Molecular understanding of the self-assembly of an N-isopropylacrylamide delivery system for the loading and temperature-dependent release of curcumin.

Global changes and drug abuse are forcing humanity to face various disease problems, and alternative therapies with safe natural substances have important research value. This paper combines various techniques in quantum chemical calculations and molecular simulations to provide molecular-level insight into the dynamics of the self-assembly of N-isopropylacrylamide (NIPAM) for loading curcumin (CUR). The results indicate that increasing the chain length of NIPAM molecules reduces their efficiency in encapsulating and locking CUR, and electrostatic interactions and van der Waals interactions are the main driving forces behind the evolution of system configurations in these processes. The isopropyl groups of NIPAM and the two phenolic ring planes of CUR are the main contact areas for the interaction between the two types of molecules. The thermosensitive effect of NIPAM can alter the distribution of isopropyl groups in NIPAM molecules around CUR. As a result, when the temperature rises from ambient temperature (300 K) to human characteristic temperature (310 K), the NIPAM-CUR interactions and radial distribution functions suggest that body temperature is more suitable for drug release. Our findings offer a vital theoretical foundation and practical guidance for researchers to develop temperature-sensitive drug delivery systems tailored for CUR, addressing its clinical application bottleneck.