Ferulic Acid-Loaded Nanostructure Maintains Brain Levels of ACh, Glutamate, and GABA and Ameliorates Anxiety and Memory Impairments Induced by the D-Galactose Aging Process in Rats.

Population aging is a global reality driven by increased life expectancy. This demographic phenomenon is intrinsically linked to the epidemic of cognitive disorders such as dementia and Alzheimer's disease, posing challenges for elderly and their families. In this context, the search for new therapeutic strategies to prevent or minimize cognitive impairments becomes urgent, as these deficits are primarily associated with oxidative damage and increased neuroinflammation. Ferulic acid (FA), a natural and potent antioxidant compound, is proposed to be nanoencapsulated to target the central nervous system effectively with lower doses and an extended duration of action. Here, we evaluated the effects of the nanoencapsulated FA on d-galactose (d-Gal)- induced memory impairments. Male Wistar adult rats were treated with ferulic acid-loaded nanocapsules (FA-Nc) or non-encapsulated ferulic acid (D-FA) for 8 weeks concurrently with d-Gal (150 mg/kg s.c.) injection. As expected, our findings showed that d-Gal injection impaired memory processes and increased anxiety behavior, whereas FA-Nc treatment ameliorated these behavioral impairments associated with the aging process induced by d-Gal. At the molecular level, nanoencapsulated ferulic acid (FA-Nc) ameliorated the decrease in ACh and glutamate induced by d-galactose (d-Gal), and also increased GABA levels in the dorsal hippocampus, indicating its therapeutic superiority. Additional studies are needed to elucidate the mechanisms underlying our current promising outcomes. Nanoscience applied to pharmacology can reduce drug dosage, thereby minimizing adverse effects while enhancing therapeutic response, particularly in neurodegenerative diseases associated with aging. Therefore, the strategy of brain-targeted drug delivery through nanoencapsulation can be effective in mitigating aging-related factors that may lead to cognitive deficits.

Diazepam nanocapsules as an alternative for sleep induction: Development study and toxicity assessment.

Diazepam (DZP) is a sedative medication prescribed to treat anxiety and as a sleep inducer, although its residual effects are unfavorable to patients. Nanotechnology represents a tool to improve the pharmacological characteristics of drugs, reducing their side effects. This study aimed to develop and characterize DZP nanocapsules and to evaluate their toxicity in alternative models and the hypnotic-sedative effect in mice. Nanocapsules were prepared by the nanoprecipitation method and properly characterized. Long-term and accelerated stability studies were performed. The in vitro release profile was determined by diffusion in Franz cells. The safety of the formulation was evaluated in the Caenorhabditis elegans (C. elegans) and the oral acute toxicity in mice. Pharmacological evaluation was performed using thiopental-induced sleeping time. DZP was successfully incorporated into Poly-(ɛ-caprolactone) (PCL) nanocapsules, with high entrapment efficiency. The nanocapsule did not affect the development or survival of C. elegans, different from the free drug, which affected the nematode development at the higher tested dose. No signs of toxicity, nor body mass or feed consumption changes were observed during the 14 days evaluated. Finally, this innovative formulation carrying DZP can produce a hypnotic-effect at a reduced dose compared to the free drug, with no toxicity in alternative models.

Efficacy and safety of a 0.05 % nanoencapsulated imiquimod hydrogel for the treatment of actinic cheilitis: Drug release analysis and clinical study.

Actinic cheilitis (AC) is a lip disorder, with no standard treatment. Imiquimod (IMIQ) is an immunomodulator that treat precancerous lesions; however, its commercial form causes severe adverse effects. This study aimed to assess IMQ release from a chitosan hydrogel containing 0.05 % nanoencapsulated (NANO) imiquimod (IMIQ-0.05 %-NANO) and its efficacy in AC treatment. The hydrogels were prepared by incorporating chitosan into polymeric nanocapsules (NCimiq) loaded with IMQ, produced using the interfacial deposition of preformed polymer method. IMQ release was evaluated using automated Franz Cells. A triple-blind randomized controlled trial (49 subjects) compared the efficacy of: IMIQ-0.05 %-NANO, 5 % free imiquimod (IMIQ-5 %), 0.05 % free imiquimod (IMIQ-0.05 %), and placebo hydrogel. The IMIQ-NANO-0.05 % and IMIQ-5 % groups exhibited significantly higher rates of clinical improvement (p < 0.05); however, the IMIQ-5 % group experienced more adverse effects (92.3 % of subjects) compared to other groups (p < 0.05). In conclusion, in the studied sample, IMIQ-NANO-0.05 % was a safe and effective option to treat AC.

