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Morphine is among the most powerful analgesics and pain-relieving agents. However, its addictive properties limit their medical use because patients may be susceptible to abuse and reinstatement. Morphine addiction occurs because of dopamine release in the mesolimbic brain area, implying in an increase in oxidative stress. Ferulic acid (FA), a phenolic phytochemical found in a variety of foods, has been reported to exert antioxidant and neuroprotective effects; however, its low bioavailability makes its nano-encapsulated form a promising alternative. This study aimed to evaluate the protective effects of a novel nanosystem with FA on morphine reinstatement and the consequent molecular neuroadaptations and oxidative status in the mesolimbic region. Rats previously exposed to morphine in conditioned place preference (CPP) paradigm were treated with ferulic acid-loaded nanocapsules (FA-Nc) or nonencapsulated FA during morphine-preference extinction. Following the treatments, animals were re-exposed to morphine to induce the reinstatement. While morphine-preference extinction was comparable among all experimental groups, FA-Nc treatment prevented morphine reinstatement. In the dorsal striatum, while morphine exposure increased lipid peroxidation (LP) and reactive species (RS), FA-Nc decreased LP and FA decreased RS levels. Morphine exposure increased the dopaminergic markers (D1R, D3R, DAT) and ΔFosB immunoreactivity in the ventral striatum; however, FA-Nc treatment decreased D1R, D3R, and ΔFosB and increased D2R, DAT, and NRF2. In conclusion, FA-Nc treatment prevented the morphine reinstatement, promoted antioxidant activity, and modified the dopaminergic neurotransmission, NRF2, and ΔFosB, what may indicate a neuroprotective and antioxidant role of this nanoformulation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Probiotic bacteria and bioactive compounds obtained from plant origin stand out as ingredients with the potential to increase the healthiness of functional foods, as there is currently a recurrent search for them. Probiotics and bioactive compounds are sensitive to intrinsic and extrinsic factors in the processing and packaging of the finished product. In this sense, the present study aims to evaluate the co-encapsulation by spray dryer (inlet air temperature 120 °C, air flow 40 L / min, pressure of 0.6 MPa and 1.5 mm nozzle diameter) of probiotic bacteria (L.plantarum) and compounds extracted from red beet stems (betalains) in order to verify the interaction between both and achieve better viability and resistance of the encapsulated material. When studying the co-encapsulation of L.plantarum and betalains extracted from beet stems, an unexpected influence was observed with a decrease in probiotic viability in the highest concentration of extract (100 %), on the other hand, the concentration of 50 % was the best enabled and maintained the survival of L.plantarum in conditions of 25 °C (63.06 %), 8 °C (88.80 %) and -18 °C (89.28 %). The viability of the betalains and the probiotic was better preserved in storage at 8 and -18 °C, where the encapsulated stability for 120 days was successfully achieved. Thus, the polyfunctional formulation developed in this study proved to be promising, as it expands the possibilities of application and development of new foods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study aimed to develop a functional strawberry pulp containing the combination of Lactobacillus casei and bioactive compounds from red onion peel extract into the microparticles formulations to improve bacteria survival during storage and product consumption. To achieve this goal, the addition of different concentrations of red onion peel extract added to the microparticles was evaluated: 5, 20 and 40 %. Microparticles were morphologically characterized and the encapsulation efficiency of the bioactive compounds were evaluated. The physicochemical and microbiological characteristics of the fruit pulp were within the required standards, regardless of the formulation evaluated. As for the pulp added from the microparticles, their physicochemical and microbiological features and probiotic survival under simulated gastrointestinal conditions and storage were analyzed; the size of the microparticles ranged from 136.00 to 305.00 µm. The encapsulation efficiency of both, probiotics and compounds was satisfactory over the different treatments. Indeed, the results pointed out values in the range from 77.77 to 92.11 % for probiotic bacteria; from28.88 to 50.18 % for reducing compounds; 35.72 to 69.01 % for flavonoids; and 25.39 to 60.00 % for total monomeric anthocyanins. The formulations of alginate microparticles and alginate +5 % extract had the best results of L. casei probiotic viability in strawberry pulp under simulated gastrointestinal conditions and during storage at -18 °C for 60 days. In conclusion, red onion peel extract at low concentrations can help the survival of the probiotic L. casei under different conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Essential oils (EO) are aromatic compounds from the plant secondary metabolism. Melaleuca alternifolia EO is well known for its medicinal properties and promising use as an antimicrobial agent. Pythiosis is a difficult-to-treat and emerging disease caused by the oomycete Pythium insidiosum. This study evaluated a nanoemulsion formulation of M. alternifolia (NEMA) in topical and intralesional application to treat experimental pythiosis. Dermal toxicity tests were performed on M. alternifolia EO in Wistar rats. Pythiosis was reproduced in rabbits (n = 9) that were divided into groups: group 1 (control), cutaneous lesions with daily topical application of a non-ionizable gel-based formulation and intralesional application of sterile distilled water every 48 h; group 2 (topical formulation), lesions treated daily with topical application of a non-ionizable gel-based formulation containing 5 mg/ml of NEMA; and group 3 (intralesional formulation), lesions treated with NEMA at 5 mg/ml in aqueous solution applied intralesionally/48 h. The animals were treated for 45 days, and the subcutaneous lesion areas were measured every 5 days. M. alternifolia EO showed no dermal toxicity. The lesion areas treated with intralesional NEMA reduced at the end of treatment, differing from groups 1 and 2 (P < 0.05). In the topically treated group, the lesion areas did not differ from the control group, although the number of hyphae significantly reduced (P < 0.05). Under the experimental conditions of this study, the NEMA formulations presented a favorable safety profile. However, further studies are required to evaluate if this safety applies to higher concentrations of NEMA and to validate its use in clinical pythiosis., (© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

