Fresh Carrier for an Old Topical Local Anesthetic: Benzocaine in Nanostructured Lipid Carriers.

Nanostructured lipid carriers (NLC) have emerged as innovative drug delivery systems, offering distinct advantages over other lipid-based carriers, such as liposomes and solid lipid nanoparticles. Benzocaine (BZC), the oldest topical local anesthetic in use, undergoes metabolism by pseudocholinesterase, leading to the formation of p-aminobenzoic acid, a causative agent for allergic reactions associated with prolonged BZC usage. In order to mitigate adverse effects and enhance bioavailability, BZC was encapsulated within NLC. Utilizing a 23 factorial design, formulations comprising cetyl palmitate (solid lipid), propylene glycol monocaprylate (liquid lipid), and Pluronic F68 as surfactants were systematically prepared, with variations in the solid/liquid lipid mass ratios (60:40-80:20%), total lipid contents (15-25%), and BZC concentrations (1-3%). The optimized formulation underwent characterization by dynamic light scattering, differential scanning calorimetry, Raman imaging, X-ray diffraction, small-angle neutron scattering, nanotracking analysis, and transmission electron microscopy (TEM)/cryo-TEM, providing insights into the nanoparticle structure and the incorporation of BZC into its lipid matrix. NLCBZC exhibited a noteworthy encapsulation efficiency (%EE = 96%) and a 1 year stability when stored at 25 °C. In vitro kinetic studies and in vivo antinociceptive tests conducted in mice revealed that NLCBZC effectively sustained drug release for over 20 h and prolonged the anesthetic effect of BZC for up to 18 h. We therefore propose the use of NLCBZC to diminish the effective anesthetic concentration of benzocaine (from 20 to 3% or less), thus minimizing allergic reactions that follow the topical administration of this anesthetic and, potentially, paving the way for new routes of BZC administration in pain management.

Benzocaine and eugenol as anesthetics for pangasius juveniles, Pangasianodon hypophthalmus

The aim of this study was to evaluate the effect and efficacy of different concentrations of eugenol and benzocaine for pangasius juveniles (Pangasianodon hypophthalmus) and determine the anesthetic and concentration most appropriate for carrying out routine fish farming practices for this species. One hundred juveniles with an average weight of 32.10 ± 4.9 g and an average total length of 15.32 ± 0.57 cm were used. Four concentrations of both anesthetics were evaluated: 0, 25, 50, 75 and 100 mg/L, with four induction time stages and three recovery stages. During the time that the fish remained anesthetized, biometric procedures were performed. Then, they were transferred to a 10-liter aquarium containing clean water, without adding the anesthetic to observe the recovery time. After recovery, the animals were kept in aquariums for 72 hours to check for mortality. Eugenol, at all concentrations evaluated, and benzocaine, at a concentration of 25 mg/L, were not effective in sedating juveniles of pangasius. Benzocaine concentrations of 75 and 100 mg/L were effective for anesthesia and recovery of fish within the time span of five and seven minutes. However, considering animal welfare, the use of a concentration of 100 mg/L is recommended, as it resulted in shorter latency and recovery times.

O objetivo deste trabalho foi avaliar o efeito e a eficácia de diferentes concentrações de benzocaína e eugenol em juvenis de pangasius (Pangasianodon hypophthalmus) para determinar o anestésico mais eficiente e a concentração mais adequada para realização das práticas rotineiras em piscicultura para esta espécie. Foram utilizados 100 juvenis, com peso médio de 32,10 ± 4,9 g e comprimento total médio de 15,32 ± 0,57 cm. Foram avaliadas quatro concentrações para ambos os anestésicos: 0, 25, 50, 75 e 100 mg/L, sendo observados quatro estágios de tempo de indução e três estágios de recuperação. Durante o tempo em que os peixes permaneceram anestesiados, foram realizados os procedimentos de biometria. Em seguida, os animais foram transferidos para um aquário de 10 L contendo água limpa, sem adição do anestésico, para observar o tempo de recuperação. Após a recuperação, os animais foram mantidos nos aquários por 72 horas para verificação da mortalidade. O eugenol, em todas as concentrações avaliadas, e a benzocaína, na concentração de 25 mg/L, não foram eficazes na sedação de juvenis de pangasius. As concentrações de benzocaína de 75 e 100 mg/L foram eficientes para anestesia e recuperação dos peixes considerando a faixa de tempo pré-estabelecida de cinco e sete minutos, respectivamente. Entretanto, considerando o bem-estar animal, recomenda-se o uso da concentração de 100 mg/L, uma vez que resultou em menor tempo de latência e recuperação.

