title: Encapsulation of PROLI/NO in biodegradable microparticles.
abstract: Biodegradable hydrophilic polymers poly-lactic-co-glycolic acid (PLGA) and polyethylene oxide-co-lactic acid (PELA) were used to encapsulate a small hydrophilic prodrug (PROLI/NO) as a strategy to deliver nitric oxide (NO) by inhalation. The microparticles were prepared using double emulsion and solvent evaporation, followed by freeze-drying. The NO release kinetics were characterized by three parameters: the maximum concentration of NO per unit weight of microparticles, C(max) (nM mg(-1)); the window of time for which the concentration exceeded 50% of C(max), W(50) (min); and the initial rate of release, R(i) (nM mg(-1) min(-1)). PLGA-based microparticles did not encapsulate PROLI/NO. PELA-based microparticles demonstrated an entrapment efficiency rate of 43%, a mass median diameter of 2.3 micro m, and NO release in a physiological buffer characterized by C(max) = 123, W(50) = 4.11, and R(i) = 78.7. Addition of gelatin as a hydrophilic binding moiety in the first emulsion allowed PLGA-based microparticles to encapsulate PROLI/NO; however, the mass median diameter was too large for inhalation (23.5 micro m). It is concluded that the hydrophilic polyethylene glycol-moiety in PELA allows for efficient encapsulation of PROLI/NO, and PELA-based microparticles might be a strategy to generate a stable inhalable form of NO.
authors.affiliation: Department of Chemical Engineering and Materials Science, University of California, Irvine, CA 92697-2575, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Jeh
authors.forename: S
authors.initials: S
authors.lastname: Lu
authors.forename: S C
authors.initials: SC
authors.lastname: George
mesh_terms: D001672:Biocompatible Materials; D004337:Drug Carriers; D004339:Drug Compounding / Q000379:methods; D005780:Gelatin / Q000737:chemistry; D006016:Glycolates / Q000737:chemistry; D006801:Humans; D007773:Lactates / Q000737:chemistry; D019344:Lactic Acid; D008863:Microspheres; D009569:Nitric Oxide / Q000008:administration & dosage*; D009589:Nitrogen Oxides; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D011355:Prodrugs / Q000008:administration & dosage*; D011392:Proline / Q000008:administration & dosage* / Q000031:analogs & derivatives*
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D006016:Glycolates; D007773:Lactates; D009589:Nitrogen Oxides; D011108:Polymers; D011355:Prodrugs; C102043:proline-nitric oxide; C058523:polyethylene oxide-polylactic acid block copolymer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D009569:Nitric Oxide; D019344:Lactic Acid; D011092:Polyethylene Glycols; D005780:Gelatin; D011392:Proline