Liposome-encapsulated 3H-5FU in rabbits

Area of Science:

• Ophthalmology
• Pharmacokinetics
• Drug Delivery Systems

Background:

• 5-fluorouracil (5FU) is a chemotherapy agent with potential ophthalmic applications.
• Achieving sustained therapeutic drug levels in ocular tissues is challenging due to rapid clearance.
• Liposomal encapsulation is a strategy to modify drug release kinetics and improve tissue penetration.

Purpose of the Study:

• To compare the ocular pharmacokinetics of liposome-encapsulated 5-fluorouracil (3H-5FU-Lipo) versus 5-fluorouracil in buffered saline (3H-5FU-PBS).
• To evaluate the impact of liposomal formulation on drug distribution and retention in rabbit eyes after subconjunctival and intravitreal injections.

Main Methods:

• Liposomes were formulated using phosphatidylcholine, phosphatidic acid, and alpha-tocopherol.
• Tritiated 5FU (as 3H-5FU-Lipo or 3H-5FU-PBS) was administered via subconjunctival or intravitreal injection in rabbits.
• Ocular tissues (vitreous and aqueous humor) were analyzed for drug concentrations at various time points post-injection.

Main Results:

• Subconjunctival injection of 3H-5FU-Lipo resulted in significantly higher drug levels in the vitreous and aqueous humor compared to 3H-5FU-PBS at multiple time points.
• Intravitreal injection of 3H-5FU-Lipo demonstrated significantly higher vitreal drug concentrations from 6 hours onwards compared to 3H-5FU-PBS.
• At 48 hours post-intravitreal injection, vitreal drug levels for 3H-5FU-Lipo were substantially higher (578 µg/mL) than for 3H-5FU-PBS (1.06 µg/mL).

Conclusions:

• Liposome encapsulation significantly enhances the retention and concentration of 5-fluorouracil within the rabbit eye following both subconjunctival and intravitreal administration.
• This liposomal formulation holds promise for improving the efficacy of 5FU-based therapies in treating ocular diseases by prolonging drug exposure.