Evaluation of benzocaine-based anesthetic gel in anuran skins extracts: A case study using the frog Lithodytes lineatus (Anura: Leptodactylidae).

Extracts made from the skin of dead Lithodytes lineatus frog individuals with the application of the benzocaine-based anesthetic gel, introduced into the oral cavity, were analyzed by 1H Nuclear Magnetic Resonance to investigate whether the application of this product (oral) can make studies that use extracts from the skins of these animals unfeasible. For comparison, we used skins of another species of anuran following the same death protocol. No trace of the benzocaine substance was found in the 1H-NMR spectra of the skin extracts from any of the tested anuran species. Still, using the hierarchical clustering model, it was possible to observe the formation of well-defined groups between the skin extracts of anurans and the anesthetic used to kill these animals. Our results suggest that the lethal dose of benzocaine in gel used inside the mouth of frogs may have no influence on potential results regarding the chemical composition or even bioassays using extracts made from the skin of these animals killed under this protocol since there was no detection of this substance for the analyzed samples.

Potential of mucoadhesive nanocapsules in drug release and toxicology in zebrafish.

Mucoadhesive polymeric nanocapsules have attracted interest of researchers from different fields from natural sciences because of their ability to interact with the mucosa and increase drug permeation. Anesthesia by immersion causes absorption through the skin and gills of fish, so it is important to evaluate the exposure of these organs to drug nanosystems. Benzocaine (BENZ) is one of the most popular anesthetic agents used in fish anesthesia, but it has drawbacks because of its low bioavailability, resulting in weak absorption after immersion. Here we describe method developed for preparing and characterizing chitosan-coated PLGA mucoadhesive nanoparticles containing BENZ (NPMAs) for zebrafish immersion anesthesia. We determined the lowest effective concentration, characterized the interaction of the mucoadhesive system with fish, measured the anesthetic efficacy, and evaluated possible toxic effects in embryos and adults exposed to the nanoformulations. This study opens perspectives for using nanoformulations prepared with BENZ in aquaculture, allowing reduction of dosage as well as promoting more effective anesthesia and improved interaction with the mucoadhesive system of fish.

Effectiveness of benzocaine as anesthetic at different water temperatures for early juvenile curimba (Prochilodus lineatus valenciennes, 1836), a neotropical fish species / Eficácia da benzocaina como anestésico em diferentes temperaturas de água para juvenis de curimba (Prochilodus lineatus valenciennes, 1836), uma espécie de peixe neotropical

Anesthetics have been used frequently in aquaculture to minimize stress during handling. However, several factors can affect the efficiency of anesthetics. For example, temperature is one of the abiotic factors that control animal metabolism and consequently, the effect of anesthetics. This study aimed to evaluate the effectiveness of benzocaine as an anesthetic for early juveniles of curimba Prochilodus lineatus at different water temperatures. Juveniles (4.7 ± 1.6 g and total length of 7.4 ± 0.7 cm) were submitted to anesthesia at concentrations of 30, 40, 50, 60, 70, and 80 mg L-1 of benzocaine and temperatures of 22, 25, 28, and 31 °C. The effects were evaluated by measuring the induction time to deep and surgical anesthesia, recovery time, time to appetite return, and 96-h mortality rate. The higher temperatures (25, 28 and 31°C) provided shorter induction times to reach deep anesthesia and at 50 mg L-1 of benzocaine, the induction time was between 2 and 3 min. Juveniles at temperatures of 28 and 31 °C showed lower surgical anesthesia induction time at concentrations ranging from 60 to 80 mg L-1. Recovery time was longer at 22 °C at all concentrations. The time to appetite return occurred in the first 24 h after anesthesia and the 96-h mortality rate was lower than 10%. Under these conditions, for deep anesthesia, benzocaine concentration of 50 mg L-1 for water temperatures of 25, 28, and 31 °C and 60 mg L-1 for 22 °C are recommended. Surgical anesthesia can be performed with 50 mg L-1 of benzocaine at all four water temperatures. The differences documented in the present study underline the need for adequate concentrations of anesthetics depending on the prevalent water temperature for Neotropical fish species. This should be considered in recommendations for large-scale use.(AU)