Indole-3-carbinol loaded-nanocapsules modulated inflammatory and oxidative damages and increase skin wound healing in rats.

This study evaluated the effects of topically applied hydrogels (HG) containing nanoencapsulated indol-3-carbinol (I3C) and its free form in a rat model of skin wounds. Formulations were topically applied twice a day for five days to the wounds. On days 1, 3, and 6, the wound area was measured to verify the % of regression. On the sixth day, the animals were euthanized for the analysis of the inflammatory and oxidative profile in wounds. The nanocapsules (NC) exhibited physicochemical characteristics compatible with this kind of suspension. After five hours of exposure to ultraviolet C, more than 78% of I3C content in the suspensions was still observed. The NC-I3C did not modify the physicochemical characteristics of HG when compared to the HG base. In the in vivo study, an increase in the size of the wound was observed on the 3rd experimental day, which was lower in the treated groups (mainly in HG-NC-I3C) compared to the control. On the 6th day, HG-I3C, HG-NC-B, and HG-NC-I3C showed lower regression of the wound compared to the control. Additionally, HG-NC-I3C exhibited an anti-inflammatory effect (as observed by decreased levels of interleukin-1B and myeloperoxidase), reduced oxidative damage (by decreased reactive species, lipid peroxidation, and protein carbonylation levels), and increased antioxidant defense (by improved catalase activity and vitamin C levels) compared to the control. The current study showed more satisfactory results in the HG-NC-I3C group than in the free form of I3C in decreasing acute inflammation and oxidative damage in wounds.

I3C nanocapsules exhibited characteristics compatible with this kind of suspension;On 3rd day, I3C nanocapsules prevented the increase of wound area;I3C nanocapsules decreased oxidative damage in wound tissue;Inflammatory proteins were decreased in I3C nanocapsules treated group.

Development and pharmacological evaluation of liposomes and nanocapsules containing paroxetine hydrochloride.

Depression is one of the most common psychiatric disorders. Nanotechnology has emerged to optimize the pharmacological response. Therefore, the aim of this work was to develop and characterize liposomes and nanocapsules containing paroxetine hydrochloride and evaluate their antidepressant-like effect using the open field and tail suspension tests in mice. Liposomes and nanocapsules were prepared using the reverse-phase evaporation and nanoprecipitation methods, respectively. The particle size of the formulation ranged from 121.81 to 310.73 nm, the polydispersity index from 0.096 to 0.303, the zeta potential from -11.94 to -34.50 mV, the pH from 5.31 to 7.38, the drug content from 80.82 to 94.36 %, and the association efficiency was 98 %. Paroxetine hydrochloride showed slower release when associated with liposomes (43.82 %) compared to nanocapsules (95.59 %) after 10 h. In Vero cells, in vitro toxicity showed a concentration-dependent effect for paroxetine hydrochloride nanostructures. Both nanostructures decreased the immobility time in the TST at 2.5 mg/kg without affecting the number of crossings in the open field test, suggesting the antidepressant-like effect of paroxetine. In addition, the nanocapsules decreased the number of groomings, reinforcing the anxiolytic effect of this drug. These results suggest that the nanostructures were effective in preserving the antidepressant-like effect of paroxetine hydrochloride even at low doses.

Toxicological analysis of chronic exposure to polymeric nanocapsules with different coatings in Drosophila melanogaster.

