Evaluation of epithelial transport and oxidative stress protection of nanoengineered curcumin derivative-cyclodextrin formulation for ocular delivery

Ocular drug delivery has been a well-knownroute for the drug administration for the treatment of oculardiseases. However, numerous anatomical and physiologicalbarriers prevailing in the eye itself create considerablechallenges for achieving the necessitated therapeutic efficacyalong with ocular bioavailability. However, recentadvances in nanoengineered strategies hold definite promisesin terms of devising improved ophthalmic medicinesfor the effective drug delivery to target the sites withenhanced ocular bioavailability. Curcumin, a hydrophobicpolyphenol yellow colored compound, and its metabolicreduced product, tetrahydrocurcumin (THC), have beenknown for their beneficial pharmacological functions, suchas anti-inflammatory or anti-oxidant activities at varioustissue sites. However, the low aqueous solubility of thesecompounds results in their poor bioavailability, therebylimiting their widespread application. Therefore, in thepresent study, we investigated the changes in drug solubilityby forming inclusion complexes with differentderivatives of hydroxypropyl (HP)-cyclodextrins (CD). To this end, the spray drying technique was used for nanoengineeringcurcumin or THC-loaded formulations toimprove the stability of formulations during the storage. The formulations were characterized in terms of physicochemicalproperties and cellular permeability. The resultsdemonstrated that the encapsulation of curcumin (or THC)into the HP-CDs significantly increased the drug solubilityand enhanced the corneal and retinal epithelial permeability. Curcumin or THC complexes in HP-CDs withimproved bioavailability also induced anti-oxidant activity(SOD1, CAT1, and HMOX1) in higher levels in the ocularepithelial cells and showed oxidative protection effects inrabbit cornea tissues that will boost up their application inocular medicine.