International Journal of Nanomedicine, 2015, 10(default):1569-1584.

layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics

Amy Gavin, Jimmy TH Pham, Dawei Wang, et al

College of Dental Medicine, Midwestern University, Glendale, AZ, USA; et al

Oral cavity and oropharyngeal cancers are considered the eighth most common cancer worldwide, with relatively poor prognosis (62% of patients surviving 5 years, after diagnosis). The aim of this study was to develop a proof-of-concept mucoadhesive lozenge/buccal tablet, as a potential platform for direct sustained delivery of therapeutic antimitotic nanomedicines. Our system would serve as an adjuvant therapy for oral cancer patients undergoing full-scale diagnostic and operative treatment plans. We utilized lipid-based nanocarriers, namely nanoemulsions (NEs), containing mixed-polyethoxylated emulsifiers and a tocopheryl moiety–enriched oil phase. Prototype NEs, loaded with the proapoptotic lipophilic drug genistein (Gen), were further processed into buccal tablet formulations. The chitosan polyelectrolyte solution overcoat rendered NE droplets cationic, by acting as a mucoadhesive interfacial NE layer. With approximate size of 110 nm, the positively charged chitosan-layered NE (+25 mV) vs negatively charged chitosan-free/primary aqueous NE (−28 mV) exhibited a controlled-release profile and effective mucoadhesion for liquid oral spray prototypes. When punch-pressed, porous NE-based buccal tablets were physically evaluated for hardness, friability, and swelling in addition to ex vivo tissue mucoadhesion force and retention time measurements. Chitosan-containing NE tablets were found equivalent to primary NE and placebo tablets in compression tests, yet significantly superior in all ex vivo adhesion and in vitro release assays (P≤0.05). Following biocompatibility screening of prototype chitosan-layered NEs, substantial anticancer activity of selected cationic Gen-loaded NE formulations, against two oropahryngeal carcinomas, was observed. The data strongly indicate the potential of such nanomucoadhesive systems as maintenance therapy for oral cancer patients awaiting surgical removal, or postresection of identified cancerous lesions.

新西兰《国际纳米医学杂志》

层式纳米乳液作为粘附口腔的方法用于口腔癌疗法的控制药物输送

美国中西部大学牙科医学院，格伦代尔，美国; et al

口腔和口咽癌被认为是全球第八大常见癌症，预后相对较差（62％的患者在诊断后存活5年）。这项研究的目的是开发一个概念验证粘膜粘合剂锭剂/口腔片，作为直接持续递送治疗性抗生物素的纳米药物的潜在平台。我们的系统将作为接受全面诊断和手术治疗计划的口腔癌患者的辅助治疗。我们利用脂质纳米载体，即含有混合聚乙氧基化乳化剂和富含生育酚基团的油相的纳米乳剂（NE）。将载有促凋亡亲脂性药物染料木黄酮（Gen）的原型NE进一步加工成颊片剂。通过充当粘膜粘附界面NE层，壳聚糖聚电解质溶液外涂层使NE液滴阳离子化。近似大小为110nm，带正电荷的壳聚糖层状NE（+25mV）与带负电荷的无壳聚糖/初级含水NE（-28mV）呈现出液体口服喷雾原型的控制释放曲线和有效粘膜粘附。当冲压时，除了离体组织粘膜粘附力和保留时间测量之外，物理地评估多孔的NE-基颊片的硬度，脆性和肿胀。发现含有壳聚糖的NE片剂在压缩试验中与原代NE和安慰剂片相当，但在所有离体粘附和体外释放试验中均显着优于（P≤0.05）。在生物相容性筛选原型壳聚糖层状NE之后，观察到选择的阳离子加载NE的制剂对两种oropahryngeal癌具有显着的抗癌活性。这些数据强烈地表明这种纳米粘附系统作为等待手术切除的口腔癌患者的维持治疗或确定的癌性病变的后期的潜力。