title: Protein bioactivity and polymer orientation is affected by stabilizer incorporation for double-walled microspheres.
abstract: Double-walled microspheres present an improved drug delivery technique for sustained release of encapsulated substrates. In this study, the release kinetics and biological activity of lysozyme was analyzed from microspheres comprised of poly(lactic-co-glycolic acid) (PLGA) and poly(L-lactide) (PLLA). In addition, coencapsulation of the anionic surfactant, docusate sodium salt (AOT), was investigated as a method of decreasing protein denaturation during microsphere fabrication. Herein, we show that through the inclusion of AOT, the capacity for two chemically similar polymers to phase separate and form double-walled (DW) microspheres is impaired leading to unique protein release kinetics. Additionally, we present the time period over which our released enzyme, lysozyme, remains biologically active. The consequences of AOT on protein bioactivity are also assessed and provide strong implications for the importance of appropriate stabilizer analysis in future studies involving drug co-encapsulates in polymer based microsphere systems.
authors.affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Kokai
authors.forename: Huaping
authors.initials: H
authors.lastname: Tan
authors.forename: Siddharth
authors.initials: S
authors.lastname: Jhunjhunwala
authors.forename: Steven R
authors.initials: SR
authors.lastname: Little
authors.forename: Jason W
authors.initials: JW
authors.lastname: Frank
authors.forename: Kacey G
authors.initials: KG
authors.lastname: Marra
mesh_terms: D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004143:Dioctyl Sulfosuccinic Acid / Q000737:chemistry*; D004337:Drug Carriers; D004339:Drug Compounding; D004795:Enzyme Stability; D005079:Excipients / Q000737:chemistry*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000737:chemistry; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D008863:Microspheres; D008968:Molecular Conformation; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011489:Protein Denaturation; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D011091:Polyesters; C039217:fluorescein isothiocyanate bovine serum albumin; D004143:Dioctyl Sulfosuccinic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid; C033616:poly(lactide); D009113:Muramidase; D016650:Fluorescein-5-isothiocyanate