Tunable Decoupling of Dual Drug Release of Oppositely Charged, Stimuli-Responsive Anisotropic Nanoparticles

Multicompartmentalized nanostructures are of interest because they can provide unique physicochemical properties and multifunctionalities in each compartment. Furthermore, stimuli-responsive anisotropic nanostructures (ANPs) with distinct opposite charges would be useful for drug delivery systems because different drug release kinetics could be achieved from each compartment in response to both charge and stimuli. In this study, stimuli-responsive ANPs were formed via electrohydrodynamic cojetting of poly(N-isopropylacrylamide)-based copolymers with opposite charges. The positively charged compartment consisted of poly(N-isopropylacylamide-co-stearyl acrylate-co-allylamine) (poly(NIPAM-co-SA-co-AAm)) (i.e., PNSAAm) and poly(N-isopropylacylamide-co-stearyl acrylate-co-acrylic acid) (poly(NIPAM-co-SA-co-AAc)) (i.e., PNSAAc). The two distinct compartments of ANPs were physically cross-linked through hydrophobic interactions within the copolymers. Oppositely charged, small-molecule model drugs (fluorescein sodium salt and rhodamine 6G) were separately encapsulated within each compartment and released based on changes in noncovalent interactions and temperature. Furthermore, two different biomacromolecule drugs with opposite charges, bovine serum albumin and lysozyme (which were complexed with polysaccharides by hydrophobic ion pairing), were loaded within the ANPs. Electrostatic interactions between the encapsulated drugs and each ANP compartment controlled the rate of drug release from the ANPs. In addition, these ANPs showed a thermally induced actuation, leading to drug release at different rates due to the collapse of poly(NIPAM)-based copolymers under aqueous conditions. This work may be useful for decoupled drug release kinetics.