Department of Applied Thai Traditional Medicine, Faculty of Medicine, Thammasat University, Khlong Nueng 12120, Pathumthani, Thailand.
Centre of Excellence, Applied Thai Traditional Medicine Research (CEATMR), Thammasat University, Khlong Nueng 12120, Pathumthani, Thailand.
ScientificWorldJournal. 2022 Aug 30;2022:9217268. doi: 10.1155/2022/9217268. eCollection 2022.
Alpha-mangostin, a natural xanthone mainly extracted from the pericarp of , has been shown to have promising anticancer properties in many types of cancer. However, the therapeutic potential of -mangostin has been limited so far due to its poor aqueous solubility and low oral bioavailability, which limited its biopharmaceutical applications. Furthermore, -mangostin failed to specifically reach tumors at a therapeutic concentration due and rapid elimination . We hypothesized that this drawback could be overcome by loading the drug within a delivery system conjugated to transferrin (Tf), whose receptors are overexpressed on many cancer cells and would enhance the specific delivery of -mangostin to cancer cells, thereby enhancing its therapeutic efficacy. The objectives of this study were therefore to prepare and characterize transferrin-conjugated lipid-polymer hybrid nanoparticles (LPHN) entrapping -mangostin, as well as to evaluate their therapeutic efficacy . We successfully prepared -mangostin loaded LPHN using a one-step nanoprecipitation method with high drug entrapment efficiency. The conjugation of Tf to the LPHN was achieved by using the thiol-maleimide "click" reaction, leading to an increase in the particle hydrodynamic size of Tf-LPHN compared to that of unconjugated (control) LPHN (Ctrl-LPHN). Both Tf-LPHN and Ctrl-LPHN were bearing negative surface charges. Tf-LPHN and Ctrl-LPHN exhibited a sustained release of -mangostin at pH 7.4, following an initial burst release, unlike rapid release of drug solution. The entrapment of -mangostin in the LPHN led to an increase in -mangostin uptake by cancer cells, and thus improved its antiproliferative activity compared to that observed with the drug solution. In conclusion, -mangostin entrapped in the Tf-LPHN is therefore a highly promising therapeutic system that should be further optimized as therapeutic tools for cancer treatment.
α-倒捻子素是一种天然的呫吨酮，主要从果皮中提取，已被证明在许多类型的癌症中有很好的抗癌特性。然而，到目前为止，由于其较差的水溶性和低口服生物利用度，-倒捻子素的治疗潜力受到限制，这限制了其生物制药的应用。此外，由于迅速消除，-倒捻子素未能在治疗浓度下特异性到达肿瘤。我们假设，通过将药物加载到与转铁蛋白（Tf）结合的递药系统中，可以克服这一缺点，Tf 的受体在许多癌细胞上过表达，这将增强-倒捻子素向癌细胞的特异性递药，从而增强其治疗效果。因此，本研究的目的是制备和表征负载-倒捻子素的转铁蛋白偶联的脂质-聚合物杂化纳米粒（LPHN），并评估其治疗效果。我们成功地使用一步纳米沉淀法制备了负载-倒捻子素的 LPHN，该方法具有高药物包封效率。通过使用巯基-马来酰亚胺“点击”反应将 Tf 偶联到 LPHN 上，与未偶联的（对照）LPHN（Ctrl-LPHN）相比，Tf-LPHN 的颗粒水动力粒径增加。Tf-LPHN 和 Ctrl-LPHN 均带负表面电荷。与药物溶液的快速释放不同，Tf-LPHN 和 Ctrl-LPHN 在 pH 7.4 下均表现出-倒捻子素的持续释放，最初有突释释放。-倒捻子素在 LPHN 中的包封导致癌细胞摄取-倒捻子素增加，从而提高了其抗增殖活性，优于观察到的药物溶液。总之，负载在 Tf-LPHN 中的-倒捻子素是一种很有前途的治疗系统，应进一步优化，作为癌症治疗的治疗工具。
