Lupeol-loaded PLGA particles conserve anti-topoisomerase activity and decrease the cytotoxicity of lupeol

IF 2.7 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2025-07-15 DOI:10.1016/j.tiv.2025.106107

Francisco Fabián Razura-Carmona , Mayra Herrera-Martínez , Jorge Alberto Sánchez-Burgos , Alejandro Pérez-Larios , Karina Janice Guadalupe Díaz-Reséndiz , Manuel Iván Girón-Pérez , Marco Vinicio Ramírez-Mares

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引用次数: 0

Abstract

Lupeol (LP), a bioactive triterpene, has been extensively studied for its chemoprotective, anti-inflammatory, and anti-arthritic properties. To enhance its bioavailability, lupeol-loaded polylactic-co-glycolic acid (PLGA) nanoparticles, designated T_LP14, were developed using the emulsification-evaporation method. These nanoparticles exhibited an average size of 339.8 nm, a polydispersity index (PdI) of 0.240, and an encapsulation efficiency of 38 %. In topoisomerase II inhibition assays, T_LP14 retained activity comparable to that of lupeol free, indicating that encapsulation does not impair its biological function. In vitro cytotoxicity assays on BEAS-2 and HEPG2 cell lines demonstrated that concentrations above 1250 μg/mL of T_LP14 induced minimal cytotoxic effects, suggesting low toxicity in non-tumor cells. Furthermore, ex vivo studies on peripheral blood mononuclear cells showed that a 1000 μg/mL concentration of free lupeol induced 28.01 % apoptosis, while the encapsulated formulation significantly reduced this adverse effect. These findings support the potential of T_LP14 nanoparticles as an effective controlled-release system for lupeol, enhancing its safety profile while preserving its therapeutic activity.

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负载lupeol的PLGA颗粒保持抗拓扑异构酶活性，降低lupeol的细胞毒性。

Lupeol （LP）是一种生物活性三萜，因其化学保护、抗炎和抗关节炎的特性而被广泛研究。为了提高其生物利用度，采用乳化蒸发法制备了载聚乳酸-羟基乙酸（PLGA）纳米粒子TLP14。这些纳米颗粒的平均尺寸为339.8 nm，多分散指数（PdI）为0.240，包封效率为38 %。在拓扑异构酶II抑制实验中，TLP14保留了与不含lupeol的活性相当的活性，这表明包封不会损害其生物学功能。对BEAS-2和HEPG2细胞株的体外细胞毒实验表明，浓度高于1250 μg/mL的TLP14对非肿瘤细胞的细胞毒作用最小，表明其毒性较低。此外，对外周血单个核细胞的体外研究表明，1000 μg/mL浓度的游离lup柚醇可诱导28.01 %的细胞凋亡，而包封制剂可显著降低这种不良反应。这些发现支持了TLP14纳米颗粒作为一种有效的lupeol控释系统的潜力，增强了其安全性，同时保持了其治疗活性。

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

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.