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

Abstract

Purpose The goal of the present study is to develop a poly (ethylene oxide) N10 (PEO N10) based melt-cast matrix system for efficient and prolonged delivery of hesperetin (HT), a promising bioflavonoid, to the posterior segment of the eye through the topical route. Methods HT film was prepared by melt-cast method using PEO N10 and cut into 4 mm × 2 mm segments, each weighing 8 mg. This film was evaluated with respect to in vitro release rates and also transmembrane delivery across Spectra/Por® membrane (MWCO: 10000 Daltons) and isolated rabbit corneas. Ocular tissue concentrations were also determined post application of the film in ex vivo and in vivo models. Results HT release from the film was determined to be about 95.3 % within 2 h. In vitro transcorneal flux was observed to be 0.58 ± 0.05 μg/min/cm2 across the isolated rabbit cornea. High levels of HT were detected in the retina-choroid (RC) and vitreous humor (VH) in the ex vivo model following topical application of the film. Significant levels of HT were observed in both anterior and posterior segment ocular tissues 1h post topical application of the 10 and 20 %w/w HT films on the rabbit eye. Moreover, HT was detected in the VH and RC even after 6h following topical application of the film in vivo. Conclusion The results from this study suggest that the melt-cast films can serve as a viable platform for sustained topical delivery of bioflavonoids, and other therapeutic agents, into the back-of-the eye tissues.

Ocular disposition of ciprofloxacin from topical, PEGylated nanostructured lipid carriers: Effect of molecular weight and density of poly (ethylene) glycol

“…Drug release from the nanoparticles appears to be controlled by erosion and diffusion mechanisms through lipid matrix (45, 46). Interaction between nanoparticles and ocular epithelial cells could be attributed to endocytosis mechanism.…”

Hesperetin-loaded lipid-core nanocapsules in polyamide: a new textile formulation for topical drug delivery

“…1 Hesperetin (Hst), 5,7,3′-trihydroxy-4′-methoxyflavanone, is a natural bioflavonoid found abundantly in citrus fruits with promising antioxidant and antiinflammatory properties. 2,3 Several studies have shown that citrus flavonoids can exert antiatherogenic and vasculoprotective effects by modulating the expression of molecules related to inflammation, preventing the formation of foam cells, reducing the area of atherosclerotic plaques, improving the lipid profile, inhibiting the adhesion of monocytes to the endothelium and modulating cell migration. 4 Furthermore, Hst via the inhibition of L-type voltage-gated Ca 2+ channels and the enhancement of voltage-gated K + channel currents of the myocytes has a direct vasorelaxant effect.…”

Melt-Cast Noninvasive Ocular Inserts for Posterior Segment Drug Delivery

“…Ocular tissues namely IC and RC are in dynamic equilibrium with AH and VH, so the therapeutic levels required in AH and VH could be interpreted to be good therapeutic response indicators in the ocular tissues. Drug levels obtained in all the ocular tissues, post 2 h, with inserts were several folds higher than the reported minimal concentrations, demonstrating that inserts could maintain therapeutic drug levels for prolonged durations following topical application (35, 36). …”