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

• Melt-cast film for efficient delivery of hesperetin (HT) to the back-of-the eye.
• Release of HT from the film followed the Higuchi model.
• Development of “membrane-film-cornea” sandwich model to mimic precorneal loss.
• Matrix film delivers neuroprotectant levels of HT for at least 6 h post application.

PurposeThe goal of the present study was 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.MethodsHT 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: 10,000 Daltons) and isolated rabbit corneas. Ocular tissue concentrations were also determined postapplication of the film in ex vivo and in vivo models.ResultsHT 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 1 h 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 6 h following topical application of the film in vivo.ConclusionThe 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.

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