Release Of Lidocaine Research Articles

Impact of Carbon Source on Bacterial Cellulose Network Architecture and Prolonged Lidocaine Release.

The biosynthesis of bacterial cellulose (BC) is significantly influenced by the type of carbon source available in the growth medium, which in turn dictates the material's final properties. This study systematically investigates the effects of five carbon sources-raffinose (C18H32O16), sucrose (C12H22O11), glucose (C6H12O6), arabinose (C5H10O5), and glycerol (C3H8O3)-on BC production by Komagataeibacter hansenii. The varying molecular weights and structural characteristics of these carbon sources provide a framework for examining their influence on BC yield, fiber morphology, and network properties. BC production was monitored through daily measurements of optical density and pH levels in the fermentation media from day 1 to day 14, providing valuable insights into bacterial growth kinetics and cellulose synthesis rates. Scanning electron microscopy (SEM) was used to elucidate fibril diameter and pore size distribution. Wide-angle X-ray scattering (WAXS) provided a detailed assessment of crystallinity. Selected BC pellicles were further processed via freeze-drying to produce a foam-like material that maximally preserves the natural three-dimensional structure of BC, facilitating the incorporation and release of lidocaine hydrochloride (5%), a widely used local anesthetic. The lidocaine-loaded BC foams exhibited a sustained and controlled release profile over 14 days in simulated body fluid, highlighting the importance of the role of carbon source selection in shaping the BC network architecture and its impact on drug release profile. These results highlight the versatility and sustainability of BC as a platform for wound healing and drug delivery applications. The tunable properties of BC networks provide opportunities for optimizing therapeutic delivery and improving wound care outcomes, positioning BC as an effective material for enhanced wound management strategies.

Dual-functional core–shell microneedle patches for oral ulcers treatment

Microneedle patches have been widely used in transdermal drug delivery due to their painless and enhanced drug delivery. Despite their established success, their application within the oral cavity, characterized by a dense distribution of nociceptor, remains largely unexplored. Here, we introduce a well-designed dual-functional core–shell microneedle patches to address oral ulcers. The outer shell of the microneedle tips is crafted from hyaluronic acid (HA) and loaded with lidocaine, while the inner core, composed of gelatin methyl methacrylate (GelMA) encapsulates dexamethasone. The HA shell rapidly dissolves upon application, facilitating the immediate release of lidocaine to induce anesthesia at the ulcer site, thereby alleviating the associated painful sensations. Simultaneously, GelMA imparts mechanical strength and ensured the sustained release of dexamethasone. In vivo experiments further demonstrated that the Dex@MN group exhibiting the most rapid healing rate also displayed the highest levels of collagen deposition and the lowest concentrations of inflammatory factors. This collective evidence underscores the considerable potential of dual-functional core–shell microneedle patches in the treatment of oral diseases.

Development and Characterization of Tannic Acid‐Modified PVA‐κCarrageenan Gel for Sustained Release of Lidocaine

Development and Characterization of Tannic Acid‐Modified PVA‐κCarrageenan Gel for Sustained Release of Lidocaine

Lidocaine-Loaded Iontophoresis-Driven Fiber-Based Microneedle Patch for Controllable and Long-Lasting Transdermal Local Analgesia

AbstractThe acute pain induced by clinical procedures, such as venipuncture, dental operations, and dermatological treatments, as well as postoperative pain, drives the advancement of anesthetic techniques aimed at alleviating discomfort. This situation underscores the ongoing significance of effective pain management strategies within the field of anesthesia. This paper presents an integrated iontophoresis (ITP)-driven fiber-based microneedle patch (IFMP) regulated by a smartphone for controllable, long-lasting lidocaine transdermal delivery. The IFMP integrates pure cotton fiber canvas-based dissolving microneedles (MNs) with ITP into a patch, with the MNs tips and gel layers significantly increasing the drug-loading capacity, achieving a one-step drug administration strategy of “dissolution, diffusion, and ITP.” Lidocaine is released via the microchannels of MNs by passive diffusion. Additionally, an electric current initiates active ITP for lidocaine delivery, creating synergy. User-requirement-based drug release by precisely modulating electrical signals in rat pain models is described herein. A smartphone application enables precise dosage control. It offers three different delivery modes: single-dose, pulse delivery, and sustained-release, ensuring rapid onset, and long-lasting pain relief. This versatility makes the system suitable for various pain conditions. The IFMP represents a promising system for patient-controlled local analgesia treatment, enabling active and long-term local self-controlled pain management in a safe and regulated manner. Graphical Abstract The iontophoresis-driven fiber-based microneedle patch combines fiber-based dissolving microneedles with iontophoresis, facilitating controlled lidocaine release through diffusion and electrical activation for enhanced effect. Precise modulation of electrical signals allows user-requirement-based drug release in rat pain models. A smart application supports precise dosing in single-dose, pulse, or sustained-release modes, ensuring efficient and prolonged pain management.