Nanotechnology involves the utilization of nanomaterials, including polymeric nanocapsules (NCs) that are drug carriers. For modify drug release and stability, nanoformulations can feature different types of polymers as surface coatings: Polysorbate 80 (P80), Polyethylene glycol (PEG), Chitosan (CS) and Eudragit (EUD). Although nanoencapsulation aims to reduce side effects, these polymers can interact with living organisms, inducing events in the antioxidant system. Thus far, little has been described about the impacts of chronic exposure, with Drosophila melanogaster being an in vivo model for characterizing the toxicology of these polymers. This study analyzes the effects of chronic exposure to polymeric NCs with different coatings. Flies were exposed to 10, 50, 100, and 500 µL of NCP80, NCPEG, NCCS, or EUD. The survival rate, locomotor changes, oxidative stress markers, cell viability, and Nrf2 expression were evaluated. Between the coatings, NCPEG had minimal effects, as only 500 µL affected the levels of reactive species (RS) and the enzymatic activities of catalase (CAT) and glutathione S-transferase (GST) without reducing Nrf2 expression. However, NCEUD significantly impacted the total flies killed, RS, CAT, and Superoxide dismutase from 100 µL. In part, the toxicity mechanisms of these coatings can be explained by the imbalance of the antioxidant system. This research provided initial evidence on the chronic toxicology of these nanomaterials in D. melanogaster to clarify the nanosafety profile of these polymers in future nanoformulations. Further investigations are essential to characterize possible biochemical pathways involved in the toxicity of these polymeric coatings.

Cytotoxicity, anti-inflammatory effect, and acute oral toxicity of a novel Attalea phalerata kernel oil-loaded nanocapsules.

The kernel oil of the Attalea phalerata Mart. Ex Spreng (Acurí) is traditionally used in several Latin American countries to treat respiratory problems, inflammation, and fever. However, it cannot be found on the literature any attend to use this oil in pharmaceutical formulation. In this paper, it was developed Acurí oil-loaded nanocapsules, and it was evaluated the cytotoxicity against cancer cells, the antinflammatory activity and the oral acute toxicity in rats. Acurí oil contains lauric acid as the predominant saturated fatty acid (433.26 mg/g) and oleic acid as the main unsaturated fatty acid (180.06 mg/g). The Acurí oil-loaded nanocapsules showed a size of 237 nm, a polydispersity index of 0.260, and a high ζ-potential of -78.75 mV. It was obtained an encapsulation efficiency of 88.77%, and the nanocapsules remain stable on the shelf for 180 days. The nanocapsules showed a rapid release profile (98.25% in 40 minutes). Nanocapsules at a dose of 10 mg/kg exhibit an anti-inflammatory effect similar to indomethacin at the same dose. The nanocapsules showed excellent antiproliferative effect and selectivity index against prostate tumor cells (IC50 2.09 µg/mL, SI=119.61) and kidney tumor cells (IC50 3.03 µg/mL, SI=82.50). Both Acurí oil and Acurí oil-loaded nanocapsules are nontoxic at a dose of 2000 mg/kg. Additionally, they reduce serum triglyceride and total cholesterol levels in rat and could find application in nutraceutical formulations. The Acurí oil-loaded nanocapsules emerge as a promising candidate for new antitumor therapies.

Carvacrol nanocapsules as a new antifungal strategy: Characterization and evaluation against fungi important for grape quality and to control the synthesis of ochratoxins.

Fungi are a problem for viticulture as they can lead to deterioration of grapes and mycotoxins production. Despite the widespread use of synthetic fungicides to control fungi, their impact on the agricultural ecosystem and human health demand safer and eco-friendly alternatives. This study aimed to produce, characterize and assess the antifungal activity of carvacrol loaded in nanocapsules of Eudragit® and chia mucilage as strategy for controlling Botrytis cinerea, Aspergillus flavus, Aspergillus carbonarius, and Aspergillus niger. Eudragit® and chia mucilage were suitable wall materials, as both favored the encapsulation of carvacrol into nanometric diameter particles. Fourier Transform Infrared Spectroscopy (FTIR) analysis suggested a successful incorporation of carvacrol into both nanocapsules, which was confirmed by presenting a good encapsulation efficiency and loading capacity. Thermogravimetric Analysis (TGA) and Differential Scanning Calorimetry (DSC) analyses revealed adequate thermal resistance. All fungi were sensible to carvacrol treatments and B. cinerea was the most sensitive compared to the Aspergillus species. Lower concentrations of encapsulated carvacrol than the unencapsulated form were required to inhibit fungi in the in vitro and grape assays. Additionally, lower levels of carvacrol (unencapsulated or encapsulated) were used to inhibit fungal growth and ochratoxin synthesis on undamaged grapes in comparison to those superficially damaged, highlighting the importance of management practices designed to preserve berry integrity during cultivation, storage or commercialization. When sublethal doses of carvacrol were used, the growth of A. niger and A. carbonarius was suppressed by at least 45 %, and ochratoxins were not found. The nanoencapsulation of carvacrol using Eudragit® and chia mucilage has proven to be an alternative to mitigate the problems with fungi and mycotoxins faced by the grape and wine sector.

