Development and in vitro-in vivo evaluation of fenretinide-loaded oral mucoadhesive patches for site-specific chemoprevention of oral cancer.
Development and in vitro-in vivo evaluation of fenretinide-loaded oral mucoadhesive patches for site-specific chemoprevention of oral cancer.
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DOI：
10.1007/s11095-011-0489-3
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发表时间：
2011-10
影响因子：
3.7
通讯作者：
Schwendeman, Steven P.
中科院分区：
文献类型：
--
作者：
Desai, Kashappa-Goud H.;Mallery, Susan R.;Holpuch, Andrew S.;Schwendeman, Steven P.
关键词：
开发芬维A胺口腔粘膜粘附贴片制剂，并评价其体外和体内释放性能，用于口腔癌的未来位点特异性化学预防。通过掺入非离子表面活性剂（Tween® 20和80以及Brij® 35和98）、胆汁盐（胆酸、牛磺胆酸、甘氨胆酸和脱氧胆酸的钠盐）、磷脂（卵磷脂）和新型聚合增溶剂（Souplus®），研究芬维A胺在模拟唾液（SS）中的增溶作用。粘合剂（聚卡波非：通过溶剂流延制备药物释放层（具有或不具有增溶剂的芬维A胺/Eudragit® RL PO）。通过将药物和粘合剂层附着到背衬层（TegadosilTM膜）上来形成口腔粘膜粘附贴剂。通过X射线衍射（XRD）检查Eudragit®膜中药物的物理状态。分别在含有5%w/v脱氧胆酸钠的SS和家兔中进行体外和体内芬维A胺贴剂释放的评价。采用高效液相色谱法对芬维A胺进行定量。Tween® 20和80、Brij® 98和脱氧胆酸钠在增溶剂中表现出最高的芬维A胺增溶潜力。Eudragit®膜中的药物负载效率为90%-97%。XRD分析表明，在无增溶剂和负载增溶剂的薄膜中，芬维A胺是无定形的。无增溶剂贴剂的体外和体内药物控释性能均较差。载药量的增加（5- 10wt%）或聚合物基质渗透性的变化不能提供连续的药物释放。在芬维A胺/Eudragit®贴剂中共掺入单一或混合增溶剂（20重量% Tween® 20、Tween® 80和脱氧胆酸钠或20重量% Tween® 80 + 40重量%脱氧胆酸钠增溶剂）导致显著改善的体外/体内芬维A胺连续释放。具有20重量% Tween® 80 + 40重量%脱氧胆酸钠增溶剂的芬维A胺/Eudragit® RL PO贴剂表现出优异的释放行为，用于口腔癌化学预防的进一步临床前和/或临床评价。
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. 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. 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. 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.
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影响因子：
11.5
作者：
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通讯作者：
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