Buccal lidocaine mucoadhesive patches for pediatrics’ teething pain: overcoming possible hazards of oral gels

Objectives The utilization of pharmaceutical products in pediatric medicine, while established for use in adults, often presents uncertainties due to differences in application for children. The FDA discourages the use of local anesthetic gels, notably lidocaine, for teething pain in pediatrics due to concerns regarding potential adverse effects if inadvertently swallowed excessively. Therefore, significant attention is being directed towards modifying available marketed products to make them suitable for pediatric use. Here, we introduce mucoadhesive patches that not only have an adjusted dose of lidocaine but also feature a controlled release profile to manage teething pain with prolonged effect. This design helps to prevent issues related to gel liquefaction and swallowing, thereby reducing the potential hazardous side effects of lidocaine in the pediatric population. Methods The study involved the development of controlled-release lidocaine HCl-loaded pellets forming a matrix for inclusion in mucoadhesive patches. Characterization was performed to ensure prolonged drug release, particularly during overnight use, aiming to improve pediatric patient compliance and enable precise dosing. Key findings The mucoadhesive patches exhibited sustained lidocaine release lasting 24 h, potentially offering overnight relief suitable for pediatric application. The analysis of lidocaine content revealed that the developed patches maintained stable levels compared to doses obtained from commercially available oral gels. This finding implies effective pain control without the need for frequent reapplications, alongside controlled doses that decrease the likelihood of side effects. Conclusion The formulated medicated patches demonstrated consistent lidocaine content, effectively controlled drug release, and consequently, reduced the likelihood of undesired side effects when compared to oral gel administration.

A Bilayer Microneedle for Modulated Sequential Release of Adrenaline and Lidocaine for Prolonged Local Anesthesia.

Chronic pain emerges as a major global health issue, significantly impacting individuals' health and quality of life. In this study, we designed a bilayer microneedle loaded with lidocaine nanocomposites in the inner layer and adrenaline (Adr) in the outer layer (HCP MNs) for modulated sequential release to achieve prolonged local anesthesia. The obtained HCP MNs featured an intact structure with adequate mechanical strength for efficient skin penetration. The bilayer structure of MNs was evidenced by loading two fluorescent dyes in each layer. Furthermore, these HCP MNs were capable of inducing rapid as well as prolonged local anesthetic effects in guinea pigs. Hence, the bilayer MN coloaded with Adr and lidocaine nanocomposite serves as a promising transdermal delivery platform for chronic pain management.

Assessment of the Pharmacokinetics and Pharmacodynamics of Injectable Lidocaine and a Lidocaine-Impregnated Latex Band for Castration and Tail Docking in Lambs.

The objectives of this study were to assess the pharmacokinetics and pharmacodynamics of the current standard-of-care for pain mitigation in lambs during castration and tail docking (injectable lidocaine) and assess the ability of Lidocaine-Loaded Bands (LLBs) to deliver therapeutic concentrations into the contacted tissues over time. The study was comprised of four different trials: (1) investigation of in vitro release of lidocaine from LLBs; (2) pharmacokinetics and pharmacodynamics of injectable lidocaine in scrotal and tail tissue; (3) pharmacokinetics and pharmacodynamics of in vivo delivery of lidocaine with LLBs placed on the tail and scrotum of lambs; and (4) a "proof-of-concept" study comparing the sensation of control- versus LLB-banded tail tissue over time. The use of injectable lidocaine provides effective short-term anesthesia for 120 to 180 min following the injection; however, additional strategies are needed to manage long-term pain. The use of an LLB could provide an alternative where tissue lidocaine concentrations meet or exceed the EC50 for at least 21-28 days and, based on electrostimulation data, provides local anesthesia for at least 3 days when compared to a control band. Further studies are needed to compare the use of an injectable local anesthetic to the LLBs.

