title: Injectable controlled release depots for large molecules.
abstract: Biodegradable, injectable depot formulations for long-term controlled drug release have improved therapy for a number of drug molecules and led to over a dozen highly successful pharmaceutical products. Until now, success has been limited to several small molecules and peptides, although remarkable improvements have been accomplished in some of these cases. For example, twice-a-year depot injections with leuprolide are available compared to the once-a-day injection of the solution dosage form. Injectable depots are typically prepared by encapsulation of the drug in poly(lactic-co-glycolic acid) (PLGA), a polymer that is used in children every day as a resorbable suture material, and therefore, highly biocompatible. PLGAs remain today as one of the few "real world" biodegradable synthetic biomaterials used in US FDA-approved parenteral long-acting-release (LAR) products. Despite their success, there remain critical barriers to the more widespread use of PLGA LARproducts, particularly for delivery of more peptides and other large molecular drugs, namely proteins. In this review, we describe key concepts in the development of injectable PLGA controlled-release depots for peptides and proteins, and then use this information to identify key issues impeding greater widespread use of PLGA depots for this class of drugs. Finally, we examine important approaches, particularly those developed in our research laboratory, toward overcoming these barriers to advance commercial LAR development.
authors.affiliation: Department of Pharmaceutical Sciences, The Biointerfaces Institute, North Campus Research Complex, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI 48109, USA; Department of Biomedical Engineering, The Biointerfaces Institute, North Campus Research Complex, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Schwendeman
authors.affiliation: Department of Pharmaceutical Sciences, The Biointerfaces Institute, North Campus Research Complex, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
authors.forename: Ronak B
authors.initials: RB
authors.lastname: Shah
authors.affiliation: Department of Pharmaceutical Sciences, The Biointerfaces Institute, North Campus Research Complex, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
authors.forename: Brittany A
authors.initials: BA
authors.lastname: Bailey
authors.affiliation: Department of Medicinal Chemistry, The Biointerfaces Institute, North Campus Research Complex, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Schwendeman
mesh_terms: D001672:Biocompatible Materials / Q000008:administration & dosage; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004337:Drug Carriers; D004339:Drug Compounding; D006801:Humans; D007267:Injections; D019344:Lactic Acid; D046911:Macromolecular Substances / Q000008:administration & dosage*; D010599:Pharmacokinetics; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D046911:Macromolecular Substances; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Biodegradable; Controlled release; Depot; PLGA; Peptide; Protein