Os anestésicos têm sido usados com frequência na aquicultura para minimizar o estresse durante o manejo. Entretanto, vários fatores podem afetar a eficiência do anestésico. Por exemplo, a temperatura é um dos fatores abióticos que controlam o metabolismo animal e, consequentemente, os efeitos anestésicos. Este estudo teve como objetivo avaliar a eficácia da benzocaína como anestésico em juvenis de curimba Prochilodus lineatus em diferentes temperaturas da água. Juvenis (4,7 ± 1,6 g e comprimento total de 7,4 ± 0,7 cm) foram submetidos à anestesia nas concentrações de 30, 40, 50, 60, 70 e 80 mg de benzocaína L-1 e temperaturas de 22, 25, 28 e 31 °C. Os efeitos foram avaliados medindo-se o tempo de indução à anestesia profunda e cirúrgica, tempo de recuperação, tempo de retorno do apetite e taxa de mortalidade em 96 horas. As maiores temperaturas (25, 28 e 31 °C) proporcionaram menores tempos de indução a anestesia profunda e em 50 mg de benzocaína L-1 o tempo de indução foi entre 2 e 3 min. Juvenis nas temperaturas de 28 e 31 °C apresentaram menor tempo de indução a anestesia cirúrgica nas concentrações variando de 60 a 80 mg L-1. O tempo de recuperação foi superior a 22 ° C em todas as concentrações. O tempo de retorno do apetite ocorreu nas primeiras 24 horas após a anestesia e a taxa de mortalidade após 96 horas foi inferior a 10%. Nestas condições, para anestesia profunda, recomenda-se a concentração de 50 mg L-1 de benzocaína nas temperaturas de 25, 28 e 31 °C e 60 mg L-1 para 22 °C. A anestesia cirúrgica pode ser realizada com 50 mg de benzocaína L-1nas quatro temperaturas. As diferenças documentadas no presente estudo reforçam a necessidade de adequar a concentração do anestésico à temperatura da água para as espécies de peixes neotropicais, devendo ser reconsiderada na recomendação para uso em larga escala.(AU)

Effectiveness of benzocaine as anesthetic at different water temperatures for early juvenile curimba (Prochilodus lineatus valenciennes, 1836), a neotropical fish species / Eficácia da benzocaina como anestésico em diferentes temperaturas de água para juvenis de curimba (Prochilodus lineatus valenciennes, 1836), uma espécie de peixe neotropical

Anesthetics have been used frequently in aquaculture to minimize stress during handling. However, several factors can affect the efficiency of anesthetics. For example, temperature is one of the abiotic factors that control animal metabolism and consequently, the effect of anesthetics. This study aimed to evaluate the effectiveness of benzocaine as an anesthetic for early juveniles of curimba Prochilodus lineatus at different water temperatures. Juveniles (4.7 ± 1.6 g and total length of 7.4 ± 0.7 cm) were submitted to anesthesia at concentrations of 30, 40, 50, 60, 70, and 80 mg L-1 of benzocaine and temperatures of 22, 25, 28, and 31 °C. The effects were evaluated by measuring the induction time to deep and surgical anesthesia, recovery time, time to appetite return, and 96-h mortality rate. The higher temperatures (25, 28 and 31°C) provided shorter induction times to reach deep anesthesia and at 50 mg L-1 of benzocaine, the induction time was between 2 and 3 min. Juveniles at temperatures of 28 and 31 °C showed lower surgical anesthesia induction time at concentrations ranging from 60 to 80 mg L-1. Recovery time was longer at 22 °C at all concentrations. The time to appetite return occurred in the first 24 h after anesthesia and the 96-h mortality rate was lower than 10%. Under these conditions, for deep anesthesia, benzocaine concentration of 50 mg L-1 for water temperatures of 25, 28, and 31 °C and 60 mg L-1 for 22 °C are recommended. Surgical anesthesia can be performed with 50 mg L-1 of benzocaine at all four water temperatures. The differences documented in the present study underline the need for adequate concentrations of anesthetics depending on the prevalent water temperature for Neotropical fish species. This should be considered in recommendations for large-scale use.