YANIK TEDAVİSİNDE KULLANILMAK ÜZERE LİDOKAİN İÇEREN ALOE VERA JEL FORMÜLASYONUNUN HAZIRLANMASI VE İN VİTRO KARAKTERİZASYONU

Objective: In this study, topically applied in situ gel formulations were aimed to design for the modulation of burns, with the active ingredient lidocaine and the gel gained from the Aloe vera plant. The prepared in situ gels were in the liquid form at the room temperature and gelled at the body temperature and adhered to the wound surface, resulting in higher drug residence time. By improving the characteristic properties of the in situ gels, it is aimed to improve patient compliance by obtaining higher local lidocaine concentration. Material and Method: In situ gel formulations separated by giving different gel codes were examined with characteristic analyses. Within the scope of these examinations, measurement of gelation temperature, pH measurement, in vitro lidocaine release, viscosity and rheological properties and the texture profile of the formulations were determined. Result and Discussion: Poloxamer 407 based in situ gels designed for topical treatment containing Aloe vera gel and lidocaine have been shown to increase skin residence time. Among the formulations prepared with different content ratios of the polymers Poloxamer 407, Poloxamer 188, HPMC and CMC, the gels coded F5 and A21 showed acceptable gelation temperature for topical use and sustained lidocaine release for 24 hours. According to these findings, it can be revealed that Poloxamer 407-HPMC based in situ gel formulation may be an effective alternative for topical burn treatment.

Temperature-sensitive multifunctional intelligent responsive hydrogel based on carboxymethyl agarose and N-isopropylacrylamide: Controlled drug release and accelerated wound healing

Wound healing remains challenging due to posttraumatic pain. At present, most wound dressings ignore the importance of wound pain. In this study, a temperature-sensitive multifunctional intelligent hydrogel patch (CPAG) containing lidocaine has developed for wound healing. CPAG hydrogel was prepared by grafting N-isopropylacrylamide and acrylamide onto carboxymethyl agarose (CMA) modified by agarose and encapsulating gallic acid and lidocaine. FTIR, 1H NMR spectroscopy, SEM and rheology were used to investigate its structure and temperature-sensitive properties. The contraction force generated by the temperature response characteristics of CPAG at 30 °C can accelerate wound healing. In vitro release assays demonstrated that CPAG directly controlled the same amount of lidocaine release at different temperatures through the competition between polymer-polymer and polymer-water interactions. In addition, MTT, H&E staining and stimulation test further proved its biological safety. The pain behavior study showed that the pain inhibition rates of the lidocaine cataplasms and LID@CPAG were 51.16 % and 67.83 %, respectively. In vitro and in vivo studies have shown that compared with the blank group, the bleeding volume of LID@CPAG decreased by 54.3 %, and the wound healing rate reached 97 %. CPAG hydrogel can play a comprehensive therapeutic role in accelerating wound closure by controlling drug release, analgesia, antioxidation and hemostasis.

Miconazole Nitrate Microparticles in Lidocaine Loaded Films as a Treatment for Oropharyngeal Candidiasis.

Oral candidiasis is an opportunistic infection that affects mainly individuals with weakened immune system. Devices used in the oral area to treat this condition include buccal films, which present advantages over both oral tablets and gels. Since candidiasis causes pain, burning, and itching, the purpose of this work was to develop buccal films loaded with both lidocaine (anesthetic) and miconazole nitrate (MN, antifungal) to treat this pathology topically. MN was loaded in microparticles based on different natural polymers, and then, these microparticles were loaded in hydroxypropyl methylcellulose-gelatin-based films containing lidocaine. All developed films showed adequate adhesiveness and thickness. DSC and XRD tests suggested that the drugs were in an amorphous state in the therapeutic systems. Microparticles based on chitosan-alginate showed the highest MN encapsulation. Among the films, those containing the mentioned microparticles presented the highest tensile strength and the lowest elongation at break, possibly due to the strong interactions between both polymers. These films allowed a fast release of lidocaine and a controlled release of MN. Due to the latter, these systems showed antifungal activity for 24 h. Therefore, the treatment of oropharyngeal candidiasis with these films could reduce the number of daily applications with respect to conventional treatments.

β-Glucan and Fatty Acid Based Mucoadhesive Carrier for Gastrointestinal Tract Specific Local and Sustained Drug Delivery.

