Alrohaimi Abdulmohsen, Mostafa Mahmoud A H, Saad Alnour Tarig Mohamed, Alghamdi Salah, Almuraikhi Nihal, Mirdad Dahlia Soleman A, Alghamdi Hajar, Senbel Ahmed Mussad
Department of Pharmacology, College of Pharmacy, Shaqra University, Al-Dawadmi, Saudi Arabia.
Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al Madinah Al Munawarah, Saudi Arabia.
Int J Surg. 2025 Sep 1;111(9):6023-6029. doi: 10.1097/JS9.0000000000002702. Epub 2025 Jun 17.
This study investigates the impact of lipid nanoparticles on enhancing the efficacy and reducing the toxicity of doxorubicin in cancer treatment.
A high-pressure emulsification method prepared doxorubicin-loaded lipid nanoparticles (DOX-LNPs). Physicochemical properties were characterized, including particle size, zeta potential, and drug encapsulation efficiency. The cytotoxic effects of DOX-LNPs were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on MCF-7 breast cancer cells, while cellular uptake was assessed via fluorescence microscopy. In vivo , antitumor efficacy and systemic toxicity were analyzed in a murine cancer model.
The synthesized nanoparticles had an average size of 148 nm and an encapsulation efficiency of 91.3%. In vitro , DOX-LNPs exhibited 1.8-fold higher cytotoxicity (lower IC₅₀) and 2.3-fold increased cellular uptake compared to free doxorubicin. In vivo , DOX-LNPs achieved 78.5% tumor growth inhibition, outperforming free doxorubicin (56.8%). Furthermore, systemic toxicity, including cardiotoxicity and nephrotoxicity, was significantly reduced in the DOX-LNP group compared to free doxorubicin.
Lipid nanoparticles improve the therapeutic index of doxorubicin by enhancing its bioavailability and reducing off-target toxicity. These findings highlight their potential as an advanced drug delivery system, warranting further preclinical and clinical investigations.
本研究调查脂质纳米颗粒对提高阿霉素在癌症治疗中的疗效及降低其毒性的影响。
采用高压乳化法制备载阿霉素脂质纳米颗粒(DOX-LNPs)。对其理化性质进行表征,包括粒径、ζ电位和药物包封率。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法评估DOX-LNPs对MCF-7乳腺癌细胞的细胞毒性作用,同时通过荧光显微镜评估细胞摄取情况。在体内,在小鼠癌症模型中分析抗肿瘤疗效和全身毒性。
合成的纳米颗粒平均粒径为148 nm,包封率为91.3%。在体外,与游离阿霉素相比,DOX-LNPs表现出高1.8倍的细胞毒性(更低的IC₅₀)和高2.3倍的细胞摄取。在体内,DOX-LNPs实现了78.5%的肿瘤生长抑制,优于游离阿霉素(56.8%)。此外,与游离阿霉素相比,DOX-LNP组的全身毒性,包括心脏毒性和肾毒性,显著降低。
脂质纳米颗粒通过提高阿霉素的生物利用度和降低脱靶毒性来改善其治疗指数。这些发现突出了它们作为一种先进药物递送系统的潜力,值得进一步进行临床前和临床研究。