Pharmacokinetic/pharmacodynamic modeling of cortical dopamine concentrations after quetiapine lipid core nanocapsules administration to schizophrenia phenotyped rats.

Schizophrenia (SCZ) response to pharmacological treatment is highly variable. Quetiapine (QTP) administered as QTP lipid core nanocapsules (QLNC) has been shown to modulate drug delivery to the brain of SCZ phenotyped rats (SPR). In the present study, we describe the brain concentration-effect relationship after administrations of QTP as a solution or QLNC to SPR and naïve animals. A semimechanistic pharmacokinetic (PK) model describing free QTP concentrations in the brain was linked to a pharmacodynamic (PD) model to correlate the drug kinetics to changes in dopamine (DA) medial prefrontal cortex extracellular concentrations determined by intracerebral microdialysis. Different structural models were investigated to fit DA concentrations after QTP dosing, and the final model describes the synthesis, release, and elimination of DA using a pool compartment. The results show that nanoparticles increase QTP brain concentrations and DA peak after drug dosing to SPR. To the best of our knowledge, this is the first study that combines microdialysis and PK/PD modeling in a neurodevelopmental model of SCZ to investigate how a nanocarrier can modulate drug PK and PD, contributing to the development of new treatment strategies for SCZ.

Nanoemulsions and nanocapsules loaded with Melaleuca alternifolia essential oil for sepsis treatment.

Sepsis represents a complex clinical syndrome that results from a harmful host response to infection. The infections most associated with sepsis are pneumonia, intra-abdominal infection, and urinary tract infection. Tea tree oil (TTO) has shown high antibacterial activity; however, it exhibits low aqueous solubility and high volatility, which have motivated its nanoencapsulation. In this study, the performance of nanoemulsions (NE) and nanocapsules (NC) loaded with TTO was compared. These systems were prepared by spontaneous emulsification and nanoprecipitation methods, respectively. Poly-ε-caprolactone or Eudragit® RS100 were tested as polymers for NCs whereas Tween® 80 or Pluronic® F68 as surfactants in NE preparation. Pluronic® F68 and Eudragit® RS100 resulted in more homogeneous and stable nanoparticles. In accelerated stability studies at 4 and 25 °C, both colloidal suspensions (NC and NE) were kinetically stable. NCs showed to be more stable to photodegradation and less cytotoxic than NEs. After sepsis induction by the cecal ligation and puncture (CLP) model, both NE and NC reduced neutrophil infiltration into peritoneal lavage (PL) and kidneys. Moreover, the systems increased group thiols in the kidney and lung tissue and reduced bacterial growth in PL. Taken together, both systems showed to be effective against injury induced by sepsis; however, NCs should be prioritized due to advantages in terms of cytotoxicity and physicochemical stability.

Evaluation of the efficacy of different concentrations of nano-capsules containing Talaromyces flavus with two forms of powder and suspension in reducing the incidence of cotton Verticillium wilt / Avaliação da eficácia de diferentes concentrações de nanocápsulas contendo Talaromyces flavus com duas formas de pó e suspensão na redução da incidência de murcha de Verticillium do algodoeiro