Os anestésicos têm sido usados com frequência na aquicultura para minimizar o estresse durante o manejo. Entretanto, vários fatores podem afetar a eficiência do anestésico. Por exemplo, a temperatura é um dos fatores abióticos que controlam o metabolismo animal e, consequentemente, os efeitos anestésicos. Este estudo teve como objetivo avaliar a eficácia da benzocaína como anestésico em juvenis de curimba Prochilodus lineatus em diferentes temperaturas da água. Juvenis (4,7 ± 1,6 g e comprimento total de 7,4 ± 0,7 cm) foram submetidos à anestesia nas concentrações de 30, 40, 50, 60, 70 e 80 mg de benzocaína L-1 e temperaturas de 22, 25, 28 e 31 °C. Os efeitos foram avaliados medindo-se o tempo de indução à anestesia profunda e cirúrgica, tempo de recuperação, tempo de retorno do apetite e taxa de mortalidade em 96 horas. As maiores temperaturas (25, 28 e 31 °C) proporcionaram menores tempos de indução a anestesia profunda e em 50 mg de benzocaína L-1 o tempo de indução foi entre 2 e 3 min. Juvenis nas temperaturas de 28 e 31 °C apresentaram menor tempo de indução a anestesia cirúrgica nas concentrações variando de 60 a 80 mg L-1. O tempo de recuperação foi superior a 22 ° C em todas as concentrações. O tempo de retorno do apetite ocorreu nas primeiras 24 horas após a anestesia e a taxa de mortalidade após 96 horas foi inferior a 10%. Nestas condições, para anestesia profunda, recomenda-se a concentração de 50 mg L-1 de benzocaína nas temperaturas de 25, 28 e 31 °C e 60 mg L-1 para 22 °C. A anestesia cirúrgica pode ser realizada com 50 mg de benzocaína L-1nas quatro temperaturas. As diferenças documentadas no presente estudo reforçam a necessidade de adequar a concentração do anestésico à temperatura da água para as espécies de peixes neotropicais, devendo ser reconsiderada na recomendação para uso em larga escala.

Benzocaína, ms-222, eugenol e mentol como anestésicos para juvenis de tainha Mugil liza / Benzocaine, ms-222, eugenol and menthol as anesthetics for juvenile Mugil liza

A anestesia tem sido utilizada em aquicultura como técnica para facilitar a manipulação dos animais e amenizar o estresse causado pelos procedimentos de manejo. O presente estudo teve como objetivo determinar a eciência de quatro fármacos como anestésico em juvenis de tainha Mugil liza. Os peixes (6,9 ± 1,4 g) foram submetidos individualmente (N=10 por concentração) à anestesia utilizando-se quatro concentrações de benzocaína (30, 40, 50 e 60 mg L-1), MS-222 (100, 125, 150 e 175 mg L-1), eugenol (50, 70, 90 e 110 mg L-1) e mentol (175, 200, 225 e 250 mg L-1). O critério utilizado para avaliação das melhores concentrações foi a faixa de tempo máximo de três e cinco minutos para anestesia e recuperação dos peixes, respectivamente. As concentrações mais ecientes foram: Benzocaína, 50 mg L-1; MS-222, 150 mg L-1; eugenol, 70 mg L-1; e mentol, 225 mg L-1. (AU)

Anesthesia has been used as an aquaculture technique to facilitate the manipulation of the animals and to alleviate the stress caused due to the management procedures. The present study aimed to determine the anesthetic efcacy of four drugs in Mugil liza juveniles. Fish (6.9 ± 1.4 g) were individually anesthetized (N=10 by concentration) using four concentrations of benzocaine (30, 40, 50 and 60 mg L-1), MS-222 (100, 125, 150 and 175 mg L-1) eugenol (50, 70, 90 and 110 mg L-1) menthol (175, 200, 225 and 250 mg L-1). The criterion used to evaluate the best concentrations was the maximum time interval of 3 and 5 minutes for anesthesia and recovery of the sh, respectively. The most efcient concentrations were: Benzocaine 50 mg L-1, MS-222 150 mg L-1, eugenol 70 mg L-1 and menthol 225 mg L-1.(AU)

Benzocaína, ms-222, eugenol e mentol como anestésicos para juvenis de tainha Mugil liza / Benzocaine, ms-222, eugenol and menthol as anesthetics for juvenile Mugil liza

A anestesia tem sido utilizada em aquicultura como técnica para facilitar a manipulação dos animais e amenizar o estresse causado pelos procedimentos de manejo. O presente estudo teve como objetivo determinar a eciência de quatro fármacos como anestésico em juvenis de tainha Mugil liza. Os peixes (6,9 ± 1,4 g) foram submetidos individualmente (N=10 por concentração) à anestesia utilizando-se quatro concentrações de benzocaína (30, 40, 50 e 60 mg L-1), MS-222 (100, 125, 150 e 175 mg L-1), eugenol (50, 70, 90 e 110 mg L-1) e mentol (175, 200, 225 e 250 mg L-1). O critério utilizado para avaliação das melhores concentrações foi a faixa de tempo máximo de três e cinco minutos para anestesia e recuperação dos peixes, respectivamente. As concentrações mais ecientes foram: Benzocaína, 50 mg L-1; MS-222, 150 mg L-1; eugenol, 70 mg L-1; e mentol, 225 mg L-1.

