Physicochemical design and in vitro biocompatibility of thermoresponsive PNIPAM nanogels as biomedical nanoplatforms

Smart drug delivery systems have attracted considerable interest in nanomedicine because they enable controlled release of therapeutic agents. Among them, poly(N-isopropylacrylamide) (PNIPAM) nanogels are promising candidates owing to their thermoresponsive behavior. However, their biological safety must be thoroughly established before biomedical application. In this study, thermoresponsive PNIPAM nanogels were synthesized by precipitation polymerization and comprehensively characterized in terms of their physicochemical properties and in vitro biocompatibility. The nanogels exhibited a spherical and monodisperse morphology, a hydrodynamic diameter of approximately 138 nm, a lower critical solution temperature close to physiological temperature (32 °C), and a near-neutral surface charge (− 2.195 ± 0.285 mV). Biological evaluation demonstrated high hemocompatibility, with hemolysis remaining below 5% at all tested concentrations. Cell viability exceeded 90% in Caco-2, PK-15, and MRC-5 cells after 24 and 48 h of exposure, without significant alterations in metabolic activity, DNA content, or cell cycle distribution. No genotoxic effects were detected in the Allium cepa assay, while confocal microscopy suggests cellular internalization of the nanogels and their possible localization in lysosomes. Overall, these findings demonstrate that the synthesized PNIPAM nanogels combine suitable physicochemical characteristics with a favorable in vitro safety profile, supporting their potential as biocompatible platforms for controlled drug delivery and other nanomedicine applications.