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吲哚美辛与纳米结构脂质载体联合用于有效的抗癌治疗。

Combination of Indomethacin with Nanostructured Lipid Carriers for Effective Anticancer Therapy.

作者信息

Thiruchenthooran Vaikunthavasan, Espina Marta, Świtalska Marta, Bonilla-Vidal Lorena, Wietrzyk Joanna, Garcia Maria Luisa, Souto Eliana B, Sánchez-López Elena, Gliszczyńska Anna

机构信息

Department of Food Chemistry and Biocatalysis, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.

Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, University of Barcelona, Barcelona, Spain.

出版信息

Int J Nanomedicine. 2024 Jul 11;19:7033-7048. doi: 10.2147/IJN.S464239. eCollection 2024.

Abstract

PURPOSE

The anticancer potential of indomethacin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in vitro, in vivo, and in clinical trials is well known and widely reported in the literature, along with their side effects, which are mainly observed in the gastrointestinal tract. Here, we present a strategy for the application of the old drug indomethacin as an anticancer agent by encapsulating it in nanostructured lipid carriers (NLC). We describe the production method of IND-NLC, their physicochemical parameters, and the results of their antiproliferative activity against selected cancer cell lines, which were found to be higher compared to the activity of free indomethacin.

METHODS

IND-NLC were fabricated using the hot high-pressure homogenization method. The nanocarriers were physicochemically characterized, and their biopharmaceutical behaviour and therapeutic efficacy were evaluated in vitro.

RESULTS

Lipid nanoparticles IND-NLC exhibited a particle size of 168.1 nm, a negative surface charge (-30.1 mV), low polydispersity index (PDI of 0.139), and high encapsulation efficiency (over 99%). IND-NLC were stable for over 60 days and retained integrity during storage at 4 °C and 25 °C. The potential therapeutic benefits of IND-NLC were screened using in vitro cancer models, where nanocarriers with encapsulated drug effectively inhibited the growth of breast cancer cell line MDA-MB-468 at dosage 15.7 μM.

CONCLUSION

We successfully developed IND-NLC for delivery of indomethacin to cancer cells and confirmed their antitumoral efficacy in in vitro studies. The results suggest that indomethacin encapsulated in lipid nanoparticles possesses high anticancer potential. Moreover, the presented strategy is highly promising and may offer a new alternative for future therapeutic drug innovations.

摘要

目的

吲哚美辛和其他非甾体抗炎药(NSAIDs)在体外、体内及临床试验中的抗癌潜力已广为人知,且在文献中被广泛报道,同时其副作用也主要表现在胃肠道。在此,我们提出一种将旧药吲哚美辛封装于纳米结构脂质载体(NLC)中作为抗癌剂应用的策略。我们描述了IND-NLC的制备方法、其理化参数以及对所选癌细胞系的抗增殖活性结果,发现其活性高于游离吲哚美辛。

方法

采用热高压均质法制备IND-NLC。对纳米载体进行理化表征,并在体外评估其生物药剂学行为和治疗效果。

结果

脂质纳米粒IND-NLC的粒径为168.1 nm,表面带负电荷(-30.1 mV),多分散指数低(PDI为0.139),包封率高(超过99%)。IND-NLC在60多天内稳定,在4℃和25℃储存期间保持完整。使用体外癌症模型筛选了IND-NLC的潜在治疗益处,其中包封药物的纳米载体在剂量为15.7 μM时有效抑制了乳腺癌细胞系MDA-MB-468的生长。

结论

我们成功开发了用于将吲哚美辛递送至癌细胞的IND-NLC,并在体外研究中证实了其抗肿瘤功效。结果表明,封装在脂质纳米粒中的吲哚美辛具有很高的抗癌潜力。此外,所提出的策略极具前景,可能为未来的治疗药物创新提供新的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d40/11249952/1f85a83d8f85/IJN-19-7033-g0001.jpg

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