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 H 2 O 2 -induced model in hMNC. Thus, this nanocarrier formulation is promising to perform more preclinical investigations focusing on diseases involving oxidative mechanisms., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The aim of this work was to evaluate the influence of US on the properties of the fluconazole emulsions prepared using imidazolium-based ILs ([C n C 1 im]Br). The effects of the preparation method (mechanical stirring or US), US amplitude, alkyl chain length (of [C 12 C 1 im]Br or [C 16 C 1 im]Br), and IL concentration on the physicochemical properties were evaluated. Properties such as droplet size, span index, morphology, viscosity encapsulation efficiency, and drug release profile were determined. The results showed that US-prepared emulsions had a smaller droplet size and smaller polydispersity (Span) than those prepared by mechanical stirring. Additionally, the results showed that emulsions prepared with [C 16 C 1 im]Br and US had spherical shapes and increased stability compared to emulsions prepared by MS, and also depended on the IL concentration. The emulsion prepared by US at 40% amplitude had increased encapsulation efficiency. US provided a decrease in the viscosity of emulsions containing [C 12 C 1 im]Br; however, in general, all emulsions had viscosity close to that of water. Emulsions containing [C 16 C 1 im]Br had the lowest viscosities of all the emulsions. The emulsions containing the IL [C 16 C 1 im]Br had more controlled release and a lower cumulative percentage of drug release. The IL concentration required to prepare these emulsions was lower than the amount of conventional surfactant required, which highlights the potential synergic effects of ILs and US in preparing emulsions of hydrophobic drugs., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

The objective of this study was to produce microcapsules containing Lactobacillus acidophilus LA-02 by complex coacervation followed by crosslinking with transglutaminase and to evaluate the effect of their addition on different fruit juices, as well as the probiotic viability of L. acidophilus and its effect on fruit juices during storage. To this end, L. acidophilus was microencapsulated by complex coacervation, followed by crosslinking with transglutaminase at different concentrations. Probiotics, in their free and microencapsulated forms, were added to orange juice and apple juice at concentrations of 10% and 30%. The obtained microcapsules were characterized in terms of morphology. The viability of probiotics and the effects of their addition on fruit juices were assessed and the juices characterized (with respect to pH and total soluble solids) during 63 days of storage at 4 °C. Orange juice proved to be more suitable for the addition of probiotics, and the survival of probiotics was directly related to pH. The microcapsules had a protective effect on L. acidophilus, prolonging their survival, and the crosslinking process proved to be adequate and promising, ensuring probiotic viability. Thus, the complex coacervation process associated with induced enzymatic crosslinking provided protection for L. acidophilus in different fruit juices, showing an adequate methodology for adding probiotics to this adverse food matrix, guaranteeing the survival of L. acidophilus for up to 63 days, and generating products with innovative and promising probiotic appeal., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Lactobacillus acidophilus were encapsulated by complex coacervation followed by transglutaminase crosslinking, aiming to improve the resistance of the microcapsules and improve the protection for probiotics. Subsequently, microcapsules were dried by freeze drying. The encapsulation efficiency, morphology, thermal resistance, gastrointestinal simulation and storage stability were analysed for wet and dry forms. The treatments offered high encapsulation efficiency (68.20-97.72%). Transglutaminase maintained the structure rounded, multinucleate and homogeneous distribution of probiotics in the microcapsules. In relation to the thermal resistance, in general, microencapsulation was effective in protecting and crosslinked microcapsules demonstrated greater protection for probiotics, obtaining viable cell counts of up to 10 log CFU g -1 , approximately. On exposure to the simulated gastrointestinal tract, microencapsulation coupled to crosslinking demonstrated good results and the dry form was more efficient in the protection and the treatment with greater amount of transglutaminase was highlighted (9.07 log CFU g -1 ). As for storage, probiotic viability was maintained for up to 60 days in freezing temperature, with counts of up to 9.59 log CFU g -1 . The results obtained in the present work are innovative and present a promising alternative for the protection of probiotics and their addition in food products., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

