Evaluation of the Intravenous and Topical Routes for Ocular Delivery of Hesperidin and Hesperetin

Abstract

Purpose: The objective of this study was to determine the ocular bioavailability of hesperidin and hesperetin, especially with respect to their distribution into the posterior segment of the eye, following systemic and topical administration in rabbits. Methods: Hesperidin and hesperetin were administered either intravenously or topically to male New Zealand white (NZW) rabbits. Vitreous humor and plasma samples were collected after intravenous administration and analyzed to estimate the concentrations of the parent compounds and their metabolites. Ocular tissue concentrations, obtained on topical administration of hesperidin and hesperetin, were also determined. Results: In the systemic circulation, hesperidin and hesperetin were rapidly metabolized into their glucuronides, which are extremely hydrophilic in nature. Vitreal samples did not demonstrate any detectable levels of hesperidin/hesperetin following intravenous administration. Topical administration produced significant concentrations of hesperidin/hesperetin in all the ocular tissues tested at the 1 and 3 hours time points postdosing, with hesperetin showing higher levels compared to hesperidin. However, only low levels were generated in the vitreous humor. Inclusion of a penetration enhancer, benzalkonium chloride (BAK), improved the back-ofthe-eye hesperetin levels. Conclusions: Ocular delivery of hesperidin/hesperetin via the systemic route does not seem to be feasible considering the rapid generation of the hydrophilic metabolites. Topical application appears to be more promising and needs to be further developed/refined.

Evaluation of topical hesperetin matrix film for back-of-the-eye delivery

“…Ramesh et al , have previously evaluated ocular bioavailability of HT through intravenous and topical routes of application [42]. In these studies, 1 %w/v HT solution (Dose: 1 mg) for topical instillation was prepared using 10 %w/v HPβCD and 10 %w/v RMβCD.…”

“…Cumulative urinary recovery of HT suggests a bioavailability of less than 25 % after oral administration of HD and HT [21]. Poor oral bioavailability of HT can be attributed to its rapid metabolism into hydrophilic glucuronide metabolites [22] and short half-life (Plasma half-life: 6.7 h and vitreous humor half-life: 110 min) [23, 24]. …”

“…Our earlier studies demonstrate that systemic application fails to deliver HT to the ocular tissues [22]. This makes topical or intraocular/periocular application the most effective.…”

Honey: A Natural Remedy for Eye Diseases

“…A topically administered drug may penetrate into the posterior chamber tissues, such as the retina, through corneal or noncorneal routes. Topical application of flavonoids such as hesperidin/hesperetin seems more promising and their bioavailability is high as they were found in significant concentration levels in all ocular tissues [50,51]. According to a very recent animal study [52], topical application of 0.5% quercetin eye drops can help to improve the ocular surface disorders of dry eye, not only by decreasing the corneal surface irregularity but also by increasing the tear volume and the goblet cell density.…”

Hesperitin enhances the ability of daunorubicin by co-loading with MPEG-PCL nanoparticles to induce apoptosis in gastric cancer

“…Hesperetin has been suggested to exhibit biological activities of anti-cancer, anti-oxidant, antiinflammatory and chemo-preventive properties for codelivery [21][22][23]. The clinical use of HE has been limited owing to their low water solubility and bioavailability in vivo.…”