Surface functionalization of nanoparticles to control cell interactions and drug release

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Poly(dl-lactide-co-glycolide) (PLGA) nanoparticles are widely used for delivering bioactive molecules due to their biocompatibility and biodegradability.
• Controlling nanoparticle surface properties is crucial for optimizing drug release kinetics, cellular interactions, and in vivo performance.

Purpose of the Study:

• To investigate the surface modification of PLGA nanoparticles using layer-by-layer (LbL) deposition of polyelectrolytes.
• To evaluate the impact of these LbL coatings on nanoparticle release behavior, cytotoxicity, hemolytic activity, and cellular uptake efficiency.

Main Methods:

• PLGA nanoparticles were modified using LbL adsorption of two polyelectrolyte pairs: poly(allylamine hydrochloride)/poly(styrene sulfonate) (PAH/PSS) and poly(L-lysine hydrobromide)/dextran sulfate (PLL/DES).
• The study assessed release profiles, cytotoxicity (MTT assay), hemolytic activity (hemolysis assay), and cellular uptake (flow cytometry) of bare and modified nanoparticles.
• Parameters such as layer number, material composition, and crosslinking were varied to tune nanoparticle properties.

Main Results:

• Both PAH/PSS and PLL/DES coatings effectively suppressed the burst release characteristic of unmodified PLGA nanoparticles.
• Release behavior was tunable by altering layer number, materials, or crosslinking.
• No cytotoxicity was observed for bare or modified nanoparticles.
• Nanoparticles with a positively charged outermost layer (PAH or PLL) induced hemolysis, while negatively charged or bare nanoparticles did not.
• Positively charged nanoparticles exhibited higher cellular uptake by L929 fibroblast cells due to increased cell-particle affinity.

Conclusions:

• LbL coating provides a versatile strategy to control the surface properties of PLGA nanoparticles.
• Surface charge and composition of LbL-coated nanoparticles significantly influence release kinetics, hemolytic activity, and cellular uptake.
• This approach offers a promising avenue for enhancing the efficacy of nanoparticulate drug-delivery systems by tailoring nanoparticle-biomolecule interactions.