Surface-functionalized polymethacrylic acid based hydrogel microparticles for oral drug delivery

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Nanotechnology

Background:

• Poly(methacrylic acid)-chitosan-poly(ethylene glycol) (PCP) microparticles are explored for oral drug delivery.
• Thiol functionalization is a strategy to enhance drug permeation and mucoadhesion.

Purpose of the Study:

• To develop novel thiol-functionalized PCP hydrogel microparticles for oral drug delivery.
• To evaluate the impact of thiol modification on particle characteristics, cytotoxicity, paracellular permeability, and mucoadhesion.

Main Methods:

• PCP microparticles synthesized via modified ionic gelation.
• Surface thiol modification using l-cysteine and carbodiimide coupling.
• Characterization included particle size (dynamic light scattering), sulfhydryl group quantification (Ellman's method), cytotoxicity (MTT assay), paracellular permeability (Ussing chamber with Caco 2 cells and rat intestinal tissue using fluorescence dextran), and mucoadhesion (ex vivo bioadhesion).

Main Results:

• Thiol modification increased PCP microparticle size.
• Thiolated microparticles significantly enhanced paracellular permeability of fluorescence dextran across Caco 2 cell monolayers without observed toxicity.
• Permeation across excised rat intestinal membrane was limited due to high mucoadhesion of thiolated particles.

Conclusions:

• Surface thiolation of PCP microparticles is a promising strategy for enhancing paracellular permeability of hydrophilic macromolecules for oral drug delivery.
• High mucoadhesion, while beneficial for retention, can impede overall permeation across intestinal barriers.
• Further optimization is needed to balance mucoadhesion and permeability for effective oral delivery systems.