caa a22 4500 445313064 CHVBK 20180317142636.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s11095-011-0489-3 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0489-3 Development and In Vitro - In Vivo Evaluation of Fenretinide-Loaded Oral Mucoadhesive Patches for Site-Specific Chemoprevention of Oral Cancer [Elektronische Daten] [Kashappa-Goud Desai, Susan Mallery, Andrew Holpuch, Steven Schwendeman] 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 (5-10wt%) or changes in polymeric matrix permeability did not provide continuous drug release. Co-incorporation of either single or mixed solubilizers in fenretinide/Eudragit® patches, (20wt% Tween® 20, Tween® 80 and sodium deoxycholate or 20wt% Tween® 80 + 40wt% sodium deoxycholate solubilizers) led to significantly improved continuous in vitro/in vivo fenretinide release. Conclusion: Fenretinide/Eudragit® RL PO patches with 20wt% Tween® 80 + 40wt% sodium deoxycholate solubilizers exhibit excellent release behavior for further preclinical and/or clinical evaluation in oral cancer chemoprevention. Springer Science+Business Media, LLC, 2011 controlled release nationallicence Eudragit® nationallicence fenretinide nationallicence intraoral drug delivery nationallicence cancer chemoprevention nationallicence mucoadhesive patch nationallicence solubilization nationallicence Desai Kashappa-Goud Department of Pharmaceutical Sciences, University of Michigan, 428 Church St., Ann Arbor, Michigan, USA aut Mallery Susan Department of Oral Maxillofacial Surgery and Pathology, College of Dentistry and the Comprehensive Cancer Center and Solove Research Institute, The Ohio State University, Columbus, Ohio, USA aut Holpuch Andrew Department of Oral Maxillofacial Surgery and Pathology, College of Dentistry and the Comprehensive Cancer Center and Solove Research Institute, The Ohio State University, Columbus, Ohio, USA aut Schwendeman Steven Department of Pharmaceutical Sciences, University of Michigan, 428 Church St., Ann Arbor, Michigan, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/10(2011-10-01), 2599-2609 0724-8741 28:10<2599 2011 28 11095 https://doi.org/10.1007/s11095-011-0489-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0489-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Desai Kashappa-Goud Department of Pharmaceutical Sciences, University of Michigan, 428 Church St., Ann Arbor, Michigan, USA aut NATIONALLICENCE 700 1- Mallery Susan Department of Oral Maxillofacial Surgery and Pathology, College of Dentistry and the Comprehensive Cancer Center and Solove Research Institute, The Ohio State University, Columbus, Ohio, USA aut NATIONALLICENCE 700 1- Holpuch Andrew Department of Oral Maxillofacial Surgery and Pathology, College of Dentistry and the Comprehensive Cancer Center and Solove Research Institute, The Ohio State University, Columbus, Ohio, USA aut NATIONALLICENCE 700 1- Schwendeman Steven Department of Pharmaceutical Sciences, University of Michigan, 428 Church St., Ann Arbor, Michigan, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/10(2011-10-01), 2599-2609 0724-8741 28:10<2599 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer