Temperature-Responsive Multilayer Films Based on Block Copolymer-Coated Silica Nanoparticles for Long-Term Release of Favipiravir

Using surface-initiated atom-transfer radical polymerization, temperature-responsive block polymers were functionalized on the surface of silica nanocapsules (SNCs) by a "grafting-from" technique. Favipiravir, a potential medicine candidate for the treatment of coronavirus disease (COVID-19), was encapsulated in polymer-coated SNCs and further incorporated into well-defined films by layer-by-layer self-assembly. The multilayer films composed of polymer-coated SNCs and poly(methacrylic acid) (PMAA) homopolymers exhibited swelling/deswelling behaviors under the trigger of a temperature stimulus. For the first time, the impact of steric hindrance on the assembling behavior, swelling/deswelling transition, and delivering capacity of nanocapsule-based multilayer films was investigated. SNCs with coronae of higher steric hindrance resulted in a larger layering distance during film growth. Moreover, the difference in the sustained release rates of the drug indicated their diverse diffusion coefficients and intermolecular interactions within the multilayer films, due to the presence of a methyl spacer at the amino group of nanocapsule coronae and weaker ionic pairing between SNC coronae and PMAA homopolymers. The profile of drug release from the films was dependent on the temperature value of the surrounding environment. At 37 and 40 °C, the films were able to efficiently entrap favipiravir, with as low as 50% released in 80 days, whereas a faster favipiravir release was triggered by exposure to a lower temperature value at 25 °C. This work demonstrates the first proof-of-concept platform of temperature-responsive SNC-incorporated multilayered films with a well-defined internal structure and a sustained release profile for on-demand in vitro drug delivery.