Stimuli-responsive hydrogels for controlled pilocarpine ocular delivery.

Area of Science:

• Polymer Chemistry
• Materials Science
• Biomedical Engineering

Background:

• Hydrogels are versatile materials with applications in drug delivery.
• Stimuli-responsive hydrogels offer tunable release profiles.
• Incorporating amino acid residues can impart specific functionalities to hydrogels.

Purpose of the Study:

• To synthesize and characterize vinyl hydrogels with L-histidine and L-valine residues.
• To evaluate the dual-stimuli responsiveness (pH and temperature) of these hydrogels.
• To assess the drug release profile and cytotoxicity of the developed hydrogels.

Main Methods:

• Synthesis of vinyl hydrogels with varying amino acid residues (L-histidine, L-valine) and cross-linker concentrations (N,N'-ethylene-bisacrylamide).
• Swelling property evaluation at different pH and temperature conditions.
• Pilocarpine release studies under physiological conditions.
• Cytotoxicity assessment using mouse fibroblast NIH3T3 cells.

Main Results:

• Hydrogels with L-valine residues (HVa) demonstrated improved dual-stimuli responsiveness compared to L-histidine hydrogels.
• HVa hydrogels exhibited pH-dependent swelling, with phase separation at pH 4.
• Temperature increase led to decreased swelling, with sharper collapse near the critical pH.
• Sustained pilocarpine release over a week was observed, with a significant initial burst effect.
• HVa hydrogels showed a three-fold greater pilocarpine release compared to histidine-based hydrogels.
• The hydrogels were non-toxic and promoted cell proliferation in the presence of pilocarpine.

Conclusions:

• Vinyl hydrogels functionalized with L-valine residues offer tunable dual-stimuli responsiveness.
• These hydrogels are promising for controlled drug delivery applications, particularly for basic molecules like pilocarpine.
• The non-toxic nature and cell-proliferating effects of pilocarpine-loaded hydrogels warrant further investigation for therapeutic use.