School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721302, India.
Biomaterials. 2011 May;32(15):3794-806. doi: 10.1016/j.biomaterials.2011.01.027.
Celecoxib has shown potential anticancer activity against most carcinomas, especially in patients with familial adenomatous polyposis and precancerous disease of the colon. However, serious side effects of celecoxib restrict its generalized use for cancer therapy. In order to resolve these issues and develop an alternative strategy/preliminary approach, chitosan modified hydroxyapatite nanocarriers-mediated celecoxib delivery represents a viable strategy. We characterized the nanoparticle for morphology, particle size, zeta potential, crystalinity, functional group analysis, entrapment efficiency, drug release and hemocompatibility. The effects of celecoxib-loaded nanoparticles on colon cancer cell proliferation, morphology, cytoskeleton, cellular uptake and apoptosis were analysed in vitro. Further, we evaluated the antiproliferative, apoptotic and tumor inhibitory efficacy of celecoxib-loaded nanocarriers in a nude mouse human xenograft model. Nanoparticles exhibited small, narrow hydrodynamic size distributions, hemocompatibility, high entrapment efficiencies and sustained release profiles. In vitro studies showed significant antiproliferation, apoptosis and time-dependent cytoplasmic uptake of celecoxib-loaded Hap-Cht nanoparticles in HCT 15 and HT 29 colon cancer cells. Additional in vivo studies demonstrated significantly greater inhibition of tumor growth following treatment with this modified nanoparticle system. The present study indicates a promising, effective and safe means of using celecoxib, and potentially other therapeutic agents for colon cancer therapy.
塞来昔布对大多数癌症具有潜在的抗癌活性，特别是在家族性腺瘤性息肉病和结肠癌前病变患者中。然而，塞来昔布的严重副作用限制了其在癌症治疗中的广泛应用。为了解决这些问题并开发替代策略/初步方法，壳聚糖修饰的羟磷灰石纳米载体介导的塞来昔布递送代表了一种可行的策略。我们对纳米颗粒的形态、粒径、Zeta 电位、结晶度、官能团分析、包封效率、药物释放和血液相容性进行了表征。分析了载塞来昔布纳米颗粒对结肠癌细胞增殖、形态、细胞骨架、细胞摄取和凋亡的体外影响。此外，我们在裸鼠人异种移植模型中评估了载塞来昔布纳米载体的抗增殖、凋亡和肿瘤抑制功效。纳米颗粒表现出小的、窄的水动力粒径分布、血液相容性、高包封效率和持续释放特性。体外研究表明，载 Hap-Cht 纳米颗粒的塞来昔布在 HCT15 和 HT29 结肠癌细胞中具有显著的增殖抑制、凋亡和时间依赖性细胞质摄取作用。额外的体内研究表明，用这种改良的纳米颗粒系统治疗后，肿瘤生长的抑制作用显著增加。本研究表明，使用塞来昔布和潜在的其他治疗剂治疗结肠癌是一种有前途、有效和安全的方法。
