School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran.
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Biosensor Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Mater Sci Eng C Mater Biol Appl. 2019 Oct;103:109827. doi: 10.1016/j.msec.2019.109827. Epub 2019 May 30.
Non-spherical structures are beneficial to advance drug delivery effectiveness compared with common spherical ones, due to increased drug loading capability, improved bonding to a vascular wall, enhanced cellular uptake efficacy and prolonged circulation times. In this study, flower-like Zinc oxide-βcyclodextrin (βCD) nanostructures functionalized by 3-mercaptopropionic acid (MPA) as a non-spherical delivery system was successfully synthesized for aqueous delivery of curcumin (CUR) to enhance its targeting, bioavailability, and release profile. Terminal carboxyl functional groups were used for the conjugation of folic acid (FA) with the aim of active targeting to folate overexpressing breast cancer cells. The in vitro experimental study and mathematical modeling of CUR release revealed a sustained release with Fickian diffusion as the major release mechanism. MTT, colony formation and Annexin-V FITC/PI assays showed the superior anticancer effect of the system compared to free CUR against breast cancer cell line MDA-MB-231 by promoting the apoptotic respond with no cytotoxic effect on HEK293 normal cells. The efficacy of targeting strategy with FA moieties was demonstrated using the augmented cellular uptake of the FA-conjugated system on overexpressed folate receptor alpha (FRα) cells (MDA-MB-468 breast cancer cell line). Furthermore, loading of CUR to the delivery systems significantly lowered the MIC values (2.5 to 5-fold) against S. aureus and E. coli the infections of which are serious problems in cancer patients. According to the results of this study, the system can serve as a promising non-spherical delivery vehicle for enhancing bioavailability and targeting of hydrophobic anticancer agents in the future.
与常见的球形结构相比，非球形结构有利于提高药物输送效果，因为它具有更高的药物负载能力、更好的与血管壁结合能力、更高的细胞摄取效率和更长的循环时间。在这项研究中，成功合成了具有 3-巯基丙酸（MPA）官能化的花状氧化锌-β环糊精（βCD）纳米结构作为非球形给药系统，用于水相输送姜黄素（CUR），以提高其靶向性、生物利用度和释放特性。末端羧基官能团用于将叶酸（FA）与该系统缀合，以实现对叶酸过表达乳腺癌细胞的主动靶向。CUR 释放的体外实验研究和数学模型表明，该系统具有持续释放的特点，以菲克扩散为主要释放机制。MTT、集落形成和 Annexin-V FITC/PI 检测表明，与游离 CUR 相比，该系统对乳腺癌细胞系 MDA-MB-231 具有更好的抗癌效果，通过促进细胞凋亡反应而对正常细胞 HEK293 没有细胞毒性作用。通过 FRα 细胞（MDA-MB-468 乳腺癌细胞系）对具有 FA 部分的靶向策略的功效进行了证明，即通过增强对过表达叶酸受体 alpha（FRα）的细胞的摄取来实现。此外，将 CUR 载入给药系统显著降低了其对金黄色葡萄球菌和大肠杆菌感染的 MIC 值（降低了 2.5 到 5 倍），这些感染是癌症患者的严重问题。根据这项研究的结果，该系统可以作为一种有前途的非球形给药载体，用于提高疏水性抗癌药物的生物利用度和靶向性。
