Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand; Research Unit for Plant-produced Pharmaceuticals, Chulalongkorn University, Bangkok, Thailand.
National Nanotechnology Center (NANOTEC), National Science and Technology Development Agency, 111 Thailand Science Park, Phahonyothin Rd., Khlong Luang, Pathumthani 12120, Thailand.
Colloids Surf B Biointerfaces. 2021 Jan;197:111369. doi: 10.1016/j.colsurfb.2020.111369. Epub 2020 Sep 19.
Cordycepin, a derivative of the nucleotide adenosine, has displayed several pharmacological activities including enhanced apoptosis and cancer cells inhibition. However, oral administration of cordycepin has limited practical use due to its poor bioavailability in the intestine. Herein, we developed and demonstrated a hybrid nanocarrier system in the form of biloniosome-core/chitosan-shell hybrid nanocarriers (HNCs) in order to improve the bio-characteristics of cordycepin. In this study, HNCs were prepared by using a solvent (ethanol) injection method involving cordycepin as the biloniosome core and mucoadhesive chitosan biopolymer as a coating shell. Our results showed that the cordycepin-loaded HNCs were positively charged with enhanced mucoadhesive characteristics and highly stable in gastric fluid. The increased permeability of cordycepin-loaded HNCs compared with standard cordycepin was confirmed by in vitro intestinal permeation study across the human intestinal barrier. In addition, we demonstrated that the cordycepin-loaded HNCs are able to release their components in an active form resulting in enhanced anti-cancer activity in two-dimensional (2D) cell cultures as well as in three-dimensional (3D) multi-cellular spheroids of colon cancer cells. Further, quantitative real time PCR analysis of apoptotic gene expression revealed that cordycepin HNCs can induce apoptosis in cancer cells by negatively regulating the expression of B-cell lymphoma-extra large (BCL-XL). I Overall our results showed that the hybrid nanocarrier systems represent a promising strategy for improving the bio-characteristics of cordycepin which can be considered as a potential anti-cancer agent for colorectal cancer chemotherapy.
蛹虫草素是核苷酸腺苷的衍生物，具有多种药理活性，包括增强细胞凋亡和抑制癌细胞。然而，由于其在肠道中的生物利用度低，口服蛹虫草素的实际应用受到限制。在此，我们开发并展示了一种以双层囊泡-壳聚糖混合纳米载体（HNC）形式存在的混合纳米载体系统，以改善蛹虫草素的生物特性。在这项研究中，HNCs 是通过使用溶剂（乙醇）注射法制备的，其中蛹虫草素作为双层囊泡核心，粘多糖壳聚糖生物聚合物作为涂层壳。我们的结果表明，载有蛹虫草素的 HNCs 带正电荷，具有增强的粘附特性，在胃液中高度稳定。通过体外肠渗透研究证实，载有蛹虫草素的 HNCs 的渗透性比标准蛹虫草素有所提高，穿过人肠屏障。此外，我们证明载有蛹虫草素的 HNCs 能够以活性形式释放其成分，从而增强二维（2D）细胞培养和结肠癌多细胞球体中的抗癌活性。此外，凋亡基因表达的定量实时 PCR 分析表明，蛹虫草素 HNCs 可以通过负调控 B 细胞淋巴瘤-extra large（BCL-XL）的表达来诱导癌细胞凋亡。总的来说，我们的结果表明，混合纳米载体系统代表了一种改善蛹虫草素生物特性的有前途的策略，可被认为是结直肠癌化疗的潜在抗癌药物。
