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.

Nanoemulsion Containing Kojic Dipalmitate and Rosehip Oil: A Promising Formulation to Treat Melasma.

Melasma is a hard-to-treat hyperpigmentation disorder. Combined incorporation of kojic dipalmitate (KDP), the esterified form of kojic acid, and rosehip oil, an oil with antioxidant and skin-regenerating properties, into nanocarrier systems appears to be a suitable strategy to develop high-performance formulations. A high-energy method (Ultra-Turrax®) was used to develop nanoemulsions containing up to 2 mg/mL KDP, 5% rosehip oil, and 7.5% surfactant. Formulations were characterized regarding droplet size, size distribution, pH, density, morphology, KDP content, incorporation efficiency, and stability under different temperature conditions. A scale-up study was conducted. Skin permeation, antioxidant potential, and tyrosinase inhibitory activity were assessed in vitro. Cell viability studies were also performed. Results showed that nanoemulsions containing 1 and 2 mg/mL KDP had incorporation efficiencies greater than 95%, droplet size smaller than 130 nm, suitable size distribution, zeta potential of approximately -10 mV, and good stability over 30 days of refrigerated storage. The nanoemulsion containing 1 mg/mL KDP was chosen for further evaluation because it had lower nanocrystal formation, greater scale-up feasibility and allowed KDP permeation up to the epidermis similarly than observed for 2 mg/mL KDP. This formulation (1 mg/mL KDP) showed antioxidant and depigmenting efficacy, close to that of 1 mM ascorbic acid. No cytotoxicity was observed in formulations concentrations ranging from 0.06% to 1%.

Development of a Clioquinol Nanocarrier as a New, Promising Option for the Treatment of Dermatomycosis.

Dermatomycosis is a common fungal infection, and its treatment is limited by few antifungal agents. Clioquinol (CQ) is an antiparasitic agent that has been studied for new uses, such as antifungal and antiviral applications. CQ was incorporated into a lipid-based nanocarrier as a new, promising option for dermatomycosis. This study aimed to develop a CQ-loaded lipid-based nanocarrier for cutaneous application and to evaluate its antifungal activity. CQ-loaded nanoformulation (LBN-CQ) was developed using the ultrasonication method, and the particle size, polydispersity index (PDI), pH, zeta potential, and drug content were monitored for 45 days. To evaluate antifungal activity, broth microdilution and a time-kill assay were performed. LBN-CQ presented a particle size of 91 ± 3 nm and PDI of 0.102 ± 0.009. The zeta potential and pH values were -9.7 ± 2.0 mV and 6.0 ± 0.1, respectively. The drug content was 96.4 ± 2.3%, and the encapsulation efficiency was 98.4%. LBN-CQ was able to reduce the minimum inhibitory concentration (MIC) in a 2-fold or 4-fold manner in most of the tested strains. Additionally, LBN-CQ presented stable fungistatic action that was not concentration- or time-dependent. In conclusion, the developed CQ-loaded nanocarrier is a promising treatment for skin fungal infections and a promising candidate for future randomized clinical trials.

Biological activities and safety data of kojic acid and its derivatives: A review.

Kojic acid presents a variety of applications for human use, especially as a depigmenting agent. Its derivatives are also proposed in order to prevent chemical degradation, prevent adverse effects and improve efficacy. The aim of this study was to peer review the current scientific literature concerning the biological activities and safety data of kojic acid or its derivatives, aiming at human use and trying to elucidate the action mechanisms. Three different databases were assessed, and the word "kojic" was crossed with "toxicity," "adverse effect," "efficacy," "effect," "activity" and "safety." Articles were selected according to pre-defined criteria. Besides the depigmenting activity, kojic acid and derivatives can act as antioxidant, antimicrobial, anti-inflammatory, radioprotector, anticonvulsant and obesity management agents, and present potential as antitumor substances. Depigmenting activity is due to the molecules, after penetrating the cell, binding to tyrosinase active site, regulating melanogenesis factors, leucocytes modulation and free radical scavenging activity. Hence, polarity, size and ligands are also important factors for activity. Kojic acid and derivatives present cytotoxicity to some cancerous cell lines, including melanoma, hepatocellular carcinoma, ovarian cancer, breast cancer and colon cancer. Regarding safety, kojic acid or its derivatives are safe molecules for human use in the concentrations tested. Kojic acid and its derivatives have great potential for cosmetic, pharmaceutical and medical applications.

