Pharmacological and clinical implications of local anaesthetic mixtures: a narrative review.

Various techniques have been explored to prolong the duration and improve the efficacy of local anaesthetic nerve blocks. Some of these involve mixing local anaesthetics or adding adjuncts. We did a literature review of studies published between 01 May 2011 and 01 May 2021 that studied specific combinations of local anaesthetics and adjuncts. The rationale behind mixing long- and short-acting local anaesthetics to hasten onset and extend duration is flawed on pharmacokinetic principles. Most local anaesthetic adjuncts are not licensed for use in this manner and the consequences of untested admixtures and adjuncts range from making the solution ineffective to potential harm. Pharmaceutical compatibility needs to be established before administration. The compatibility of drugs from the same class cannot be inferred and each admixture requires individual review. Precipitation on mixing (steroids, non-steroidal anti-inflammatory drugs) and subsequent embolisation can lead to serious adverse events, although these are rare. The additive itself or its preservative can have neurotoxic (adrenaline, midazolam) and/or chondrotoxic properties (non-steroidal anti-inflammatory drugs). The prolongation of block may occur at the expense of motor block quality (ketamine) or block onset (magnesium). Adverse effects for some adjuncts appear to be dose-dependent and recommendations concerning optimal dosing are lacking. An important confounding factor is whether studies used systemic administration of the adjunct as a control to accurately identify an additional benefit of perineural administration. The challenge of how best to prolong block duration while minimising adverse events remains a topic of interest with further research required.

Formulation optimization, anesthetic activity, skin permeation, and transportation pathway of Alpinia galanga oil SNEDDS in zebrafish (Danio rerio).

Alpinia galanga oil (AGO) has an anesthetic activity but its water insoluble property limits its clinical applications. The aim of the present study was to develop a self-nanoemulsifying drug delivery system of AGO (SNEDDS-AGO) to avoid the use of organic solvent and investigate AGO transportation pathway and anesthetic activity. Three optimized formulations from a contour plots of droplet size; SNEDDS-AGO-1, SNEDDS-AGO-2, and SNEDDS-AGO-3, composed of AGO, Miglyol 812, Cremophor RH 40, Capmul MCM EP, and ethanol at the ratios of 40:10:35:10:5, 40:20:15:20:5, and 60:10:15:10:5, respectively were selected as they possessed different droplet size of 62 ± 0.5, 107 ± 2.8, and 207 ± 4.3 nm, respectively. It was found that the droplet size played an important role in fish anesthesia. SNEDDS-AGO-3 showed the longest anesthetic induction time (270 sec) (p < 0.03). Transportation pathway and skin permeation of SNEDDS-AGO-2 were investigated using nile red labelled AGO and detected by fluorescence microscope. AGO was found mostly in brain, gills, and skin suggesting that the transportation pathway of AGO in zebrafish is passing through the gills and skin to the brain. SNEDDS-AGO formulations showed significantly higher permeation through the skin than AGO ethanolic solution. In conclusion, SNEDDS is a promising delivery system of AGO.

Novel insights on the encapsulation mechanism of PLGA terminal groups on ropivacaine.

Currently, the influences of free terminal groups (hydroxyl, carboxyl and ester) of PLGA on encapsulating active pharmaceutical ingredient are relatively ambiguous even though PLGA types were defined as critical quality attributes in vast majority of design of experiment process. In this study, emulsion method combined with premix membrane emulsification technique has been used to encapsulate ropivacaine (RVC), a small molecule local anesthetic in clinical. Based on the narrow particle size distribution, the influences and mechanisms of the terminal groups on properties of ropivacaine loaded microspheres have been investigated in detail. It was found that microspheres prepared by PLGA with hydroxyl or ester groups exhibited lower encapsulation efficiency but faster in vitro release rate than that of carboxyl groups. In the meanwhile, on microcosmic level analysis by quartz crystal microbalance with dissipation, atomic force microscope and confocal laser scanning microscopy, we attributed this distinction to the specific interaction between ropivacaine and different terminal groups. Subsequently, the reaction activation centers were verified by density functional simulation calculation and frontier molecular orbital theory at molecular level. Additionally, pharmacokinetics and pharmacodynamic research of infiltration anesthesia model were performed to compare sustained release ability, duration and intensity of the anesthetic effect in vivo. Finally, potential safety and toxicity were evaluated by the biochemical analysis. This study not only provides a novel mechanism of drug encapsulation process but also potential flexible selections in terms of various anesthesia indications in clinical.

