title: 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.
authors.affiliation: Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Edward Kai-Hua
authors.initials: EK
authors.lastname: Chow
authors.forename: Erik
authors.initials: E
authors.lastname: Pierstorff
authors.forename: Genhong
authors.initials: G
authors.lastname: Cheng
authors.forename: Dean
authors.initials: D
authors.lastname: Ho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000737:chemistry; D002460:Cell Line; D003907:Dexamethasone / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D011108:Polymers; D003907:Dexamethasone