Anesthesia has been used as an aquaculture technique to facilitate the manipulation of the animals and to alleviate the stress caused due to the management procedures. The present study aimed to determine the anesthetic efcacy of four drugs in Mugil liza juveniles. Fish (6.9 ± 1.4 g) were individually anesthetized (N=10 by concentration) using four concentrations of benzocaine (30, 40, 50 and 60 mg L-1), MS-222 (100, 125, 150 and 175 mg L-1) eugenol (50, 70, 90 and 110 mg L-1) menthol (175, 200, 225 and 250 mg L-1). The criterion used to evaluate the best concentrations was the maximum time interval of 3 and 5 minutes for anesthesia and recovery of the sh, respectively. The most efcient concentrations were: Benzocaine 50 mg L-1, MS-222 150 mg L-1, eugenol 70 mg L-1 and menthol 225 mg L-1.

Liposomal butamben gel formulations: toxicity assays and topical anesthesia in an animal model.

The aim of this study was to evaluate the in vitro cytotoxicity and the in vivo analgesic effect and local toxicity of the local anesthetic butamben (BTB) encapsulated in conventional or elastic liposomes incorporated in gel formulations. The results showed that both gel formulations of liposomal BTB reduced the cytotoxicity (p < 0.001; one-way ANOVA/Tukey's test) and increased the topical analgesic effect (p < 0.05; one-way ANOVA/Tukey's test) of butamben, compared to plain BTB gel. The gel formulations presented good rheological properties, and stability assays detected no differences in physicochemical stability up to 30 d after preparation. Moreover, histological assessment revealed no morphological changes in rat skin after application of any of the gel formulations tested.

Efectividad de la benzocaina en gel al 20% y la lidocaina en solución al 10% en pacientes que requieren punción en la mucosa oral: un ensayo clínico controlado aleatorizado cruzado a triple ciego / Effectiveness of benzocaine gel at 20% and lidocaine solution at 10% in patients requiring puncture in the oral mucosa: a randomized controlled crossover triple blind clinical trial

El objetivo del presente estudio fue determinar y comparar la efectividad de la Benzocaína en gel al 20% y la Lidocaína en solución al 10% en pacientes que requerían punción en la mucosa oral. El presente es un ensayo clínico controlado aleatorizado a triple ciego y de diseño cross-over. Se llevó a cabo en la clínica dental de la Unidad de Segunda Especialización en Estomatología (USEE) de la Universidad Nacional de Trujillo, durante los meses de Noviembre y Diciembre del 2010 y de Enero a Marzo del 2011. La muestra estuvo conformada por 60 pacientes, cada paciente firmó un consentimiento informado y se le realizó un análisis de su estado de ansiedad mediante la escala de ansiedad estado-rasgo (IDARE). Antes de realizar la punción en la mucosa oral se aplicó 4 preparados (2 anestésicos tópicos y 2 placebos) para después determinar y comparar la efectividad de los preparados en la reducción del dolor usando la escala visual análoga (EVA). Para la recolección de los datos se usó una ficha especial para tal fin. Para la comparación de la efectividad de los preparados se empleó el Análisis de Varianza (ANOVA). La efectividad de los anestésicos en gel y en solución fue evaluada empleando el test de Tuckey para comparaciones múltiples y el T de students. La significación estadística fue del 5%. Se encontró que la Benzocaína en gel al 20% y la Lidocaína en solución al 10% son efectivos para reducir el dolor a la punción y que no existe una relación estadísticamente significativa (p= 0,0575) entre la efectividad de cada uno de ellos. La administración de Benzocaína en gel al 20% o de la Lidocaína en solución al 10% reduce el dolor a la punción en igual magnitud y pueden ser usados indistintamente en la práctica odontológica diaria.

The objective of this study was to determine the effectiveness of benzocaine 20% gel and lidocaine in 10% solution in patients requiring puncture in the oral mucosa. This is a randomized controlled clinical trial to triple-blind, cross-over design. It was held at the dental clinic of the Unit of Second Specialization in Dentistry (usee) of the National University of Trujillo, in the months of November and December 2010 and January to March 2011. The sample consisted of 60 patients, each patient signed an informed consent and underwent a review of their status by anxiety scale state-trait anxiety (STAI). Before the puncture in the oral mucosa four preparations (2 topical anesthetics and 2 placebo) and then determine and compare the effectiveness of preparations in reducing pain using a visual analogue scale (VAS) was applied. For data collection a special token was used for that purpose. For comparison of the effectiveness of preparations Analysis of Variance (ANOVA). The effectiveness of the gel and anesthetic solution was evaluated using Tukey's test for multiple comparisons and students T. Statistical significance was 5%. We found that benzocaine 20% gel and lidocaine in 10% solution are effective at reducing pain at the puncture and that there is no statistically significant relationship (p= 0.0575) between the effectiveness of each. The administration of benzocaine 20% gel or lidocaine in 10% solution to reduce pain puncture equal and can be used interchangeably in everyday dental practice.