Population pharmacokinetics of ropivacaine used for local infiltration anaesthesia during primary total unilateral and simultaneous bilateral knee arthroplasty.

BACKGROUND: Ropivacaine is commonly used in local infiltration anaesthesia (LIA) as pain management after total knee arthroplasty (TKA). Although considered safe, no studies evaluated the pharmacokinetics of high-dose ropivacaine infiltration in simultaneous bilateral TKA. METHODS: We studied 13 patients undergoing unilateral and 15 undergoing bilateral TKA. Standard LIA technique was used with ropivacaine 0.2%, 200 ml (400 mg) injected peri-articularly in each knee. Free and total plasma concentrations of ropivacaine were measured within 24 h using liquid chromatography-mass spectrometry. A population pharmacokinetic model was built using non-linear mixed-effects models. RESULTS: Peak free ropivacaine concentration was 0.030 (0.017-0.071) µg ml-1 (mean [99% confidence interval]) vs 0.095 (0.047-0.208) µg ml-1, and peak total ropivacaine concentration was 0.756 (0.065-1.222) µg ml-1vs 1.695 (0.077-3.005) µg ml-1 for unilateral and bilateral TKA, respectively. The pharmacokinetics was ascribed a one-compartment model with first-order absorption. The main identified covariates were protein binding, allometrically scaled body weight on clearance and volume, and unilateral or bilateral surgery on volume. CONCLUSIONS: This is the first study to investigate the pharmacokinetics of free and total ropivacaine after unilateral and bilateral TKA. A population model was successfully built and peak free ropivacaine concentration stayed below previously proposed toxic thresholds in patients undergoing unilateral and bilateral TKA receiving LIA with high-dose ropivacaine. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04702282.

In vitro and in vivo studies of micro-depots using tailored microemulsion for sustained local anaesthesia.

In clinical practice, lidocaine is used as local anesthetic for the management of post-operative pain. The commercial formulation including gels, injections and ointments showed short duration of action (1 to 2 h). In this paper, the efforts have being made to develop tailored lidocaine-microemulsion (o/w), which on penetration in the skin layer cause micro-depots formation due to destabilization of the microemulsion system. To identify the microemulsion region, pseudo ternary diagrams were constructed using Capmul MCM as oil, Pluronic F68 as tri-block surfactant, polyethylene glycol 200 as co-surfactant at 1:4 and 1:6 ratios (S:Co-S). The selected 5%w/v lidocaine loaded microemulsion [Ld-ME-2(1:4)] was stable in thermodynamic test and during shelf life period (3 months). In ex vivo permeability study, the lidocaine release from Ld-ME-2(1:4) microemulsion was sustained in comparison to the marketed lidocaine ointment. The skin irritation study confirmed the safety of lidocaine loaded microemulsion. Tail flick test showed improved and sustain local anaesthetic effect in comparison to the market ointment. The improved efficacy of microemulsion system, was due to high penetration in the skin layer due to local precipitation of lidocaine from microemulsion. The findings suggest that the tailored microemulsion could be a potential strategy to prolong the local anaesthesia.

Local and regional anaesthesia in dogs and cats: Overview of concepts and drugs (Part 1).

Pain management in veterinary patients is a crucial component of appropriate patient care. Multimodal analgesia that includes both systemically and locally/regionally administered drugs is generally the most effective approach to providing pain relief. Local anaesthetic drugs used in local and regional blockade are unique in that they can completely block the transmission of pain (in conscious patients) or nociceptive (in anaesthetized patients) signals, thereby providing profound analgesia. In addition, local and regional administration of drugs, when compared with systemic bolus administration, generally results in a lower incidence of dose-related adverse effects. Due to the potential to provide profound analgesia and the high safety margin (when used correctly) of this drug class, local anaesthetics are recommended as part of the analgesic protocol in the majority of patients undergoing surgical procedures or suffering traumatic injuries. This manuscript, Part 1 of a two-part instalment, emphasizes the importance of using local and regional anaesthesia as a component of multimodal analgesia, provides a review of the basic pharmacokinetics/pharmacodynamics of local anaesthetic drugs in general, lists information on commonly used local anaesthetic drugs for local and regional blockade in dogs and cats, and briefly introduces the novel liposome-encapsulated bupivacaine (NOCITA®). Part 2 is a review of local and regional anaesthetic techniques used in dogs and cats (Grubb & Lobprise, 2020).

Contemporary Approaches to Postoperative Pain Management.

