Abstract：
Irinotecan (CPT-11) is used as a first or second-line chemotherapy drug for the treatment and management of colorectal cancers. In vitro studies have shown that 7-ethyl-10-hydroxycamptothecin (SN38), the active metabolite of CPT-11, displays promising anticancer efficacy. However, its poor aqueous solubility and hydrolytic degradation result in its lower oral bioavailability and impracticable clinical application. To overcome these limitations, a novel amphiphilic chitosan derivative, deoxycholic acid decorated N\'-nonyl-trimethyl chitosan, was synthesized. Nano-micelles loaded with SN38 were subsequently prepared to enhance the bioavailability and anti-tumor efficacy of the drug through oral administration. The nano-micelles demonstrated improved dilution stability, enhanced greater mucosal adherence, significant P-gp efflux inhibition, and increased drug transport in the intestine by paracellular and transcellular pathways. Consequently, both the in vivo pharmacokinetic profile and therapeutic efficacy of SN38 against cancer were substantially improved via the micellar system. Thus, the developed polymeric micelles can potentially enhance the SN38 oral absorption for cancer therapy, offering prospective avenues for further exploration.
摘要：
伊立替康（CPT-11）用作治疗和管理结直肠癌的一线或二线化疗药物。体外研究表明，7-乙基-10-羟基喜树碱（SN38），CPT-11的活性代谢产物显示有希望的抗癌功效。然而,其水溶性差和水解降解导致其口服生物利用度较低，临床应用不可行。为了克服这些限制,一种新型的两亲性壳聚糖衍生物，脱氧胆酸修饰的N'-壬基-三甲基壳聚糖，是合成的。随后制备负载有SN38的纳米胶束以通过口服给药增强药物的生物利用度和抗肿瘤功效。纳米胶束表现出改善的稀释稳定性，增强更大的粘膜粘附，显著的P-gp外排抑制，并通过旁细胞和跨细胞途径增加肠道中的药物运输。因此,SN38的体内药代动力学特征和治疗癌症的疗效均通过胶束系统得到显著改善.因此，开发的聚合物胶束可以潜在地增强SN38口服吸收用于癌症治疗，为进一步探索提供了潜在的途径。
