In vivo release and retinal safety of intravitreal implants of thalidomide in rabbit eyes and antiangiogenic effect on the chorioallantoic membrane

Abstract

Purpose: To evaluate the in vivo release and retinal safety of a thalidomide loaded poly-d,l-lactide-co-glycolide (PLGA) intravitreal implant.

Methods: The implants were prepared by hot molding and inserted into the vitreous cavity of rabbits using a 25-gauge trocar/cannula. At different time points, eye (vitreous and aqueous humour) and blood samples were retrieved and thalidomide concentration was analyzed by high-performance liquid chromatography. The amount of drug remaining in the implants was analyzed at the end of follow-up. ERG was realized to evaluate retinal function. Clinical and histological examinations were made to assess the implants tolerance.

Results: The developed implant allowed for a controlled and prolonged delivery of thalidomide in rabbits eyes for at least 6 weeks, and at that time approximately 37.5%% of the drug was still present in the implant. No drug was found in the aqueous humor and blood samples. ERG showed that the system under study was not toxic to the normal rabbit retina. Clinical and histological observations showed that the devices were very well tolerated in the rabbit eye.

Conclusions: This study demonstrates the feasibility and tolerance of thalidomide loaded PLGA intravitreal implants. It can offer a wide range of applications for the treatment of diseases of the posterior segment of the eye because of the potential effects of the drug and the advantages of intraocular biodegradable implants.

Keywords: 503 drug toxicity/drug effects • 453 choroid: neovascularization