PLGA nanoparticles through microfluidics based on 3D microchips to deliver doxycycline

• Grant number: 24/16768-0
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: December 12, 2024
• End date: April 11, 2025
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Laura de Oliveira Nascimento
• Grantee: Rafaela Nanini Figueiredo
• Supervisor: Jin Li
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Cardiff University, Wales
• Associated to the scholarship: 23/03298-2 - Study of pharmacotechnical parameters for nanostructuring of doxycycline encapsulated with PLGA and stabilized by surfactants, BP.IC

Abstract

Doxycycline (DX) is well recognized for its broad-spectrum antibiotic properties and anti-inflammatory effects, what makes it a relevant therapeutic agent for various lung diseases, including chronic obstructive pulmonary disease, asthma, and pneumonia. DX's bioavailability and safety profile justify its use in respiratory conditions, while its side effects are generally mild compared to more potent antibiotics. Coupling its therapeutic potential with nanoparticle delivery systems can enhance drug efficacy and precision in targeting lung tissues. The development of PLGA (poly(lactic-co-glycolic acid)) nanoparticles provides biodegradability and biocompatibility, making it an ideal candidate for pharmaceutical applications and approved by the FDA. Our group was able to encapsulate up to 60% of DX in PLGA nanostructures by the nanoprecipitation method, but with relevant burst effect, which indicates high drug absorption. An alternative to precipitation is to produce them by microfluidics, which allows precise control over nanoparticle size, morphology, and drug encapsulation efficiency. However, most common chips are from PDMS and do not work well with acetone, besides the need for plasma for sealing. Since glass microchips are very expensive and fragile, 3D-printed microchips are a lower cost alternative, reproducible and allows complex geometries, optimizing fluid dynamics for better performance in nanoparticle formation. This project aims to develop PLGA nanoparticles loaded with DX through microfluidics based on microchips fabricated by a 3D printer. The microchips will have differences in starting material or flow path design. Formulations will be characterized by its physicochemical properties and compared with the ones obtained by the traditional method. We expect to obtain a narrow size distribution, higher encapsulation rate and less burst effect since microfluidic systems provide a high surface-area-to-volume ratio, enhancing mass transfer.