title: Development of Novel Chitosan Microcapsules for Pulmonary Delivery of Dapsone: Characterization, Aerosol Performance, and In Vivo Toxicity Evaluation.
abstract: Pneumocystis carinii pneumonia (PCP) is a major opportunistic infection that affects patients with human immunodeficiency virus. Although orally administered dapsone leads to high hepatic metabolism, decreasing the therapeutic index and causing severe side effects, this drug is an effective alternative for the treatment of PCP. In this context, microencapsulation for pulmonary administration can offer an alternative to increase the bioavailability of dapsone, reducing its adverse effects. The aim of this work was to develop novel dapsone-loaded chitosan microcapsules intended for deep-lung aerosolized drug delivery. The geometric particle size (D 4,3) was approximately 7 μm, the calculated aerodynamic diameter (d aero) was approximately 4.5 μm, and the mass median aerodynamic diameter from an Andersen cascade impactor was 4.7 μm. The in vitro dissolution profile showed an efficient dapsone encapsulation, demonstrating the sustained release of the drug. The in vitro deposition (measured by the Andersen cascade impactor) showed an adequate distribution and a high fine particles fraction (FPF = 50%). Scanning electron microscopy of the pulmonary tissues demonstrated an adequate deposition of these particles in the deepest part of the lung. An in vivo toxicity experiment showed the low toxicity of the drug-loaded microcapsules, indicating a protective effect of the microencapsulation process when the particles are microencapsulated. In conclusion, the pulmonary administration of the novel dapsone-loaded microcapsules could be a promising alternative for PCP treatment.
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga, 2752/Lab. 405, Porto Alegre, 90610-000, RS, Brazil.
authors: Manoel
authors: M
authors: Ortiz
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga, 2752/Lab. 405, Porto Alegre, 90610-000, RS, Brazil.
authors: Denise Soledade
authors: DS
authors: Jornada
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga, 2752/Lab. 405, Porto Alegre, 90610-000, RS, Brazil.|Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Porto Alegre, 91501-970, RS, Brazil.
authors: Adriana Raffin
authors: AR
authors: Pohlmann
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Avenida Ipiranga, 2752/Lab. 405, Porto Alegre, 90610-000, RS, Brazil. silvia.guterres@ufrgs.br.
authors: Sílvia Stanisçuaski
authors: SS
authors: Guterres
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D002214:Capsules; D048271:Chitosan / Q000737:chemistry* / Q000633:toxicity; D003622:Dapsone / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D008168:Lung / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011208:Powders; D017208:Rats, Wistar; D065589:Respiratory Tract Absorption; D012995:Solubility
chemical_list: D000336:Aerosols; D000900:Anti-Bacterial Agents; D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011208:Powders; D003622:Dapsone; D048271:Chitosan
keywords: dapsone; dry powders inhalers; in vivo toxicity; microparticles; pulmonary drug delivery
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