Development and In Vitro-In Vivo Evaluation of Fenretinide-Loaded Oral Mucoadhesive Patches for Site-Specific Chemoprevention of Oral Cancer

Abstract

Purpose To develop fenretinide oral mucoadhesive patch formulations and evaluate their in vitro and in vivo release performance for future site-specific chemoprevention of oral cancer. Methods Solubilization of fenretinide in simulated saliva (SS) was studied by incorporating nonionic surfactants (Tween® 20 and 80, and Brij® 35 and 98), bile salts (sodium salt of cholic, taurocholic, glycocholic, and deoxycholic acids), phospholipid (lecithin), and novel polymeric solubilizer (Souplus®). Adhesive (polycarbophil: hydroxypropyl methylcellulose 4KM) and drug release (Fenretinide/Eudragit® RL PO with or without solubilizers) layers were prepared by solvent casting. Oral mucoadhesive patches were formed by attaching drug and adhesive layers onto backing layer (Tegaderm™ film). Physical state of drug in Eudragit® films was examined by X-ray diffraction (XRD). Evaluation of in vitro and in vivo fenretinide release from the patch was conducted in SS containing 5%w/v sodium deoxycholate and rabbits, respectively. Fenretinide was quantified by HPLC. Results Tween® 20 and 80, Brij® 98, and sodium deoxycholate exhibited the highest fenretinide solubilization potential among the solubilizers. Drug loading efficiency in Eudragit® films was 90%–97%. XRD suggested fenretinide was amorphous in solubilizer-free and solubilizer-loaded films. Solubilizer-free patch exhibited poor in vitro and in vivo controlled drug release behavior. Increases in drug loading (5–10 wt%) or changes in polymeric matrix permeability did not provide continuous drug release. Co-incorporation of either single or mixed solubilizers in fenretinide/Eudragit® patches, (20 wt% Tween® 20, Tween® 80 and sodium deoxycholate or 20 wt% Tween® 80 + 40 wt% sodium deoxycholate solubilizers) led to significantly improved continuous in vitro/in vivo fenretinide release. Conclusion Fenretinide/Eudragit® RL PO patches with 20 wt% Tween® 80 + 40 wt% sodium deoxycholate solubilizers exhibit excellent release behavior for further preclinical and/or clinical evaluation in oral cancer chemoprevention.

Development and in�vitro evaluation of mucoadhesive patches of methotrexate for targeted delivery in oral cancer

“…The cast polymer solution was allowed to dry at room temperature. Dried M-F7 and M-LP-F7 films measuring 1 cm 2 were packed in aluminum foil, and stored in desiccators at room temperature (27).…”

Advanced Drug Delivery Systems for Local Treatment of the Oral Cavity

“…In another work, Holpuch et al evaluated a novel mucoadhesive patch for local delivery to the oral cavity of the chemopreventive vitamin A analog fenretinide [85,86]. This drug was dispersed in Eudragit, a poly(meth)acrylate-based polymer, with a surrounding adhesive layer consisting of polycarbophil and hydroxypropyl methylcellulose, all well-known mucoadhesives.…”

Integrative review on oral cancer

“…The sequelae of tumors in the mouth lead the patient to face major functional and aesthetic sequelae due to the loss of essential tissues and thus decrease their quality of life. 6 The quality of life of patients with oral cancer is impaired, given that some surgical procedures necessary to remove the tumor may lead to a significant disability, including facial deformity, loss of hard and soft tissue, impaired speech, swallowing and chewing. 33 These complications have a significant impact on the functions of the patient, including the basic need to eat, drink or speak.…”