Enhancing efficacy of combretastatin A4 by encapsulation in solid lipid nanoparticles: Implications for anti-angiogenic cancer therapy

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics Pub Date : 2025-04-30 DOI:10.1016/j.ijpharm.2025.125669

Fariba Bagherieh , Maryam Ebrahimi Nik , Asma Mahmoudi , Leila Gholami , Farzin Hadizadeh , Hamid Reza Sadeghnia , Reza Kazemi Oskuee , Bizhan Malaekeh-Nikouei

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Abstract

Background

Nanotechnology-based drug delivery systems, such as solid lipid nanoparticles (SLNs), offer promising strategies to enhance the efficacy and stability of therapeutic agents. In this study, we explored the characterization, stability, and therapeutic efficacy of SLNs loaded with Combretastatin A4 (CA4) in cancer treatment.

Methods

SLNs loaded with CA4 were characterized for particle size, zeta potential, and encapsulation efficiency. The stability of CA4 SLNs was assessed over six months. The MTT assay was used to evaluate the cytotoxicity of free CA4 and SLNs loaded with CA4 on C26 mouse colon carcinoma cells and HUVEC human umbilical vein endothelial cells. The anti-angiogenic activity was analyzed using the CAM assay. An in vivo study was conducted to assess the therapeutic efficacy of SLNs loaded with CA4 in combination with Doxil in a mouse tumor model.

Results

Blank SLNs and SLNs loaded with CA4 exhibited a homogeneous particle size distribution (60–70 nm and 80–90 nm, respectively), low polydispersity index, and a negative zeta potential. Encapsulation efficiency of CA4 was around 60 %. SLNs demonstrated excellent physicochemical stability over six months. The MTT assay revealed enhanced cytotoxicity of SLNs loaded with CA4 compared to free CA4, particularly in C26 cells. The CAM assay showed a concentration-dependent reduction in vessel density with CA4 treatment. In in vivo studies, SLNs loaded with CA4 significantly inhibited tumor growth and improved survival rates, especially when combined with Doxil.

Conclusion

These findings suggest that SLNs loaded with CA4 could be a valuable strategy for enhancing therapeutic outcomes in cancer treatment.

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用固体脂质纳米颗粒包封增强康布他汀A4的疗效：对抗血管生成癌症治疗的意义

基于纳米技术的药物传递系统，如固体脂质纳米颗粒（SLNs），为提高治疗剂的疗效和稳定性提供了有前途的策略。在这项研究中，我们探讨了负载Combretastatin A4 （CA4）的sln在癌症治疗中的特性、稳定性和治疗效果。方法对负载CA4的ssln进行粒径、zeta电位和包封效率表征。在6个月内评估CA4 sln的稳定性。MTT法评价游离CA4和载CA4 sln对C26小鼠结肠癌细胞和HUVEC人脐静脉内皮细胞的细胞毒性。用CAM法测定其抗血管生成活性。在体内研究了负载CA4的sln与Doxil联合对小鼠肿瘤模型的治疗效果。结果空白SLNs和负载CA4 SLNs的粒径分布均匀（分别为60 ~ 70 nm和80 ~ 90 nm），多分散性指数低，zeta电位为负。CA4的包封率约为60%。sln在六个月内表现出优异的物理化学稳定性。MTT实验显示，与游离CA4相比，装载CA4的sln细胞毒性增强，特别是在C26细胞中。CAM实验显示CA4处理后血管密度呈浓度依赖性降低。在体内研究中，装载CA4的sln显著抑制肿瘤生长并提高生存率，特别是与Doxil联合使用时。结论负载CA4的sln可能是提高癌症治疗效果的一种有价值的策略。

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

International Journal of Pharmaceutics 医学-药学

CiteScore

10.70

自引率

8.60%

发文量

951

审稿时长

72 days

期刊介绍： The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.