Enhanced properties of discrete pulmonary deoxyribonuclease I (DNaseI) loaded PLGA nanoparticles during encapsulation and activity determination

• Published in: International journal of pharmaceutics 2011-04, Vol.408 (1-2), p.257-265
• Main Authors: Osman, Rihab, Kan, Pei Lee, Awad, Gehanne, Mortada, Nahed, EL-Shamy, Abd-Elhameed, Alpar, Oya
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Aerosols; atomization; Biological and medical sciences; Cell Line, Tumor; Cell Survival - drug effects; cytotoxicity; deoxyribonuclease I; Deoxyribonuclease I - administration & dosage; Deoxyribonuclease I - metabolism; DNaseI; DPPC; Drug Carriers - chemistry; Drug Compounding - methods; Drug Stability; Emulsion-solvent evaporation; emulsions; encapsulation; epithelial cells; Epithelial Cells - cytology; Epithelial Cells - drug effects; evaporation; General pharmacology; Humans; Lactic Acid - chemistry; Leucine; Lung - cytology; Lung - metabolism; Medical sciences; Microscopy, Electron, Transmission; Nanoparticles; Nanoparticles - chemistry; Nebulizers and Vaporizers; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Polyglycolic Acid - chemistry; Pulmonary; Radial enzyme diffusion; Solubility; solvents; Surface Properties
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2011.02.013

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 6μm) 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.