LEARNING OBJECTIVES: After reading this article, the participant should be able to: 1. Describe the fundamental concepts of multimodal analgesia techniques and how they target pain pathophysiology. 2. Effectively educate patients on postoperative pain and safe opioid use. 3. Develop and implement a multimodal postoperative analgesia regimen. SUMMARY: For many years, opioids were the cornerstone of postoperative pain control, contributing to what has become a significant public health concern. This article discusses contemporary approaches to multimodal, opioid-sparing postoperative pain management in the plastic surgical patient.

Polymer-tetrodotoxin conjugates to induce prolonged duration local anesthesia with minimal toxicity.

There is clinical and scientific interest in developing local anesthetics with prolonged durations of effect from single injections. The need for such is highlighted by the current opioid epidemic. Site 1 sodium channel blockers such as tetrodotoxin (TTX) are extremely potent, and can provide very long nerve blocks but the duration is limited by the associated systemic toxicity. Here we report a system where slow release of TTX conjugated to a biocompatible and biodegradable polymer, poly(triol dicarboxylic acid)-co-poly(ethylene glycol) (TDP), is achieved by hydrolysis of ester linkages. Nerve block by the released TTX is enhanced by administration in a carrier with chemical permeation enhancer (CPE) properties. TTX release can be adjusted by tuning the hydrophilicity of the TDP polymer backbone. In vivo, 1.0-80.0 µg of TTX released from these polymers produced a range of durations of nerve block, from several hours to 3 days, with minimal systemic or local toxicity.

Transversus Abdominal Plane Block in Children: Efficacy and Safety: A Randomized Clinical Study and Pharmacokinetic Profile.

BACKGROUND: The transversus abdominis plane (TAP) block has become a common regional anesthesia technique for pain management in a wide variety of abdominal procedures. Evidence to support any particular local anesthetic regimen as well as pharmacokinetic and systemic toxicity risks of TAP block remain insufficiently studied in children. The aim of this study was to compare the analgesic effects and investigate pharmacokinetic profile of levobupivacaine after ultrasound-guided TAP block using a low volume/high concentration (LVHC) or a high volume/low concentration (HVLC) solution in children. METHODS: This prospective randomized study included children scheduled for day-case inguinal surgery. Children were randomized to receive TAP block using 0.4 mg·kg levobupivacaine as either HVLC (0.2 mL·kg of 0.2% levobupivacaine) or LVHC (0.1 mL·kg of 0.4% levobupivacaine). The primary outcome was the number of children who required opioid rescue analgesia postoperatively. Pharmacokinetic profile study of levobupivacaine was also performed. RESULTS: Seventy patients were equally randomized, and 65 were included in the final analysis. Seventy-one percent of patients did not require any postoperative opioid analgesia. The number of patients who received rescue analgesia was 12 (35%) in the LVHC group and 7 (23%) in the HVLC group (relative risk, 0.64; 95% confidence interval [CI], 0.29-1.42; P = .26). Mean pain scores (FLACC [faces, legs, activity, cry, and consolability]) at postanesthesia care unit discharge did not differ between LVHC and HVLC groups, respectively, 0.39 ± 0.86 and 1 ± 1.71 with mean group difference -0.60 (95% CI, -1.27 to 0.06; P = .08). The pharmacokinetic profile of levobupivacaine was comparable in the 2 groups: the mean total and free levobupivacaine peak concentrations were 379 ± 248 and 3.95 ± 3.16 ng·mL, respectively, occurring 22.5 ± 11 minutes after injection. The highest total and free levobupivacaine concentrations collected, respectively, 1360 and 15.1 ng·mL, remained far below theoretical toxic thresholds. CONCLUSIONS: In children, quality of postoperative pain control provided by TAP block using levobupivacaine 0.4 mg·kg administered as either HVLC or LVHC did not differ and was associated with a very low risk of local anesthetic systemic toxicity.

Preclinical studies of ropivacaine extended-release from a temperature responsive hydrogel for prolonged relief of pain at the surgical wound.

