title: Redispersible liposomal-N-acetylcysteine powder for pulmonary administration: development, in vitro characterization and antioxidant activity.
abstract: Liposomal dry powders of N-acetylcysteine (SD-NAC-Lip) were developed for pulmonary administration. Liposomes were prepared by reverse phase evaporation and spray dried using lactose (10%, w/w) as drying adjuvant. The powders were characterized according to process yield, drug content, residual water content, particle size distribution, morphology and redispersion behavior. In vitro aerosol performance was evaluated using an eight-stage Andersen Cascade Impactor. Moreover, in vitro antioxidant activity was determined by measuring thiobarbituric acid reactive species (TBARS) present in the lungs of healthy Wistar rats after induction of oxidation by iron/EDTA. The spray-drying process had a high yield (71%±2), drug content (mg/g) according to the expected value, moisture content below 9%, geometric mean diameter under 3μm with span value lower than 1. Spherical particles were observed by scanning electron microscopy. Liposomal dry-powders were able to recover the nanometric size of the original dispersion after their redispersion in aqueous medium, as shown by laser diffraction and transmission electron microscopy. Furthermore, the powders presented aerodynamic diameter of about 7μm and respirable fraction above 30%, indicating suitable properties for pulmonary use. The encapsulation of N-acetylcysteine in liposomes was essential to maintain its in vitro antioxidant activity after the drying process. In addition, the powder containing the encapsulated drug had better in vitro antioxidant activity than the liquid and solid formulations containing the non-encapsulated drug, which makes it a good candidate for the treatment of pulmonary diseases associated with oxidative stress.
authors.affiliation: Programa de Pós-Graduação em Nanotecnologia Farmacêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Aline Ferreira
authors.initials: AF
authors.lastname: Ourique
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Paula Dos Santos
authors.initials: Pdos S
authors.lastname: Chaves
authors.affiliation: Programa de Pós-Graduação em Nanotecnologia Farmacêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Gabriele Dadalt
authors.initials: GD
authors.lastname: Souto
authors.affiliation: Programa de Pós-Graduação em Nanotecnologia Farmacêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Adriana Raffin
authors.initials: AR
authors.lastname: Pohlmann
authors.affiliation: Programa de Pós-Graduação em Nanotecnologia Farmacêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Silvia Stanisçuaski
authors.initials: SS
authors.lastname: Guterres
authors.affiliation: Programa de Pós-Graduação em Nanotecnologia Farmacêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. Electronic address: ruy.beck@ufrgs.br.
authors.forename: Ruy Carlos Ruver
authors.initials: RC
authors.lastname: Beck
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000280:Administration, Inhalation; D000336:Aerosols / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000379:methods; D058995:Dry Powder Inhalers / Q000379:methods; D008081:Liposomes / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D011208:Powders / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000336:Aerosols; D000975:Antioxidants; D008081:Liposomes; D011208:Powders; D000111:Acetylcysteine
keywords: Antioxidant; Dry powder inhaler; Liposomes; N-acetylcysteine; Pulmonary