Evaluation of activity and toxicity of combining clioquinol with ciclopirox and terbinafine in alternative models of dermatophytosis.

Dermatophytosis is a superficial fungal infection that affects humans and is very common in small animals. The treatment using the most commonly used antifungals is failing, and new therapeutic alternatives are required to combat the resistance of these fungal infections. Previous studies by the group have shown that clioquinol is an important therapeutic alternative in the treatment of dermatophytosis. The object was to conduct studies of antidermatophytic activity and the irritant potential from the double and triple combinations of clioquinol, terbinafine and ciclopirox in ex vivo and in vivo alternative models. To evaluate the irritant potential of antifungal combinations, the alternative HET-CAM method (chicken egg test chorioallantoic membrane) was used. Ex vivo models were used to assess the effectiveness of antifungal combinations, using pig hooves and veterinary fur. Any possible tissue damage was to assess through in histopathology of swine ears. HET-CAM results showed that all combinations can be classified as non-irritating, corroborated by the results of the histopathological evaluation of the pig's ear skin. Only the double combinations managed to remove 100% of the colony-forming units (CFU) formed on the pig's hooves. The clioquinol + terbinafine combination and the triple combination were more effective than clioquinol + ciclopirox in eradicating the preformed biofilm in fur of veterinary origin. These results show the potential of formulations of clioquinol in combination with antifungals for use in humans and in the veterinary field to combat dermatophytosis, as an important alternative therapy, for use in the near future.

Ex vivo potential of a quinoline-derivative nail lacquer as a new alternative for dermatophytic onychomycosis treatment.

Introduction. Onychomycosis infections currently show a significant increase, affecting about 10 % of the world population. Trichophyton rubrum is the main agent responsible for about 80 % of the reported infections. The clinical cure for onychomycosis is extremely difficult and effective new antifungal therapy is needed.Hypothesis/Gap Statement. Ex vivo onychomycosis models using porcine hooves can be an excellent alternative for evaluating the efficacy of new anti-dermatophytic agents in a nail lacquer.Aim. Evaluation of the effectiveness of a nail lacquer containing a quinoline derivative on an ex vivo onychomycosis model using porcine hooves, as well as the proposal of a plausible antifungal mechanism of this derivative against dermatophytic strains.Methodology. The action mechanism of a quinoline derivative was evaluated through the sorbitol protection assay, exogenous ergosterol binding, and the determination of the dose-response curves by time-kill assay. Scanning electron microscopy evaluated the effect of the derivative in the fungal cells. The efficacy of a quinoline-derivative nail lacquer on an ex vivo onychomycosis model using porcine hooves was evaluated as well.Results. The quinoline derivative showed a time-dependent fungicidal effect, demonstrating reduction and damage in the morphology of dermatophytic hyphae. In addition, the ex vivo onychomycosis model was effective in the establishment of infection by T. rubrum.Conclusion. Treatment with the quinoline-derivative lacquer showed a significant inhibitory effect on T. rubrum strain in this infection model. Finally, the compound presents high potential for application in a formulation such as nail lacquer as a possible treatment for dermatophytic onychomycosis.

Monoolein-based nanoparticles containing indinavir: a taste-masked drug delivery system.

OBJECTIVE: This study developed a novel child-friendly drug delivery system for pediatric HIV treatment: a liquid, taste-masked, and solvent-free monoolein-based nanoparticles formulation containing indinavir (0.1%). SIGNIFICANCE: Adherence to antiretroviral therapy by pediatric patients is difficult because of the lack of dosage forms adequate for children. METHODS: Monoolein-based nanoparticles were developed. The particle size, zeta potential, pH, drug content, small angle X-ray scattering, stability, in vitro drug release profile, biocompatibility, toxicity, and taste-masking properties were evaluated. RESULTS: Monoolein-based formulations containing indinavir had nanosized particles with 155 ± 7 nm, unimodal particle size distribution, and polydispersity index of 0.16 ± 0.03. The zeta potential was negative (-31.3 ± 0.3 mV) and pH was neutral (7.78 ± 0.01). A 96% drug incorporation efficiency was achieved, and the indinavir concentration remained constant for 30 days. Polarized light microscopy revealed isotropic characteristics. Transmission electron microscopy images showed spherical shaped morphology. Small-angle X-ray scattering displayed a form factor broad peak. Indinavir had a sustained release from the nanoparticles. The system was nonirritant and was able to mask drug bitter taste. CONCLUSIONS: Monoolein-based nanoparticles represent a suitable therapeutic strategy for antiretroviral treatment with the potential to reduce the frequency of drug administration and promote pediatric adherence.