The oral route is considered the most convenient route of drug administration for both systemic and local delivery. Besides stability and transportation, another unmet but important issue regarding oral medication is retention duration within the specific region of the gastrointestinal (GI) tract. We hypothesize that an oral vehicle that can adhere and maintain retention within the stomach for a longer duration can be more effective to treat stomach-related diseases. Therefore, in this project, we developed a carrier that is highly specific to the stomach and maintains its retention for a longer duration. We developed a vehicle composed of β-Glucan And Docosahexaenoic Acid (GADA) to observe its affinity and specificity to the stomach. GADA forms a spherical-shaped particle with negative zeta potential values that vary based on the feed ratio of docosahexaenoic acid. Docosahexaenoic acid is an omega-3 fatty acid that has transporters and receptors throughout the GI tract, such as CD36, plasma membrane-associated fatty acid-binding protein (FABP (pm)), and a family of fatty acid transport proteins (FATP1-6). The in vitro studies and characterization data showed that GADA has the capability to carry a payload of hydrophobic molecules and specifically deliver the payload to the GI tract, exert its therapeutic effects, and help to maintain stability for more than 12 h in the gastric and intestinal fluid. The particle size and surface plasmon resonance (SPR) data showed that GADA has a strong binding affinity with mucin in the presence of simulated gastric fluids. We observed a comparatively higher drug release of lidocaine in gastric juice than that in intestinal fluids, demonstrating the influence of the pH values of the media on drug-release kinetics. In vivo and ex vivo imaging of mice demonstrated that GADA maintains its retention within the stomach for at least 4 hr. This stomach-specific oral vehicle holds strong promise to translate various injectable therapeutic drugs to oral form upon further optimizations.

Mussel-Inspired Adhesive Hydrogels Based on Laponite-Confined Dopamine Polymerization as a Transdermal Patch.

Transdermal patch for local drug delivery has attained huge attention as an attractive alternative to existing drug delivery techniques as it is painless and user-friendly. However, most adhesive hydrogels either do not have adequate adhesion with the skin or cause discomfort while being removed from the skin surface due to excessive adhesion. To address this challenge, we developed an adhesive hydrogel based on laponite-confined dopamine polymerization as a transdermal patch. Laponite RDS nanoclay was used to control the hydrogel's viscous behavior and dopamine polymerization. The laponite polymerized polydopamine (l-PDA) was incorporated into poly(vinyl alcohol) (PVA) to make the PVA-l-PDA hydrogel. The laponite-confined polymerization improved the hydrogels' water contact angle and adhesion strength. The adhesion strength of the PVA-l-PDA hydrogel was adequate to adhere to the evaluated goat skin, glass, and polypropylene surfaces. Notably, the PVA-l-PDA hydrogel was easy to peel off from the skin. Further, we evaluated the drug release profile in goat skin using lidocaine as a model drug. We observed the controlled release of lidocaine from the PVA-l-PDA hydrogel compared to the PVA-PDA hydrogel. In addition, the nanoclay-confined adhesive hydrogel did not show any cytotoxic effect in fibroblasts. Altogether, PVA-l-PDA hydrogels offer appropriate adhesive strength, toughness, and biocompatibility. Thus, the PVA-l-PDA hydrogel has the potential to be an efficient transdermal patch.

Fabrication of a controlled-release delivery system for relieving sciatica nerve pain using an ultrasound-responsive microcapsule.

Lidocaine, a potent local anesthetic, is clinically used in nerve block and pain management. However, due to its short half-life, repeated administration is required. For this reason, here we designed and prepared a lidocaine-encapsulated polylactic acid-glycolic acid (Lidocaine@PLGA) microcapsule with ultrasound responsiveness to relieve the sciatica nerve pain. With a premixed membrane emulsification strategy, the fabricated lidocaine-embedded microcapsules possessed uniform particle size, good stability, injectability, and long-term sustained release both in vitro and in vivo. More importantly, Lidocaine@PLGA microcapsules had the function of ultrasonic responsive release, which made the drug release controllable with the effect of on-off administration. Our research showed that using ultrasound as a trigger switch could promote the rapid release of lidocaine from the microcapsules, achieving the dual effects of long-term sustained release and short-term ultrasound-triggered rapid release, which can enable the application of ultrasound-responsive Lidocaine@PLGA microcapsules to nerve root block and postoperative pain relief.

Amphiphilic Chitosan Porous Membranes as Potential Therapeutic Systems with Analgesic Effect for Burn Care.

