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Mucoadhesive Fenretinide Patches for Site-Specific Chemoprevention of Oral Cancer: Enhancement of Oral Mucosal Permeation of Fenretinide by Coincorporation of Propylene Glycol and Menthol
journal contribution
posted on 2012-04-02, 00:00 authored by Xiao Wu, Kashappa-Goud H. Desai, Susan
R. Mallery, Andrew S. Holpuch, Maynard P. Phelps, Steven P. SchwendemanThe objective of this study was to enhance oral mucosal
permeation
of fenretinide by coincorporation of propylene glycol (PG) and menthol
in fenretinide/Eudragit RL PO mucoadhesive patches. Fenretinide is
an extremely hydrophobic chemopreventive compound with poor tissue
permeability. Coincorporation of 5–10 wt % PG (mean Js = 16–23 μg cm–2 h–1; 158–171 μg of fenretinide/g
of tissue) or 1–10 wt % PG + 5 wt % menthol (mean Js = 18–40 μg cm–2 h–1; 172–241 μg of fenretinide/g of tissue)
in fenretinide/Eudragit RL PO patches led to significant ex
vivo fenretinide permeation enhancement (p < 0.001). Addition of PG above 2.5 wt % in the patch resulted
in significant cellular swelling in the buccal mucosal tissues. These
alterations were ameliorated by combining both enhancers and reducing
PG level. After buccal administration of patches in rabbits, in vivo permeation of fenretinide across the oral mucosa
was greater (∼43 μg fenretinide/g tissue) from patches
that contained optimized permeation enhancer content (2.5 wt % PG
+ 5 wt % menthol) relative to permeation obtained from enhancer-free
patch (∼17 μg fenretinide/g tissue) (p < 0.001). In vitro and in vivo release of fenretinide from patch was not significantly increased
by coincorporation of permeation enhancers, indicating that mass transfer
across the tissue, and not the patch, largely determined the permeation
rate control in vivo. As a result of its improved
permeation and its lack of deleterious local effects, the mucoadhesive
fenretinide patch coincorporated with 2.5 wt % PG + 5 wt % menthol
represents an important step in the further preclinical evaluation
of oral site-specific chemoprevention strategies with fenretinide.
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Keywords
Oral CancerRLpermeation rate controlPropylene Glycolpermeation enhancersmucoadhesive fenretinide patch coincorporatedbuccal mucosal tissuesPOvivo releasewtMucoadhesive Fenretinide PatchesMentholThe objectivemass transferOral Mucosal Permeationtissue permeabilitychemopreventive compoundpropylene glycolvivo permeationbuccal administrationPG levelmucosal permeationvivo fenretinide permeation enhancement
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