Hydrophobically-modified poly(vinyl pyrrolidone) as a physically-associative, shear-responsive ophthalmic hydrogel

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Ophthalmology

Background:

• Developing advanced hydrogels for ophthalmic applications requires materials with tunable properties like shear-responsiveness and self-association.
• Poly(vinyl pyrrolidone) (PVP) is a versatile polymer, but its modification is key to achieving desired functionalities for ocular use.

Purpose of the Study:

• To demonstrate the potential of hydrophobically-modified PVP as a shear-responsive, self-associative hydrogel for ophthalmic applications.
• To investigate the tunability of hydrogel properties based on hydrophobic modification and its impact on viscosity, self-association, and drug delivery.

Main Methods:

• Synthesized hydrophobically-modified PVP via copolymerization of N-vinylpyrrolidone and N-vinylformamide, followed by hydrolysis and grafting of alkyl chlorides.
• Characterized hydrogel properties including shear-thinning behavior, viscosity changes over time, transparency, and drug release kinetics.
• Evaluated in vitro cytotoxicity using human corneal epithelial and retinal pigment epithelial cells.
• Assessed in vivo safety and biocompatibility in rabbit and rat eyes following anterior and intravitreal application.

Main Results:

• The modified PVP formed transparent, shear-responsive physical hydrogels with tunable shear thinning over 4-5 decades of viscosity.
• Hydrophobe chain length influenced self-association and gelation kinetics, with longer chains (C18) forming stiffer gels over weeks.
• Controlled release of doxorubicin was achieved, and polymers showed minimal in vitro cytotoxicity.
• In vivo studies in rabbits and rats revealed no significant adverse effects, indicating excellent ocular biocompatibility.

Conclusions:

• Hydrophobically-modified PVP hydrogels are promising shear-thinning materials for ophthalmic drug delivery (anterior and posterior segments) and potential vitreal replacement.
• The tunable nature of these hydrogels allows for facile administration and controlled therapeutic release.
• These materials demonstrate excellent safety profiles for ocular applications.