Previous domestic and foreign studies have shown the significant effect of Talaromyces flavus on growth inhibition of some important plant pathogens including Verticillium dahliae, Fusarium oxysporum f. sp. lycopersici and Fusarium oxysporum f. sp. cucumerinum. In Iran, it is necessary to produce new formulations of this fungus based on modern technologies given the importance of attracting companies producing biological control agents and transferring the technical knowledge of mass production of formulations of these agents to them. In the present study, based on the method presented in the Pesticide Research Department of the Iranian Plant Protection Research Institute, two types of T. flavus formulations in the form of nano-capsules containing Talaromyces flavus with two forms of powder and suspension were prepared using nanotechnology. In the next step, during the greenhouse examination, the efficiency of each of these new formulations in concentrations of one to five per thousand for soil addition method and concentration of five per thousand for seed impregnation method (six treatments for each of the two new formulations) was compared with the registered formulation of Talaromin in two methods of seed impregnation and soil addition with healthy control and infected control to control cotton Verticillium wilt disease, in the form of a randomized complete block design with 16 treatments and 5 replications. After statistical analysis of the data obtained by Duncan's Multiple Range Test by MS TAT C software, the results showed that in terms of disease severity among treatments with the previous formulation (Talaromin) with each of the methods of soil addition and seed impregnation, there was no statistically significant difference between nano-suspension with each of the concentrations of one, four and five per thousand by the soil addition method and nano-powder with each of the concentrations of two and three per thousand by soil addition method, and the mentioned treatments were included in one statistical group in terms of disease severity with healthy control.

Estudos anteriores nacionais e internacionais mostraram o efeito significativo de Talaromyces flavus na inibição do crescimento de alguns importantes patógenos de plantas, incluindo Verticillium dahliae, Fusarium oxysporum f. sp. lycopersici e Fusarium oxysporum f. sp. cucumerinum. No Irã, é necessário produzir novas formulações desse fungo com base em tecnologias modernas, dada a importância de atrair empresas produtoras de agentes de controle biológico e transferir para elas o conhecimento técnico de produção em massa das formulações desses agentes. No presente estudo, com base no método apresentado no Departamento de Pesquisa de Pesticidas, do Instituto Iraniano de Pesquisa em Proteção de Plantas, dois tipos de formulações de T. flavus, na forma de nanocápsulas contendo T. flavus com duas formas de pó e suspensão, foram preparados usando nanotecnologia. Na etapa seguinte, durante o exame em casa de vegetação, a eficiência de cada uma dessas novas formulações em concentrações de um a cinco por mil para o método de adição de solo e de cinco por mil para o método de impregnação de sementes (seis tratamentos para cada uma das duas novas formulações) foi comparada com a formulação registrada de Talaromin em dois métodos de impregnação de sementes e adição de solo com controle sadio e controle infectado para controle da murcha de Verticillium do algodoeiro, na forma de delineamento em blocos completos casualizados com 16 tratamentos e 5 repetições. Após análise estatística dos dados obtidos pelo Duncan's Multiple Range Test por meio do software MS TAT C, os resultados mostraram que, em termos de severidade da doença entre os tratamentos com a formulação anterior (Talaromin), com cada um dos métodos de adição de solo e impregnação de sementes, não houve diferença estatisticamente significativa entre a nanossuspensão com cada uma das concentrações de um, quatro e cinco por mil pelo método de adição de solo e entre o nanopó com cada uma das concentrações de dois e três por mil pelo método de adição de solo, e os tratamentos mencionados foram incluídos em um grupo estatístico em termos de gravidade da doença com controle saudável.

Effect of Inlet Air Temperature and Quinoa Starch/Gum Arabic Ratio on Nanoencapsulation of Bioactive Compounds from Andean Potato Cultivars by Spray-Drying.

Nanoencapsulation of native potato bioactive compounds by spray-drying improves their stability and bioavailability. The joint effect of the inlet temperature and the ratio of the encapsulant (quinoa starch/gum arabic) on the properties of the nanocapsules is unknown. The purpose of this study was to determine the best conditions for the nanoencapsulation of these compounds. The effects of two inlet temperatures (96 and 116 °C) and two ratios of the encapsulant (15 and 25% w/v) were evaluated using a factorial design during the spray-drying of native potato phenolic extracts. During the study, measurements of phenolic compounds, flavonoids, anthocyanins, antioxidant capacity, and various physical and structural properties were carried out. Higher inlet temperatures increased bioactive compounds and antioxidant capacity. However, a higher concentration of the encapsulant caused the dilution of polyphenols and anthocyanins. Instrumental analyses confirmed the effective encapsulation of the nuclei in the wall materials. Both factors, inlet temperature, and the encapsulant ratio, reduced the nanocapsules' humidity and water activity. Finally, the ideal conditions for the nanoencapsulation of native potato bioactive compounds were determined to be an inlet temperature of 116 °C and an encapsulant ratio of 15% w/v. The nanocapsules obtained show potential for application in the food industry.

