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.
Highlights
In cancer, surgery is the treatment of choice
Local treatment is generally complemented by radiation therapy and high doses of chemotherapy that cause numerous side effects [1,2], limiting the success of metastasis treatment [3]
The SLPs were labeled with a fluorescent dye (3,30 -dioctadecyloxacarbocyanine perchlorate (DiO)), which was used for detection and imaging purposes
Summary
It is often not an option because many cancer cells have already escaped from the primary tumor and colonized distant tissues. Most patients with advanced metastatic disease confront a terminal illness. There are currently no effective treatments to stop or prevent this process, so there is an urgent need to find new diagnostic and therapeutic approaches. Local treatment is generally complemented by radiation therapy and high doses of chemotherapy that cause numerous side effects [1,2], limiting the success of metastasis treatment [3]. Systemically applied cytotoxic drugs are not effective in preventing the spread of metastatic cells that cause 90% of cancer deaths [4]
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