Ferulic acid-loaded nanocapsules: Evaluation of mucosal interaction, safety and antioxidant activity in human mononucleated cells.

Ferulic acid (FA) is a phenolic compound that has antioxidant, anti-inflammatory and anticarcinogenic properties besides presenting cytoprotective activity. It has limited oral bioavailability what is a challenge to its therapeutic application. In this way, this investigation aimed to develop FA-loaded nanocapsule suspensions (NC-FA) prepared with ethylcellulose and evaluate their in vitro release profile, mucoadhesion and irritation potential; scavenging capacity, cytotoxicity, cytoprotection and genoprotection against hydrogen peroxide-induced damage in hMNC (human Mononucleated Cells) culture. The nanocapsules presented physicochemical characteristics compatible with colloidal systems (NC-FA: 112 ± 3 nm; NC-B (without FA): 107 ± 3 nm; PdI < 0.2; Span<2.0 and negative zeta potential). In addition, the nanoparticulate system promoted the FA controlled release, increasing the half-life twice through the in vitro dialysis method. NC-FA and NC-B were able to interact with mucin, which is an indicative of mucoadhesive properties and the association of FA with nanocapsules showed decreased irritation by HET-CAM method. Besides, the NC-FA did not present cytotoxicity in hMNC and improved the ATBS radical scavenging capacity. Besides, it prevented, treated and reversed oxidative conditions in a H2O2-induced model in hMNC. Thus, this nanocarrier formulation is promising to perform more preclinical investigations focusing on diseases involving oxidative mechanisms.

Development of nanoemulsions containing Physalis peruviana calyx extract: A study on stability and antioxidant capacity.

The aim of this study was to develop and evaluate the physicochemical and antioxidant stability of nanoemulsions containing a Physalis peruviana calyx extract (CPp-NE) and free extracts under different storage conditions (7 and 25 °C) and with absence or incidence of light for 120 days. The calyx extracts were prepared with ethanol 60% and characterized for later preparation of the nanoemulsions by spontaneous emulsification. The formulations presented nanometric sizes, low polydispersity index, negative zeta potential, acid pH, rutin content (11 µg·mL-1), and encapsulation efficiency of 85%. Regarding the stability, the droplet size and PdI of the CPp-NE stored at refrigeration temperature in the dark, room temperature in the dark, and refrigeration temperature with light incidence were stable for 120 days and with no visible changes in the formulations. The antioxidant capacity was related to the reducing capacity, and the best results were found for nanoemulsions stored at room temperature and in absence of light. In addition, CPp-NE presented higher antioxidant and reducing capacity in relation to the free extracts.

Co-Nanoencapsulation of Vitamin D3 and Curcumin Regulates Inflammation and Purine Metabolism in a Model of Arthritis.

We analyzed the effects of a nanoencapsulated association of curcumin and vitamin D3 on purine metabolism enzymes in neutrophils, lymphocytes, and platelets in a model of adjuvant-induced arthritis (AIA) in rats. Following AIA induction, the animals were treated for 15 days with free and nanoencapsulated curcumin (4 mg/kg), nanocapsules of vitamin D3 (VD3) (15.84 IU/day), a nanoencapsulated combination of curcumin and VD3, vehicle, or blank nanocapsules. The animals were euthanized, and blood was collected to evaluate the activities of E-NTPDase, adenosine deaminase (ADA), and myeloperoxidase (MPO), as well as reactive oxygen species (ROS) levels and biochemical parameters. Also, the liver and kidney were collected for histological analysis. The changes in the activities of purinergic enzymes indicated that inflammation was significantly reverted by vitamin D3 and curcumin co-nanoencapsulation treatments in the arthritic rats. The reduction of inflammation was confirmed by the reduction in the signs and symptoms of AIA, as well as in MPO activity by all formulations. The treatments with nanocapsules reverted histological alterations in the kidney. Serum parameters were not altered by the induction or treatments. Our results suggest that co-nanoencapsulation of vitamin D3 and curcumin is an efficient alternative adjuvant treatment for rheumatoid arthritis as it reverts the changes in the purine metabolism and reduces arthritis-associated inflammation.

