Purpose:
To evaluate aqueous humor (AH) concentrations of latanoprost following subconjunctival injection of a sustained release hydrogel depot in New Zealand White Rabbits
Methods:
Latanoprost was encapsulated in poly(lactide-co-glycolide) (PLGA) microparticles. The microparticles were suspended in a cross-linkable PEG solution and mixed with a trilysine (cross-linker) solution at ~ 500ug latanoprost per 50ul injection. The mixture was injected in the superior subconjunctiva to form in situ an eluting hydrogel depot of latanoprost. Depots were formed in 15 animals (30 eyes). AH was sampled at time points up to 9 weeks and analyzed by LC-MS/MS for latanoprost acid concentration.
Results:
As shown in Figure 1, low levels of latanoprost free acid can still be found in the AH after 9 weeks of implantation.
Conclusions:
The latanoprost PLGA microparticles entrapped in the hydrogel matrix are subject to hydrolytic degradation, resulting in slow, local release of latanoprost. The drug diffuses out to the surrounding tissues, converting to the active free acid form. The results suggest that latanoprost encapsulated and entrapped in a hydrogel subconjunctival depot can be delivered into the AH in a sustained fashion up to 9 weeks. In future work, higher levels of latanoprost free acid in the AH as well as more extended delivery time can be achieved by using slower degrading microparticles and higher drug loadings. Such a depot can provide a reduction in IOP for extended durations and can potentially be suitable for therapy of patients with elevated IOP.