Lychnopholide loaded in surface modified polylactide nanocapsules (LYC-PLA-PEG-NC) cure mice infected by Trypanosoma cruzi strain a prototype of resistance to benznidazole and nifurtimox: First insights of its mechanism of action.

Chagas disease (CD) remains neglected and causes high morbidity and mortality. The great difficulty is the lack of effective treatment. The current drugs cause side effects and have limited therapeutic efficacy in the chronic phase. This study aims to fulfil some gaps in studies of the natural substance lychnopholide nanoencapsulated LYC-PLA-PEG-NC (LYC-NC) and free (Free-LYC): the activity in epimastigotes and amastigotes to determine its selectivity index (SI), the therapeutic efficacy in mice infected with Colombian Trypanosoma cruzi strain and insight of the mechanism of LYC-NC action on T. cruzi. The SI was obtained by calculation of the ratio between the IC50 value toward H9c2 cells divided by the IC50 value in the anti-T. cruzi test. Infected Swiss mice were treated with 2 and 12 mg/kg/day via intravenous and oral, respectively, and the therapeutic efficacy was determined. The IC50 of LYC-NC and Free-LYC for epimastigotes of T. cruzi were similar. Both were active against amastigotes in cell culture, particularly Free-LYC. The SI of LYC-NC and Free-LYC were 45.38 and 32.11, respectively. LYC-NC 2 and 12 mg/kg/day cured parasitologically, 62.5% and 80% of the animals, respectively, infected with a strain resistant to treatment. The fluorescent NC was distributed in the cardiomyocyte cytoplasm, infected or not, and interacted with the trypomastigotes. Together, these results represent advances in demonstrating LYC as a potent new therapeutic option for treating CD.

Immunostimulant effects of diet supplementation with yellow (Pouteria campechiana), white (Casimiroa edulis), and black (Diospyros digyna) sapote nanocapsules on laying hens: in vitro and in vivo study.

Poultry is commonly infected by different bacteria and parasites in the environment, resulting in increased morbidity and mortality, but immunostimulants have been enhancing non-specific defense mechanisms conferring laying hens' protection. For this purpose, the pulp of yellow (Pouteria campechiana), white (Casimiroa edulis), and black (Diospyros digyna) sapotes were nanoencapsulated (YWB-SN) and evaluated in laying hens' peripheral blood leukocytes to test their addition to the experimental diets at a concentration of 0.5% (5g/kg of dry food) for 1 month (with two samples at days 15 and 30). The YWB-SN were safe when exposed to peripheral blood leukocytes (PBLs). The in vitro experiment showed that these nanocapsules enhanced reactive oxygen species production, and B-SN stimulated phagocytosis activity. Concerning the proinflammatory cytokine (TNF-α) transcription, this gene was upregulated after W-SN stimulation, while B-SN upregulated the IgG gene expression significantly. IgM was upregulated with any YBW-SN in PBLs after 24 h of stimulation. The in vivo study showed a notable B-SN immunostimulation in serum and an upregulation of TNF-α, IgM, and IgG mRNA transcription. Therefore, this study provides a new result of the yellow, white, and black sapote nanocapsules as a functional food for the poultry industry, highlighting the black sapote Diospyros digyna immunostimulant effect.

Polymeric Nanocapsules Containing Ozonated Oil and Terbinafine Hydrochloride as a Potential Treatment Against Dermatophytes.

