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Development of Novel Chitosan Microcapsules for Pulmonary Delivery of Dapsone: Characterization, Aerosol Performance, and In Vivo Toxicity Evaluation

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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.

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ACKNOWLEDGMENTS

The authors wish to thank CAPES, Rede Nanotecnologia Farmacêutica CAPES, CNPq/Brasilia/Brazil, INCT-IF CNPq/MCT, Pronem and Pronex FAPERGS-CNPq, and FAPERGS.

Conflict of Interest

The authors report no conflicts of interest.

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Authors and Affiliations

  1. 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

    Manoel Ortiz, Denise Soledade Jornada, Adriana Raffin Pohlmann & Sílvia Stanisçuaski Guterres

  2. Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves, 9500, Porto Alegre, 91501-970, RS, Brazil

    Adriana Raffin Pohlmann

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  1. Manoel Ortiz
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  2. Denise Soledade Jornada
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  4. Sílvia Stanisçuaski Guterres
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Correspondence to Sílvia Stanisçuaski Guterres.

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Ortiz, M., Jornada, D.S., Pohlmann, A.R. et al. Development of Novel Chitosan Microcapsules for Pulmonary Delivery of Dapsone: Characterization, Aerosol Performance, and In Vivo Toxicity Evaluation. AAPS PharmSciTech 16, 1033–1040 (2015). https://doi.org/10.1208/s12249-015-0283-3

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