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

YAMILA CONTESSI; JAZMÍN TORRES; CÉSAR PRUCCA; GERMAN GIL; MÓNICA GARCÍA; MANUELA GARCÍA

Rosario

Simposio; RICIFA: 7ma Reunión Internacional de Ciencias Farmacéuticas; 2023

RICIFA

Natural products (NP) have historically made an important contribution to pharmacotherapy andhave served as an invaluable source of inspiration for the development of new drugs. However, theirstructural complexity, low solubility, toxicity, and unfavorable pharmacokinetics may limit theirclinical translation. To overcome these drawbacks, pharmaceutical nanotechnology has emerged asa highly useful strategy. Currently, great efforts in the field of NP research are centered in the searchfor new chemical entities as anticancer agents aimed at improving the therapy of this disease, whichremains as one of the leading causes of death worldwide. Previously, we reported that Solanumpseudocapsicum (Solanaceae family) is a plant species that contains a significant amount of thesteroidal alkaloid solanocapsine (SCP). This compound has demonstrated a relevant ability to inducesynthetic 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 onother 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 extractwere performed, leading to the isolation of a global alkaloid extract, which was further purified toobtain SCP (0.21 g). In subsequent stages, the antitumor activity of this natural compound wasevaluated against MCF-7 and MDA-MB-231 breast cancer cell lines (at concentrations ranging from6.25 to 50 µg/mL). After confirming its biological activity, PM based on Pluronic® F127 (generallyrecognized as safe (GRAS) polymer) were developed and SCP was incorporated into them. Differenttechniques 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, usingdifferent organic solvents for film formation (ethanol and chloroform). Six different samples wereprepared 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% atthe evaluated concentrations, and showed anticancer activity comparable or even greater thantamoxifen and doxorubicin at the same concentrations. PM were obtained by the differentmethodologies evaluated, and PBS allowed for the lower polymer sizes compared to those of otheraqueous media. Smaller sizes and a narrow size distribution of SCP-loaded PM were obtained bythe thin-film hydration method, using ethanol and PBS for obtaining the film and during therehydration 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 thatSCP could be effectively loaded into the developed PM and that their reduced size could be exploitedfor passive targeting in cancer nanomedicine.