Eliminating or at least lessening the pain is a crucial aspect of burns management, as pain can negatively affect mental health and quality of life, and it can also induce a delay on wound healing. In this context, new amphiphilic chitosan 3D porous membranes were developed and investigated as burns therapeutic systems with analgesic effect for delivery of lidocaine as local anesthetic. The highly porous morphology of the membranes and the structural modifications were evidenced by scanning electron microscopy (SEM), energy dispersive X-ray (EDX) analysis and infrared spectroscopy (FTIR). Improved compression mechanical properties, long-term hydrolytic degradation (28 days) evaluation and high swelling capacities (ranging from 8 to 22.6 g/g) indicate an increased capacity of the prepared membranes to absorb physiological fluids (burns exudate). Lidocaine in vitro release efficiency was favored by the decreased content of cross-linking agent (reaching maximum value of 95.24%) and the kinetic data modeling, indicating that lidocaine release occurs by quasi-Fickian diffusion. In addition to the in vitro evaluation of analgesic effect, lidocaine-loaded chitosan membranes were successfully investigated and proved antibacterial activity against most common pathogens in burns infections: Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus.

Ultrasound-Triggered on Demand Lidocaine Release Relieves Postoperative Pain.

Safe and non-invasive on-demand relief is a crucial and effective treatment for postoperative pain because it considers variable timing and intensity of anesthetics. Ultrasound modulation is a promising technique for this treatment because it allows convenient timed and non-invasive controlled drug release. Here, we created an ultrasound-triggered lidocaine (Lido) release platform using an amino acid hydrogel functioning as three-dimensional (3D) scaffold material (Lido-PPIX@ER hydrogel). It allows control of the timing, intensity and duration of lidocaine (Lido) to relieve postoperative pain. The hydrogel releases Lido due to the elevated reactive oxygen species (ROS) levels generated by PPIX under ultrasound triggering. The Lido-PPIX@ER hydrogel under individualized ultrasound triggering released lidocaine and provided effective analgesia for more than 72 h. The withdrawal threshold was higher than that in the control group at all time points measured. The hydrogel showed repeatable and adjustable ultrasound-triggered nerve blocks in vivo, the duration of which depended on the extent and intensity of insonation. On histopathology, no systemic effect or tissue reaction was observed in the ultrasound-triggered Lido-PPIX@ER hydrogel-treated group. The Lido-PPIX@ER hydrogel with individualized (highly variable) ultrasound triggering is a convenient and effective method that offers timed and spatiotemporally controlled Lido release to manage postoperative pain. This article presents the delivery system for a new effective strategy to reduce pain, remotely control pain, and offer timed and spatiotemporally controlled release of Lido to manage postoperative pain.

Intravesical sustained release system of lidocaine and oxybutynin results from in vitro and animal study.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic debilitating condition of unknown etiology. Intravesical lidocaine demonstrated pain relief in patients with IC/BPS. Intravesical oxybutynin has shown therapeutic efficacy in patients with urinary bladder disorders. However, loss of drug with urination requiring multiple administrations and immediate dilution of drug concentration by residual urine in the bladder mitigated intravesical use of both drugs in clinical practice. The aim of this study was to evaluate the efficacy and safety of fixed-dose combination of lidocaine and oxybutynin, forming in the urine a sustained delivery system named TRG-042. In-vitro, we have quantitatively tested the concentration of lidocaine and oxybutynin released from TRG-042 in artificial urine. Following the successful in-vitro study weekly formulation of TRG-042 was instilled intravesically to six pigs. All pigs were followed with cystoscopy to assess the gradual degradation of the delivery system and to evaluate bladder response over 7 days. Daily blood samples were tested for drug quantization. In-vitro studies have demonstrated oxybutynin and lidocaine sustained release over 1-week period coupled with full degradation of the matrix. None of the animals demonstrated any side effects following instillation. Cystoscopy examination observed gradual disintegration of TRG-042 over 1-week with no adverse reaction to the mucosa. Plasma concentrations of oxybutynin and lidocaine were uniformly stable over the 1-week period [1.46 ± 0.176ng/ml and 4.29 ± 2.48ng/ml respectively(mean ± SEM)] with almost undetectable concentration of N-desethyloxybutynin (NDO)[0.032 ± 0.068ng/ml]. The in-vitro and animal data demonstrated that TRG-042 can safely be used for intravesical sustained release of lidocaine and oxybutynin in the treatment of BPS/IC.

