title: Role of a novel multifunctional excipient poly(ethylene glycol)-block-oligo(vinyl sulfadimethoxine) in controlled release of lysozyme from PLGA microspheres.
abstract: This study investigated the effect of ion-pairing of anionic polyelectrolytes: our novel poly(ethylene glycol)-block-oligo(vinyl sulfadimethoxine) (PEG-OVSDM) and poly(ethylene glycol)-block-poly(l-aspartic acid) (PEG-PAA) with cationic lysozyme on retention of protein stability during emulsification. Soluble lysozyme recovery after exposure to the deleterious interface was 42-88% (when ion-paired with PEG-OVSDM, PEG-OVSDM concentration dependent) compared to only 30% for free lysozyme. PEG-OVSDM provided a higher stabilization of lysozyme than PEG-PAA (36-60%). Lysozyme when recovered in the aqueous phase and analyzed by chromatography, enzymatic assay, fluorescence, and mass spectrometry showed no significant physicochemical change when compared with a lysozyme standard. Lysozyme was incorporated into poly(lactide-co-glycolide) (PLGA) microspheres via the typical double emulsion method. Incorporation of lysozyme complexes led to a higher encapsulation efficiency and loading amount, and a lower incidence of insoluble lysozyme aggregates compared to the control microspheres containing lysozyme only. More significantly, ion-pairing was able to dramatically reduce the initial lysozyme release to 18% compared with 50% from control microspheres and provided an overall better control of protein release. PEG-PAA was less effective than PEG-OVSDM in controlling the release probably due to weaker interactions between this polyelectrolyte and lysozyme. Manipulation of such polyelectrolyte-protein complexation may play a role in protein-controlled delivery.
authors.affiliation: Department of Pharmaceutics & Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84108, USA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Taluja
authors.forename: You Han
authors.initials: YH
authors.lastname: Bae
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D004355:Drug Stability; D004655:Emulsions; D005079:Excipients; D019344:Lactic Acid; D008752:Methylene Chloride; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009113:Muramidase / Q000008:administration & dosage* / Q000737:chemistry; D053758:Nanoparticles; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011485:Protein Binding; D013412:Sulfadimethoxine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013501:Surface-Active Agents
chemical_list: D000900:Anti-Bacterial Agents; D004655:Emulsions; D005079:Excipients; D013501:Surface-Active Agents; C531533:poly(ethylene glycol)-block-oligo(vinyl sulfadimethoxine); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D013412:Sulfadimethoxine; D019344:Lactic Acid; D011092:Polyethylene Glycols; D008752:Methylene Chloride; D009113:Muramidase