Therapeutic Effect of Ophthalmic Formulation containing Nilvadipine Nanoparticles on Retinal Dysfunction in Rats Injected with Streptozotocin

Abstract

Purpose : Retinopathy leads to irreparable vision loss via capillary closure and areas of nonperfusion, although, the current instillation systems do not allow a sufficient amounts of drugs to treat retinopathy to reach the posterior segment. In this study, we designed the dispersions containing nilvadipine nanoparticles (NIL_nano), and evaluated the therapeutic effect in retinal dysfunction.

Methods : NIL_nano ophthalmic formulation were prepared by using wet bead mill method and various additives (2-hydroxypropyl-β-cyclodextrin, benzalkonium chloride, D-mannitol, and methylcellulose). The retinal dysfunction was caused by intraperitoneally injecting streptozotocin to rats (100 mg/kg×2; STZ rat). Changes in retinal function were evaluated by electroretinogram (ERG) and immunological method, respectively.

Results : The NIL microparticles were crushed with a bead mill, which reduced the mean particle size from 16 mm to 77 nm. Additionally, no aggregation or precipitation of NIL nanoparticles was observed for NIL_nano (mean particle size of NIL_nano 2 weeks after preparation was 82 nm). Retinal dysfunction was observable 2 weeks after rats received intraperitoneal injections of streptozotocin (100 mg/kg×2, consecutive days, STZ rat), and the changes in retinal function were evaluated by ERG and immunological methods. the levels of a-wave, b-wave and oscillatory potentials amplitude in rats decreased 2 weeks after the injection of streptozotocin. In addition, the increases in the inner plexiform layer as well as the outer- and inner-nuclear layer (neural layer) were observed in the retinas of STZ rats. The distance between cells in the neural layer in normal and STZ rats were 71.0 ± 3.57 mm and 130.6 ± 5.46 mm, respectively, and that the enhanced retinal thickening caused the decrease in ERG. The instillation of NIL_nano allowed the topical supplement of nilvadipine into the retina, and NIL_nano (2 times/day) prevented the retinal disorders caused by the injection of excessive streptozotocin.

Conclusions : The retinal dysfunctions in rats injected with streptozotocin are attenuated by instillation of NIL_nano ophthalmic formulation. These findings provide significant information that can be used to design further studies aimed at therapeutic treatment of retinopathy.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.