The use of electronic tongue and sensory panel on taste evaluation of pediatric medicines: a systematic review.

The palatability of medications is an essential factor for children's adherence to drug treatment. Several methods for drug taste assessment have been developed. The aim of this review is to explore the literature reports of the main methods for the evaluation of medicines taste, named electronic tongue (e-tongue, in vitro) and human sensory panel. A systematic search was performed up to March 2020 and a total of 88 articles were selected. The e-tongue (57.5%) has been more frequently described than the sensory panel (10.3%), while some articles (32.2%) used both techniques. 74.7% of the articles mentioned 'pediatric', 'paediatric' or 'children' in the text, but only 19.5% developed formulations targeting pediatric audience and sensory testing in children is rarely seen. The e-tongue has predominance of use in the taste evaluation of pediatric medicines probably since it is fast, easy to perform and risk free, besides presenting less imprecise data and no fatigue. The human panel is more realistic, despite its intrinsic variability. In this sense, it is proposed the use of e-tongue as a fast way to select the most promising sample(s) and, after that, the sensory panel should be applied in order to confirm the taste masking.

Taste-masked nanoparticles containing Saquinavir for pediatric oral administration.

This research has aimed to improve the stability and taste-masking properties by developing nanostructured dosage forms containing Saquinavir. Liquid formulations were developed using Eudragit RS100® and Pullulan as polymers. The physicochemical characteristics, stability, in vitro drug release, morphology, mucoadhesion and taste masking capacity were evaluated. The Saquinavir-nanoparticles had average diameters between 136 and 158 nm, with a Span below 1.4. These formulations presented a drug content above 80%, a high encapsulation efficiency (>97%), slightly acidic pH levels, low dynamic viscosity and controlled drug release. Electron microscopy revealed irregular spherical nanoparticles. The formulations prepared with higher amounts of Eudragit RS100® had greater mucoadhesion. Both polymers were able to improve drug stabilization, taste-masking properties and protection against drug cytotoxicity. The Saquinavir-nanoparticles exhibited stability and control releasing properties, thus making it a promising liquid dosage form with taste-masking properties intended for application in pediatric treatment.

Omeprazole nanoparticles suspension: Development of a stable liquid formulation with a view to pediatric administration.

Omeprazole (OME) is often used to treat disorders associated with gastric hypersecretion in children but a liquid pediatric formulation of this medicine is not currently available. The aim of this study is to develop OME loaded nanoparticles with a view to the obtention of a liquid pharmaceutical dosage form. Eudragit® RS100 was selected as the skeleton material in the inner core and pH-sensitive Eudragit® L100-55 was used as the outer coating of the nanoparticles prepared by the nanoprecipitation method. Pharmacological activity was evaluated by induction of ethanol ulcers in mice. The OME nanoparticles exhibited mean diameters of 174 nm (±17), polydispersity index of 0.229 (±0.01), zeta potential values of -13 mV (±2.60) and encapsulation efficiency of 68.1%. The in vivo pharmacological assessment showed the ability of nanoparticles to protect mice stomach against ulcer formation. The prepared suspension of OME nanoparticles represents effective therapeutic strategy in a liquid pharmaceutical form with the possibility of pediatric administration.

Improved sensory properties of a nanostructured ritonavir suspension with a pediatric administration perspective.

