Arya Malti, Tiwari Prakash, Tripathi Chandra Bhushan, Parashar Poonam, Singh Mahendra, Sinha Priyam, Yadav Narayan P, Kaithwas Gaurav, Gupta Krishna P, Saraf Shubhini A
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University , Vidya Vihar, Raebareli Road, Lucknow-226025, U.P., India.
Environmental Carcinogenesis Division, CSIR-Indian Institute of Toxicology Research , Post Box No. 80, Mahatma Gandhi Marg, Lucknow-226001, U.P., India.
Mol Pharm. 2017 Mar 6;14(3):928-939. doi: 10.1021/acs.molpharmaceut.6b01147. Epub 2017 Feb 16.
Cancer is a global health problem and chemoprevention is a promising approach for reducing cancer burden. Inositol hexaphosphate (IP6), a natural bioactive constituent of cereals, legumes, etc., has momentous potential as an antiangiogenic agent, that specifically affects malignant cells. The shortcoming is its quick absorption on oral/topical administration. Niosomes are flexible carriers for topical drug delivery. The central venture of current research was to optimize and characterize niosomal delivery system of IP6 for treatment of skin cancer. Thin film hydration method was utilized to prepare IP6 niosomes, and these were dispersed as a suspension in a suitable base. Developed formulations were analyzed for various physicochemical and pharmacological parameters such as particle size, encapsulation efficiency, morphology, drug release, texture analysis, irritability, cell line studies, Western blotting, RT-PCR, and histopathology. IP6 niosomal suspension and IP6 in acetone displayed IC value at the concentration of 0.96 mM (0.63 mg/mL) and 1.39 mM (0.92 mg/mL), respectively. IP6 niosomal suspension showed significantly higher (p < 0.05) activity and showed cytotoxic effect in SK-MEL-2 cancer cell line. Crucial events of cellular proliferation and differentiation, like expression of ornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA), cycloxygenase-2 (COX-2) and Cyclin D1 were initiated from the fourth hour through application of 7,12-dimethylbenzanthracene (DMBA) on albino mice. The DMBA altered expression of aforesaid enzymes was significantly (P < 0.001) prevented by concomitant application of niosomal formulations. Results of cell line study, Western blotting, RT-PCR, and histopathology suggested that IP6 niosomal suspension could constitute a promising approach for prevention of cellular proliferation as well as DMBA induced dysregulation of cellular proliferation/differentiation and inflammation.
癌症是一个全球性的健康问题，化学预防是减轻癌症负担的一种有前景的方法。肌醇六磷酸（IP6）是谷物、豆类等的一种天然生物活性成分，作为一种抗血管生成剂具有巨大潜力，它能特异性地影响恶性细胞。缺点是口服/局部给药时吸收迅速。脂质体是用于局部药物递送的灵活载体。当前研究的核心任务是优化并表征用于治疗皮肤癌的IP6脂质体递送系统。采用薄膜水化法制备IP6脂质体，并将其作为悬浮液分散在合适的基质中。对所开发的制剂进行各种物理化学和药理学参数分析，如粒径、包封率、形态、药物释放、质地分析、刺激性、细胞系研究、蛋白质印迹法、逆转录聚合酶链反应以及组织病理学。IP6脂质体悬浮液和丙酮中的IP6在浓度分别为0.96 mM（0.63 mg/mL）和1.39 mM（0.92 mg/mL）时显示出IC值。IP6脂质体悬浮液显示出显著更高（p < 0.05）的活性，并在SK-MEL-2癌细胞系中表现出细胞毒性作用。细胞增殖和分化的关键事件，如鸟氨酸脱羧酶（ODC）、增殖细胞核抗原（PCNA）、环氧化酶-2（COX-2）和细胞周期蛋白D1的表达，在对白化病小鼠应用7,12-二甲基苯并蒽（DMBA）后从第四小时开始启动。同时应用脂质体制剂可显著（P < 0.001）阻止DMBA对上述酶表达的改变。细胞系研究、蛋白质印迹法、逆转录聚合酶链反应以及组织病理学的结果表明，IP6脂质体悬浮液可能是预防细胞增殖以及DMBA诱导的细胞增殖/分化失调和炎症的一种有前景的方法。