Antiproliferative potential and phenolic compounds of infusions and essential oil of chamomile cultivated with homeopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: Chamomilla recutita (Asteraceae) is used worldwide as a soothing, anti-inflammatory and aromatherapy. In Brazil, it is one of the most cultivated medicinal species. However, the cultivation form may alter the production of compounds in the secondary metabolism and compromise the therapeutic purpose of this species. AIM OF THE STUDY: Evaluation of antiproliferative and genotoxic effects of infusions and essential oil of chamomile, cultivated with homeopathy, on the cell cycle of Allium cepa, as well as the determination of the phenolic compounds present in the infusions of the chamomile inflorescences. MATERIAL AND METHODS: For the Allium cepa test, two concentrations of 10 and 40 g L-1 of inflorescences of chamomile were used for the preparation of the infusions and essential oil diluted to 0.10%, referring to the six treatments obtained in field cultivation, in which were carried out the applications of homeopathy from the emergence to the harvest of the plants. Distilled water and ethanol were used as negative control and glyphosate 2% as a positive control. The determination of phenolic compounds present in the infusions was carried by liquid chromatography in a UHPLC apparatus. RESULTS: Chamomile infusions at concentrations of 10 and 40 g L-1 of inflorescence reduced mitotic index and emphasized antiproliferative activity on the cell cycle of Allium cepa. However, the treatments related to essential oil diluted to 0.10% showed a response variation dependent on the dynamization used, as well as for apigenin concentration. CONCLUSIONS: Therefore, cultivation with homeopathy does not induce a genotoxic effect in the use of infusions and essential oil of chamomile and it emphasize antiproliferative activity on the cell cycle of Allium cepa, favoring the sustainable cultivation and the safe use of this medicinal species when cultivated with homeopathy.

In vitro and ex vivo activity of Melaleuca alternifolia against protoscoleces of Echinococcus ortleppi.

Cystic echinococcosis is a zoonotic disease of difficult diagnosis and treatment. The use of protoscolicidal agents in procedures is of utmost importance for treatment success. This study was aimed at analysing the in vitro and ex vivo activity of Melaleuca alternifolia oil (tea tree oil - TTO), its nanoemulsion formulation (NE-TTO) and its major component (terpinen-4-ol) against Echinococcus ortleppi protoscoleces obtained from cattle. Concentrations of 2·5, 5 and 10 mg mL-1 of TTO, 10 mg mL-1 of NE-TTO and 1, 1·5 and 2 mg mL-1 of terpinen-4-ol were evaluated in vitro against protoscoleces at 5, 10, 15 and 30 min. TTO was also injected directly into hydatid cysts (ex vivo analysis, n = 20) and the viability of protoscoleces was evaluated at 5, 15 and 30 min. The results indicated protoscolicidal effect at all tested formulations and concentrations. Terpinen-4-ol (2 mg mL-1) activity was superior when compared with the highest concentration of TTO. NE-TTO reached a gradual protoscolicidal effect. TTO at 20 mg mL-1 showed 90% protoscolicidal action in hydatid cysts at 5 min. The results showed that TTO affects the viability of E. ortleppi protoscoleces, suggesting a new protoscolicidal option to the treatment of cystic equinococcosis.

In Vitro Activity of Melaleuca alternifolia (Tea Tree) in Its Free Oil and Nanoemulsion Formulations Against Pythium insidiosum.