The pediatric adherence to antiretroviral therapy is critical to therapeutic success. Ritonavir, a protease inhibitor drug, is commercially available as an oral solution containing a high amount of ethanol and propylene glycol, contraindicated in children younger than 4 years. Moreover, this medicine presents a bitter taste, which is limiting for the adherence to treatment. This study aims to develop ritonavir nanoparticles followed by polymeric coating for sensory characteristics improvement. The nanoparticles were coated with Eudragit® L 100-55 and characterized. A human sensory panel evaluated the proposed formulations regarding its bitter taste. The formulation showed nanotechnological features, with 130 and 134 nm for ritonavir nanoparticles and ritonavir coated nanoparticles, respectively. The pH, zeta potential, drug content and encapsulation efficiency results were suitable for oral administration. The coated nanoparticles were capable of decreasing the drug bitter taste as shown in the sensory analysis. The ritonavir incorporation in nanoparticles, followed by polymer coating can be a reasonable strategy to obtain alcohol free taste-masked medicines, which are promising for pediatric therapy.

Azelaic acid-loaded nanoemulsion with hyaluronic acid - a new strategy to treat hyperpigmentary skin disorders.

OBJECTIVE: To develop an azelaic acid (AzA)-loaded nanoemulsion with hyaluronic acid (HA) as a double targeting strategy to increase drug retention and tyrosinase inhibition activity. SIGNIFICANCE: Dermic melasma is a recalcitrant disease. Therefore, the development of new technologies that allow a deeper penetration in the skin while enhancing the efficacy of a safe and well-known dermatological active, like AzA, is a very promising alternative to improve the treatment of this disease. METHODS: An oil-in-water nanoemulsion was developed and characterized according to its droplet size distribution, zeta potential, pH value, drug content, encapsulation efficiency, spectroscopic characteristics, morphology, and stability. In vitro mushroom tyrosinase inhibition assay, cytotoxicity, and permeation studies were performed. A descriptive sensory evaluation was also carried out. RESULTS: Drug content was 10 mg/ml, particle size 419 ± 23 nm with monomodal distribution, encapsulation efficiency was 84.65%, zeta potential -10.9 ± 0.44 mV and pH 5.01 ± 0.01. The nanoemulsion was stable for 30 days (30 °C/65% RH). The nanoemulsion decreased tyrosinase activity and permeated through the skin, reaching viable epidermis and dermis and did not show signs of cytotoxicity. Sensory evaluation profile showed a higher spreadability with lesser whitening residue. CONCLUSION: The nanoemulsion presented characteristics within the nanoscale and reached the deeper layers of the skin while improving in vitro tyrosinase inhibition; hence, it could be a promising treatment to dermic melasma.

Toxicity of fullerene and nanosilver nanomaterials against bacteria associated to the body surface of the estuarine worm Laeonereis acuta (Polychaeta, Nereididae).

This study analyzed the growth and biochemical responses of six bacterial colonies isolated from the mucus of the estuarine polychaeta Laeonereis acuta (Nereididae) after exposure to a water suspension of fullerene (nC60) and nanosilver (nAg) separately (0.01; 0.10; and 1.00 mg/L) and together (0.01; 0.10; and 1.00 mg/L of nanosilver and 1.00 mg/L of fullerene added to each nAg concentration). Exposures were performed in darkness during 24 h and then samples were taken from the worms and inoculated on agar during 24 h to analyze colonies growth. After this the material was analyzed biochemically. Colonies growth (tested by wet biomass weight) was inhibited at 0.01 and 0.10 mg/L of nAg and 0.01 and 0.10 mg/L nAg + constant 1.00 mg/L of nC60 (p < 0.05). Lipid peroxidation damage was significant from the control for the concentrations of 0.01 and 0.10 mg/L of nC60 and glutathione-S-transferase (GST) activity was significantly higher for the concentration of 1.00 mg/L mg/L nAg + constant 1.00 mg/L of nC60 (p < 0.05). Although nC60 did not induced growth inhibition, it triggered lipid peroxidation alone and increased GST activity together with nAg.60 Contrary to nC60, nanosilver inhibited bacterial growth, although the biochemical measurements indicate that this response is not due to reactive oxygen species generation.

