title: Investigation of Fragment Antibody Stability and Its Release Mechanism from Poly(Lactide-co-Glycolide)-Triacetin Depots for Sustained-Release Applications.
abstract: Achieving long-term drug release from polymer-based delivery systems continues to be a challenge particularly for the delivery of large hydrophilic molecules such as therapeutic antibodies and proteins. Here, we report on the utility of an in situ-forming and injectable polymer-solvent system for the long-term release of a model antibody fragment (Fab1). The delivery system was prepared by dispersing a spray-dried powder of Fab1 within poly(lactide-co-glycolide) (PLGA)-triacetin solution. The formulation viscosity was within the range 1.0 ± 0.3 Pa s but it was injectable through a 27G needle. The release profile of Fab1, measured in phosphate-buffered saline (PBS), showed a lag phase followed by sustained-release phase for close to 80 days. Antibody degradation during its residence within the depot was comparable to its degradation upon long-term incubation in PBS. On the basis of temporal changes in surface morphology, stiffness, and depot mass, a mechanism to account for the drug release profile has been proposed. The unprecedented release profile and retention of greater than 80% of antigen-binding capacity even after several weeks demonstrates that PLGA-triacetin solution could be a promising system for the long-term delivery of biologics.
authors.affiliation: Drug Delivery Department, Genentech Inc., South San Francisco, California, 94080.
authors.forename: Debby P
authors.initials: DP
authors.lastname: Chang
authors.affiliation: Drug Delivery Department, Genentech Inc., South San Francisco, California, 94080.
authors.forename: Vivek Kumar
authors.initials: VK
authors.lastname: Garripelli
authors.affiliation: Protein Analytical Chemistry Department, Genentech Inc., South San Francisco, California, 94080.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rea
authors.affiliation: Drug Delivery Department, Genentech Inc., South San Francisco, California, 94080.
authors.forename: Robert
authors.initials: R
authors.lastname: Kelley
authors.affiliation: Drug Delivery Department, Genentech Inc., South San Francisco, California, 94080.
authors.forename: Karthikan
authors.initials: K
authors.lastname: Rajagopal
mesh_terms: D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D003890:Desiccation; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000737:chemistry; D007128:Immunoglobulin Fragments / Q000008:administration & dosage / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties; D014215:Triacetin / Q000008:administration & dosage / Q000737:chemistry*; D014783:Viscosity; D014867:Water / Q000032:analysis
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D014215:Triacetin
keywords: PLGA; controlled release; injectables; protein delivery; spray drying; stability