Depolymerizable Poly(O-vinyl carbamate-alt-sulfones) as Customizable Macromolecular Scaffolds for Mucosal Drug Delivery

Interest in stimulus responsive materials and polymers has grown over the years, having shown great promise in a diverse set of applications. For drug delivery, stimulus-responsive polymers have been shown to encapsulate therapeutics such as small molecule drugs or proteins, deliver them to specific locations in the body, and release them so that they can induce a therapeutic effect in the patient. Most hydrolytically degradable polymers are synthesized via nucleophilic, anionic, or cationic polymerization, which generally requires protection of nucleophilic or protic side chains prior to polymerization. Here, we report the synthesis of novel, alternating copolymers of sulfur dioxide and O-vinyl carbamate monomers that boast excellent functional group tolerance and pH-dependent instability. Alternating copolymers were synthesized containing pendant functionalities such as alcohol, carboxylic acid, ester, and azide without deprotection or postpolymerization modification. The copolymers were then formulated via nanoprecipitation into polymer nanoparticles capable of encapsulating small molecule dyes. The polymer nanoparticles were found to degrade rapidly at pH > 6 but were stable even in highly acidic conditions. Based on this observation, a proof-of-concept study for mucosal delivery was performed using polymer nanoparticles entrapped in a mucus model. At pH 8, the diffusion of encapsulated dye was found to be similar to free dye, while at pH 5 the diffusion coefficient was an order of magnitude lower. Cell viability was retained at 200 μg/mL particles after 24 h incubation. These polymers thus show promise as customizable scaffolds for mucosal drug delivery.