Postoperative pain is a common form of acute pain that has been treated commonly by local anesthetics through regional nerve blocking. In this study, a series of experiments were conducted using rats to investigate the pharmacokinetic, distribution, and efficacy of a temperature responsive hydrogel-based drug delivery device (PF-72) containing ropivacaine (0.75%) for extended relief of postoperative pain by allowing the prolonged release of ropivacaine. When the ropivacaine was administered using PF-72, its concentration-time curve (AUClast) and peak concentration (Cmax) were 577.0 h*ng/mL and 271.9 ng/mL, respectively. In contrast when the ropivacaine solution was administered using saline solution, its AUClast and Cmax were 982.8 h*ng/mL and 423.6 ng/mL, respectively. In the tissue distribution study, the peak concentration and mean area under the curve of the ropivacaine in injection area (target tissue) were found about 2-fold higher in the case of PF-72 compared with the case of conventional ropivacaine solution. These results clearly demonstrate the capability of PF-72 hydrogel to retain the ropivacaine at the injection site for an extended period. Effective extended (at least 24 h) pain relief of ropivacaine administered using PF-72 was found in the pharmacodynamic study of prolonged analgesic effect. The results of this study indicated that local drug delivery by PF-72 hydrogel formulation may be an effective method to achieve extended relief of pain. Other advantages of ropivacaine administration using PF-72 include reduced systemic side effects and high localization of a drug in target tissues.

Pharmacokinetics of 400 mg Locally Infiltrated Ropivacaine After Total Knee Arthroplasty Without Perioperative Tourniquet Use.

BACKGROUND AND OBJECTIVES: Local infiltration analgesia (LIA) with ropivacaine for total knee arthroplasty (TKA) is increasingly used. Despite the high doses of ropivacaine, LIA is considered safe, and this perception is sustained by pharmacokinetic data demonstrating that maximum concentrations of ropivacaine stay well below the toxic threshold in plasma. These pharmacokinetic studies all involve TKA procedures with the use of a tourniquet. Recently, performing TKA without the use of a tourniquet is gaining popularity, but no pharmacokinetic data exist when LIA is administered for TKA without the use of a tourniquet. The purpose of this study was to describe the pharmacokinetic profile of a single-shot ropivacaine (200 mL 0.2%) and 0.75 mg epinephrine (1000 µg/mL) when used for LIA in patients for TKA without a tourniquet. METHODS: In this prospective cohort study, 20 patients treated with LIA for TKA without a tourniquet were studied. Plasma samples were taken at 20, 40, 60, 90, 120, 240, 360, 480, 600, 720, and 1440 minutes after local anesthetic infiltration, in which total and unbound ropivacaine concentrations were determined. RESULTS: Results are given as median (interquartile range [IQR]). Median peak ropivacaine concentration was 1.16 µg/mL (IQR, 0.46); median peak unbound ropivacaine concentration was 0.05 µg/mL (IQR, 0.02). The corresponding times to reach the maximum concentration for total and unbound ropivacaine were 360 (IQR, 240) and 360 (IQR, 360) minutes, respectively. CONCLUSIONS: Although great interindividual variability in ropivacaine concentration was found, both total and unbound maximum serum concentrations remained below the assumed systemic toxic thresholds in all samples. CLINICAL TRIAL REGISTRATION: This study was registered at Netherlands Trial Registry (http://www.trialregister.nl), trial ID NTR6306.

Local sustained delivery of bupivacaine HCl from a new castor oil-based nanoemulsion system.

Bupivacaine HCl (1-butyl-2',6'-pipecoloxylidide hydrochloride), an amide local anesthetic compound, is a local anesthetic drug utilized for intraoperative local anesthesia, post-operative analgesia and in the treatment of chronic pain. However, its utility is limited by the relative short duration of analgesia after local administration (approximately 9 h after direct injection) and risk for side effects. This work is aimed to develop a nanoemulsion of bupivacaine HCl with sustained local anesthetics release kinetics for improved pain management, by exhibiting extended analgesic action and providing reduced peak levels in the circulation to minimize side effects. Herein, biodegradable oils were evaluated for use in nanoemulsions to enable sustained release kinetics of bupivacaine HCl. Only with castor oil, a clear and stable nanoemulsion was obtained without the occurrence of phase separation over a period of 3 months. High loading of bupivacaine HCl into the castor oil-based nanoemulsion system was achieved with about 98% entrapment efficiency and the resulting formulation showed high stability under stress conditions (accelerated stability test) regarding changes in visual appearance, drug content, and droplet size. We show herein that the in vitro release and in vivo pharmacokinetic profiles as well as pharmacodynamic outcome (pain relief test) after subcutaneous administration in rats correlate well and clearly demonstrate the prolonged release and extended duration of activity of our novel nanoformulation. In addition, the lower Cmax value achieved in the blood compartment suggests the possibility that the risk for systemic side effects is reduced. We conclude that castor oil-based nanomulsion represents an attractive pain treatment possibility to achieve prolonged local action of bupivacaine HCl.

