Delineating penetration enhancer-enriched liquid crystalline nanostructures as novel platforms for improved ophthalmic delivery

Liquid crystalline nanostructures (LCNs), for instance cubosomes, have been widely used as a promising carrier for drug delivery through the last few years. To date, the ophthalmic application of these platforms was not well explored, and the effect of integrating penetration enhancers (PEs) into LCNs has not been investigated yet. Hence, the present work aimed coupling novel PEs into glyceryl monooleate-based cubosomes for ocular administration. Various enhancers viz, free fatty acids (oleic and linoleic acids), natural terpenes (D-limonene and cineole), medium-chain triglycerides (Captex (R) 1000 and Captex (R) 8000), mono-/di-glycerides (Capmul (R) MCM, Capmul (R) PG-8, and Capmul (R) PG-12) were tested at different amounts. The morphology of the formed LCNs was investigated using transmission electron microscopy (TEM). The crystallinity and thermal behavior studies were also conducted. The ocular safety of optimized formulae was tested via hen's egg test-chorioallantoic membrane (HET-CAM), rabbit eye Draize test, and histopathological examinations of ocular tissues. Confocal laser scanning microscopy (CLSM) was utilized to assess the enhanced permeation of fluorescently-labeled LCNs across corneal layers. The acceptable formulations exhibited relatively homogenous particle nano-sizes ranging from 139.26 +/- 3.68 to 590.56 +/- 24.86 nm carrying negative surface charges. TEM images, X-ray patterns and DSC thermograms demonstrated the influential effect of PEs in developing altered crystalline structures. The ocular compatibility of optimized LCNs was confirmed. The corneal distribution using CLSM proved the disseminated fluorescence intensity of LCNs enriched with oleic acid, Captex (R) 8000 and Capmul (R) MCM. Selected LCNs showed good physical stability upon storage and lyophilization. The results demonstrated the efficiency of tailored PEmodified LCNs in enhancing the ocular transport with no evidence of any irritation potential, and hence suggested their prospective applicability in ophthalmic drug delivery.