Rendimento de coalhada obtida a partir de leite fresco, resfriado e congelado de ovelhas da raça Lacaune e caracterização física do soro obtido / Curd yeld obtained from fresh, cooled and frozen Laucane sheep milk and physical characteristics of the obtained whey

A composição do leite, que pode ser afetada pelo resfriamento ou congelamento, é determinante para o rendimento na fabricação de queijos, sendo um parâmetro muito importante em termos econômicos. O presente estudo teve como objetivo avaliar o efeito do resfriamento e do congelamento do leite, durante sete dias, sobre o rendimento da coalhada produzida a partir de leite de ovelha e sobre as características físicas do soro obtido. Entre janeiro e dezembro de 2011, foram coletadas mensalmente amostras de leite de ovelha, diretamente dos tanques de resfriamento. Uma parte foi submetida à análise no mesmo dia, denominada leite fresco, e as restantes armazenadas até sete dias, uma em refrigeração (5°C - leite resfriado) e outra em congelamento doméstico (-4°C - leite congelado). Determinou-se o rendimento da coalhada e densidade, pH e acidez titulável do soro obtido. Verificou-se diferença significativa (P<0,05) no rendimento da coalhada entre os tratamentos aplicados, sendo que o rendimento obtido com leite resfriado (3,64±0,34L kg-1) e congelado (3,18±0,23L kg-1) não apresentaram diferenças com o de leite fresco (3,38±0,22L kg-1), porém estes tratamentos diferiram entre si. A densidade média do soro obtido (1,025g mL-1) não apresentou diferenças entre os tratamentos aplicados. O pH e acidez titulável do soro foram semelhantes nos tratamentos de leite fresco e congelado, havendo diferenças (P<0,05) com o soro de leite resfriado, que apresentou-se mais ácido. Embora o soro da coalhada obtida a partir de leite resfriado apresente-se mais ácido, o resfriamento e o congelamento do leite ovino, por um período de sete dias, não afetam o rendimento na fabricação de queijos e o soro obtido não apresenta diferença de densidade entre os tratamentos aplicados.

Milk composition that can be affected by cooling or freezing is crucial for the performance of chesese making, and it is an important parameter in economic terms. The objective of this study was to evaluate, during 7 days, the effect of milk cooling and freezing on the yield of the curd produced with the sheep milk and on the physical characteristics of the obtained whey. Between January and December 2011 samples of the sheep milk were collected every month, directly from the bulk tanks. A part of it was subject to analysis in the same day, and the rest was stored for up to 7 days. One of the samples was kept under refrigeration (5°C - cooled milk) and another was kept in a domestic freezer (-4°C - frozen milk). The yield and density of the curd, pH and titratable acidity of the obtained whey was determined. The treatment applied showed a significant difference (P<0.05) in the yield of the curd, whereas the yield obtained with the cooled milk (3.64±0.34L kg-1) and the frozen milk (3.18±0.23L kg-1) showed no differences with the fresh milk (3.38±0.22 L kg-1), but these treatments were not the same. The average density of the obtained whey (1.025g mL-1) did not present differences between the applied treatments. The whey pH and titratable acidity were similar in both fresh and frozen milk treatments, but there was a difference (P<0.05) with the cooled milk, which had a higher acidity. Even though the whey of the curb obtained from the cooled milk is more acid, the cooling and freezing of the sheep milk, for a period of 7 days, do not affect the yield in cheese making, and the obtained whey does not present density differences between the applied treatments.

Rendimento de coalhada obtida a partir de leite fresco, resfriado e congelado de ovelhas da raça Lacaune e caracterização física do soro obtido / Curd yeld obtained from fresh, cooled and frozen Laucane sheep milk and physical characteristics of the obtained whey

A composição do leite, que pode ser afetada pelo resfriamento ou congelamento, é determinante para o rendimento na fabricação de queijos, sendo um parâmetro muito importante em termos econômicos. O presente estudo teve como objetivo avaliar o efeito do resfriamento e do congelamento do leite, durante sete dias, sobre o rendimento da coalhada produzida a partir de leite de ovelha e sobre as características físicas do soro obtido. Entre janeiro e dezembro de 2011, foram coletadas mensalmente amostras de leite de ovelha, diretamente dos tanques de resfriamento. Uma parte foi submetida à análise no mesmo dia, denominada leite fresco, e as restantes armazenadas até sete dias, uma em refrigeração (5°C - leite resfriado) e outra em congelamento doméstico (-4°C - leite congelado). Determinou-se o rendimento da coalhada e densidade, pH e acidez titulável do soro obtido. Verificou-se diferença significativa (P 0,05) no rendimento da coalhada entre os tratamentos aplicados, sendo que o rendimento obtido com leite resfriado (3,64±0,34L kg-1) e congelado (3,18±0,23L kg-1) não apresentaram diferenças com o de leite fresco (3,38±0,22L kg-1), porém estes tratamentos diferiram entre si. A densidade média do soro obtido (1,025g mL-1) não apresentou diferenças entre os tratamentos aplicados. O pH e acidez titulável do soro foram semelhantes nos tratamentos de leite fresco e congelado, havendo diferenças (P 0,05) com o soro de leite resfriado, que apresentou-se mais ácido. Embora o soro da coalhada obtida a partir de leite resfriado apresente-se mais ácido, o resfriamento e o congelamento do leite ovino, por um período de sete dias, não afetam o rendimento na fabricação de queijos e o soro obtido não apresenta diferença de densidade entre os tratamentos aplicados.(AU)

