Development of method for obtaining solid lipid nanoparticles: Comparative study of top-down and self-assembled processes

• Grant number: 25/21966-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2025
• End date: October 31, 2026
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Maria Vitória Lopes Badra Bentley
• Grantee: Maria Fernanda dos Santos Ambrósio
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 25/13788-2 - Lipid nanoparticles: development of processes for obtaining and therapeutically applying multifunctional systems., AP.R

Abstract

Solid lipid nanoparticles (SLNs) are promising colloidal systems for controlled drug delivery, offering advantages in terms of safety, efficacy, and stability of active ingredients. However, their physicochemical characteristics can be directly influenced by their production method, impacting parameters such as stability, safety, and bioavailability. This project aims to compare top-down and self-assembled production methods, evaluating the stability of the SLNs obtained by each approach. The top-down production methods used will be sonication and high-pressure homogenization. Although both involve heating the aqueous phase above the melting point of the solid lipid, they differ in the size reduction mechanism. In sonication, the collapse between them will generate nanosized particles; in high-pressure, the intense shear, impact, and cavitation forces will reduce the particles to nanosized sizes. The self-assembled approach will employ microfluidics, where the lipid phase and the aqueous phase will be introduced into microfluidic channels with flow control and a concentration gradient, which will promote the controlled self-organization of the lipids, forming the NLS. Comparing these approaches will allow us to evaluate the impact of the production method on the physicochemical stability of the NLS. This work plan will not involve pharmaceuticals because the objective is to standardize production parameters in both methods, understand them, and subsequently apply this knowledge to more assertive proposals for the encapsulation of therapeutic molecules. This is necessary to provide a more solid learning experience for the student and also to acquire knowledge of the microfluidic process, which is still new to the research group. The data obtained in this study will contribute to the proposal of a more appropriate method, considering the criteria of colloidal properties, stability, production viability, and biological performance of the obtained NLS.General ObjectivesInvestigate and compare the different top-down and self-assembled methods for obtaining NLS, analyzing their impact on the colloidal properties, stability, and production viability of the obtained NLS.Specific Objectives* Obtain NLS using the top-down and bottom-up methods. This stage will evaluate different preparation conditions: lipid composition, processing time (sonication and high-pressure homogenization), process temperature, lipid concentration, organic to aqueous phase ratio, flow rate in the microfluidics process, among others.* Characterize the colloidal properties of NLS (size, PdI, zeta potential, nanoparticle concentration).* Evaluate the stability of NLS (colloidal properties) produced by both methods.Brief description of the impact on the fellow's trainingParticipation in the project will provide the fellow with solid scientific training through the development of skills in laboratory techniques for the preparation, characterization, and stability assessment of NLS. The proposed work involves current methods and is one of the main aspects of nanoparticle synthesis, microfluidics, as it offers advantages such as scalability, precision, and reproducibility in obtaining different types of nanosystems. Furthermore, NPLs are the main systems used for drug and gene delivery, as seen in the NPLs for mRNA delivery used in the control of COVID-19 (Moderna and Pfizer vaccines). The fellow will also have the opportunity to deepen the theoretical principles of nanotechnology applied to the pharmaceutical field, with direct contact with the team at Professor M. Vitória Bentley's laboratory and with current pharmacotechnical methods, in addition to enhancing their critical analysis skills in the interpretation of scientific data and problem-solving.