Polyketal-conjugated tafluprost microparticles enable long-acting glaucoma therapy

Area of Science:

• Biomaterials Science
• Drug Delivery
• Ophthalmology

Background:

• Long-acting drug formulations are crucial for managing chronic diseases.
• Conventional drug-conjugated microparticles often have short release durations and release inactive oligomers.
• Minimally invasive drug delivery platforms are highly desirable.

Purpose of the Study:

• To develop surface-erodible, drug-conjugated polyketal microparticles for extended release of active drug.
• To evaluate the release profile and efficacy of tafluprost-polyketal microparticles.
• To assess the safety and performance compared to existing treatments.

Main Methods:

• Synthesized surface-erodible, drug-conjugated polyketal microparticles using the anti-glaucoma agent tafluprost.
• Investigated in vitro drug release kinetics over 540 days.
• Performed subconjunctival injections in rat models to evaluate intraocular pressure reduction and tissue response.

Main Results:

• Microparticles demonstrated controlled release of unmodified tafluprost, followed by tafluprost acid, with ~78% cumulative release over 540 days in vitro.
• No detectable drug-conjugated oligomers were found in the release medium.
• In vivo studies showed sustained intraocular pressure reduction for ~3 months in rats with minimal adverse effects.

Conclusions:

• Surface-erodible polyketal microparticles provide a promising platform for extended release of active drugs, avoiding inactive byproducts.
• Tafluprost-polyketal microparticles offer a safe and effective long-acting treatment for lowering intraocular pressure.
• This technology has broad implications for advancing extended drug delivery systems for chronic disease management.