Solid lipid nanoparticles improve octyl gallate antimetastatic activity and ameliorate its renal and hepatic toxic effects

Abstract

Metastasis is the main cause of cancer-related death and requires the development of effective treatments with reduced toxicity and effective anticancer activity. Gallic acid derivatives have shown significant biological properties including antitumoral activity as shown in a previous study with octyl gallate (G8) in vitro. Thus, the aim of this work was to evaluate the antimetastatic effect of free and solid lipid nanoparticle-loaded G8 in mice in a lung metastasis model. Animals inoculated with melanoma cells presented metastasis in lungs, which was significantly inhibited by treatment with G8 and solid lipid nanoparticle-loaded G8, named G8-NVM. However, G8-treated mice showed an increase in several toxicological parameters, which were almost completely circumvented by G8-NVM treatment. This study supports the need for pharmacological studies on new potential medicinal plants to treat cancer and can provide new perspectives on using nanotechnology to improve biological activities while decreasing the chemotherapy toxicological effects of anticancer drugs.

Octyl gallate induces hepatic steatosis in HepG2 cells through the regulation of SREBP-1c and PPAR-γ gene expression

“…Studies with other food additives (Collison et al, 2013[ 4 ]; Chen et al, 2017[ 3 ]; Jensen et al, 2018[ 16 ]) or therapeutic drugs (Gentilucci et al, 2006[ 14 ]; Menter et al, 2009[ 23 ]; Zhao et al, 2014[ 36 ]) have also found lipid accumulation in the liver. Our results are also in agreement with an in vivo study showing that OG induced liver toxicity, as its treatment increased the oxidative stress (Cordova et al, 2017[ 5 ]). Considering that the excess of free fatty acids increases the production of reactive oxygen species (Svegliati-Baroni et al, 2019[ 30 ]), it is possible that these mechanisms are associated.…”

“…An animal model study showed that OG, at high doses, was able to induce strong inhibition of gluconeogenesis, which could be considered as harmful (Eler et al, 2015[ 10 ]). In addition, OG has been shown to induce toxicity in mice liver, as its use increased serum levels of AST and ALT, oxidative stress and histological damage (Cordova et al, 2017[ 5 ]). However, no studies have evaluated its effect on lipid metabolism.…”

Solid Lipid Particles for Lung Metastasis Treatment

“…In previous studies, SLPs have been demonstrated to be effective against metastasis using chemotherapeutic drugs such as paclitaxel [58], etoposide [59], and gallic acid ester derivatives [60], among others. Our results indicate that these particles exhibit a higher antimetastatic effect than unformulated DOX without any detectable toxicity.…”

Advancements in nanoparticle-based treatment approaches for skin cancer therapy

“…Some of the notable investigations on SLNs that endowed extraordinary results against skin cancer include omega-3 α-linolenicacid/ α-tocopheryl linolenate, sodium taurocholate, tween 20/ melanoma [ 308 ] , Mentha longifolia , Mentha pulegium essential oils/ stearic acid, span 60, tween 80/ melanoma [ 309 ] , octyl gallate/ Astrocaryum murumuru (seed butter), tween 80/ melanoma [ 310 ] , doxorubicin/ lecithin, sodium taurodeoxycholate/ melanoma, squamous cell carcinoma [ 311 ] , paclitaxel/ stearic acid, egg lecithin/ squamous cell carcinoma [ 312 ] , microRNA-34a, paclitaxel/ glyceryl monostearate, cholesterol, soy phosphatidylcholine, dimethyldioctadecyl ammonium bromide/ melanoma [ 313 ] .…”