Interaction of PLGA-based nanoparticles with model lipid membranes

This study centers on the characterization and membrane interaction analysis of PLGA-based nanoparticles (NPs) synthesized by a collaborative group at Fiocruz (Recife). PLGA is a widely used polymer in biomedical applications due to its biocompatibility and ability to encapsulate diverse drugs, both hydrophilic and hydrophobic. The coatings of Pluronic® and chitosan were used to enhance the hydrophilicity of the NPs, allowing for better interaction with biological membranes and potentially improving the pharmacokinetic profile of the encapsulated drugs. Moreover, these coatings play a crucial role in modulating the surface charge, which directly impacts cellular uptake and endocytosis processes.

We employed a multi-technique approach for the primary characterization of these NPs, using Dynamic Light Scattering (DLS) and Zeta Potential techniques to assess their size, polydispersity index, and surface charge density. Additionally, we explored the interaction of these NPs with model lipid membranes of varying sizes—specifically giant and large unilamellar vesicles (GUVs and LUVs)—by combining DLS, Zeta Potential measurements post-interaction, Isothermal Titration Calorimetry (ITC), and phase-contrast microscopy. These techniques provided insights into how the surface properties of NPs, influenced by the choice of coating and presence of TCZ, affect their interaction with lipid membranes—a critical factor in determining the efficiency of drug delivery systems.

The results offer the first insights into the mechanisms of NP interaction with membranes and the optimization of experimental setups. We observed that the surface coatings of the NPs significantly influence their interactions, particularly due to surface charge. Microscopy of interactions with giant unilamellar vesicles (GUVs) revealed alterations in the bilayer structure, indicating potential changes in membrane dynamics. 

By characterizing these NPs and understanding their interactions with lipid membranes, this research aims to optimize nanoparticle formulations for more effective drug delivery. The study's findings could contribute to the development of more targeted and controlled release systems, especially for therapies that require precise modulation of inflammatory responses, such as in the treatment of respiratory conditions exacerbated by cytokine storms, like COVID-19.