A high-performing photoactivatable NOPD with a green fluorescent reporter loaded in thermoresponsive gel for ocular application.

The biological effects of nitric oxide (NO) have been shown to be highly site- and dosage-dependent. For this reason, quantification, and localization of NO released has a central role in the therapeutic approaches involving NO. One way to address this task is to use systems which are based on the principle of the “release with fluorescence reporting”. In these types of systems, the molecular constructs can activate the fluorescence concomitantly to the NO release, that permits the easy and in real-time quantification of the amount of NO released. In the ophthalmic formulation the topical instillation of drugs through eyedrops is the most important and well-accepted route of administration for the treatment of various eye disorders. A smart strategy to prolong the contact time of ophthalmic formulations with the ocular tissues is to use in situ gel-forming ophthalmic drug delivery system prepared from polymers that exhibit reversible phase sol-gel temperature dependent. In this work a novel NO donor (NOPD), activatable by visible blue light with an in-built green fluorescence reporter, was loaded in the thermoresponsive Pluronics® based formulation. This NO photodonor, based on the nitrosamino (NBF-NO) derivative of amino-nitro-benzofurazan (NBF) reports the largest quantum yield of NO release never seen for a nonmetal-containing NO donors activatable by visible light.