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Intranasal administration of budesonide-loaded nanocapsule microagglomerates as an innovative strategy for asthma treatment

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Abstract

The co-existence with rhinitis limits the control of asthma. Compared with oral H1 receptor antagonists, intranasal corticosteroids have been demonstrated to provide greater relief of all symptoms of rhinitis and are recommended as first-line treatment for allergic rhinitis. Intrinsic limitations of nasal delivery, such as the presence of the protective mucous layer, the relentless mucociliary clearance, and the consequent reduced residence time of the formulation in the nasal cavity, limit budesonide efficacy to the treatment of local nasal symptoms. To overcome these limitations and to enable the treatment of asthma via nasal administration, we developed a budesonide-loaded lipid-core nanocapsule (BudNC) microagglomerate powder by spray-drying using a one-step innovative approach. BudNC was obtained, as a white powder, using L-leucine as adjuvant with 75 ± 6% yield. The powder showed a bimodal size distribution curve by laser diffraction with a principal peak just above 3 μm and a second one around 0.45 μm and a drug content determined by HPLC of 8.7 mg of budesonide per gram. In vivo after nasal administration, BudNC showed an improved efficacy in terms of reduction of immune cell influx; production of eotaxin-1, the main inflammatory chemokine; and arrest of airways remodeling when compared with a commercial budesonide product in both short- and long-term asthma models. In addition, data showed that the results in the long-term asthma model were more compelling than the results obtained in the short-term model.

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Funding

This study is part of the National Institute of Science and Technology in Pharmaceutical Nanotechnology: a transdisciplinary approach (INCT-NANOFARMA), which is supported by São Paulo Research Foundation (FAPESP, Brazil) Grant no.2014/50928-2, and by the Brazilian National Council for Scientific and Technological Development (CNPq, Brazil) Grant no. 465687/2014-8. The project is also supported by the Research Support Foundation of the State of Rio Grande do Sul (PRONEX FAPERGS/CNPq 12/2014 #16/2551-0000467-6) and Research Support Foundation of the State of Rio de Janeiro (Grant no. E-26/010.000983/2019)(NanoHEALTH). Professors Guterres, S.S., Pohlmann AR, and Martins MA are recipient of Productivity Grants in CNPq.

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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, Av. Ipiranga 2752, Porto Alegre, 90610-000, Brazil

    Manoel Ortiz, Taís Lusa Durli, Adriana Raffin Pohlmann & Sílvia Stanisçuaski Guterres

  2. Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Av. Brasil, 4365, Rio de Janeiro, 21040-360, Brazil

    Diego de Sa Coutinho, Bianca Torres Ciambarella, Everton Tenorio de Souza, Ana Paula Leite D’Almeida, Patrícia Machado Rodrigues e Silva, Andressa Bernardi & Marco Aurelio Martins

  3. Dipartimento di Scienze degli Alimenti e del Farmaco, Università degli studi di Parma, Parco Area delle Scienze, 27/A, 43124, Parma, Italy

    Fabio Sonvico

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

    Adriana Raffin Pohlmann

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  1. Manoel Ortiz
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  11. Marco Aurelio Martins
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Correspondence to Marco Aurelio Martins or Sílvia Stanisçuaski Guterres.

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Conflict of interest

Diego de Sa Coutinho, Bianca Torres Ciambarella, Everton Tenorio de Souza, Ana Paula Leite D’Almeida, Taís Lusa Durli, Patrícia Machado Rodrigues e Silva, Andressa Bernardi, Fabio Sonvico, and Marco Aurelio Martins declare that they have no conflict of interest. Manoel Ortiz, Adriana Raffin Pohlmann, and Silvia Stanisçuaski Guterres have the potential conflict of interest because of a patent application related to the topic of the study (INPI BR 102013019136-1 A2; 2013).

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Ortiz, M., de Sa Coutinho, D., Ciambarella, B.T. et al. Intranasal administration of budesonide-loaded nanocapsule microagglomerates as an innovative strategy for asthma treatment. Drug Deliv. and Transl. Res. 10, 1700–1715 (2020). https://doi.org/10.1007/s13346-020-00813-5

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