Temperature-Responsive Multilayer Films of Micelle-Based Composites for Controlled Release of a Third-Generation EGFR Inhibitor

Lung cancer is a complicated long-term disease, which is extremely difficult to cure. A traditional single drug delivery system cannot achieve desired long-term controlled release of therapeutic compounds. Our previous studies have found that temperature-responsive micelles demonstrated high loading efficiency and a long-term controlled release rate, which allows them to be an efficient drug delivery system. We utilized temperature-responsive micelles and hyaluronic acid biopolymers to create a sandwich-like membrane based on hydrogen bonding by layer-by-layer (LBL) self-assembly technology. The multilayer films efficiently absorbed osimertinib the third-generation inhibitor for nonsmall cell lung cancer (NSCLC) treatment. The release profile of osimertinib from the films is controlled by environmental stimuli. Block copolymer micelles with a poly(N-isopropylacrylamide) (PNIPAM) core were deposited into the multilayer films to introduce temperature sensitivity to the composite thin films. By the above approach, we built a drug carrier for the delivery of an anticancer drug, which potentially demonstrates good loading capacity, high morphology stability, and a controllable drug release mode. We investigated the films' responsive behavior to temperature and ionic strength and loading capacity of the composite membrane and explored the influence of each component on the response of the drug release profile to environmental triggers. The films retained their morphology integrity after several temperature-triggered swelling/deswelling cycles based on atomic force microscopy and ellipsometry measurements. The mechanism of the intermolecular interaction and molecular motions in the system was studied to elucidate the relationship between structure and delivering efficiency of the system. Development of the LBL films can provide ideas for the modification of traditional drug delivery materials. More importantly, nanoparticle layer-by-layer self-assembly and micro/nanoscale structure manipulation for controlled release of therapeutic compounds are also beneficial to future design and development of innovative functional materials.