Co-delivery of latanoprost and timolol from micelles-laden contact lenses for the treatment of glaucoma

Abstract

Glaucoma is a group of irreversible ocular diseases which result in damage to the optic nerve and vision loss. The objective of the present work was to develop micelles-laden contact lenses (CLs-M) that could achieve the sustained release of timolol and latanoprost simultaneously for the treatment of glaucoma. CLs-M were obtained by free radical polymerization of HEMA monomer with timolol and latanoprost loaded mPEG-PLA micelles. The prepared CLs-M had a minimal impact on critical CLs properties, and could release timolol and latanoprost in simulated tear fluid for 144 h and 120 h individually, which is promising for extended drugs release applications. The in vivo PK study on rabbit eyes showed sustained timolol and latanoprost release for up to 120 h and 96 h in tear fluid, respectively. There was significant improvement of the mean residence time (79.6-fold and 122.2-fold) and bioavailability (2.2-fold and 7.3-fold) for both timolol and latanoprost delivered by CLs-M compared with eye drops. An in vivo PD study in a rabbit model with high IOP showed sustained reduction in the IOP for over 168 h. The relative pharmacological availability (PA) of CLs-M was 9.8 times as high as the eye drops. The protein adsorption, ocular irritation study and histological examination study indicated the safety of CLs-M. Therefore, this work has demonstrated the promising potential of micelles-laden CLs to co-deliver timolol and latanoprost for an extended period of time to treat glaucoma.