Copolymeric nanofilm platform for controlled and localized therapeutic delivery

Abstract

Nanomaterials such as block copolymeric membranes provide a platform for both cellular interrogation and biological mimicry. Their biomimetic properties are based upon the innate possession of hydrophilic and hydrophobic units that enable their integration with a broad range of therapeutic materials. As such, they can be engineered for specific applications in nanomedicine, including controlled/localized drug delivery. Here we describe a method for the functionalization of the polymethyloxazoline-polydimethylsiloxane-polymethyloxazoline (PMOXA-PDMS-PMOXA) block copolymer with anti-inflammatory molecules to develop copolymer-therapeutic hybrids, effectively conferring biological functionality to a versatile synthetic nanomembrane matrix and creating a platform for an anti-inflammatory drug delivery system. Utilizing self-assembly and Langmuir-Blodgett deposition methods, we mixed copolymers with dexamethasone (Dex), an anti-inflammatory glucocorticoid receptor agonist. The successful mixing of the copolymer with the drug was confirmed by surface pressure isotherms and fluorescence microscopy. Furthermore, at 4 nm thick per layer, orders of magnitude thinner than conventional drug delivery coatings, these dexamethasone-copolymer mixtures (PolyDex) suppressed in vitro expression of the inflammatory cytokines/signaling elements interleukin 6 (IL-6), interleukin 12 (IL-12), tumor necrosis factor alpha (TNFalpha), inducible nitric oxide synthase (iNOS), and interferon gamma inducible protein (IP-10). Finally, PolyDex maintained its anti-inflammatory properties in vivo confirmed through punch biopsies with tissue imagery via hematoxylin/eosin and macrophage specific staining using CD11b. Thus, we demonstrated that PolyDex may be utilized as a localized, highly efficient drug-copolymer composite for active therapeutic delivery to confer anti-inflammatory protection or as a platform material for broad drug elution capabilities.