Polymeric nanomicelles based on inulin D α-tocopherol succinate for the treatment of diabetic retinopathy

There is a great demand for efficient ocular dosage forms for the treatment of diabetic retinopathy. Nanomicelles named INVITE C, consisting in amphiphilic inulin-D-α-tocopherol succinate bioconjugates (INVITE) and loaded with the antioxidant curcumin, were tested with the aim to suggest a therapy against the bilateral damage of retinal blood vessels occurring in diabetic retinopathy. In vitro sensitivity to enzymatic hydrolysis and antioxidant activity measurements demonstrate that INVITE is hydrolyzed by enzymes releasing α-tocopherol, which possesses antioxidant activity. INVITE C shows high antioxidant activity, too. Furthermore, an active efflux from apical to basolateral sides for curcumin, as free or encapsulated forms, is evidenced by transport experiments on polarized monolayers of human retinal pigment epithelium (HRPE) cells. Finally, INVITE C appears able to stabilize the transepithelial electrical resistance of the HRPE monolayer, whose values were drastically decreased by high glucose conditions. Therefore, the intraocular injection of INVITE C could be useful in the treatment of the hyperpermeability of blood-retina barrier induced by diabetic conditions.