Kaur Jaskiran, Gulati Monica, Gowthamarajan K, Vishwas Sukriti, Kumar Chellappan Dinesh, Gupta Gaurav, Dua Kamal, Pandey Narendra Kumar, Kumar Bimlesh, Singh Sachin Kumar
School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India.
Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India; Centre of Excellence in Nanoscience & Technology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India.
Med Hypotheses. 2021 Nov;156:110679. doi: 10.1016/j.mehy.2021.110679. Epub 2021 Sep 14.
Colon cancer is characterised by the persistent change in bowel habits due to the formation of polyps (cancerous) in the inner lining of the colon. Clinically, there are several anticancer drugs available to treat colon cancer. Oxaliplatin (third generation platinum drug) is widely prescribed anticancer drug due to its broad range anticancer properties and low toxicities over cisplatin and carboplatin. Currently, use of oxaliplatin as adjuvant chemotherapy represents a standard care for the treatment of advanced colon cancer. Despite this, its rapid degradation in systemic circulations upon administration, lack of tumor specificity, and low bioavailability limits its anticancer potential. On the other hand, vanillic acid (VA) has shown anticancer potential in colon cancer by targeting mTOR/Ras pathway, HIF-1α inhibition, NF-ĸB, and Nrf2 that regulate cell growth, cell survival, proliferation and adaptation to cancer microenvironment. Normal oral delivery of these two drugs offers non-specific drug release in gastrointestinal tract that leads to unwanted toxicity and very less amount of drug become available for colonic site. Therefore, loading of these two drugs in polysaccharide based functionalized polymeric micelles (FPMs) can offer selective targeting at colonic site and could offer better therapeutic efficacy at much lesser doses of drugs. Therefore, a new hypothesis has been proposed that the combination of vanillic acid with oxaliplatin co-loaded in FPMs could provide colon targeting ability with enhanced potency and safety profile by targeting multiple pathways than current adjuvant chemotherapies available in the market for the treatment of colon cancer.
结肠癌的特征是由于结肠内层形成息肉(癌性)而导致排便习惯持续改变。临床上,有几种抗癌药物可用于治疗结肠癌。奥沙利铂(第三代铂类药物)因其广泛的抗癌特性以及相对于顺铂和卡铂较低的毒性而被广泛处方。目前,使用奥沙利铂作为辅助化疗是晚期结肠癌治疗的标准方案。尽管如此,其在给药后在体循环中迅速降解、缺乏肿瘤特异性以及低生物利用度限制了其抗癌潜力。另一方面,香草酸(VA)已通过靶向调节细胞生长、细胞存活、增殖以及对癌症微环境适应的mTOR/Ras通路、抑制HIF-1α、NF-κB和Nrf2,在结肠癌中显示出抗癌潜力。这两种药物的常规口服给药在胃肠道中提供非特异性药物释放,这会导致不必要的毒性,并且只有极少量的药物可到达结肠部位。因此,将这两种药物负载于基于多糖的功能化聚合物胶束(FPMs)中可实现结肠部位的选择性靶向,并能以更低剂量的药物提供更好的治疗效果。因此,有人提出了一种新的假说,即负载于FPMs中的香草酸与奥沙利铂联合使用,通过靶向多种通路,相比于目前市场上用于治疗结肠癌的辅助化疗,可提供具有更强效力和安全性的结肠靶向能力。