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基于食品级载姜黄素中链甘油三酯包封κ-卡拉胶(CUR-MCT-KC)凝胶珠的口服给药制剂的处方开发

Formulation Development of a Food-Graded Curcumin-Loaded Medium Chain Triglycerides-Encapsulated Kappa Carrageenan (CUR-MCT-KC) Gel Bead Based Oral Delivery Formulation.

作者信息

Tan Kei-Xian, Ng Ling-Ling Evelyn, Loo Say Chye Joachim

机构信息

School of Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore.

Esco Aster, Block 71, Ayer Rajah Crescent, Singapore 139951, Singapore.

出版信息

Materials (Basel). 2021 May 24;14(11):2783. doi: 10.3390/ma14112783.

Abstract

In recent years, curcumin has been a major research endeavor in food and biopharmaceutical industries owing to its miscellaneous health benefits. There is an increasing amount of research ongoing in the development of an ideal curcumin delivery system to resolve its limitations and further enhance its solubility, bioavailability and bioactivity. The emergence of food-graded materials and natural polymers has elicited new research interests into enhanced pharmaceutical delivery due to their unique properties as delivery carriers. The current study is to develop a natural and food-graded drug carrier with food-derived MCT oil and a seaweed-extracted polymer called k-carrageenan for oral delivery of curcumin with improved solubility, high gastric resistance, and high encapsulation of curcumin. The application of k-carrageenan as a structuring agent that gelatinizes o/w emulsion is rarely reported and there is so far no MCT-KC system established for the delivery of hydrophobic/lipophilic molecules. This article reports the synthesis and a series of in vitro bio-physicochemical studies to examine the performance of CUR-MCT-KC as an oral delivery system. The solubility of CUR was increased significantly using MCT with a good encapsulation efficiency of 73.98 ± 1.57% and a loading capacity of 1.32 ± 0.03 mg CUR/mL MCT. CUR was successfully loaded in MCT-KC, which was confirmed using FTIR and SEM with good storage and thermal stability. Dissolution study indicated that the solubility of CUR was enhanced two-fold using heated MCT oil as compared to naked or unformulated CUR. In vitro release study revealed that encapsulated CUR was protected from premature burst under simulated gastric environment and released drastically in simulated intestinal condition. The CUR release was active at intestinal pH with the cumulative release of >90% CUR after 5 h incubation, which is the desired outcome for CUR absorption under human intestinal conditions. A similar release profile was also obtained when CUR was replaced with beta-carotene molecules. Hence, the reported findings demonstrate the potencies of MCT-KC as a promising delivery carrier for hydrophobic candidates such as CUR.

摘要

近年来,姜黄素因其多种健康益处而成为食品和生物制药行业的主要研究对象。为了解决其局限性并进一步提高其溶解度、生物利用度和生物活性,人们正在开展越来越多关于开发理想姜黄素递送系统的研究。食品级材料和天然聚合物的出现,因其作为递送载体的独特性质,引发了对增强药物递送的新研究兴趣。当前的研究旨在开发一种天然且食品级的药物载体,该载体由食品来源的中链甘油三酯(MCT)油和一种从海藻中提取的名为κ-卡拉胶的聚合物组成,用于口服递送姜黄素,以提高其溶解度、增强胃耐受性并实现姜黄素的高包封率。κ-卡拉胶作为使油包水乳液凝胶化的结构化剂的应用鲜有报道,并且目前尚未建立用于递送疏水/亲脂性分子的MCT-κC系统。本文报道了合成过程以及一系列体外生物物理化学研究,以考察CUR-MCT-κC作为口服递送系统的性能。使用MCT可显著提高CUR 的溶解度,包封效率良好,为73.98±1.57%,载药量为1.32±0.03 mg CUR/mL MCT。通过傅里叶变换红外光谱(FTIR)和扫描电子显微镜(SEM)证实CUR成功负载于MCT-κC中,且具有良好的储存和热稳定性。溶出度研究表明,与未处理或未配制的CUR相比,使用加热的MCT油可使CUR的溶解度提高两倍。体外释放研究表明,在模拟胃环境下,包封的CUR可防止过早突释,并在模拟肠道条件下急剧释放。CUR在肠道pH值下具有活性,孵育5小时后CUR的累积释放率>90%,这是人体肠道条件下CUR吸收的理想结果。当用β-胡萝卜素分子替代CUR时,也获得了类似的释放曲线。因此,所报道的研究结果证明了MCT-κC作为CUR等疏水性候选物的有前景的递送载体的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4215/8197192/83943b06dfc2/materials-14-02783-g0A1.jpg

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