Valdivia Lourdes, García-Hevia Lorena, Bañobre-López Manuel, Gallo Juan, Valiente Rafael, López Fanarraga Mónica
Nanomedicine Group, University of Cantabria-IDIVAL, Herrera Oria s/n, 39011 Santander, Spain.
Advanced (Magnetic) Theranostic Nanostructures Laboratory, Nanomedicine Unit, International Iberian Nanotechnology Laboratory (INL), Av. Mestre José Veiga s/n, 4715-330 Braga, Portugal.
Pharmaceutics. 2021 Jan 13;13(1):93. doi: 10.3390/pharmaceutics13010093.
Solid lipid particles (SLPs) can sustainably encapsulate and release therapeutic agents over long periods, modifying their biodistribution, toxicity, and side effects. To date, no studies have been reported using SLPs loaded with doxorubicin chemotherapy for the treatment of metastatic cancer. This study characterizes the effect of doxorubicin-loaded carnauba wax particles in the treatment of lung metastatic malignant melanoma in vivo. Compared with the free drug, intravenously administrated doxorubicin-loaded SLPs significantly reduce the number of pulmonary metastatic foci in mice. In vitro kinetic studies show two distinctive drug release profiles. A first chemotherapy burst-release wave occurs during the first 5 h, which accounts for approximately 30% of the entrapped drug rapidly providing therapeutic concentrations. The second wave occurs after the arrival of the particles to the final destination in the lung. This release is sustained for long periods (>40 days), providing constant levels of chemotherapy in situ that trigger the inhibition of metastatic growth. Our findings suggest that the use of chemotherapy with loaded SLPs could substantially improve the effectiveness of the drug locally, reducing side effects while improving overall survival.
固体脂质颗粒（SLPs）能够长期可持续地包裹并释放治疗药物，改变其生物分布、毒性和副作用。迄今为止，尚未有关于使用载有阿霉素化疗药物的SLPs治疗转移性癌症的研究报道。本研究表征了载有阿霉素的巴西棕榈蜡颗粒在体内治疗肺转移性恶性黑色素瘤的效果。与游离药物相比，静脉注射载有阿霉素的SLPs可显著减少小鼠肺部转移灶的数量。体外动力学研究显示出两种不同的药物释放曲线。第一个化疗爆发释放波在最初5小时内出现，约占包封药物的30%，迅速提供治疗浓度。第二个波在颗粒到达肺部最终目的地后出现。这种释放可持续很长时间（>40天），在原位提供恒定水平的化疗，从而触发对转移生长的抑制。我们的研究结果表明，使用载有药物的SLPs进行化疗可显著提高药物的局部疗效，减少副作用，同时提高总体生存率。
