Gavin Amy, Pham Jimmy Th, Wang Dawei, Brownlow Bill, Elbayoumi Tamer A
College of Dental Medicine, Midwestern University, Glendale, AZ, USA.
Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA.
Int J Nanomedicine. 2015 Feb 23;10:1569-84. doi: 10.2147/IJN.S75474. eCollection 2015.
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.
口腔癌和口咽癌被认为是全球第八大常见癌症，预后相对较差（诊断后5年生存率为62%）。本研究的目的是开发一种概念验证性的粘膜粘附含片/口腔贴片，作为治疗性抗有丝分裂纳米药物直接持续递送的潜在平台。我们的系统将作为接受全面诊断和手术治疗方案的口腔癌患者的辅助治疗。我们使用了基于脂质的纳米载体，即纳米乳剂（NEs），其含有混合聚乙氧基化乳化剂和富含生育酚部分的油相。负载促凋亡亲脂性药物染料木黄酮（Gen）的原型纳米乳剂被进一步加工成口腔贴片制剂。壳聚糖聚电解质溶液外涂层通过作为粘膜粘附界面纳米乳剂层使纳米乳剂液滴带阳离子。与带负电荷的无壳聚糖/原始水性纳米乳剂（-28 mV）相比，带正电荷的壳聚糖层纳米乳剂（+25 mV）尺寸约为110 nm，对液体口腔喷雾原型表现出控释特性和有效的粘膜粘附性。冲压成型后，对基于纳米乳剂的多孔口腔贴片进行了物理评估，包括硬度、脆碎度和溶胀度，以及体外组织粘膜粘附力和保留时间测量。含壳聚糖的纳米乳剂片在压缩试验中被发现与原始纳米乳剂片和安慰剂片相当，但在所有体外粘附和体外释放试验中明显更优（P≤0.05）。在对原型壳聚糖层纳米乳剂进行生物相容性筛选后，观察到所选阳离子负载Gen的纳米乳剂制剂对两种口咽癌具有显著的抗癌活性。数据有力地表明了这种纳米粘膜粘附系统作为等待手术切除的口腔癌患者或已切除确定癌性病变患者维持治疗的潜力。
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