title: Enhanced properties of discrete pulmonary deoxyribonuclease I (DNaseI) loaded PLGA nanoparticles during encapsulation and activity determination.
abstract: In the present work, DNaseI loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for pulmonary delivery were prepared using emulsion solvent evaporation. The effects of the various formulation and experimental variables on the size and morphological characteristics of the particles as well as on the encapsulation efficiency were investigated. The stability of the encapsulated DNaseI was evaluated and the respirable fraction was determined. Cytotoxicity of the NPs was evaluated on lung epithelial cells. The results showed that by using leucine and dipalmito-phosphatidyl-choline (DPPC), discrete NPs with 76% retained biological activity were prepared. A high respirable fraction (particles below 6 μm) reaching 71.3% was achieved after nebulization of the NP suspension. The results revealed the suitability of the prepared particles for pulmonary delivery and highlighted the role of excipients in the stabilization of DNaseI against the stresses encountered during preparation.
authors.affiliation: School of Pharmacy, London University, 29-39 Brunswick Square, London WC1N1AX, UK. rihabosman@yahoo.com
authors.forename: Rihab
authors.initials: R
authors.lastname: Osman
authors.forename: Pei Lee
authors.initials: PL
authors.lastname: Kan
authors.forename: Gehanne
authors.initials: G
authors.lastname: Awad
authors.forename: Nahed
authors.initials: N
authors.lastname: Mortada
authors.forename: Abd-Elhameed
authors.initials: AE
authors.lastname: El-Shamy
authors.forename: Oya
authors.initials: O
authors.lastname: Alpar
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003850:Deoxyribonuclease I / Q000008:administration & dosage* / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D013499:Surface Properties
chemical_list: D000336:Aerosols; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003850:Deoxyribonuclease I