Terbinafine hydrochloride is a synthetic allylamine whose mechanism of action consists of inhibiting the enzyme squalene epoxidase that participates in the first stage of ergosterol synthesis, interfering with fungal membrane function. Ozonated oils are used for topical application of ozone, producing reactive oxygen species that cause cellular damage in microorganisms, therefore being an alternative treatment for acute and chronic skin infections. This study aimed to develop and characterize Eudragit® RS100 nanocapsules, obtained by interfacial deposition of preformed polymer method, containing 0.5% terbinafine hydrochloride and 5% ozonated sunflower seed oil as a potential treatment against dermatophytes. The polymeric nanocapsules were characterized regarding particle size, zeta potential, pH, drug content, encapsulation efficiency, and stability. The in vitro drug release, in vitro skin permeation, and in vitro antifungal activity were also evaluated. The particle size was around 150 nm with a narrow size distribution, the zeta potential was around + 6 mV, and the pH was 2.2. The drug content was close to 95% with an encapsulation efficiency of 53%. The nanocapsules were capable to control the drug release and the skin permeation. The in vitro susceptibility test showed greater antifungal activity for the developed nanocapsules, against all dermatophyte strains tested, compared to the drug solution. Therefore, the polymeric nanocapsules suspension containing terbinafine hydrochloride and ozonated oil can be considered a potential high-efficacy candidate for the treatment of dermatophytosis, with a possible reduction in the drug dose and frequency of applications. Studies to evaluate safety and efficacy in vivo still need to be performed.

Development of Essential Oil-Loaded Polymeric Nanocapsules as Skin Delivery Systems: Biophysical Parameters and Dermatokinetics Ex Vivo Evaluation.

Essential oils (EOs) are natural antioxidant alternatives that reduce skin damage. However, EOs are highly volatile; therefore, their nanoencapsulation represents a feasible alternative to increase their stability and favor their residence time on the skin to guarantee their effect. In this study, EOs of Rosmarinus officinalis and Lavandula dentata were nanoencapsulated and evaluated as skin delivery systems with potential antioxidant activity. The EOs were characterized and incorporated into polymeric nanocapsules (NC-EOs) using nanoprecipitation. The antioxidant activity was evaluated using the ferric thiocyanate method. The ex vivo effects on pig skin were evaluated based on biophysical parameters using bioengineering techniques. An ex vivo dermatokinetic evaluation on pig skin was performed using modified Franz cells and the tape-stripping technique. The results showed that the EOs had good antioxidant activity (>65%), which was maintained after nanoencapsulation and purification. The nanoencapsulation of the EOs favored its deposition in the stratum corneum compared to free EOs; the highest deposition rate was obtained for 1,8-cineole, a major component of L. dentata, at 1 h contact time, compared to R. officinalis with a major deposition of the camphor component. In conclusion, NC-EOs can be used as an alternative antioxidant for skin care.

Nanoencapsulation of Phenolic Extracts from Native Potato Clones (Solanum tuberosum spp. andigena) by Spray Drying.

Native potato clones grown in Peru contain bioactive compounds beneficial to human health. This study aimed to optimize the spray-drying nanoencapsulation of native potato phenolic extracts utilizing a central composite design and response surface methodology, obtaining the optimal treatment to an inlet temperature of 120 °C and an airflow of 141 L/h in the nano spray dryer B-90, which allowed maximizing the yield of encapsulation, antioxidant capacity (DPPH), encapsulation efficiency (EE), total phenolic compounds, and total flavonoids; on the other hand, it allowed minimizing hygroscopicity, water activity (Aw), and moisture. Instrumental characterization of the nanocapsules was also carried out, observing a gain in lightness, reddening of the color, and spherical nanoparticles of heterogeneous size (133.09-165.13 nm) with a negative ζ potential. Thermal, infrared, and morphological analyses confirmed the encapsulation of the core in the wall materials. Furthermore, an in vitro release study of phenolic compounds in an aqueous solution achieved a maximum value of 9.86 mg GAE/g after 12 h. Finally, the obtained nanocapsules could be used in the food and pharmaceutical industry.

The Anti-Arthritic Activity of Diclofenac Lipid-Core Nanocapsules: Stereological Analysis Showing More Protection of Deep Joint Components.

