Synergistic Enhancement of Carboplatin Efficacy through pH-Sensitive Nanoparticles Formulated Using Naturally Derived Boswellia Extract for Colorectal Cancer Therapy.

IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Sherif Ashraf Fahmy, Nada K Sedky, Hatem A F M Hassan, Nour M Abdel-Kader, Noha Khalil Mahdy, Muhammad Umair Amin, Eduard Preis, Udo Bakowsky
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Abstract

Carboplatin (Cp) is a potent chemotherapeutic agent, but its effectiveness is constrained by its associated side effects. Frankincense, an oleo-gum resin from the Boswellia sacra tree, has demonstrated cytotoxic activity against cancer cells. This study explored the synergistic potential of nanoparticles formulated from Boswellia sacra methanolic extract (BME), to enhance the therapeutic efficacy of Cp at reduced doses. Nanoparticles were prepared via the nanoprecipitation method, loaded with Cp, and coated with positively charged chitosan (CS) for enhanced cell interaction, yielding Cp@CS/BME NPs with an average size of 160.2 ± 4.6 nm and a zeta potential of 12.7 ± 1.5 mV. In vitro release studies revealed a pH-sensitive release profile, with higher release rates at pH 5.4 than at pH 7.4, highlighting the potential for targeted drug delivery in acidic tumor environments. In vitro studies on HT-29 and Caco-2 colorectal cancer cell lines demonstrated the nanoformulation's ability to significantly increase Cp uptake and cytotoxic activity. Apoptosis assays further confirmed increased induction of cell death with Cp@CS/BME NPs. Cell-cycle analysis revealed that treatment with Cp@CS/BME NPs led to a significant increase in the sub-G1 phase, indicative of enhanced apoptosis, and a marked decrease in the G1-phase population coupled with an increased G2/M-phase arrest in both cell lines. Further gene expression analysis demonstrated a substantial downregulation of the anti-apoptotic gene Bcl-2 and an upregulation of the pro-apoptotic genes Bax, PUMA, and BID following treatment with Cp@CS/BME NPs. Thus, this study presents a promising and innovative strategy for enhancing the therapeutic efficacy of chemotherapeutic agents using naturally derived ingredients while limiting the side effects.

利用天然乳香提取物配制的 pH 值敏感纳米颗粒协同增强卡铂治疗结直肠癌的疗效
卡铂(Cp)是一种强效化疗药物,但其有效性受到相关副作用的限制。乳香是一种来自乳香树的油胶树脂,对癌细胞具有细胞毒性活性。本研究探讨了用乳香甲醇提取物(BME)配制的纳米颗粒的协同潜力,以提高Cp的疗效,减少用药剂量。通过纳米沉淀法制备纳米颗粒,载入 Cp,并包覆带正电荷的壳聚糖(CS)以增强与细胞的相互作用,得到平均粒径为 160.2 ± 4.6 nm、Zeta 电位为 12.7 ± 1.5 mV 的 Cp@CS/BME NPs。体外释放研究显示了对 pH 值敏感的释放曲线,pH 值为 5.4 时的释放率高于 pH 值为 7.4 时的释放率,这凸显了在酸性肿瘤环境中靶向给药的潜力。对 HT-29 和 Caco-2 大肠癌细胞系进行的体外研究表明,纳米制剂能够显著提高 Cp 的吸收和细胞毒性活性。细胞凋亡检测进一步证实了 Cp@CS/BME NPs 诱导细胞死亡的能力增强。细胞周期分析表明,用 Cp@CS/BME NPs 处理后,两种细胞系的亚 G1 期显著增加,表明细胞凋亡增强,G1 期细胞数量明显减少,G2/M 期停滞增加。进一步的基因表达分析表明,经 Cp@CS/BME NPs 处理后,抗凋亡基因 Bcl-2 大量下调,而促凋亡基因 Bax、PUMA 和 BID 上调。因此,本研究提出了一种利用天然成分提高化疗药物疗效并限制副作用的前景广阔的创新策略。
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来源期刊
Pharmaceutics
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.
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