Perillyl alcohol in Solid Lipid Nanoparticles (SLN-PA): Cytotoxicity and antitumor potential in sarcoma 180 mice model

Cancer is a group of diseases characterized by the uncontrolled growth of cells. These cells invade organs and tissues by extension or direct dissemination and can spread to other regions of the body. Nanomedicine offers many possibilities to prevent the spread of cancer tissue and help cure the disease. In this work, solid lipid nanoparticles (SLN) were used to encapsulate perillyl alcohol (PA), a volatile monoterpene with proven anticancer activity. Encapsulation of PA into SLN (SLN-PA) is expected to promote controlled release, increase PA bioavailability, and impair the volatility of the monoterpene. SLN-PA prepared by high-shear homogenization showed average particle diameter around 254 nm, polydispersity index ~ 0.35, zeta potential ~ -14.7 mV, and encapsulation efficiency 84.6%. Scanning electron microscope analysis revealed a decrease in crystallinity, suggesting the encapsulation of PA in the SLN, confirming the spherical shape and the loading of the monoterpene in the SLN. In vitro cytotoxicity assays against murine fibroblasts (L929) showed that SLN-PA in both treated doses did not induce any cytotoxicity on non-tumoral cells. In vivo antitumor effect of the SLN-PA was evaluated in sarcoma 180-transplanted mice. The in vivo results demonstrated a significant tumor inhibition rate of 51.76 and 54.49% via intraperitoneal application of SLN-PA at doses of 100 and 200 mg/kg/day (p < 0.05), respective when compared to the negative control (dimethyl sulfoxide). Adverse side effects of SLN-PA were not noticed in the liver, the kidney, or spleen tissue. The developed SLN-PA can be considered as a safe approach for site-specific antitumor effect in vivo, reinterpreting new nanoparticles- based cancer therapy.This work was supported by the Banco do Nordeste (grant FUNDECI/2016.0015), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe (Fapitec) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Eliana B. Souto would like to acknowledge the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the project UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Silver nanoparticles-composing alginate/gelatine hydrogel improves wound healing in vivo

Polymer hydrogels have been suggested as dressing materials for the treatment of cutaneous wounds and tissue revitalization. In this work, we report the development of a hydrogel composed of natural polymers (sodium alginate and gelatin) and silver nanoparticles (AgNPs) with recognized antimicrobial activity for healing cutaneous lesions. For the development of the hydrogel, different ratios of sodium alginate and gelatin have been tested, while different concentrations of AgNO3 precursor (1.0, 2.0, and 4.0 mM) were assayed for the production of AgNPs. The obtained AgNPs exhibited a characteristic peak between 430450 nm in the ultraviolet-visible (UVVis) spectrum suggesting a spheroidal form, which was confirmed by Transmission Electron Microscopy (TEM). Fourier Transform Infra-red (FTIR) analysis suggested the formation of strong intermolecular interactions as hydrogen bonds and electrostatic attractions between polymers, showing bands at 2920, 2852, 1500, and 1640 cm1. Significant bactericidal activity was observed for the hydrogel, with a Minimum Inhibitory Concentration (MIC) of 0.50 µg/mL against Pseudomonas aeruginosa and 53.0 µg/mL against Staphylococcus aureus. AgNPs were shown to be non-cytotoxic against fibroblast cells. The in vivo studies in female Wister rats confirmed the capacity of the AgNP-loaded hydrogels to reduce the wound size compared to uncoated injuries promoting histological changes in the healing tissue over the time course of wound healing, as in earlier development and maturation of granulation tissue. The developed hydrogel with AgNPs has healing potential for clinical applications.This research received funding from the Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES), Fundação de Amparo à Pesquisa do Estado de Sergipe (FAPITEC), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, #443238/2014-6, #470388/2014-5), and from the Portuguese Science and Technology Foundation (FCT) projects M-ERA-NET/0004/2015 (PAIRED) and UIDB/04469/2020 (strategic fund).info:eu-repo/semantics/publishedVersio

Anti-tumor efficiency of Perillylalcohol/β-Cyclodextrin inclusion complexes in a sarcoma S180-induced mice model

