Treatment of endotoxin-induced uveitis by topical application of cyclosporine a-loaded PolyGel™ in rabbit eyes

Publication date: 5 October 2019Source: International Journal of Pharmaceutics, Volume 569Author(s): Aws Alshamsan, Mohd Abul Kalam, Mohammad Reza Vakili, Ziyad Binkhathlan, Mohammad Raish, Raisuddin Ali, Turki A. Alturki, Nazila Safaei Nikouei, Afsaneh LavasanifarAbstractThe main objective of this study was to investigate the potential of poly(α-carboxylate-co-α-benzylcarboxylate-ε-caprolactone)-block-poly(ethylene glycol)-block-poly(α-carboxylate-co-α-benzylcarboxylate-ε-caprolactone) (PCBCL-b-PEG-b-PCBCL; denoted as PolyGel™) as an in situ gel system for ocular delivery of CyA. The newly developed formulation was systematically assessed and its profile was compared to Restasis®, 0.5% CyA extemporaneous preparation, and CyA-loaded poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) a non-gelling micelle formulation. In vivo Draize test showed that CyA-loaded PolyGel™ was well tolerated with only moderate irritation that resolved within 24 h. Both ex vivo corneal permeation and in vivo pharmacokinetics in aqueous humor (AqH) showed sustained release of CyA from PolyGel™. Non-compartmental analysis of CyA concentrations in AqH showed significant changes in pharmacokinetic parameters of CyA among different formulations. The highest Cmax and AUC0-∞ in AqH were achieved with Restasis® followed by PolyGel™. Nonetheless, CyA-loaded PolyGel™ had approximately 87% longer t1/2 for CyA compared to Restasis®. Pharmacological and histopathological studies...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research