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


METHODS
HT film was prepared by melt-cast method using PEO N10 and cut into 4mm×2mm segments, each weighing 8mg. 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.


RESULTS
HT release from the film was determined to be about 95.3% within 2h. In vitro transcorneal flux was observed to be 0.58±0.05μg/min/cm(2) 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.


CONCLUSIONS
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.
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, MS, USA.
Goutham R
GR
Adelli
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, MS, USA.
Tushar
T
Hingorani
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, MS, USA.
Nagendra
N
Punyamurthula
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, MS, USA.
Sai Prachetan
SP
Balguri
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, MS, USA; Research Institute of Pharmaceutical Sciences, The University of Mississippi, MS, USA; National Center for Natural Product Research, The University of Mississippi, MS, USA. Electronic address: majumso@olemiss.edu.
Soumyajit
S
Majumdar
D000287:Administration, Topical; D000818:Animals; D003315:Cornea / Q000378:metabolism*; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005123:Eye / Q000378:metabolism; D006569:Hesperidin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry*; D011817:Rabbits; D013997:Time Factors; D014018:Tissue Distribution
D011092:Polyethylene Glycols; D006569:Hesperidin; C013015:hesperetin
Back-of-the eye delivery; Bioflavonoids; Hesperetin; Hot melt extrusion; Melt-cast technology; Polyethylene oxide; Polymeric matrix film; Sustained delivery; Topical application