The low solubility and high volatility of perillyl alcohol (POH) compromise its bioavailability and potential use as chemotherapeutic drug. In this work, we have evaluated the anticancer activity of POH complexed with -cyclodextrin (-CD) using three complexation approaches. Molecular docking suggests the hydrogen-bond between POH and -cyclodextrin in molar proportion was 1:1. Thermal analysis and Fourier-transform infrared spectroscopy (FTIR) confirmed that the POH was enclosed in the -CD cavity. Also, there was a significant reduction of particle size thereof, indicating a modification of the -cyclodextrin crystals. The complexes were tested against human L929 fibroblasts after 24 h of incubation showing no signs of cytotoxicity. Concerning the histopathological results, the treatment with POH/-CD at a dose of 50 mg/kg promoted approximately 60% inhibition of tumor growth in a sarcoma S180-induced mice model and the reduction of nuclear immunoexpression of the Ki67 antigen compared to the control group. Obtained data suggest a significant reduction of cycling cells and tumor proliferation. Our results confirm that complexation of POH/-CD not only solves the problem related to the volatility of the monoterpene but also increases its efficiency as an antitumor agent.This work was supported by the Banco do Nordeste (grant FUNDECI/2016.0015), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe (Fapitec) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Eliana B. Souto would like to acknowledge the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) for the project UIDB/04469/2020 (strategic fund), co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio

Correction: Diniz et al. Silver Nanoparticles-Composing Alginate/Gelatine Hydrogel Improves Wound Healing In Vivo. Nanomaterials 2020, 10, 390

In the original publication, there was a mistake in Figure 6 as published [...]info:eu-repo/semantics/publishedVersio

Photobiomodulation reduces the cytokine storm syndrome associated with Covid-19 in the zebrafish model

Although the exact mechanism of the pathogenesis of COVID-19 is not fully understood, oxidative stress and the release of pro-inflammatory cytokines have been highlighted as playing a vital role in the pathogenesis of the disease. In this sense, alternative treatments are needed to reduce the inflammation caused by COVID-19. Therefore, this study aimed to investigate the potential effect of red PBM as an attractive therapy to downregulate the cytokine storm caused by COVID-19 from a zebrafish model. RT-PCR analyses and protein-protein interaction prediction among SARS-CoV-2 and Danio rerio proteins showed that rSpike was responsible for generating systemic inflammatory processes with significantly increased pro-inflammatory (il1b, il6, tnfa, and nfkbiab), oxidative stress (romo1) and energy metabolism (slc2a1a, coa1) mRNA markers, with a pattern like those observed in COVID-19 cases in humans. On the other hand, PBM treatment decreased the mRNA levels of these pro-inflammatory and oxidative stress markers compared with rSpike in various tissues, promoting an anti-inflammatory response. Conversely, PBM promotes cellular and tissue repair of injured tissues and significantly increases the survival rate of rSpike-inoculated individuals. Additionally, metabolomics analysis showed that the most impacted metabolic pathways between PBM and the rSpike-treated groups were related to steroid metabolism, immune system, and lipids metabolism. Together, our findings suggest that the inflammatory process is an incisive feature of COVID-19, and red PBM can be used as a novel therapeutic agent for COVID-19 by regulating the inflammatory response. Nevertheless, the need for more clinical trials remains, and there is a significant gap to overcome before clinical trials.publishedVersio

Structuring of Bacterioplankton Diversity in a Large Tropical Bay

Structuring of bacterioplanktonic populations and factors that determine the structuring of specific niche partitions have been demonstrated only for a limited number of colder water environments. In order to better understand the physical chemical and biological parameters that may influence bacterioplankton diversity and abundance, we examined their productivity, abundance and diversity in the second largest Brazilian tropical bay (Guanabara Bay, GB), as well as seawater physical chemical and biological parameters of GB. The inner bay location with higher nutrient input favored higher microbial (including vibrio) growth. Metagenomic analysis revealed a predominance of Gammaproteobacteria in this location, while GB locations with lower nutrient concentration favored Alphaproteobacteria and Flavobacteria. According to the subsystems (SEED) functional analysis, GB has a distinctive metabolic signature, comprising a higher number of sequences in the metabolism of phosphorus and aromatic compounds and a lower number of sequences in the photosynthesis subsystem. The apparent phosphorus limitation appears to influence the GB metagenomic signature of the three locations. Phosphorus is also one of the main factors determining changes in the abundance of planktonic vibrios, suggesting that nutrient limitation can be observed at community (metagenomic) and population levels (total prokaryote and vibrio counts)