Articaine Versus Lidocaine Concentration in the Palatal Tissues After Supraperiosteal Buccal Infiltration Anesthesia.

PURPOSE: Palatal local anesthetic injection is a painful procedure. Previous studies have reported successful extraction of maxillary teeth using only buccal infiltration of 4% articaine without palatal anesthesia. The aim of the present study was to determine levels of 4% articaine solution in palatal bone and mucosal tissues after buccal injection and compare those levels with 2% lidocaine solution in New Zealand white rabbits. MATERIALS AND METHODS: Eight rabbits received 2 different injections of 0.6 mL of 4% articaine with 1:100,000 epinephrine and 0.6 mL of 2% lidocaine with 1:100,000 epinephrine buccal to the right and left maxillary first molar, respectively, in a split-mouth study design using quantitative syringes. All injections were administered using the buccal infiltration technique without any palatal injection. Ten minutes later, palatal bone and mucosa specimens were collected for analysis. Levels of the 2 local anesthetic agents were measured in palatal tissues using high-performance liquid chromatography (HPLC). RESULTS: HPLC analysis showed markedly higher 4% articaine solution values (0.319 ± 0.037) in palatal mucosal tissues compared with palatal mucosal concentrations of 2% lidocaine solution (0.0839 ± 0.017). In palatal bone, the mean concentration of 2% lidocaine solution was markedly lower than the mean concentration of 4% articaine solution (0.085 ± 0.012 vs 0.155 ± 0.012, respectively). There was no relevant difference between levels of 2% lidocaine in the palatal bone and mucosal tissues. However, the mean concentration of 4% articaine in the palatal mucosa was markedly higher than its concentration in palatal bone. CONCLUSIONS: The buccal vestibule-palatal diffusion of 4% articaine solution with 1:100,000 epinephrine is greater than 2% lidocaine solution with 1:100,000 epinephrine in a rabbit model.

Axillary local anesthetic spread after the thoracic interfacial ultrasound block - a cadaveric and radiological evaluation / Dispersão axilar de anestésico local após bloqueio interfascial torácico guiado por ultrassom - estudo radiológico e em cadáver

Abstract Background Oral opioid analgesics have been used for management of peri- and postoperative analgesia in patients undergoing axillary dissection. The axillary region is a difficult zone to block and does not have a specific regional anesthesia technique published that offers its adequate blockade. Methods After institutional review board approval, anatomic and radiological studies were conducted to determine the deposition and spread of methylene blue and local anesthetic injected respectively into the axilla via the thoracic inter-fascial plane. Magnetic Resonance Imaging studies were then conducted in 15 of 34 patients scheduled for unilateral breast surgery that entailed any of the following: axillary clearance, sentinel node biopsy, axillary node biopsy, or supernumerary breasts, to ascertain the deposition and time course of spread of solution within the thoracic interfascial plane in vivo. Results Radiological and cadaveric studies showed that the injection of local anesthetic and methylene blue via the thoracic inter-fascial plane, using ultrasound guide technique, results in reliable deposition into the axilla. In patients, the injection of the local anesthetic produced a reliable axillary sensory block. This finding was supported by Magnetic Resonance Imaging studies that showed hyper-intense signals in the axillary region. Conclusions These findings define the anatomic characteristics of the thoracic interfascial plane nerve block in the axillary region, and underline the clinical potential of this novel nerve block.

Resumo Justificativa Os analgésicos orais à base de opioides têm sido usados para o manejo da analgesia nos períodos peri e pós-operatório de pacientes submetidos à linfadenectomia axilar. A região axilar é uma zona difícil de bloquear e não há registro de uma técnica de anestesia regional específica que ofereça o seu bloqueio adequado. Métodos Após a aprovação do Conselho de Ética institucional, estudos anatômicos e radiológicos foram feitos para determinar a deposição e disseminação de azul de metileno e anestésico local, respectivamente injetados na axila via plano interfascial torácico. Exames de ressonância magnética foram então feitos em 15 de 34 pacientes programados para cirurgia de mama unilateral que envolveria qualquer um dos seguintes procedimentos: esvaziamento axilar, biópsia de linfonodo sentinela, biópsia de linfonodo axilar ou mamas supranumerárias, para verificar a deposição e o tempo de propagação da solução dentro do plano interfascial torácico in vivo. Resultados Estudos radiológicos e em cadáveres mostraram que a injeção de anestésico local e azul de metileno via plano interfascial torácico com a técnica guiada por ultrassom resulta em deposição confiável na axila. Nos pacientes, a injeção de anestésico local produziu um bloqueio sensitivo axilar confiável. Esse achado foi corroborado por estudos de ressonância magnética que mostraram sinais hiperintensos na região axilar. Conclusões Esses achados definem as características anatômicas do bloqueio da região axilar e destacam o potencial clínico desses novos bloqueios.

