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

Author(s)

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

• Document type: Journal article
• Source: JOURNAL OF CONTROLLED RELEASE; v. 372, p. 16-pg., 2024-06-25.

Abstract

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)

• FAPESP's process: 22/03521-0 - Investigation of physical methods associated with drug delivery systems in the local immune and antimicrobial response
• Grantee: Renata Fonseca Vianna Lopez
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/22451-7 - Sustained drug delivery systems targeting the epithelial tissue
• Grantee: Renata Fonseca Vianna Lopez
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/07108-5 - Nanotechnological formulation for pulmonary administration of drugs for the control of SARS-CoV-2
• Grantee: Yugo Araújo Martins
• Support Opportunities: Scholarships in Brazil - Doctorate