Nano-based formulations as an approach for providing a novel identity for organoselenium compounds.

The organoselenium compounds belong to a class of synthetic molecules that displays a remarkable spectrum of promising pharmacological properties. Despite the huge amount of preclinical data that supports a bright outlook for organoselenium compounds, some toxicity issues and physicochemical limitations delay the development of more advanced studies. Currently, several scientific reports demonstrated that the association of nanotechnology has emerged as an alternative to improve solubility and safety issues of these molecules as well as enhance pharmacological properties. Therefore, our main objective was to address studies that reported the development and biological evaluations of nano-based formulations to synthetic organoselenium compounds incorporation by constructing an integrative literature review. The data survey was performed using the Science Direct, PubMed, Web of Science, and SCOPUS online databases, covering studies that were published from January 2011 up to October 2021. In the last decade, there has been an exponential growth in research regarding the incorporation of synthetic organoselenium compounds into distinct nanocarrier systems such as nanocapsules, nanoemulsions, micelles, and others, reinforcing that the association of such molecules and nanotechnology is a promising alliance. The reports investigated many nanosystems containing selenium organic molecules intending oral, intravenous, and cutaneous applications. Besides that, these systems were evaluated in a variety of in vitro techniques and in vivo models, concerning their pharmacological potential, biodistribution profile, and safety. In summary, the findings indicate that the production of nano-based formulations containing organoselenium compounds either improved physicochemical and biological properties or minimize toxicological issues of compounds.

Improved antimutagenic effect of Pyrostegia venusta (Ker Gawl. ) Miers nanostructured extract in liposome and polymeric nanoparticle

Abstract Pyrostegia venusta (Ker Gawl.) Miers, popularly known as "Cipó-de São-João", has been used in traditional medicine for its therapeutic properties. Nanotechnology is able to enhance the pharmacological activity of plant extracts. In this context, liposomes and polymeric nanoparticles containing P. venusta ethanolic extract were developed and then physico-chemically characterized to evaluate the mutagenic/antimutagenic effects of P. venusta. In addition, transaminases and serum creatinine were biochemically analyzed for liver and renal damage, respectively. The micronucleus test was performed with male Swiss mice treated orally for 15 consecutive days with free extracts and nanostructured with P. venusta, and then intraperitoneally with N-ethyl-N-nitrosurea (50 mg/kg) on the 15th day of treatment. Micronucleated polychromatic erythrocytes (MNPCE) were evaluated in bone marrow. There was a significant reduction in the frequency of MNPCE (LPEPV = 183% and NPEPV = 114%, p < 0.001), indicating antimutagenic potential of the nanostructured extracts with P. venusta. The groups treated with only nanostructured extract did not show an increase in MNPCE frequency, and biochemical analyzes showed no significant difference between treatments. The liposomes and polymeric nanoparticles containing Pyrostegia venusta ethanolic extract showed biological potential in preventing the first step of carcinogenesis under the experimental conditions

Xanthan gum-based hydrogel containing nanocapsules for cutaneous diphenyl diselenide delivery in melanoma therapy.

The aim of this study was to further evaluate the antitumoral effect of (PhSe)2-loaded polymeric nanocapsules (NC (PhSe)2) against a resistant melanoma cell line (SK-Mel-103) and develop a xanthan gum-based hydrogel intending the NC (PhSe)2 cutaneous application. For the in vitro evaluation, cells were incubated with free (PhSe)2 or NC (PhSe)2 (0.7-200 µM) and after 48 h the MTT assay, propidium iodide uptake (necrosis marker) and nitrite levels were assessed. The hydrogels were developed by thickening of the NC (PhSe)2 suspension or (PhSe)2 solution with xanthan gum and characterized in terms of average diameter, polydispersity index, pH, drug content, spreadability, rheological profiles and in vitro permeation in human skin. The results showed that NC (PhSe)2 provided a superior antitumoral effect in comparison to free (PhSe)2 (IC50 value of 47.43 µM and 65.05 µM, respectively) and increased the nitrite content. Both compound forms induced propidium iodide uptake, suggesting a necrosis-related pathway could be involved in the cytotoxic action of (PhSe)2. All hydrogels showed pH values around 7, drug content close to the theoretical values (5 mg/g) and mean diameter in the nanometric range. Besides, formulations were classified as non-Newtonian flow with pseudoplastic behavior and suitable spreadability factor. Skin permeation studies revealed that the compound content was higher for the nano-based hydrogel in the dermis layer, demonstrating its superior permeation, achieved by the compound encapsulation. It is the first report on an adequate formulation development for cutaneous application of NC (PhSe)2 that could be used as an adjuvant treatment in melanoma therapy.

p,p'-Methoxyl-diphenyl diselenide-loaded polymeric nanocapsules as a novel approach to inflammatory pain treatment: Behavioral, biochemistry and molecular evidence.

