Microfluidic platform for synthesis and optimization of nanoparticles targeting the blood-brain barrier

• Grant number: 25/20627-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: May 01, 2026
• End date: April 30, 2027
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Priscyla Daniely Marcato Gaspari
• Grantee: Franciely Rufino de Almeida Lima
• Supervisor: Helder Almeida Santos
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University Of Groningen,
• Associated to the scholarship: 24/22809-0 - Development, characterization and antitumor evaluation of lactoferrin-functionalized lipid nanoparticles for glioblastoma: Integration of natural products and antitumor agents, BP.DD

Abstract

Nanostructured Lipid Carriers (NLCs) are advanced lipid-based systems capable of co-encapsulating hydrophobic drugs such as cabazitaxel and curcumin, promoting increased stability, bioavailability, and therapeutic efficacy. The treatment of glioblastoma, a highly aggressive brain tumor, is limited by the blood-brain barrier (BBB), which prevents most chemotherapeutic agents from reaching the brain tissue at therapeutic concentrations. Therefore, the development of NLCs capable of crossing the BBB is crucial to enhance treatment efficacy and reduce undesired systemic effects. Conventional methods for NLC production often present low reproducibility and require additional steps for homogenization and size control, limiting their clinical applicability. Microfluidics emerges as an innovative alternative, enabling the continuous production of NLCs with controlled size, polydispersity, and morphology, with potential for targeted drug delivery to the brain. In this context, the aim of this project is to develop and characterize lactoferrin-functionalized NLCs for the co-encapsulation of cabazitaxel and curcumin, and to evaluate their permeability across the blood-brain barrier using in vitro microfluidic models. NLCs will be produced in glass microfluidic devices with co-flow geometry, adjusting critical parameters such as the aqueous-to-organic flow ratio, total flow rate, and lipid concentration. The particles will be characterized in terms of diameter, polydispersity, and zeta potential, and their internal structure will be analyzed by Cryo-TEM and Small-Angle X-ray Scattering (SAXS). Permeability will be assessed using microfluidic in vitro models of the BBB. It is expected to obtain stable, monodisperse, and functionalized NLCs with enhanced ability to transport cabazitaxel and curcumin across the blood-brain barrier. The results should demonstrate the feasibility of microfluidics as a continuous method for the production of functional NLCs and provide robust data on their physicochemical characteristics and BBB permeability efficiency. This project will contribute to the development of advanced microfluidic platforms for targeted drug delivery to the brain, directly supporting therapeutic strategies against glioblastoma. (AU)