Design and optimization of inherently cytotoxic nanostructured lipid carriers as drug vehicles with dual anti-cancer activity

Cancer remains to be one of the most life-threatening diseases with high rates of mortality and morbidity. The major challenge facing chemotherapy is targeting the drug molecules to malignant tissues and avoiding healthy ones. Optimal design of drug delivery carriers can assist not only in directing the drug moieties to the cancer cells but also in potentiating their action. In this study, we fabricated inherently cytotoxic nanostructured lipid carriers (NLCs) as nanovehicles for chemotherapeutic drugs for dual anticancer activity. Natural oils reported to have anticancer activity were used for the preparation of these cytotoxic nanovehicles, replacing conventionally used oils. Optimized NLCs impregnated with flaxseed or lemon oil had a size of 184±10 and 167±1 nm, respectively. Flaxseed oil impregnated NLCs lowered IC 50 against MCF-7 breast cancer cells from 214±65 μg oil/mL for conventional NLCs to 33±12 μg oil/mL (6-fold enhancement), while lemon oil NLCs lowered it to 44±17 μg oil/mL (5-fold enhancement). Loading both NLCs with curcumin, as a natural anticancer model drug, resulted in IC 50 of 2.71±1.8 and 2.79±1.5 μg curcumin/mL for flaxseed and lemon oil, respectively This was lower than IC 50 values recorded for free curcumin (12.93±6.9 μg curcumin/mL) and curcumin loaded in conventional NLCs (7.21±1.6 μg curcumin/mL). These results show that these designed cytotoxic nanovehicles can potentiate the chemotherapeutic action of any loaded drug, providing dual anticancer activity. They represent a promising drug delivery carrier in our fight against cancer. Proposed hypothesis in this study. Cancer is one of the challenging diseases worldwide. The use of combination therapy might be the way to help combat it. In this study we designed a dual functioning nano-system. Inherently cytotoxic nanostructured lipid carriers (NLCs) were fabricated by the inclusion of a cytotoxic oil in their structure. These were then loaded with a model anticancer drug- curcumin- for dual anticancer activity. The prepared particles showed superior activity against breast cancer cells compared to their blank counterparts.