Steric Effects in the Deposition Mode and Drug-Delivering Efficiency of Nanocapsule-Based Multilayer Films

[Image: see text] Using surface-initiated atom transfer radical polymerization (ATRP), block polymers with a series of quaternization degrees were coated on the surface of silica nanocapsules (SNCs) by the “grafting-from” technique. Molnupiravir, an antiviral medicine urgently approved for the treatment of SARS-CoV-2, was encapsulated in polymer-coated SNCs and further incorporated into well-defined films with polystyrene sulfonate (PSS) homopolymers by layer-by-layer (LBL) self-assembly via electrostatic interactions. We investigated the impact of the quaternization degree of the polymers and steric hindrance of functional groups on the growth mode, swelling/deswelling transition, and drug-delivering efficiency of the obtained LBL films. The SNCs were derived from coronas of parent block polymers of matched molecular weights—poly(N-isopropylacrylamide)-block-poly(N,N-dimethylaminoethyl methacrylate) (PNIPAM-b-PDMAEMA)—by quaternization with methyl sulfate. As revealed by the data results, SNCs with coronas with higher quaternization degrees resulted in a larger layering distance of the film structure because of weaker ionic pairing (due to the presence of a bulky methyl spacer) between SNCs and PSS. Interestingly, when comparing the drug release profile of the encapsulated drugs from SNC-based films, the release rate was slower in the case of capsule coronas with higher quaternization degrees because of the larger diffusion distance of the encapsulated drugs and stronger hydrophobic–hydrophobic interactions between SNCs and drug molecules.