Diclofenac is the most prescribed nonsteroidal anti-inflammatory drug worldwide and is used to relieve pain and inflammation in inflammatory arthritis. Diclofenac is associated with serious adverse effects, even in regular-dose regimens. Drug delivery systems can overcome this issue by reducing adverse effects and optimizing their efficacy. This study evaluated the activity of lipid-core nanocapsules loaded with diclofenac (DIC-LNCs) in an experimental model of adjuvant-induced arthritis. The diclofenac nanoformulation was obtained via self-assembly. A stereological analysis approach was applied for the morphological quantification of the volume, density, and cellular profile count of the metatarsophalangeal joints of rats. Proinflammatory cytokines and biochemical profiles were also obtained. Our results showed that the diclofenac nanocapsule DIC-LNCs were able to reduce arthritis compared with the control group and the DIC group. DIC-LNCs efficiently reduced proinflammatory cytokines, C-reactive protein, and xanthine oxidase levels. Additionally, DIC-LNCs reduced the loss of synoviocytes and chondrocytes compared with the DIC (p < 0.05) and control groups (p < 0.05). These data suggest that DIC-LNCs have anti-arthritic activity and preserve joint components, making them promising for clinical use.

Poly-ɛ-caprolactone nanocapsules loaded with copaiba essential oil reduce inflammation and pain in mice.

Diverse drugs have been used for the management of inflammation disorders and pain. However, they present many side effects and stimulate the search for new pharmacotherapeutic alternatives. Plant-derived products such as copaiba essential oil (CO) offer beneficial pharmacological effects. On the other hand, essential oil's low water solubility and physical instability hinder its in vivo application. Thus, poly-ɛ-caprolactone (PCL)-based nanocarriers have been used to increase their stability and efficacy. This work aimed to encapsulate CO in PCL nanocapsules and evaluate their effect on inflammation models and pain. The polymeric nanocapsules loading CO (CO-NC) were prepared by nanoprecipitation technique, characterized, and analyzed for their anti-inflammatory effect in vitro and in vivo. The results showed that CO-NC presented a spherical shape, 229.3 ± 1.5 nm diameter, and a negative zeta potential (approximately -23 mV). CO and CO-NC presented anti-inflammatory and antioxidant effects by LPS-activated macrophages (J774 cells). In addition, CO-NC significantly reduced TNF-α secretion (3-fold) compared to CO. In vivo, pre-treatment with CO or CO-NC (50, 100, 200 mg/kg, intraperitoneal; i.p) reduced the mechanical allodynia, paw edema, and pro-inflammatory cytokines induced by intraplantar (i.pl) injection of carrageenan in mice. Specifically, CO-NC (200 mg/kg; i.p.) reduced the production of TNF-α similar to the control group. Our results support using polymeric nanocapsules for CO delivery in inflammatory conditions.

Formulation of benznidazole-lipid nanocapsules: Drug release, permeability, biocompatibility, and stability studies.

Benznidazole, a poorly soluble in water drug, is the first-line medication for the treatment of Chagas disease, but long treatment periods at high dosages cause several adverse effects with insufficient activity in the chronic phase. According to these facts, there is a serious need for novel benznidazole formulations for improving the chemotherapy of Chagas disease. Thus, this work aimed to incorporate benznidazole into lipid nanocapsules for improving its solubility, dissolution rate in different media, and permeability. Lipid nanocapsules were prepared by the phase inversion technique and were fully characterized. Three formulations were obtained with a diameter of 30, 50, and 100 nm and monomodal size distribution with a low polydispersity index and almost neutral zeta potential. Drug encapsulation efficiency was between 83 and 92 % and the drug loading was between 0.66 and 1.04 %. Loaded formulations were stable under storage for one year at 4 °C. Lipid nanocapsules were found to protect benznidazole in simulated gastric fluid and provide a sustained release platform for the drug in a simulated intestinal fluid containing pancreatic enzymes. The small size and the almost neutral surface charge of these lipid nanocarriers improved their penetration through mucus and such formulations showed a reduced chemical interaction with gastric mucin glycoproteins. LNCs. The incorporation of benznidazole in lipid nanocapsules improved the drug permeability across intestinal epithelium by 10-fold compared with the non-encapsulated drug while the exposure of the cell monolayers to these nanoformulations did not affect the integrity of the epithelium.