A preformulation study of marine alkaloid aaptamine: Physicochemical properties investigation and liposomal formulation development toward hepatocellular carcinoma treatment

IF 1.8 3区农林科学 Q3 FOOD SCIENCE & TECHNOLOGY

European Journal of Lipid Science and Technology Pub Date : 2024-09-09 DOI:10.1002/ejlt.202400102

Tianjiao Geng, Haitao Xue, Can Kong, Luping He, Shuping Wang, Ling Ding, Xiaoyan Zou, Zhichun Gu, Hongze Liao, Houwen Lin

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引用次数: 0

Abstract

Hepatocellular carcinoma (HCC) is a global health concern with high prevalence and mortality. A marine alkaloid, AP‐427, has been reported to show potential for HCC treatment. However, its use is limited by low solubility and high toxicity. We aimed to investigate the preformulation parameters and develop AP‐427 liposomes to improve its clinical suitability. A stability‐indicating HPLC assay was established, and the physicochemical properties of AP‐427 were analyzed. Afterward, AP‐427 liposomes were prepared and characterized, and their cytotoxicity was evaluated. AP‐427 had a low solubility at physiological pH, a LogD of 2.56 ± 0.03, and a basic pKa of 3.24 ± 0.12. An entrapment efficiency of 52.71 ± 3.2% was achieved after optimization. The resulting AP‐427 liposomes were 147.2 ± 3.4 nm and stable up to three months when stored in a pellet form at 4°C. The crystallization of AP‐427 in liposomes became less ordered, and AP‐427 liposomes exhibited a controlled release fitted in Korsmeyer–Peppas model, indicating the release was driven by diffusion. Furthermore, AP‐427 liposomes showed a 3.6 times reduced cytotoxicity against HepG2 cells compared with free AP‐427, potentially enhancing its antitumor efficacy. In conclusion, the precise preformulation parameters advanced the AP‐427 liposomal formulation development, which showed potential for HCC treatment.Practical Applications: The aaptamine derivative AP‐427 has shown cytotoxic effects against hepatocellular carcinoma. However, the low solubility and high toxicity limit its clinical application. The present study aims to prepare liposomal formulation to solve the current problems. Results obtained from this study shed light on challenges related to drug solubility and have paved the way for the development of an effective AP‐427 liposomal formulation with promising application in hepatocellular carcinoma therapy.

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海洋生物碱aptamine的制剂前研究：理化性质研究和治疗肝细胞癌的脂质体配方开发

肝细胞癌（HCC）是一个全球关注的健康问题，发病率和死亡率都很高。据报道，一种海洋生物碱 AP-427 具有治疗 HCC 的潜力。然而，由于其溶解度低、毒性大，其使用受到了限制。我们旨在研究其预配制参数并开发 AP-427 脂质体，以提高其临床适用性。我们建立了稳定性指示高效液相色谱法，并分析了 AP-427 的理化性质。随后，制备了AP-427脂质体并对其进行了表征和细胞毒性评估。AP-427在生理pH值下溶解度低，LogD为2.56 ± 0.03，碱性pKa为3.24 ± 0.12。经过优化后，其包载效率为 52.71 ± 3.2%。得到的 AP-427 脂质体直径为 147.2 ± 3.4 nm，在 4°C 下以颗粒形式储存可稳定三个月。AP-427在脂质体中的结晶变得不那么有序，AP-427脂质体表现出符合Korsmeyer-Peppas模型的控制释放，表明释放是由扩散驱动的。此外，与游离 AP-427 相比，AP-427 脂质体对 HepG2 细胞的细胞毒性降低了 3.6 倍，这可能会增强其抗肿瘤功效。总之，精确的制剂前参数推进了 AP-427 脂质体制剂的开发，显示出其治疗 HCC 的潜力：aptamine衍生物AP-427对肝细胞癌具有细胞毒性作用。然而，低溶解度和高毒性限制了其临床应用。本研究旨在制备脂质体制剂，以解决目前存在的问题。本研究的结果揭示了与药物溶解度相关的挑战，为开发有效的 AP-427 脂质体制剂铺平了道路，有望应用于肝细胞癌治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Journal of Lipid Science and Technology 工程技术-食品科技

CiteScore

5.50

自引率

0.00%

发文量

101

审稿时长

6-16 weeks

期刊介绍： The European Journal of Lipid Science and Technology is a peer-reviewed journal publishing original research articles, reviews, and other contributions on lipid related topics in food science and technology, biomedical science including clinical and pre-clinical research, nutrition, animal science, plant and microbial lipids, (bio)chemistry, oleochemistry, biotechnology, processing, physical chemistry, and analytics including lipidomics. A major focus of the journal is the synthesis of health related topics with applied aspects. Following is a selection of subject areas which are of special interest to EJLST: Animal and plant products for healthier foods including strategic feeding and transgenic crops Authentication and analysis of foods for ensuring food quality and safety Bioavailability of PUFA and other nutrients Dietary lipids and minor compounds, their specific roles in food products and in nutrition Food technology and processing for safer and healthier products Functional foods and nutraceuticals Lipidomics Lipid structuring and formulations Oleochemistry, lipid-derived polymers and biomaterials Processes using lipid-modifying enzymes The scope is not restricted to these areas. Submissions on topics at the interface of basic research and applications are strongly encouraged. The journal is the official organ the European Federation for the Science and Technology of Lipids (Euro Fed Lipid).

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