Solid Lipid Particles for Lung Metastasis Treatment

Abstract

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.

The use of RNA-based treatments in the field of cancer immunotherapy

“…Multiple delivery strategies have been developed for neoantigens, including synthetic long peptides (SLPs) and nucleic acid (DNA/ mRNA) based vaccines, either through direct injection of unformulated antigens, DC-based autologous transfer, or biomaterial-based delivery system [742]. In a pioneered phase I clinical study, a selected pool of 20 SLPs were SC administered together with adjuvant polyICLC to 6 patients with advanced cutaneous melanoma [743]. These SLPs were shown to induce both CD4 + T cells and CD8 + T cells response [744].…”

“…These SLPs were shown to induce both CD4 + T cells and CD8 + T cells response [744]. Four of the six patients were cancer-free 25 months post-treatment, demonstrating the viability of neoantigen vaccination in anticancer treatment [743]. However, peptides have limited immunogenicity, rapid clearance, and different physical-chemical properties restricting their clinical applications [744].…”

Insights into the Effect of Magnetic Confinement on the Performance of Magnetic Nanocomposites in Magnetic Hyperthermia and Magnetic Resonance Imaging

“…In this context, hybrid magnetic nanosystems have enticed researchers’ attention as smart remotely controlled platforms, able to pool together diagnostic, monitoring, and combinatorial therapy features. Over the last decades, advances in the field of theranostics (therapy plus diagnosis) have brought a variety of organic/inorganic hybrid nanocomposites with a high level of integration and complexity, featuring tunable functions strictly related to well-defined architectures. − Nevertheless, the integration of diagnostic and therapeutic functionalities in a smart all-in-one platform in the form of hybrid nanocomposites remains a big challenge.…”

Preclinical Evaluation of Lipid-Based Nanosystems

“…M.L. Fanarraga et al [ 6 ] developed doxorubicin-loaded lipid particles (SLPs) (also known as SLN) for the treatment of lung metastatic malignant melanoma. In this study, the authors conducted comparative in vivo experiments in mice, with intravenous doxorubicin-loaded SLPs and intravenous free drug, and observed that the former significantly reduced the number of pulmonary metastatic foci.…”