{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T13:41:43Z","timestamp":1768484503919,"version":"3.49.0"},"reference-count":64,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,12]],"date-time":"2020-09-12T00:00:00Z","timestamp":1599868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008425","name":"Conseller\u00eda de Cultura, Educaci\u00f3n e Ordenaci\u00f3n Universitaria, Xunta de Galicia","doi-asserted-by":"publisher","award":["ED431F 2016\/010"],"award-info":[{"award-number":["ED431F 2016\/010"]}],"id":[{"id":"10.13039\/501100008425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RTI2018-094131-A-I00"],"award-info":[{"award-number":["RTI2018-094131-A-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministerio de Ciencia, Innovaci\u00f3n y Universidades","doi-asserted-by":"publisher","award":["RTI2018-101627-B-I00"],"award-info":[{"award-number":["RTI2018-101627-B-I00"]}],"id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["AeMAT-BIOMEDCO2, ED431E 2018\/08"],"award-info":[{"award-number":["AeMAT-BIOMEDCO2, ED431E 2018\/08"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["AEI"],"award-info":[{"award-number":["AEI"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["FEDER"],"award-info":[{"award-number":["FEDER"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","award":["RYC2014-15239"],"award-info":[{"award-number":["RYC2014-15239"]}],"id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"publisher","award":["S2018\/BAA-4480, Biopieltec-CM"],"award-info":[{"award-number":["S2018\/BAA-4480, Biopieltec-CM"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"C\u00e1tedra Fundaci\u00f3n Ram\u00f3n Areces","award":["CFRA"],"award-info":[{"award-number":["CFRA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The delivery of bioactive agents using active wound dressings for the management of pain and infections offers improved performances in the treatment of wound complications. In this work, solid lipid microparticles (SLMPs) loaded with lidocaine hydrochloride (LID) were processed and the formulation was evaluated regarding its ability to deliver the drug at the wound site and through the skin barrier. The SLMPs of glyceryl monostearate (GMS) were prepared with different LID contents (0, 1, 2, 4, and 10 wt.%) using the solvent-free and one-step PGSS (Particles from Gas-Saturated Solutions) technique. PGSS exploits the use of supercritical CO2 (scCO2) as a plasticizer for lipids and as pressurizing agent for the atomization of particles. The SLMPs were characterized in terms of shape, size, and morphology (SEM), physicochemical properties (ATR-IR, XRD), and drug content and release behavior. An in vitro test for the evaluation of the influence of the wound environment on the LID release rate from SLMPs was studied using different bioengineered human skin substitutes obtained by 3D-bioprinting. Finally, the antimicrobial activity of the SLMPs was evaluated against three relevant bacteria in wound infections (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa). SLMPs processed with 10 wt.% of LID showed a remarkable performance to provide effective doses for pain relief and preventive infection effects.<\/jats:p>","DOI":"10.3390\/pharmaceutics12090870","type":"journal-article","created":{"date-parts":[[2020,9,13]],"date-time":"2020-09-13T21:11:32Z","timestamp":1600031492000},"page":"870","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Lidocaine-Loaded Solid Lipid Microparticles (SLMPs) Produced from Gas-Saturated Solutions for Wound Applications"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5477-1762","authenticated-orcid":false,"given":"Clara","family":"L\u00f3pez-Iglesias","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Pharmacy and Pharmaceutical Technology, I+D Farma group (GI-1645), Faculty of Pharmacy, Agrupaci\u00f3n Estrat\u00e9gica de Materiales (AeMAT) and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}]},{"given":"Cristina","family":"Qu\u00edlez","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Aerospace Engineering, Universidad Carlos III de Madrid (UC3M), 28911 Legan\u00e9s (Madrid), Spain"}]},{"given":"Joana","family":"Barros","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade da Universidade do Porto (i3S), Instituto de Engenharia Biom\u00e9dica (INEB), Faculdade de Engenharia (FEUP), Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1531-1595","authenticated-orcid":false,"given":"Diego","family":"Velasco","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Aerospace Engineering, Universidad Carlos III de Madrid (UC3M), 28911 Legan\u00e9s (Madrid), Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8546-7085","authenticated-orcid":false,"given":"Carmen","family":"Alvarez-Lorenzo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacy and Pharmaceutical Technology, I+D Farma group (GI-1645), Faculty of Pharmacy, Agrupaci\u00f3n Estrat\u00e9gica de Materiales (AeMAT) and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}]},{"given":"Jos\u00e9 L.","family":"Jorcano","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Aerospace Engineering, Universidad Carlos III de Madrid (UC3M), 28911 Legan\u00e9s (Madrid), Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1361-4605","authenticated-orcid":false,"given":"Fernando J.