Milk composition that can be affected by cooling or freezing is crucial for the performance of chesese making, and it is an important parameter in economic terms. The objective of this study was to evaluate, during 7 days, the effect of milk cooling and freezing on the yield of the curd produced with the sheep milk and on the physical characteristics of the obtained whey. Between January and December 2011 samples of the sheep milk were collected every month, directly from the bulk tanks. A part of it was subject to analysis in the same day, and the rest was stored for up to 7 days. One of the samples was kept under refrigeration (5°C - cooled milk) and another was kept in a domestic freezer (-4°C - frozen milk). The yield and density of the curd, pH and titratable acidity of the obtained whey was determined. The treatment applied showed a significant difference (P 0.05) in the yield of the curd, whereas the yield obtained with the cooled milk (3.64±0.34L kg-1) and the frozen milk (3.18±0.23L kg-1) showed no differences with the fresh milk (3.38±0.22 L kg-1), but these treatments were not the same. The average density of the obtained whey (1.025g mL-1) did not present differences between the applied treatments. The whey pH and titratable acidity were similar in both fresh and frozen milk treatments, but there was a difference (P 0.05) with the cooled milk, which had a higher acidity. Even though the whey of the curb obtained from the cooled milk is more acid, the cooling and freezing of the sheep milk, for a period of 7 days, do not affect the yield in cheese making, and the obtained whey does not present density differences between the applied treatments.(AU)

Evaluation of lipoic acid topical application on rats skin wound healing.

PURPOSE: To evaluate the effects of lipoic acid (thioctic acid) topical application on wound healing on rats skin, and the consequences of lipoic acid nanoencapsulation on this process. METHODS: The model used was the healing activity on wounds induced by surgical incision on rats skin (n = 44). The parameters analyzed (11 days) were wound healing rate and histology (vascular proliferation, polymorphonuclear or mononuclear cells, and collagen synthesis or reepithelialization), after application of free lipoic acid or lipoic acid- loaded nanocapsules. The antioxidant activity of these formulations was evaluated by lipid peroxidation test. RESULTS: It was demonstrated for the first time that the topical application of lipoic acid improves wound healing. On the seventh day after surgery, the animals treated with lipoic acid showed increased healing rate (60.7 ± 8.4%) compared to the negative control group (43.0 ± 17.4%), as so improvement of histological parameters. The nanoencapsulation reverted the pro-oxidant activity presented in vitro by lipoic acid, whereas diminished wound repair. CONCLUSIONS: The topical application of lipoic acid produced an increase in the skin wound healing, which may be related to its pro-oxidant activity. On the other hand, the nanoencapsulation of the lipoic acid reversed the pro-oxidant activity, although presented minor healing activity.

Evaluation of lipoic acid topical application on rats skin wound healing

PURPOSE: To evaluate the effects of lipoic acid (thioctic acid) topical application on wound healing on rats skin, and the consequences of lipoic acid nanoencapsulation on this process. METHODS: The model used was the healing activity on wounds induced by surgical incision on rats skin (n = 44). The parameters analyzed (11 days) were wound healing rate and histology (vascular proliferation, polymorphonuclear or mononuclear cells, and collagen synthesis or reepithelialization), after application of free lipoic acid or lipoic acid- loaded nanocapsules. The antioxidant activity of these formulations was evaluated by lipid peroxidation test. RESULTS: It was demonstrated for the first time that the topical application of lipoic acid improves wound healing. On the seventh day after surgery, the animals treated with lipoic acid showed increased healing rate (60.7 ± 8.4%) compared to the negative control group (43.0 ± 17.4%), as so improvement of histological parameters. The nanoencapsulation reverted the pro-oxidant activity presented in vitro by lipoic acid, whereas diminished wound repair. CONCLUSIONS: The topical application of lipoic acid produced an increase in the skin wound healing, which may be related to its pro-oxidant activity. On the other hand, the nanoencapsulation of the lipoic acid reversed the pro-oxidant activity, although presented minor healing activity.

