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

Abstract

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 therapeutic cargo 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 post-polymerization 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 and were stable even in highly acidic conditions. Based on this observation, a proof-of-concept study for mucosal delivery was performed in 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 highly customizable scaffolds for mucosal drug delivery.

Stimuli-responsive temporary adhesives: enabling debonding on demand through strategic molecular design

“…114,115 The molecular design of SIPs most commonly centers around the type of polymer backbone and the end cap identities. 77,116 The endless combinations of backbones and end caps lends well to a vast range of applications including, but not limited to, sensing, [117][118][119][120][121][122] drug delivery, [123][124][125][126] lithography, [127][128][129][130][131][132][133][134][135][136][137][138] electronics, [139][140][141][142][143] and smart composites. [144][145][146] Maximizing the potential of SIPs in these applications relies on a radical difference in the properties of the polymer and the monomer states.…”

Polyglyoxylamides with a pH-Mediated Solubility and Depolymerization Switch

“…Self-immolative polymers (SIPs) are a class of degradable polymers that undergo end-to-end depolymerization to small molecules after the cleavage of their backbone or stabilizing end-cap by a stimulus. − Unlike traditional degradable or stimuli-responsive polymers, only a single bond cleavage is needed to initiate complete SIP degradation. This property makes SIPs attractive for applications such as sensing, , patterning, − degradable/recyclable plastics, − and drug delivery, − where an amplified or highly sensitive response to stimuli is desired. Several SIP backbones have been developed, including poly­(benzyl carbamates), , poly­(benzyl ethers), poly­(acetals), − poly­(olefin sulfones), , and more recently poly­(benzyl esters), polythioesters, , polycarboxypyrroles, polycyclopentenes, and polydisulfides .…”

Base-Triggered Degradation of Poly(vinyl ester sulfone)s with Tunable Sensitivity

“…Poly­(olefin sulfone)­s (POS)­s are copolymers formed from the free-radical copolymerization of sulfur dioxide and an olefin monomer . These polymers are known to depolymerize when exposed to heat, ionizing radiation and base − and these characteristics have been targeted in the development of photoresists and other degradable materials. − Base depolymerization traditionally proceeds through a mechanism involving the deprotonation of the polymer backbone, chain unzipping, and ultimately the regeneration of the monomer units . This mechanism of degradation has been exploited in the development of a number of base depolymerizable polymer systems.…”