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade da Universidade do Porto (i3S), Instituto de Engenharia Biom\u00e9dica (INEB), Faculdade de Engenharia (FEUP), Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9542-3679","authenticated-orcid":false,"given":"Carlos A.","family":"Garc\u00eda-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacy and Pharmaceutical Technology, I+D Farma group (GI-1645), Faculty of Pharmacy, Agrupaci\u00f3n Estrat\u00e9gica de Materiales (AeMAT) and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.carbpol.2017.05.040","article-title":"Advanced multi-targeted composite biomaterial dressing for pain and infection control in chronic leg ulcers","volume":"172","author":"Catanzano","year":"2017","journal-title":"Carbohyd. Polym."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Briggs, M., Nelson, E.A., and Martyn-St James, M. (2012). Topical agents or dressings for pain in venous leg ulcers. Cochrane Database Syst. Rev.","DOI":"10.1002\/14651858.CD001177.pub3"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.12968\/bjcn.2017.22.Sup9.S38","article-title":"Wound management should not be a pain","volume":"22","author":"Jones","year":"2017","journal-title":"Br. J. Community Nurs."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/S1130-8621(18)30062-7","article-title":"Pain, stress, and sleep quality in chronic wound patients","volume":"28","author":"Fauziyah","year":"2018","journal-title":"Enferm. Cl\u00ednica"},{"key":"ref_5","first-page":"92","article-title":"Wound-related pain: Anxiety, stress and wound healing","volume":"6","author":"Woo","year":"2010","journal-title":"Wounds UK"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.bjan.2018.01.016","article-title":"Effects of local anesthetics on wound healing","volume":"68","author":"Kesici","year":"2018","journal-title":"Braz. J. Anesthesiol. (Engl. Ed.)"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1089\/jpm.2017.0010","article-title":"Topical treatments for acute and chronic wound pain","volume":"20","author":"Steele","year":"2017","journal-title":"J. Palliat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/j.cvsm.2019.07.004","article-title":"Local anesthetics","volume":"49","author":"Barletta","year":"2019","journal-title":"Vet. Clin. N. Am. Small"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s10096-018-03460-4","article-title":"A review and new insights to antimicrobial action of local anesthetics","volume":"38","author":"Razavi","year":"2019","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1097\/00000637-199909000-00003","article-title":"Antimicrobial activity of lidocaine against bacteria associated with nosocomial wound infection","volume":"43","author":"Parr","year":"1999","journal-title":"Ann. Plast. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.addr.2018.04.008","article-title":"Drug delivery systems and materials for wound healing applications","volume":"127","author":"Saghazadeh","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"621","DOI":"10.2174\/1389201016666150206113720","article-title":"Drug delivery systems for wound healing","volume":"16","author":"Johnson","year":"2015","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1126\/science.8128245","article-title":"Biodegradable long-circulating polymeric nanospheres","volume":"263","author":"Gref","year":"1994","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Chakravarty, P., Famili, A., Nagapudi, K., and Al-Sayah, M.A. (2019). Using supercritical fluid technology as a green alternative during the preparation of drug delivery systems. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11120629"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"711","DOI":"10.4155\/tde-2016-0039","article-title":"Microparticles to enhance delivery of drugs and growth factors into wound sites","volume":"7","author":"Ranjan","year":"2016","journal-title":"Ther. Deliv."},{"key":"ref_16","first-page":"45","article-title":"Nanostructured lipid carriers: A novel generation of solid lipid drug carriers","volume":"17","author":"Radtke","year":"2005","journal-title":"Pharm. Technol. Eur."