Enhancing pulmonary delivery and immunomodulation of respiratory diseases through virus-mimicking nanoparticles

Autor(es)

Martins, Yugo Araujo ; Guerra-Gomes, Isabel Cristina ; Rodrigues, Tamara Silva ; Tapparel, Caroline ; Lopez, Renata Fonseca Vianna

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CONTROLLED RELEASE; v. 372, p. 16-pg., 2024-06-25.

Resumo

This study introduces the nanobromhexine lipid particle (NBL) platform designed for effective pulmonary drug delivery. Inspired by respiratory virus transport mechanisms, NBL address challenges associated with mucus permeation and inflammation in pulmonary diseases. Composed of low molecular weight polyethylene glycolcoated lipid nanoparticles with bromhexine hydrochloride, NBL exhibit a size of 118 +/- 24 nm, a neutral zeta potential, osmolarity of 358 +/- 28 mOsmol/kg, and a pH of 6.5. Nebulizing without leakage and showing no toxicity to epithelial cells, NBL display mucoadhesive properties with a 60% mucin-binding efficiency. They effectively traverse the dense mucus layer of Calu-3 cultures in an air -liquid interface, as supported by a 55% decrease in MUC5AC density and a 29% increase in nanoparticles internalization compared to non -exposed cells. In assessing immunomodulatory effects, NBL treatment in SARS-CoV-2-infected lung cells leads to a 40 -fold increase in anti-inflammatory MUC1 gene expression, a proportional reduction in pro -inflammatory IL -6 expression, and elevated anti-inflammatory IL -10 expression. These findings suggest a potential mechanism to regulate the excessive IL -6 expression triggered by virus infection. Therefore, the NBL platform demonstrates promising potential for efficient pulmonary drug delivery and immunomodulation, offering a novel approach to addressing mucus permeation and inflammation in pulmonary diseases. (AU)

• Processo FAPESP: 22/03521-0 - Investigação de métodos físicos associados à sistemas de liberação de fármacos na resposta imune e antimicrobiana local
• Beneficiário: Renata Fonseca Vianna Lopez
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/22451-7 - Sistemas de liberação sustentada e direcionada de fármacos para o tecido epitelial
• Beneficiário: Renata Fonseca Vianna Lopez
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 20/07108-5 - Formulação nanotecnológica para a administração pulmonar de fármacos para o controle da SARS-CoV-2
• Beneficiário: Yugo Araújo Martins
• Modalidade de apoio: Bolsas no Brasil - Doutorado