Pythium insidiosum is an important aquatic oomycete which can cause pythiosis in both animals and humans. This microorganism shows low susceptibility to antifungal drugs available. This study analyzed the in vitro antimicrobial activity of Melaleuca alternifolia in its free oil (FO) and nanoemulsion (NE) formulations against Brazilian P. insidiosum isolates. The antimicrobial activity evaluation was performed by the broth microdilution method according to CSLI M38-A2 document adapted to phytopharmaceuticals. Twenty-six P. insidiosum isolates were evaluated, and the minimum inhibitory concentration was determined at 100 % growth inhibition. Melaleuca alternifolia essential oil or FO was obtained commercially. The NE containing 1 % M. alternifolia essential oil was prepared by the spontaneous emulsification method. All P. insidiosum isolates evaluated showed minimum inhibitory concentrations (MIC) ranging from 531.5 to 2125 µg/mL for the FO formulation; MIC50 and MIC90 showed values between 1062.5 and 2125 µg/mL, respectively. When the NE formulation was evaluated, MIC values ranged from 132.7 to 2125 µg/mL and both MIC50 and MIC90 corresponded to 1062.5 µg/mL. FO and NE formulations of M. alternifolia showed antimicrobial activity against P. insidiosum. This study demonstrated that M. alternifolia oil can be an additional therapy in pythiosis treatment; however, further studies are needed to evaluate the applicability of the plant essential oils in the treatment of clinical pythiosis.

Nanoencapsulation of rice bran oil increases its protective effects against UVB radiation-induced skin injury in mice.

Excessive UV-B radiation by sunlight produces inflammatory and oxidative damage of skin, which can lead to sunburn, photoaging, and cancer. This study evaluated whether nanoencapsulation improves the protective effects of rice bran oil against UVB radiation-induced skin damage in mice. Lipid-core nanocapsules containing rice bran oil were prepared, and had mean size around 200 nm, negative zeta potential (∼-9 mV), and low polydispersity index (<0.20). In order to allow application on the skin, a hydrogel containing the nanoencapsulated rice bran oil was prepared. This formulation was able to prevent ear edema induced by UVB irradiation by 60 ± 9%, when compared with a hydrogel containing LNC prepared with a mixture of medium chain triglycerides instead of rice bran oil. Protein carbonylation levels (biomarker of oxidative stress) and NF-κB nuclear translocation (biomarker of pro-inflammatory and carcinogenesis response) were reduced (81% and 87%, respectively) in animals treated with the hydrogel containing the nanoencapsulated rice bran oil. These in vivo results demonstrate the beneficial effects of nanoencapsulation to improve the protective properties of rice bran oil on skin damage caused by UVB exposure.

Improved photostability and reduced skin permeation of tretinoin: development of a semisolid nanomedicine.

The aims of this work were to increase the photostability and to reduce the skin permeation of tretinoin through nanoencapsulation. Tretinoin is widely used in the topical treatment of various dermatological diseases such as acne, psoriasis, skin cancer, and photoaging. Tretinoin-loaded lipid-core polymeric nanocapsules were prepared by interfacial deposition of a preformed polymer. Carbopol hydrogels containing nanoencapsulated tretinoin presented a pH value of 6.08±0.14, a drug content of 0.52±0.01 mg g(-1), pseudoplastic rheological behavior, and higher spreadability than a marketed formulation. Hydrogels containing nanoencapsulated tretinoin demonstrated a lower photodegradation (24.17±3.49%) than the formulation containing the non-encapsulated drug (68.64±2.92%) after 8h of ultraviolet A irradiation. The half-life of the former was seven times higher than the latter. There was a decrease in the skin permeability coefficient of the drug by nanoencapsulation, independently of the dosage form. The liquid suspension and the semisolid form provided K(p)=0.31±0.15 and K(p)=0.33±0.01 cm s(-1), respectively (p≤0.05), while the samples containing non-encapsulated tretinoin showed K(p)=1.80±0.27 and K(p)=0.73±0.12 cm s(-1) for tretinoin solution and hydrogel, respectively. Lag time was increased two times by nanoencapsulation, meaning that the drug is retained for a longer time on the skin surface.