Multiple-drug resistance in human cancer is a major problem. To circumvent this issue, clinicians combine several drugs. However, this strategy could backfire resulting in more toxic or ineffective treatments. Carbon nanotubes (CNTs), and particularly multi-walled nanotubes (MWCNTs), display intrinsic properties against cancer interfering with microtubule dynamics and triggering anti-proliferative, anti-migratory and cytotoxic effects in vitro that result in tumor growth inhibition in vivo . Remarkably, these effects are maintained in tumors resistant to traditional microtubule-binding chemotherapies such as Taxol ® . In the view of these properties, we investigate the use of MWCNTs in the development of active-by-design nanocarriers, attempting to enhance the effect of broadly-used chemotherapies. We compare the cytotoxic and the anti-tumoral effect of 5-Fluorouracil (5-FU) -an antimetabolite treatment of various forms of cancer- with that of the drug physisorbed onto MWCNTs. Our results demonstrate how the total effect of the drug 5-FU is remarkably improved (50% more effective) when delivered intratumorally coupled to MWCNTs both in vitro and in vivo in solid tumoral models. Our results demonstrate how using MWCNTs as anti-cancer drug delivery platforms is a promising approach to boost the efficacy of traditional chemotherapies, while considerably reducing the chances of resistance in cancer cells.

No 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.