Encapsulation of Variabilin in Stearic Acid Solid Lipid Nanoparticles Enhances Its Anticancer Activity in Vitro.

Mookho S Lerata,Toufiek Samaai,Nicole R S Sibuyi,Denzil R Beukes,Sarah D'Souza,Admire Dube,Edith M Antunes,Mervin Meyer

doi:10.3390/molecules25040830

Mookho S Lerata, Toufiek Samaai + Show 6 more

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https://doi.org/10.3390/molecules25040830

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The use of natural products as chemotherapeutic agents is well established; however, many of these are associated with undesirable side effects, including high toxicity and instability. Furthermore, the development of drug resistant cancers makes the search for new anticancer lead compounds a priority. In this study, the extraction of an Ircinia sp. sponge resulted in the isolation of an inseparable mixture of (7E,12E,20Z)-variabilin (1) and (7E,12Z,20Z)-variabilin (2) and structural assignment was established using standard 1D and 2D NMR experiments. The cytotoxic activity of the compound against three solid tumour cell lines displayed moderate anti-cancer activity through apoptosis, together with a general lack of selectivity among the cancer cell lines studied. Structural assignment and cytotoxic evaluation of variabilin was complicated and further aggravated by its inherent instability. Variabilin was therefore incorporated into solid lipid nanoparticles (SLNs) and the stability and cytotoxic activity evaluated. Encapsulation of variabilin into SLNs led to a marked improvement in stability of the natural product coupled with enhanced cytotoxic activity, particularly against the prostate (PC-3) cancer cell line, with IC50 values of 87.74 μM vs. 8.94 μM for the variabilin alone and Var-SLN, respectively. Both variabilin and Var-SLN revealed comparable activity to Ceramide against the MCF-7 breast cancer cell line, revealing IC50 values of 34.8, 38.1 and 33.6 μM for variabilin, Var-SLN and Ceramide, respectively. These samples revealed no activity (>100 μM for all) against HT-29 (colon) cell lines and MCF-12 (normal breast) cell lines. Var-SLNs induced 47, 48 and 59% of apoptosis in HT-29, MCF-7 and PC-3 cells, respectively, while variabilin alone revealed 38, 29 and 29% apoptotic cells for HT-29, MCF-7 and PC-3 cell lines, respectively. The encapsulation of natural products into SLNs may provide a promising approach to overcome some of the issues hindering the development of new anticancer drugs from natural products.

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The Ircinia sponge was selected for study on the basis of its preliminary cytotoxic activity (>50% growth inhibition at 50 μg/mL) against an MCF-7 breast cancer cell line
The cytotoxic activity (>50% growth inhibition at 50 μg/mL) against an MCF-7 breast cancer cell line
The results show that Var-solid lipid nanoparticles (SLNs) induced a more significant apoptotic effects on non-cancerous cells

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IntroductionCancer continues continuesto to be one the leading causes andhealth is a major burdenCancer be one of theofleading causes of death of anddeath is a major burdenhealth worldwide [1].worldwide [1].theBreast cancer, the most diagnosed cancer [2], fordiagnosed25% of all diagnosed cancersBreast cancer, most diagnosed cancer [2], accounts for accounts25% of all cancers with with 20% malignancy related mortalitiesAfrican women [3], whilecancer prostate has the highest malignancy related mortalities in Africanin women [3], while prostate hascancer the highest incidence incidence rate reported among African men [4].The burden of cancer is only expected to increase rate reported among African men [4]. Cancer continues continuesto to be one the leading causes andhealth is a major burden. Cancer be one of theofleading causes of death of anddeath is a major burdenhealth worldwide [1]. The most diagnosed cancer [2], fordiagnosed. Most diagnosed cancer [2], accounts for accounts. 25% of all cancers with with 20% malignancy related mortalities. African women [3], whilecancer prostate has the highest malignancy related mortalities in Africanin women [3], while prostate hascancer the highest incidence incidence rate reported among African men [4]. The burden of cancer is only expected to increase rate reported among African men [4]. The burden of cancer is only expected to increase among low- and among low- andpopulations middle-income populations to adaptation of and western lifestyles and increased middle-income due to adaptationdue of western lifestyles increased life expectancy [5]

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