Pharmaceutical development of powdered polymeric nanostructures to deliver doxycycline to the lungs

• Grant number: 23/10824-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: January 17, 2024
• End date: January 16, 2025
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Laura de Oliveira Nascimento
• Grantee: Victória Soares Soeiro
• Supervisor: Hugh David Charles Smyth
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: University of Texas at Austin (UT), United States
• Associated to the scholarship: 21/12561-3 - Mucus-penetrative nanoparticles with doxycycline: physicalchemical, biopharmaceutical, immunomodulatory and microbiological in vitro evaluation for pulmonary delivery, BP.DR

Abstract

Antibiotics constitute the main treatment component for lung infections, wich includes Doxycycline (DX). This antimicrobial drug acts against gram-positive and gram-negative microorganisms, besides aiding in inflammation control. Pulmonary delivery may enhance local targeting and decrease systemic effects, but drugs cannot permeate quickly. To address drug distribution and retention, PLGA nanosystems comes as a FDA approved and biodegradable option. However, powder offers better stability, compactibility and evasion of the cold chain, which requires drying process development. Therefore, this project aims to obtain powdered PLGA nanoparticles loaded with doxycycline (DX-PLGA) and characterize liquid and dry formulations acording to the quality attributes for pulmonary drug delivery and antimicrobial effectiveness in vitro. For that, DX-PLGA nanoparticles will be obtained by nanoprecipitation method and further analyzed concerning particle size (DLS), zeta potential and DX quantification and encapsulation efficiency (HPLC). The liquid dispersions will be submitted to spray-drying (SD) and spray freeze-drying (SFD), followed by evaluation of aerosol performance, drug release and physical properties (size, cristanility, surface area, density). The most promissing formulations will be evaluated against biofilm formation of Maltophilia species and stability assessment. The developments of this project will bring process insyghts for better nanoparticle drying related to pulmonary delivery and antibiotic in vitro performance, besides an important evolution of the current PhD on going project.