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.

中文翻译：

---

固体脂质颗粒治疗肺转移

固体脂质颗粒（SLP）可以长期持续地封装和释放治疗剂，从而改变了它们的生物分布，毒性和副作用。迄今为止，尚无关于使用负载阿霉素化疗的SLP治疗转移性癌症的研究报道。这项研究的特点是负载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，静脉内施用阿霉素的SLP可显着减少小鼠的肺转移灶数量。体外动力学研究显示了两种独特的药物释放曲线。第一个化学疗法爆发释放波发生在最初的5小时内，约占所包埋药物的30％，迅速提供治疗浓度。第二波发生在粒子到达肺部的最终目的地之后。这种释放可以持续很长时间（> 40天），提供恒定水平的原位化学疗法，从而触发转移性生长的抑制。我们的研究结果表明，使用带有SLP的化学疗法可以显着提高局部药物的疗效，减少副作用，同时提高整体生存率。