alexa Effects of Ophthalmic Formulations Containing Cilostazol Nanoparticles on Retinal Vasoconstriction in Rats Injected with Endothelin-1

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Effects of Ophthalmic Formulations Containing Cilostazol Nanoparticles on Retinal Vasoconstriction in Rats Injected with Endothelin-1

Cilostazol (CLZ) is useful for the management of diabetic retinal vascular dysfunction and neuronal degeneration. However, drugdelivery in a posterior segment, such as retina,is not possible using eye drops with traditional formulations.In this study, we designed new ophthalmic formulations containing CLZ solid nanoparticles, and investigated whether these ophthalmic formulations provide noninvasive delivery systems targeting the posterior segment of the eye. The new ophthalmic formulations containing 1% CLZ solid nanoparticles were prepared byadding various additives [0.005% benzalkonium chloride (BAC), 0.5% d-mannitol, 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 1% methylcellulose] and subjecting the mixtures to mill methods(CLZnano ophthalmic formulations; particle size 61 ± 43 nm, mean ± S.D.). The addition of HPβCD and mannitol enhanced the stability of the CLZ dispersion (CLZnano), and no precipitation from the CLZnano ophthalmic formulations was observed until 21 days after preparation. In addition, in the measurement of the antimicrobial activity against Escherichia coli (ATCC 8739),the CLZ nanoparticles in ophthalmic formulations didn’t affect the antimicrobial activityby preservative, such as BAC. In this study, retinal vasoconstriction was produced in rats by intravitreal injection of 1×10-5 M endotheline-1 (15 µL, ET-1); retinal vasoconstriction in ET-1-injected ratsreturned to normal by 48 h after injection. On the other hand, the instillation of CLZnano ophthalmic formulations suppressed the retinal vasoconstriction in ET-1-injected rats, and theretinal vascular caliber in rats instilled with CLZnano was similar than that in non-treated rats 3 h after intravitreal injection. It is possible that dispersions containing CLZ nanoparticles provide new possibilities for an effective, noninvasive method to deliver therapeutic agents to intraocular tissues such as the retina, and that an ocular drug delivery system using drug nanoparticles may expand their usage as therapy in the ophthalmologic field.

Citation: Nagai N, Yoshioka C, Tanabe W, Tanino T, Ito Y, et al (2015) Effects of Ophthalmic Formulations Containing Cilostazol Nanoparticles on Retinal Vasoconstriction in RatsInjected with Endothelin-1. Pharm Anal Acta 6:354. doi: 10.4172/2153-2435.1000351

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