Efficacy of Benzocaine 20% Topical Anesthetic Compared to Placebo Prior to Administration of Local Anesthesia in the Oral Cavity: A Randomized Controlled Trial.

The aim of the present study was to compare the effects of a topical anesthetic to a placebo on pain perception during administration of local anesthesia in 2 regions of the oral cavity. A split-mouth, double-blind, randomized clinical trial design was used. Thirty-eight subjects, ages 18-50 years, American Society of Anesthesiologists I and II, received 4 anesthetic injections each in regions corresponding to the posterior superior alveolar nerve (PSA) and greater palatine nerve (GPN), totaling 152 sites analyzed. The side of the mouth where the topical anesthetic (benzocaine 20%) or the placebo was to be applied was chosen by a flip of a coin. The needle used was 27G, and the anesthetic used for administration of local anesthesia was 2% lidocaine with 1:100,000 epinephrine. After receiving the administration of local anesthesia, each patient reported pain perception on a visual analog scale (VAS) of 100-mm length. The results showed that the topical anesthetic and the placebo had similar effects: there was no statistically significant VAS difference between the PSA and the GPN pain ratings. A higher value on the VAS for the anesthesia of the GPN, relative to the PSA, was observed for both groups. Regarding gender, male patients had higher values on the VAS compared with female patients, but these differences were not meaningful. The topical anesthetic and the placebo had similar effects on pain perception for injection of local anesthesia for the PSA and GPN.

Benzocaine and eugenol as anesthetics for Brycon hilarii / Benzocaína e eugenol como anestésicos para piraputanga (Brycon hilarii)

Anesthetic products are frequently employed during fish handling practices; however, the correct doses of the various chemicals for different species are still unknown. This study determined the ideal concentrations of benzocaine and eugenol as anesthetics used in Brycon hilarii juveniles. The fish were acquired from a commercial fish farm located in western Paraná state, Brazil, totaling 104 juveniles, with average body weight and length of 50.04 ± 20.80 g and 16.30 ± 12.32 cm respectively. The study was carried out at the Aquiculture Laboratory from the Aquaculture Management Study Group - GEMAq at the West Parana State University. Five benzocaine concentrations (50.0, 100.0, 150.0, 200.0 and 250.0 mg L

A utilização de produtos anestésicos durante práticas de manejo é frequentemente empregada, porém doses corretas de diferentes fármacos e para espécies distintas ainda estão em fases de pesquisa. O objetivo do estudo foi determinar a melhor concentração de benzocaína e eugenol para juvenis de piraputanga (B. hilarii).Foram utilizados 104 juvenis de piraputanga com peso médio de 50,04 ± 20,80 g e comprimento total médio de16,30 ± 12,32 cm adquiridos em uma piscicultura comercial localizada na região Oeste do Estado do Paraná. O trabalho foi conduzido no Laboratório de Aquicultura do Grupo de Estudos de Manejo na Aquicultura -GEMAq da Universidade Estadual do Oeste do Paraná. Os animais foram submetidos a cinco concentrações de benzocaína (50,0; 100,0; 150,0; 200,0 e 250,0 mg L

Benzocaine and eugenol as anesthetics for Brycon hilarii / Benzocaína e eugenol como anestésicos para piraputanga (Brycon hilarii)

Anesthetic products are frequently employed during fish handling practices; however, the correct doses of the various chemicals for different species are still unknown. This study determined the ideal concentrations of benzocaine and eugenol as anesthetics used in Brycon hilarii juveniles. The fish were acquired from a commercial fish farm located in western Paraná state, Brazil, totaling 104 juveniles, with average body weight and length of 50.04 ± 20.80 g and 16.30 ± 12.32 cm respectively. The study was carried out at the Aquiculture Laboratory from the Aquaculture Management Study Group - GEMAq at the West Parana State University. Five benzocaine concentrations (50.0, 100.0, 150.0, 200.0 and 250.0 mg L <->1) and seven eugenol concentrations (50.0, 100.0, 150.0, 200.0, 250.0, 300.0 and 350 mg L-

