels by radical polymerization among vinyl groups of monomers. The PTX loading capacity, encapsulation efficiency and in vitro release were analyzed by HPLC. The cumulative release profile of the PTX-loaded nanohydrogels within 144h showed a faster drug release at acid pH (pH 5), similar to those observed at lysosome compartment, whereas a fewer PTX amount was released from NGs at pH similar to plasma levels. Cellular uptake assays revealed rapid penetration and intracellular accumulation of those nanogels in MCF7, HeLa and T47D cells after 48h incubation. MTT assays showed cell viability dependence on concentration and time incubation. Finally, the PTX effect on cell viability showed a G2/M cell arrest after using PTX-loaded NGs and pure PTX.