Evaluation of the antitumor activity of solanocapsine and its loading in nanometric micelles: an integral phytonanotechnological approach

CONTESSI, YAMILA ; TORRES, JAZMIN; GIL, GERMÁN ; PRUCCA, CÉSAR ; GARCIA, MANUELA; GARCIA, MONICA

ROSARIO

Congreso; 7ma Reunión Internacional de Ciencias Farmacéuticas (RICiFa 2023); 2023

Natural products (NP) have historically made an important contribution to pharmacotherapy and have served as an invaluable source of inspiration for the development of new drugs. However, their structural complexity, low solubility, toxicity, and unfavorable pharmacokinetics may limit their clinical translation. To overcome these drawbacks, pharmaceutical nanotechnology has emerged as a highly useful strategy. Currently, great efforts in the field of NP research are centered in the search for new chemical entities as anticancer agents aimed at improving the therapy of this disease, which remains as one of the leading causes of death worldwide. Previously, we reported that Solanum pseudocapsicum (Solanaceae family) is a plant species that contains a significant amount of the steroidal alkaloid solanocapsine (SCP). This compound has demonstrated a relevant ability to induce synthetic lethality in BRCA-deficient tumor cells, inducing cell death through selective cytotoxicity. On the basis of these findings, the aim of this work was to evaluate the antitumor activity of SCP on other breast cancer cells and to load this NP into polymer micelles (PM).An exhaustive extraction of fresh fruits of S. pseudocapsicum (470 g) was carried out using ethanol (5 cycles, 500 mL each). Subsequently, different acid-base fractionations of the ethanolic extract were performed, leading to the isolation of a global alkaloid extract, which was further purified to obtain SCP (0.21 g). In subsequent stages, the antitumor activity of this natural compound was evaluated against MCF-7 and MDA-MB-231 breast cancer cell lines (at concentrations ranging from 6.25 to 50 μg/mL). After confirming its biological activity, PM based on Pluronic® F127 (generally recognized as safe (GRAS) polymer) were developed and SCP was incorporated into them. Different techniques were evaluated to obtain SCP-loaded PM: direct method in aqueous medium (water, physiological solution or buffer solution at pH 7.4 (PBS)) or thin-film hydration method, using different organic solvents for film formation (ethanol and chloroform). Six different samples were prepared and their interfacial properties (hydrodynamic diameter (dH) and polydispersity index (PDI)) were evaluated.SCP exhibited antitumor activity against both cell lines, achieving cell viabilities lower than 50% at the evaluated concentrations, and showed anticancer activity comparable or even greater than tamoxifen and doxorubicin at the same concentrations. PM were obtained by the different methodologies evaluated, and PBS allowed for the lower polymer sizes compared to those of other aqueous media. Smaller sizes and a narrow size distribution of SCP-loaded PM were obtained by the thin-film hydration method, using ethanol and PBS for obtaining the film and during the rehydration process, respectively, compared to the direct method, using the same aqueous medium (dH= 26.34 nm, PDI= 0.239 and dH= 33.08 nm, PDI= 0.456, respectively). The results suggest that SCP could be effectively loaded into the developed PM and that their reduced size could be exploited for passive targeting in cancer nanomedicine.