title: Multimonth controlled small molecule release from biodegradable thin films.
abstract: Long-term, localized delivery of small molecules from a biodegradable thin film is challenging owing to their low molecular weight and poor charge density. Accomplishing highly extended controlled release can facilitate high therapeutic levels in specific regions of the body while significantly reducing the toxicity to vital organs typically caused by systemic administration and decreasing the need for medical intervention because of its long-lasting release. Also important is the ability to achieve high drug loadings in thin film coatings to allow incorporation of significant drug amounts on implant surfaces. Here we report a sustained release formulation for small molecules based on a soluble charged polymer-drug conjugate that is immobilized into nanoscale, conformal, layer-by-layer assembled films applicable to a variety of substrate surfaces. We measured a highly predictable sustained drug release from a polymer thin film coating of 0.5-2.7 μm that continued for more than 14 mo with physiologically relevant drug concentrations, providing an important drug delivery advance. We demonstrated this effect with a potent small molecule nonsteroidal anti-inflammatory drug, diclofenac, because this drug can be used to address chronic pain, osteoarthritis, and a range of other critical medical issues.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139;Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;Institute for Soldier Nanotechnologies, Cambridge, MA 02139; and.
authors.forename: Bryan B
authors.initials: BB
authors.lastname: Hsu
authors.affiliation: Department of Chemistry, Sahmyook University, Seoul 139-742, Korea; and.
authors.forename: Myoung-Hwan
authors.initials: MH
authors.lastname: Park
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Hagerman
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139;Institute for Soldier Nanotechnologies, Cambridge, MA 02139; andDepartment of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139 hammond@mit.edu.
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D001672:Biocompatible Materials; D004008:Diclofenac / Q000008:administration & dosage; D016503:Drug Delivery Systems; D011108:Polymers / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001672:Biocompatible Materials; D011108:Polymers; D004008:Diclofenac
keywords: NSAID; polyelectrolyte multilayers; polymer prodrug
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