Exploiting hydrogen bonding to enhance lidocaine loading and stability in a poly ethylene-co-vinyl acetate carrier matrix

Sustained release of lidocaine from poly ethylene-co-vinyl acetate (EVA) implants can significantly improve pain management outcomes; however, poor drug loading is a major limitation. Recently, myristic acid was found to improve drug loading in EVA by inhibiting the crystallization of lidocaine. Here, lidocaine’s interaction with myristic acid was studied by differential scanning calorimetry. Spectra of lidocaine-myristic acid mixtures were analysed using two-dimensional correlation (2DCOS) maps. Furthermore, spectroscopic analysis of EVA matrices containing lidocaine, alone and in combination with myristic acid, was also performed and drug release was evaluated in vitro. A eutectic was obtained on combining lidocaine and myristic acid at the molar ratio of 1:1 due to loss of myristic acid’s dimeric conformation resulting in hydrogen bonding of its COOH group with lidocaine’s amide I moieties. In EVA, hydrogen bonding between adjacent lidocaine molecules caused crystallization above a threshold concentration and could be inhibited by incorporation of myristic acid by eutectic formation. By altering the molecular confirmation and solid state properties of lidocaine in EVA, myristic acid reduces lidocaine crystallization, increases drug loading and influences drug release kinetics. Exploiting these interactions and promoting further hydrogen bonding through the addition of specific excipients presents a viable strategy to enhance and stabilise drug loading in polymer matrices for various applications.

Designer self-assembling peptide nanofibers induce biomineralization of lidocaine for slow-release and prolonged analgesia

The burst release of small molecular water-soluble drugs is a major problem when pursuing their long-acting formulations. Although various types of carrier materials have been developed for tackling this problem, it is still a big challenge to prevent water-soluble small molecules from fast release and diffusion. In this study, a biomineralization strategy based upon a self-assembling peptide is proposed for the slow release of lidocaine, a classic anesthetic with high solubility and a very small molecular weight. A bolaamphiphilic peptide was designed to self-assemble and produce negatively charged nanofibers, which were used as the template to absorb positively charged lidocaine molecules through an electrostatic interaction. The biomineralization of lidocaine was then induced by adjusting the pH, which lead to the formation of lidocaine microcrystals with a homogenous size. The microcrystals were incorporated into a hyaluronic acid hydrogel to form an injectable formulation. This formulation slowly released lidocaine and generate a prolonged anesthetic and analgesic effect in rodent models. Due to the constrained local and plasma lidocaine concentration, as well as the biocompatibility and biodegradability of the peptide materials, this formulation also showed considerable safety. These results suggest that nanofiber assisted biomineralization can provide a potential strategy for the fabrication of long-acting formulations for small molecular water-soluble drugs. Statement of significanceLong-acting formulations are highly pursued to achieve stronger therapeutic effect, or to avoid repeated administration of drugs, especially through painful injection. Using carrier materials to slow down the release of bioactive molecules is a common strategy to reach this goal. However, for many water-soluble small molecular drugs currently used in clinic, it is notoriously difficult to slow down their release and diffusion. This study proposes a novel strategy based on a controllable mineralization process using self-assembling peptide nanofibers as the template. Taking lidocaine as an example, we showed how peptide-drug microcrystals with well-controlled size and shape could be obtained, which exhibit significantly prolonged anesthetic and analgesic effect. As a proof-of-concept study, this work proposes a promising strategy to control the release of water-soluble small molecular drugs.

MP37-14 A DOSE-ESCALATING PHASE I STUDY OF AN INJECTION OF LIDOCAINE PASTE FOR PROLONGED SPERMATIC CORD BLOCK IN MEN WITH CHRONIC SCROTAL CONTENT PAIN

