Dual crosslinked hydrogel nanoparticles by nanogel bottom-up method for sustained-release delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Polymer Chemistry

Background:

• Developing effective nanocarriers for drug delivery requires optimizing circulation time and minimizing non-specific interactions.
• Hybrid nanogels combining polysaccharides and polyethylene glycol (PEG) offer tunable properties for biomedical applications.

Purpose of the Study:

• To synthesize and characterize polysaccharide-PEG hybrid nanogels (CHPOA-PEGSH) with enhanced stability and prolonged circulation.
• To investigate the impact of experimental parameters on nanogel size and degradation kinetics.
• To evaluate the in vivo performance of these nanogels as injectable nanocarriers.

Main Methods:

• Synthesis of CHPOA-PEGSH nanogels via reaction of acryloyl-modified cholesterol-bearing pullulan (CHPOA) and thiol-modified poly(ethylene glycol) (PEGSH).
• Characterization of nanogel size (50-150 nm) and degradation kinetics using dynamic light scattering (DLS) and asymmetrical flow field-flow fractionation (AF4).
• In vivo evaluation of nanogel blood circulation time in mice using a fluorescence assay.

Main Results:

• CHPOA-PEGSH nanogels exhibited an elimination half-life of 18 hours, approximately 15-fold longer than unmodified CHP nanogels (1.2 hours).
• The enhanced circulation is attributed to PEG chains preventing protein adsorption and slow hydrolysis of ester crosslinks.
• Nanogel size and degradation kinetics were tunable by adjusting CHPOA concentration, substitution degree, and initial component amounts.

Conclusions:

• The hybrid CHPOA-PEGSH nanogels demonstrate significantly improved in vivo stability and prolonged circulation.
• These nanogels possess low surface fouling and slow hydrolysis rates, ideal for injectable drug and protein delivery systems.
• The tunable nature of these nanogels offers a promising platform for advanced nanomedicine applications.