Singh Sima, Kotla Niranjan G, Tomar Sonia, Maddiboyina Balaji, Webster Thomas J, Sharma Dinesh, Sunnapu Omprakash
Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
Technologies for the Advancement of Science, Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, Karnataka, India.
Int J Nanomedicine. 2015 Nov 23;10:7175-82. doi: 10.2147/IJN.S89030. eCollection 2015.
Targeted drug delivery plays a significant role in disease treatment associated with the colon, affording therapeutic responses for a prolonged period of time with low side effects. Colorectal cancer is the third most common cancer in both men and women with an estimated 102,480 cases of colon cancer and 40,340 cases of rectal cancer in 2013 as reported by the American Cancer Society. In the present investigation, we developed an improved oral delivery system for existing anticancer drugs meant for colon cancer via prebiotic and probiotic approaches. The system comprises three components, namely, nanoparticles of drug coated with natural materials such as guar gum, xanthan gum (that serve as prebiotics), and probiotics. The natural gums play a dual role of protecting the drug in the gastric as well as intestinal conditions to allow its release only in the colon. In vitro results obtained from these experiments indicated the successful targeted delivery of 5-fluorouracil to the colon. Electron microscopy results demonstrated that the prepared nanoparticles were spherical in shape and 200 nm in size. The in vitro release data indicated that the maximum release occurs at pH 7.2 and 7.4 with 93% of the drug released in the presence of 4% (w/v) of rat cecal content. In vivo results conclude a practical mechanism to maintain the integrity and intactness of the intestinal/colonic microflora, in the face of a "chemical attack" by oral colon-targeted drug delivery for colon cancer treatment.
靶向给药在与结肠相关的疾病治疗中发挥着重要作用,能在长时间内提供治疗效果且副作用低。根据美国癌症协会的报告,结直肠癌是男性和女性中第三大常见癌症,2013年估计有102,480例结肠癌病例和40,340例直肠癌病例。在本研究中,我们通过益生元和益生菌方法开发了一种用于现有结肠癌抗癌药物的改进口服给药系统。该系统由三个部分组成,即包裹有天然材料(如瓜尔胶、黄原胶,它们作为益生元)的药物纳米颗粒和益生菌。天然胶在胃和肠道环境中起到保护药物的双重作用,使其仅在结肠中释放。这些实验获得的体外结果表明5-氟尿嘧啶成功靶向递送至结肠。电子显微镜结果表明制备的纳米颗粒呈球形,尺寸为200nm。体外释放数据表明最大释放在pH 7.2和7.4时发生,在存在4%(w/v)大鼠盲肠内容物的情况下93%的药物被释放。体内结果得出了一种实际机制,即在口服结肠靶向给药用于结肠癌治疗的“化学攻击”面前,维持肠道/结肠微生物群的完整性和完好性。