Evaluation of lipoic acid topical application on rats skin wound healing

PURPOSE: To evaluate the effects of lipoic acid (thioctic acid) topical application on wound healing on rats skin, and the consequences of lipoic acid nanoencapsulation on this process. METHODS: The model used was the healing activity on wounds induced by surgical incision on rats skin (n = 44). The parameters analyzed (11 days) were wound healing rate and histology (vascular proliferation, polymorphonuclear or mononuclear cells, and collagen synthesis or reepithelialization), after application of free lipoic acid or lipoic acid- loaded nanocapsules. The antioxidant activity of these formulations was evaluated by lipid peroxidation test. RESULTS: It was demonstrated for the first time that the topical application of lipoic acid improves wound healing. On the seventh day after surgery, the animals treated with lipoic acid showed increased healing rate (60.7 ± 8.4%) compared to the negative control group (43.0 ± 17.4%), as so improvement of histological parameters. The nanoencapsulation reverted the pro-oxidant activity presented in vitro by lipoic acid, whereas diminished wound repair. CONCLUSIONS: The topical application of lipoic acid produced an increase in the skin wound healing, which may be related to its pro-oxidant activity. On the other hand, the nanoencapsulation of the lipoic acid reversed the pro-oxidant activity, although presented minor healing activity.(AU)

Intraperitoneal exposure to nano/microparticles of fullerene (C60) increases acetylcholinesterase activity and lipid peroxidation in adult zebrafish (Danio rerio) brain.

Even though technologies involving nano/microparticles have great potential, it is crucial to determine possible toxicity of these technological products before extensive use. Fullerenes C60 are nanomaterials with unique physicochemical and biological properties that are important for the development of many technological applications. The aim of this study was to evaluate the consequences of nonphotoexcited fullerene C60 exposure in brain acetylcholinesterase expression and activity, antioxidant responses, and oxidative damage using adult zebrafish as an animal model. None of the doses tested (7.5, 15, and 30 mg/kg) altered AChE activity, antioxidant responses, and oxidative damage when zebrafish were exposed to nonphotoexcited C60 nano/microparticles during 6 and 12 hours. However, adult zebrafish exposed to the 30 mg/kg dose for 24 hours have shown enhanced AChE activity and augmented lipid peroxidation (TBARS assays) in brain. In addition, the up-regulation of brain AChE activity was neither related to the transcriptional control (RT-qPCR analysis) nor to the direct action of nonphotoexcited C60 nano/microparticles on the protein (in vitro results) but probably involved a posttranscriptional or posttranslational modulation of this enzymatic activity. Taken together these findings provided further evidence of toxic effects on brain after C60 exposure.

Toxicological effects induced by the nanomaterials fullerene and nanosilver in the polychaeta Laeonereis acuta (Nereididae) and in the bacteria communities living at their surface.

Fullerene (nC60) and nanosilver (nAg) are nanomaterials with bactericide properties. The increments in their use raise questions about their potential environmental impacts, including estuarine ones. The polychaete Laeonereis acuta (Nereididae) secretes mucus that is colonized by bacteria communities. We analyzed the antioxidant and oxidative damage responses of anterior, middle and posterior region of L. acuta and bacteria communities after nC60 or nAg exposure during 24 h. Molecular analysis showed a prevalence of Vibrio genera in the communities. Bacteria biomass was lowered in worms exposed to 1.0 mg/L of nAg. nC60 reduced total antioxidant capacity of bacteria from worms exposed to 0.1 mg/L. Worms anterior region presented lower antioxidant capacity after exposure to 1.0 mg nC60/L, and the same was observed in the posterior region of worms exposed to 1.0 mg nAg/L. Lipid peroxidation was reduced in the anterior region of worms exposed to nC60 and the opposite was observed in the posterior region.