Poster J17 - Synthesis of polymeric nanoparticles of tunable physicochemical properties for drug delivery application

Saturday, October 26, 2024

10:00 AM – 11:00 AM EST

Location: Exhibit Hall E, F & G

Presenting Author(s)

Isabel Mittal

Undergraduate researcher
University of Virginia
South Riding, Virginia, United States

Co-Author(s)

Paul Sagoe

PhD Candidate
Syracuse University
Syracuse, New York, United States

Last Author(s)

EJ

Era Jain, PhD (she/her/hers)

Assistant Professor
Syracuse University
Syracuse , New York, United States

Introduction: Polymeric nanoparticles (NPs) have emerged as a versatile tool in various biomedical applications, including drug delivery, imaging, and diagnostics. While several polymers exist to be used for nanoparticles synthesis, poly(lactide-co-glycolide) (PLGA) due to its biodegradability, biocompatibility, and FDA approval stand out as a preferred material for producing nanoparticles for drug delivery applications. However, PLGA often suffers from short circulation time in the bloodstream as it is easily identified by plasmatic opsonin and cleared by mononuclear phagocytic system (MPS) cells. These limitations, however, can be addressed by PEGylation, upon coating the surface of PLGA nanoparticles with polyethylene glycol (PEG), a polymer notable for its hydrophilicity and inert surface charge. These unique properties of PEG offer several benefits including prolonging circulation time, reducing particle aggregation, and minimizing protein corona formation. Thus, nanoparticles of PEG-PLGA copolymer remains desirable for the synthesis of particulate systems for the encapsulation and release of drugs and other biomolecules including proteins, nucleic acids, etc. for cellular interaction and targeted delivery application.

Moreover, aside the material composition, the efficacy of nanoparticles in these applications is heavily influenced by their physicochemical characteristics among being particle size, surface charge, and shape, thus designing PEG-PLGA nanoparticles with tailored properties to match specific application requirements remains a promising strategy for drug delivery purposes.

Herein, by optimizing several fabrication parameters such as polymer (PEG-PLGA) concentration, surfactant concentration, type of organic solvent, and surfactant type, we demonstrate that nanoparticles of different sizes and charges can be synthesized for subsequent drug delivery application.

Materials and

Methods: All polymeric nanoparticles were produced using nanoprecipitation. To synthesize nanoparticles, a polymer emulsion comprising a solvent-water ratio of 1:50, was formed by injecting an organic phase made up of 1% w/v PEG-PLGA (Sigma Aldrich) in acetone (Thermo Fisher) into an aqueous phase consisting of 1% w/v polyvinyl alcohol (PVA, Thermo Fisher) under a stir rate of 600rpm. The particles produced by these fabrication parameters were adopted as a reference formulation (REF-NP) and then characterized for size, charge, and morphology using dynamic light scattering and transmission electron microscope. To synthesize positive and negative charge particles, 1% w/v hexadecyltrimethylammonium bromide (CTAB, Sigma Aldrich) and 1% w/v sodium dodecyl sulfate (SDS, Sigma Aldrich) were respectively used as the surfactant in the aqueous phase instead of PVA. To investigate the toxicity of the residual surfactant on particle surface, Raw 264.7 macrophages (ATCC) were seeded in a 96 well plate at a density of 5000 cells/well and further incubated with equal concentrations of neutral particles, positive (+) particles, and negative (-) particles.

Furthermore, by incubating REF-NPs with Raw 264.7 macrophages, an initial investigation into particle uptake was studied using confocal microscope.

Results, Conclusions, and Discussions: Using the nanoprecipitation method, we show herein that we can produce PEG-PLGA nanoparticles under 100 nm with low polydispersity and high batch-to-batch reproducibility (Fig. 1A), overcoming several critical challenges associated with nanoprecipitation and other conventional fabrication techniques. The nanoparticles generated were characterized by a spherical morphology and very narrow size distribution making them ideal for studying cellular uptake by macrophages (Fig 1C). Further, using the nanoprecipitation method, we could fabricate nanoparticles of similar size (~100 nm) but with different surface charges. Neutral, anionic and cationic PLGA nanoparticles were obtained using polyvinyl alcohol (PVA), (CTAB) and SDS as surfactant respectively (Fig. 2). Further we were able to vary the degree of surface charge by surfactant concentration. For instance, by using a CTAB concentration of 1% w/v we could get a surface charge of 8 mV while 5% CTAB gave nanoparticles with 52 mV surface charge. Finally, we observed robust uptake of the ~100 nm particles in RAW macrophages

Acknowledgements (Optional):