The current study investigated the effect of organoselenium compound p,p'-methoxyl-diphenyl diselenide [(OMePhSe)2], free or incorporated into nanocapsules, on behavioral, biochemical and molecular alterations in an inflammatory pain model induced by complete Freund's adjuvant (CFA). Male Swiss mice received an intraplantar injection of CFA in the hindpaw and 24 h later they were treated via the intragastric route with a single (OMePhSe)2 administration, in its free form (dissolved in canola oil) or (OMePhSe)2 NC. The anti-hypernociceptive time- and dose-response curves were carried out using the von Frey hair test. Biochemical and histological parameters were determined in samples of injected paws and those of cerebral contralateral cortex were collected to determine immuno content of inflammatory proteins. Both (OMePhSe)2 forms reduced the hypernociception induced by CFA as well as attenuated the altered parameters of the inflammatory process in the paw (paw edema, myeloperoxidase and histological). However, the (OMePhSe)2 NC had a more prolonged anti-hypernociceptive action (7h) at a lower dose (10mg/kg) and superior effects on the paw alterations than the free compound form (4h and 25mg/kg). Furthermore, independent of the (OMePhSe)2 form, its administration decreased the MAPKs pathway activation (JNK;ERK1,2; p38) as well as iNOS, COX-2, Nf-κB and IL-1ß protein contents in the cerebral contralateral cortex that were increased by paw CFA injection. Therefore, (OMePhSe)2 NC had superior anti-inflammatory action, which possibly occurs by the inflammatory protein content modulation and also attenuates paw biochemical and histological inflammatory alterations induced by CFA injection.

Influence of Harvest Season and Cultivar on the Variation of Phenolic Compounds Composition and Antioxidant Properties in Vaccinium ashei Leaves.

The effect of variation of harvest season and cultivar on the total phenolic content (TPC), total flavonoid content (TFC), HPLC-UV/DAD profile and antioxidant properties in Vaccinium ashei (Rabbiteye blueberry) leaves grown in Brazil was evaluated. The cultivars collected in December and March were Aliceblue, Powderblue, Climax, Bluegem and FloridaM. It was observed that leaves from March had the highest TPC values (222 ± 1 mg gallic acid equivalents/g to Aliceblue cultivar) and highest TFC values (49.8 ± 0.8 and 48.7 ± 0.7 µg rutin/g to Clímax and Powderblue cultivars, respectively). The chromatographic profile was quantitatively similar, however, the proportions of each compound were influenced by cultivar and harvest season. Chlorogenic acid and rutin were the main identified phenolic compounds, but chlorogenic acid was the most abundant in both harvest seasons. Antioxidant capacities values ranged from 5.80 ± 0.04 to 105 ± 2 µg/mL (DPPH) and 178 ± 5 to 431 ± 8 mmol Trolox/100 g (ORAC). The cultivar Bluegem by March had the highest values in both assays. The results indicate that the blueberry leaves from different cultivars and harvest seasons have different phenolic compounds content and different antioxidant capacities. In addition, the antioxidant properties demonstrated a high correlation with rutin content.

Pomegranate seed oil nanoemulsions improve the photostability and in vivo antinociceptive effect of a non-steroidal anti-inflammatory drug.

The combination of pomegranate seed oil and ketoprofen in nanoemulsions aiming to improve the antinociceptive effect was evaluated according to the writhing test and Complete Freud's Adjuvant induced paw inflammation in mice. The formulations showed adequate characteristics and improved ketoprofen's photostability against UVC radiation exposure. The dialysis bag technique showed that 100% of the drug was released from the nanoemulsions after 3h and the oil amount had no influence on the releasing. Furthermore, time- and dose-response curves were obtained to determine the antinociceptive effect of the formulations. In the post-test, the nanoemulsion containing ketoprofen significantly reduced abdominal constrictions in time-response curve, showing effect up to 12h while the free ketoprofen showed effect up to 3h. In addition, the blank nanoemulsion presented a reduction of abdominal constriction up to 1h of pre-treatment. Regarding the dose-response curve, the free ketoprofen presents effect at 0.5mg/Kg dose and nanoemulsion at 1.0mg/Kg dose. Time- and dose-response curves were performed to determine the antinociceptive effect in inflammatory pain. After the evaluation of mechanical allodynia testing at the Von Frey Hair, the free ketoprofen showed effect up to 6h while nanoemulsions presented effect up to 10h. Moreover, acute toxicity was performed with ALT and AST activity evaluations and urea levels. After 7 days of treatment, no toxic effects for nanoemulsions were found. In conclusion, ketoprofen-loaded pomegranate seed oil nanoemulsions presented adequate characteristics and a high antinociceptive activity in the animal models tested.