We analyzed the effects of a nanoencapsulated association of curcumin and vitamin D 3 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 D 3 (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 D 3 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 D 3 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.

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., (Copyright © 2019. Published by Elsevier B.V.)

Haloperidol is a widely used antipsychotic, despite the severe motor side effects associated with its chronic use. This study was carried out to compare oral dyskinesia induced by different formulations of haloperidol-loaded nanocapsules containing caprylic/capric triglycerides, fish oil or grape seed oil (GSO) as core, as well as free haloperidol. Haloperidol-loaded lipid-core nanocapsules formulations were prepared, physicochemical characterized and administered (0.5 mg kg -1 -ip) to rats for 28 days. Oral dyskinesia was evaluated acutely and subchronically and after that cell viability and free radical generation in cortex and substantia nigra. All formulations presented satisfactory physicochemical parameters. Acutely, all formulations were able to prevent oral dyskinesia development in comparison to free haloperidol, except haloperidol-loaded nanocapsules containing GSO, whose effect was only partial. After subchronic treatment, all haloperidol-loaded nanocapsules formulations prevented oral dyskinesia in relation to free drug. Also, haloperidol-loaded nanocapsules containing fish oil and GSO were more effective than caprylic/capric triglycerides nanocapsules and free haloperidol in cell viability preservation and control of free radical generation. Our findings showed that fish oil formulation may be considered as the best formulation of haloperidol-loaded lipid-core nanocapsules, being able to prevent motor side effects associated with chronic use of antipsychotic drugs, as haloperidol.

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.

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; MIC 50 and MIC 90 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 MIC 50 and MIC 90 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.

This work aimed to obtain solid formulations from polymeric nanocapsules and nanoemulsions containing tioconazole, a broad spectrum antifungal drug. Two dehydration methods were used: spray-drying and freeze drying, using lactose as adjuvant (10%, w/v). The liquid formulations had a mean particle size around 206 nm and 182 nm for nanocapsules and nanoemulsions, respectively, and an adequate polydispersity index. Tioconazole content was close to the theoretical amount (1.0 mg/mL). After drying, the content ranged between 98 and 102%with a mean nanometric size of the dried products after redispersion. Scanning electron microscopy showed that the particles are rounded, sphere-shaped for the dried products obtained by spray-drying, and shapeless and irregular shapes for those obtained by freeze-drying. In the microbiological evaluation, all dried products remained active against the yeast Candida albicans when compared to the original systems. The dried products obtained by spray-drying from nanocapsules presented better control of the tioconazole release when compared to the freeze-drying products.

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., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Desonide is a topical corticoid used in the treatment of skin diseases and is marketed in different pharmaceutical dosage forms. Recently, the poor photostability of a commercially available hair solution after direct exposure to UVA light was verified. In this study, we investigated the ability of the antioxidants ascorbic acid, butylhydroxyanisole (BHA), butylhydroxytoluene (BHT), α-tocopherol, and the UV filter benzophenone-3 (BP-3) to prevent the photodegradation of desonide in hair solution (desonide 0.1%) and the stability of the proposed formulation under environmental conditions. The tested antioxidants were not able to prevent the photolysis of desonide, whereas the addition of 0.3% BP-3 enhanced the photostability of the drug. After 15 h of direct exposure to UVA radiation, the desonide remaining content in the hair solution with BP-3 was approximately 98%. Higher photostability was also verified under UVC radiation. Additionally, the results indicated that the formulation was stable under accelerated and room temperature conditions for 70 days, corresponding to the total period of the study.

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., (Copyright © 2011 Elsevier B.V. All rights reserved.)