Preparation and characterization of textile-based carrier systems for anal fissure treatment.

Anal fissure is common and painful disease of anorectum. In this study, microparticles containing nifedipine and lidocaine HCl were prepared by spray drying and applied to bio-degradable and bio-stable tampons. Characterization of microparticles was determined by visual analyses, mass yield, particle size measurement, encapsulation efficiency, drug loading and in vitro drug release. Mass yield was between 5.5 and 45.9%. The particle size was between 15.1 and 26.8 µm. Encapsulation efficiency were 96.142 ± 5.931 and 85.571 ± 3.301; drug loading were 65.261 ± 3.914% and 37.844 ± 4.339% of L2 and N1, respectively. Well-separated, mainly spherical microparticles with suitable properties were obtained. Optimum microparticles were applied to tampons. Physical properties and visual characteristics of tampons were investigated before and after binder application. In vitro drug release from tampons were also examined. According to the results, textile-based carrier systems loaded microparticles containing nifedipine and lidocaine HCl will be an effective and promising alternative for current anal fissure treatment.

[Axillary local anesthetic spread after the thoracic interfacial ultrasound block - a cadaveric and radiological evaluation]. / Dispersão axilar de anestésico local após bloqueio interfascial torácico guiado por ultrassom - estudo radiológico e em cadáver.

BACKGROUND: Oral opioid analgesics have been used for management of peri- and postoperative analgesia in patients undergoing axillary dissection. The axillary region is a difficult zone to block and does not have a specific regional anesthesia technique published that offers its adequate blockade. METHODS: After institutional review board approval, anatomic and radiological studies were conducted to determine the deposition and spread of methylene blue and local anesthetic injected respectively into the axilla via the thoracic inter-fascial plane. Magnetic Resonance Imaging studies were then conducted in 15 of 34 patients scheduled for unilateral breast surgery that entailed any of the following: axillary clearance, sentinel node biopsy, axillary node biopsy, or supernumerary breasts, to ascertain the deposition and time course of spread of solution within the thoracic interfascial plane in vivo. RESULTS: Radiological and cadaveric studies showed that the injection of local anesthetic and methylene blue via the thoracic inter-fascial plane, using ultrasound guide technique, results in reliable deposition into the axilla. In patients, the injection of the local anesthetic produced a reliable axillary sensory block. This finding was supported by Magnetic Resonance Imaging studies that showed hyper-intense signals in the axillary region. CONCLUSIONS: These findings define the anatomic characteristics of the thoracic interfascial plane nerve block in the axillary region, and underline the clinical potential of this novel nerve block.

A novel local anesthetic system: transcriptional transactivator peptide-decorated nanocarriers for skin delivery of ropivacaine.

PURPOSE: Barrier properties of the skin and physicochemical properties of drugs are the main factors for the delivery of local anesthetic molecules. The present work evaluates the anesthetic efficacy of drug-loaded nanocarrier (NC) systems for the delivery of local anesthetic drug, ropivacaine (RVC). METHODS: In this study, transcriptional transactivator peptide (TAT)-decorated RVC-loaded NCs (TAT-RVC/NCs) were successfully fabricated. Physicochemical properties of NCs were determined in terms of particle size, zeta potential, drug encapsulation efficiency, drug-loading capacity, stability, and in vitro drug release. The skin permeation of NCs was examined using a Franz diffusion cell mounted with depilated mouse skin in vitro, and in vivo anesthetic effect was evaluated in mice. RESULTS: The results showed that TAT-RVC/NCs have a mean diameter of 133.2 nm and high drug-loading capacity of 81.7%. From the in vitro skin permeation results, it was observed that transdermal flux of TAT-RVC/NCs was higher than that of RVC-loaded NCs (RVC/NCs) and RVC injection. The evaluation of in vivo anesthetic effect illustrated that TAT-RVC/NCs can enhance the transdermal delivery of RVC by reducing the pain threshold in mice. CONCLUSION: These results indicate that TAT-decorated NCs systems are useful for overcoming the barrier function of the skin, decreasing the dosage of RVC and enhancing the anesthetic effect. Therefore, TAT-decorated NCs can be used as an effective transdermal delivery system for local anesthesia.