Enhancing the solubility and potency of tetrahydrocurcumin as an anti-cancer agent using a β-cyclodextrin inclusion complex approach

Author:

Low Zhi XuanORCID,Teo Michelle Yee MunORCID,Juliana Nordin Fariza,Palanirajan Vijayaraj KumarORCID,Morak-Młodawska BeataORCID,Saleem Qazi Asma,In Lionel Lian Aun

Abstract

Curcuminoids originating from turmeric roots are renowned for their diverse pharmacological applications, particularly as a natural anticancer agent. Unfortunately, harnessing the full potential of curcumin derivatives in cancer therapy has been impeded by its inherent limitations, specifically instabilities owing to poor solubility, leading to low systemic bioavailability under normal physiological circumstances. To circumvent this, a novel organic-based drug delivery system employing physically adsorbed β-cyclodextrin (βCD) as an excipient was developed in this study. This resulted in improved aqueous dispersion coupled with anticancer enhancements of tetrahydrocurcumin (THC) at a molar ratio of 2:1. Encapsulation of this agent was confirmed by physicochemical characterisation using UV–vis spectroscopy, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and both in vitro and in vivo approaches. Through the presence of an inclusion complex, a higher aqueous dispersion (65-fold) resulting in a higher drug content and an elevated release profile was achieved. Athymic nude (Nu/Nu) mice exposed to this treatment displayed improvements in tumour regression compared to stand-alone agents, consistent with in vitro cytotoxicity assays with an SI value > 10. The inclusion complex further enhanced apoptosis, as well as anti-migration and anti-invasion rates. Mechanistically, this formulation was consistent in terms of caspase 3 activation. Furthermore, the inclusion complex exhibited reduced systemic toxicity, including reduced inflammation in vital organs as examined by hematoxylin and eosin (H&E) staining. This study also revealed a notable sequential reduction in serum levels of tumour markers, including carcinoembryonic antigen (CEA) and mouse Cytochrome P450 1A2 (CYP1A2), correlating with a significant decrease in tumour bulk volume upon treatment commencement. These compelling findings highlight the potential of this formulation to empower insoluble or poorly soluble hydrophobic agents, thus offering promising prospects for their effective utilisation in colorectal cancer (CRC) chemotherapy.

Funder

Ministry of Higher Education, Malaysia

UCSI University Research Excellence & Innovation Grant

National University of Medical Sciences

Publisher

Public Library of Science (PLoS)

Reference57 articles.

1. Genetic resources of Curcuma: diversity, characterization and utilization;B. Sasikumar;Plant Genet Resour,2005

2. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: A review of preclinical and clinical research;JS Jurenka;Altern Med Rev,2009

3. Zingiberaceae extracts for pain: A systematic review and meta-analysis;SE Lakhan;Nutr J,2015

4. Anti-cancer and anti-angiogenic effects of curcumin and tetrahydrocurcumin on implanted hepatocellular carcinoma in nude mice;P Yoysungnoen;World J Gastroenterol,2008

5. Chemical Composition and Product Quality Control of Turmeric (Curcuma longa L.).;S. Li;Pharm Crop.,2011

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3