You have accessJournal of UrologyCME1 May 2022MP37-14 A DOSE-ESCALATING PHASE I STUDY OF AN INJECTION OF LIDOCAINE PASTE FOR PROLONGED SPERMATIC CORD BLOCK IN MEN WITH CHRONIC SCROTAL CONTENT PAIN Luke Witherspoon, Claudia Kesch, Veronika Schmitt, Graeme Boniface, Colin Lundeen, J. Curtis Nickel, Ryan Paterson, Martin Gleave, and Ryan Flannigan Luke WitherspoonLuke Witherspoon More articles by this author , Claudia KeschClaudia Kesch More articles by this author , Veronika SchmittVeronika Schmitt More articles by this author , Graeme BonifaceGraeme Boniface More articles by this author , Colin LundeenColin Lundeen More articles by this author , J. Curtis NickelJ. Curtis Nickel More articles by this author , Ryan PatersonRyan Paterson More articles by this author , Martin GleaveMartin Gleave More articles by this author , and Ryan FlanniganRyan Flannigan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002591.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Spermatic cord block with local anesthetics provides pain relief in a subset of subjects with chronic scrotal content pain (CSCP), but relief is short-lived due to the rapid elimination of local anesthetics. This Phase I trial assessed the safety, tolerability, pharmacokinetics and efficacy of a long-acting formulation of lidocaine in patients with CSCP. METHODS: This was a prospective, single center, open label, single arm, Phase I dose-escalating trial. Male patients ≥19 years with unilateral scrotal pain lasting ≥3 months who reported an average daily maximum pain score over 7 days of ≥4 on a 0-10 numerical rating scale (NRS) were recruited. The investigational drug ST-01 (sustained-release lidocaine polymer solution for injection) is a long-acting lidocaine injected into the spermatic cord. ST-01 has two inactive ingredients, polyethylene glycol (PEG) and poly(lactic-co-glycolic acid) (PLGA) which slow the release of lidocaine. The study had 3 planned dose-escalating cohorts: cohort I: 2 mL of 140 mg/mL ST-01 (280 mg lidocaine); cohort II: 3 mL of 140 mg/mL ST-01 (420 mg lidocaine); cohort III: 4 mL of 140 mg/mL ST-01 (560 mg lidocaine). Subjects recorded their pain (NRS) three times a day on days 0–14, and once on days 15-27 of the study. The Chronic Epididymitis Symptom Index (CESI) was completed by patients on days 0, 7, 14, and 28 (end of study). RESULTS: Twenty subjects were screened, with 12 subjects being enrolled. NRS (mean, median) was reduced across all cohorts studied. Patients in cohort II (420 mg lidocaine) were identified via the dose escalation protocol. This group reported a baseline mean (median) NRS score of 5.3 (5), compared to an end of study score of 3.3 (3.5). Assessment of CESI score showed reduced scores over the study period with cohort II reporting a baseline mean (median) score of 19.8 (19) and an end of study value of 16.8 (17.5). Serum lidocaine concentrations were measured at 1 hour, 1 day and 7 days. Serum concentrations were similar across all cohorts at day 1 indicating only local release of the medication. There were no serious adverse events (SAE’s) reported in the study. All subjects reported at least one treatment-emergent adverse event (TEAE). Most TEAE’s were mild or moderate and related to bruising or swelling at the injection site. CONCLUSIONS: ST-01 was safely injected in 12 subjects suffering from CSCP with a promising efficacy signal. Source of Funding: This study was conducted with aid from the Vancouver Coastal Health Research Institute Translation and Innovation Award © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e614 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luke Witherspoon More articles by this author Claudia Kesch More articles by this author Veronika Schmitt More articles by this author Graeme Boniface More articles by this author Colin Lundeen More articles by this author J. Curtis Nickel More articles by this author Ryan Paterson More articles by this author Martin Gleave More articles by this author Ryan Flannigan More articles by this author Expand All Advertisement PDF DownloadLoading ...

Graphene Oxide-Reinforced Alginate Hydrogel for Controlled Release of Local Anesthetics: Synthesis, Characterization, and Release Studies.

In pain relief, lidocaine has gained more attention as a local anesthetic. However, there are several side effects that limit the use of local anesthetics. Therefore, it is hypothesized that a hydrogel system with facile design can be used for prolonged release of lidocaine. In this study, we developed a formulation comprises of sodium alginate (SA) and graphene oxide (GO) to prolong the release of lidocaine. The gelation was induced by physically crosslinking the alginate with Ca2+ ions. The formation of blank SA and GO-reinforced SA hydrogels was investigated with different concentration of Ca2+ ions. The controlled release of lidocaine hydrochloride (LH) on both hydrogel systems was studied in PBS solution. The GO-reinforced SA hydrogels exhibited more sustained release than SA hydrogels without GO. In vitro biocompatibility test in L929 fibroblast cells confirmed the non-toxic property of hydrogels. Furthermore, to prove the in-situ gelation and biodegradability of hydrogels the hydrogels were injected on mice model and confirmed the stable gel formation. The hydrogels implanted onto the subcutaneous tissue of hydrogels retained over one week. These results indicate that LH-loaded GO-reinforced SA hydrogel can be a potential biomaterial for controlled release of local anesthetics.