A utilização de produtos anestésicos durante práticas de manejo é frequentemente empregada, porém doses corretas de diferentes fármacos e para espécies distintas ainda estão em fases de pesquisa. O objetivo do estudo foi determinar a melhor concentração de benzocaína e eugenol para juvenis de piraputanga (B. hilarii).Foram utilizados 104 juvenis de piraputanga com peso médio de 50,04 ± 20,80 g e comprimento total médio de16,30 ± 12,32 cm adquiridos em uma piscicultura comercial localizada na região Oeste do Estado do Paraná. O trabalho foi conduzido no Laboratório de Aquicultura do Grupo de Estudos de Manejo na Aquicultura -GEMAq da Universidade Estadual do Oeste do Paraná. Os animais foram submetidos a cinco concentrações de benzocaína (50,0; 100,0; 150,0; 200,0 e 250,0 mg L <->1) e sete concentrações de eugenol (50,0; 100,0; 150,0; 200,0; 250,0; 300,0 e 350 mg L <->1), para a aferição dos tempos referentes à letargia. Para a recuperação, os animais foram mantidos em aquários livre do anestésico e observado o tempo em que retornaram às atividades normais. A melhor dose de benzocaína verificada foi de 100 mg L <->1, enquanto a melhor dose de eugenol foi entre 100 e 150 mg L <->1.(AU)

Transdermal delivery of butamben using elastic and conventional liposomes.

Gel formulations containing the local anesthetic butamben (BTB) encapsulated in either conventional (BTBLUV) or elastic (BTBLUV-EL) liposomes were prepared and characterized, and then evaluated in terms of their skin permeability. Parameters measured included vesicle size and surface charge, BTB fluorescence anisotropy, encapsulation efficiency, partition coefficient and liposomal membrane organization. Encapsulation efficiencies and membrane/water partition coefficients were determined using a phase separation. The partition coefficients of the elastic and conventional formulations were 2025 ± 234 and 1136 ± 241, respectively. The sizes of the elastic and conventional liposomes did not change significantly (p > 0.05) following incorporation of the anesthetic. As expected, the elastic liposomes presented order parameters that were lower than those of the conventional liposomes, as determined by electron paramagnetic resonance with a 5-stearic acid nitroxide probe incorporated into the bilayer. After 8 h, the fluxes into the receiving solution (µg/cm(2)/h) were 6.95 ± 1.60 (10% BTB), 23.17 ± 6.09 (10% BTBLUV) and 29.93 ± 6.54 (10% BTBLUV-EL). The corresponding time lags (h) were 1.90 ± 0.48, 1.23 ± 0.28 and 1.57 ± 0.38, respectively. The permeability coefficients (10(-3 )cm/h) were 1.02 ± 0.23, 2.96 ± 0.77 and 4.14 ± 0.9, for 10% BTB, 10% BTBLUV and 10% BTBLUV-EL, respectively. The results demonstrate that anesthetic access through the skin can be considerably enhanced using liposomal gel formulations, compared to plain gel formulations.

Liposomal-benzocaine gel formulation: correlation between in vitro assays and in vivo topical anesthesia in volunteers.

The aim of the present study was to characterize a liposome-based benzocaine (BZC) formulation designed for topical use on the oral mucosa and to evaluate its in vitro retention and permeation using the Franz-type diffusion cells through pig esophagus mucosa. To predict the effectiveness of new designed formulations during preclinical studies, a correlation between in vitro assays and in vivo efficacy was performed. Liposomal BZC was characterized in terms of membrane/water partition coefficient, encapsulation efficiency, size, polydispersity, zeta potential, and morphology. Liposomal BZC (BL10) was incorporated into gel formulation and its performances were compared to plain BZC gel (B10) and the commercially available BZC gel (B20). BL10 and B10 presented higher flux and retention on pig esophagus mucosa with a shorter lag time, when compared to B20. BZC flux was strongly correlated with in vivo anesthetic efficacy, but not with topical anesthesia duration. The retention studies did not correlate with any of the in vivo efficacy parameters. Thus, in vitro permeation study can be useful to predict anesthetic efficacy during preclinical tests, because a correlation between flux and anesthetic efficacy was observed. Therefore, in vitro assays, followed by in vivo efficacy, are necessary to confirm anesthetic performance.

Benzocaine-loaded polymeric nanocapsules: study of the anesthetic activities.

