Antitubercular Activity of 7-Methyljuglone-Loaded Poly-(Lactide Co-Glycolide) Nanoparticles.

IF 4.9 3区医学 Q1 PHARMACOLOGY & PHARMACY Pharmaceutics Pub Date : 2024-11-20 DOI:10.3390/pharmaceutics16111477

Bianca Diedericks, Anna-Mari Kok, Vusani Mandiwana, Bhavna Gowan Gordhan, Bavesh Davandra Kana, Suprakas Sinha Ray, Namrita Lall

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Abstract

Background/objectives: Loading of natural products into poly-(lactide-co-glycolic) acid (PLGA) nanoparticles as drug delivery systems for the treatment of diseases, such as tuberculosis (TB), has been widely explored. The current study investigated the use of PLGA nanoparticles with 7-methyljuglone (7-MJ), an active pure compound, isolated from the roots of Euclea natalensis A. DC.

Methods: 7-MJ as well as its respective PLGA nanoparticles were tested for their antimycobacterial activity against Mycobacterium smegmatis (M. smegmatis), drug-susceptible Mycobacterium tuberculosis (M. tuberculosis) (H37Rv), and multi-drug-resistant M. tuberculosis (MDR11). The cytotoxicity of 7-MJ as well as its respective PLGA nanoparticles were tested for their cytotoxic effect against differentiated human histiocytic lymphoma (U937) cells. Engulfment studies were also conducted to determine whether the PLGA nanoparticles are taken up by differentiated U937 cells.

Results: 7-MJ has been shown to have a minimum inhibitory concentration (MIC) value of 1.6 µg/mL against M. smegmatis and multi-drug-resistant M. tuberculosis and 0.4 µg/mL against drug-susceptible M. tuberculosis. Whilst promising, 7-MJ was associated with cytotoxicity, with a fifty percent inhibition concentration (IC₅₀) of 3.25 µg/mL on differentiated U937 cells. In order to lower the cytotoxic potential, 7-MJ was loaded into PLGA nanoparticles. The 7-MJ PLGA nanoparticles showed an 80-fold decrease in cytotoxic activity compared to free 7-MJ, and the loaded nanoparticles were successfully taken up by differentiated macrophage-like U937 cells.

Conclusions: The results of this study suggested the possibility of improved delivery during TB therapy via the use of PLGA nanoparticles.

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7-Methyljuglone-Loaded Poly-(Lactide Co-Glycolide) 纳米粒子的抗结核活性。

背景/目的：将天然产品装入聚乳酸-聚乙二醇（PLGA）纳米颗粒作为治疗结核病（TB）等疾病的给药系统已被广泛探索。本研究调查了 PLGA 纳米颗粒与 7-甲基朱古酮（7-MJ）的使用情况，7-甲基朱古酮是从 Euclea natalensis A. DC 的根中分离出来的一种活性纯化合物。方法：测试了 7-MJ 及其相应的 PLGA 纳米粒子对烟肉分枝杆菌（M. smegmatis）、对药物敏感的结核分枝杆菌（M. tuberculosis）（H37Rv）和对多种药物耐药的结核分枝杆菌（MDR11）的抗霉菌活性。测试了 7-MJ 及其相应的 PLGA 纳米粒子对已分化的人类组织细胞淋巴瘤（U937）细胞的细胞毒性作用。此外，还进行了吞噬研究，以确定 PLGA 纳米颗粒是否会被分化的 U937 细胞吸收：结果：研究表明，7-MJ 对烟灰质结核杆菌和耐多药结核杆菌的最低抑制浓度 (MIC) 值为 1.6 µg/mL，对易服药结核杆菌的最低抑制浓度 (MIC) 值为 0.4 µg/mL。虽然 7-MJ 很有前景，但它也有细胞毒性，对分化的 U937 细胞的五成抑制浓度（IC50）为 3.25 微克/毫升。为了降低细胞毒性，7-MJ 被载入了聚乳酸（PLGA）纳米颗粒中。与游离的7-MJ相比，7-MJ PLGA纳米颗粒的细胞毒性活性降低了80倍，负载的纳米颗粒成功地被分化的巨噬细胞样U937细胞吸收：结论：这项研究的结果表明，在结核病治疗过程中，使用 PLGA 纳米粒子可以改善给药效果。

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来源期刊

Pharmaceutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

7.90

自引率

11.10%

发文量

2379

审稿时长

16.41 days

期刊介绍： Pharmaceutics (ISSN 1999-4923) is an open access journal which provides an advanced forum for the science and technology of pharmaceutics and biopharmaceutics. It publishes reviews, regular research papers, communications, and short notes. Covered topics include pharmacokinetics, toxicokinetics, pharmacodynamics, pharmacogenetics and pharmacogenomics, and pharmaceutical formulation. Our aim is to encourage scientists to publish their experimental and theoretical details in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.