This paper describes a comparison of different polymeric nanocapsules (NCs) prepared with the polymers poly(D,L-lactide-co-glycolide), poly(L-lactide) (PLA), and poly(ε-caprolactone) and used as carrier systems for the local anesthetic (LA) benzocaine (BZC). The systems were characterized and their anesthetic activities investigated. The results showed particle size distributions with polydispersity indices below 0.135, average diameters up to 120 nm, zeta potentials up to -30 mV, and entrapment efficiencies around 70%. Formulations of BZC using the polymeric NCs presented slower release profiles, compared with that of free BZC. Slowest release (release constant, k = 0.0016 min(-1)) was obtained using the PLA NC system. Pharmacological evaluation showed that encapsulation of BZC in PLA NCs prolonged its anesthetic action. This new formulation could potentially be used in future applications involving the gradual release of local anesthetics (LAs).

Screening of formulation variables for the preparation of poly(epsilon-caprolactone) nanocapsules containing the local anesthetic benzocaine.

In this work we describe the screening of four parameters in the preparation, by nanoprecipitation, of poly(epsilon-caprolactone) nanocapsules, used as a drug carrier system for the local anesthetic, benzocaine. A 2(4-1) factorial experimental design was used to study the influence of four different independent variables (polymer, oily phase, Span 60 and Tween 80) on nanocapsule characteristics (size, polydispersion index, zeta potential) and drug loading capability. Best results were obtained using an aqueous formulation comprising 100 mg of polymer, 200 mg of oily phase, 40 mg of Span 60 and 60 mg of Tween 80 in a final volume of 10 mL which produced a colloidal system with particle size of 188 nm, zeta potential -32 mV, polydispersion index 0.07, and benzocaine association efficiency > 87%. These findings open the way for future clinical studies using such formulations.

Liposome-encapsulated ropivacaine for intraoral topical anesthesia.

OBJECTIVES: This study evaluated the efficacy of liposome-encapsulated 2% ropivacaine in topical anesthesia and its influence on pulpal response. STUDY DESIGN: Forty volunteers received the following topical formulations in the buccal fold of the maxillary lateral incisors region (bilaterally): liposome-encapsulated 2% ropivacaine gel (RL2); 20% benzocaine gel (B20); liposomal placebo gel (LP); and placebo gel (P). Formulations were kept in place for 30 minutes, during which time the teeth were electric pulp tested every 10 minutes. After this procedure, a dental needle was inserted until periosteum contact in the same site of topical application and pain was rated by a visual analog scale. Duration of soft tissue anesthesia was assessed by pinprick test. RESULTS: RL2 and B20 showed lower pain response to needle insertion and longer soft tissue anesthesia then P and LP (P = .0003 and P < .0001, respectively); however, RL2 was not different from B20 (P > .05) regarding those parameters. None of the formulations was able to induce pulpal anesthesia. CONCLUSION: RL2 was as effective as B20 in reducing pain during needle insertion and inducing soft tissue anesthesia; however, neither one was able to induce pulpal anesthesia after a 30-min application.

Liposomal encapsulation improves the duration of soft tissue anesthesia but does not induce pulpal anesthesia.

STUDY OBJECTIVE: To compare the topical and the pulpal anesthesia efficacy of liposomal and plain benzocaine formulations. DESIGN: Double-blinded, randomized crossover study. SETTING: University ambulatory dental center. PATIENTS: 30 ASA physical status I volunteers. INTERVENTIONS: Volunteers received, in three different sessions, topical application of liposome-encapsulated 10% benzocaine (LB10), 10% benzocaine gel (B10), and 20% benzocaine gel (B20) in the right maxillary canine mucobuccal fold. MEASUREMENTS: Pain associated with the needle insertion was rated by visual analog scale (VAS) and the duration of topical anesthesia was recorded. Pulpal anesthesia was evaluated using an electric pulp tester. MAIN RESULTS: VAS values (median, 1st - 3rd quartiles) were 17 cm (11 - 25), 14 cm (3 - 22), and 21 cm (9 - 21) for B10, LB10, and B20, respectively. No differences were noted among the groups (Friedman test; P = 0.58). Soft tissue anesthesia was also not different. The LB10 [10 (8 - 12) min] showed longer soft tissue anesthesia (Friedman test; P < 0.01) than the other agents [B10 = 8 (5 - 10) min, and B20 = 7 (6 - 9) min]. None of the topical benzocaine formulations tested induced pulpal anesthesia. CONCLUSIONS: The encapsulation of benzocaine into liposome increased the duration of soft tissue anesthesia. However, it did not induce pulpal anesthesia.