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S131","DOI":"10.1016\/S0169-409X(02)00118-7","article-title":"Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations","volume":"54","author":"Radtke","year":"2002","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/j.addr.2004.02.001","article-title":"Coming of age of lipid-based drug delivery systems","volume":"56","author":"Davis","year":"2004","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s12951-019-0514-y","article-title":"Nano-drug delivery systems in wound treatment and skin regeneration","volume":"17","author":"Wang","year":"2019","journal-title":"J. Nanobiotechnol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1016\/j.ymthe.2018.04.021","article-title":"Topical lyophilized targeted lipid nanoparticles in the restoration of skin barrier function following burn wound","volume":"26","author":"Li","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1517\/17425247.2.1.75","article-title":"Solid lipid microparticles: Formulation, preparation, characterisation, drug release and applications","volume":"2","author":"Jaspart","year":"2005","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1211\/jpp\/61.05.0003","article-title":"Evaluation of solid lipid microparticles produced by spray congealing for topical application of econazole nitrate","volume":"61","author":"Gavini","year":"2009","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.colsurfb.2016.04.034","article-title":"Solid lipid microparticles for enhanced dermal delivery of tetracycline HCl","volume":"145","author":"Rahimpour","year":"2016","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Thomas, S., Pothan, L.A., and Mavelil-Sam, R. (2018). Biomedical Applications of Polysaccharide and Protein Based Aerogels. Green Chemistry Series, Royal Society of Chemistry. Chapter 16.","DOI":"10.1039\/9781782629979"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1700433","DOI":"10.1002\/adhm.201700433","article-title":"Supercritical fluid technology: An emphasis on drug delivery and related biomedical applications","volume":"6","author":"Kankala","year":"2017","journal-title":"Adv. Healthc. Mater."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.supflu.2013.03.001","article-title":"Use of supercritical fluid technology for the production of tailor-made aerogel particles for delivery systems","volume":"79","author":"Smirnova","year":"2013","journal-title":"J. Supercrit. Fluid."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.supflu.2010.05.011","article-title":"Encapsulation efficiency of solid lipid hybrid particles prepared using the PGSS\u00ae technique and loaded with different polarity active agents","volume":"54","author":"Sousa","year":"2010","journal-title":"J. Supercrit. Fluid."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.supflu.2007.03.015","article-title":"Preparation of glyceryl monostearate-based particles by PGSS\u00ae\u2014Application to caffeine","volume":"43","author":"Duarte","year":"2007","journal-title":"J. Supercrit. Fluid."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.jiec.2018.02.016","article-title":"Formation, characterization and release behavior of citrus oil-polymer microparticles using particles from gas saturated solutions (PGSS) process","volume":"63","author":"Ndayishimiye","year":"2018","journal-title":"J. Ind. Eng. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.addr.2007.06.019","article-title":"Micronization processes with supercritical fluids: Fundamentals and mechanisms","volume":"60","author":"Cocero","year":"2008","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.molliq.2006.08.026","article-title":"Melting point depression by using supercritical CO2 for a novel melt dispersion micronization process","volume":"131\u2013132","author":"Dohrn","year":"2007","journal-title":"J. Mol. Liq."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.powtec.2013.04.042","article-title":"Ibuprofen nanoparticles prepared by a PGSSTM-based method","volume":"245","author":"Chen","year":"2013","journal-title":"Powder Technol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.supflu.2013.06.010","article-title":"Production of new hybrid systems for drug delivery by PGSS (Particles from Gas Saturated Solutions) process","volume":"81","author":"Fraile","year":"2013","journal-title":"J. Supercrit. Fluid."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1002\/jps.21434","article-title":"Production of solid lipid submicron particles for protein delivery using a novel supercritical gas-assisted melting atomization process","volume":"98","author":"Salmaso","year":"2009","journal-title":"J. Pharm. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ijpharm.2009.06.014","article-title":"Biopharmaceutical characterisation of insulin and recombinant human growth hormone loaded lipid submicron particles produced by supercritical gas micro-atomisation","volume":"379","author":"Salmaso","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4783","DOI":"10.1002\/jps.22684","article-title":"Characterization of new topical ketoprofen formulations prepared by drug entrapment in solid lipid matrices","volume":"100","author":"Domingo","year":"2011","journal-title":"J. Pharm. Sci."},{"key":"ref_37","first-page":"163","article-title":"Skin models for the testing of transdermal drugs","volume":"8","author":"Abd","year":"2016","journal-title":"Clin. Pharm. Adv. Appl."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Neupane, R., Boddu, S.H.S., Renukuntla, J., Babu, R.J., and Tiwari, A.K. (2020). Alternatives to biological skin in permeation studies: Current trends and possibilities. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12020152"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/exd.13531","article-title":"3D skin models for 3R research: The potential of 3D reconstructed skin models to study skin barrier function","volume":"27","author":"Niehues","year":"2018","journal-title":"Exp. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"141","DOI":"10.2217\/3dp-2018-0008","article-title":"3D human skin bioprinting: A view from the bio side","volume":"2","author":"Velasco","year":"2018","journal-title":"J. 3D Print. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1089\/wound.2017.0752","article-title":"Three-dimensional printing and cell therapy for wound repair","volume":"7","author":"Kogelenberg","year":"2018","journal-title":"Adv. Wound Care"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"189","DOI":"10.2217\/pmt-2016-0060","article-title":"Efficacy of the topical 5% lidocaine medicated plaster in the treatment of chronic post-thoracotomy neuropathic pain","volume":"7","author":"Sansone","year":"2017","journal-title":"Pain Manag."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e475","DOI":"10.1097\/SCS.0000000000002790","article-title":"The use of topical lidocaine gel during intermaxillary fixation procedure","volume":"27","author":"Jeong","year":"2016","journal-title":"J. Craniofac. Surg."},{"key":"ref_44","unstructured":"American association of blood banks, and Walker, R.H. (1993). Technical Manual, American Association of blood banks."},{"key":"ref_45","first-page":"2249","article-title":"Estimation of lidocaine-HCl in pharmaceutical drugs by HPLC-UV system","volume":"7","author":"Alnuaim","year":"2017","journal-title":"Am. J. PharmTech Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"015006","DOI":"10.1088\/1758-5090\/9\/1\/015006","article-title":"3D bioprinting of functional human skin: Production and in vivo analysis","volume":"9","author":"Cubo","year":"2016","journal-title":"Biofabrication"},{"key":"ref_47","first-page":"e56412","article-title":"A method for determination and simulation of permeability and diffusion in a 3D tissue model in a membrane insert system for multi-well plates","volume":"132","author":"Hsu","year":"2018","journal-title":"JoVE J. Vis. Exp."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1086\/381972","article-title":"Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of Gram-positive bacterial infections","volume":"38","author":"Pankey","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.biopha.2018.04.055","article-title":"Nanostructured lipid carriers for site-specific drug delivery","volume":"103","author":"Khosa","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_50","unstructured":"Sezer, A.D. (2014). Techniques for the Preparation of Solid Lipid Nano and Microparticles. Application of Nanotechnology in Drug Delivery, IntechOpen."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1208\/s12249-014-0239-z","article-title":"Masking the bitter taste of injectable lidocaine HCl formulation for dental procedures","volume":"16","author":"Wei","year":"2015","journal-title":"AAPS PharmSciTech"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.ijpharm.2009.08.033","article-title":"Production of hybrid lipid-based particles loaded with inorganic nanoparticles and active compounds for prolonged topical release","volume":"382","author":"Sousa","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1021\/je034163p","article-title":"The solubility of benzocaine, lidocaine, and procaine in liquid and supercritical carbon dioxide","volume":"49","author":"Weinstein","year":"2004","journal-title":"J. Chem. Eng. Data"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/BF03009413","article-title":"Duration of intradermal anaesthesia with mixtures of bupivacaine and lidocaine","volume":"29","author":"Sweet","year":"1982","journal-title":"Canad. Anaesth. Soc. J."},{"key":"ref_55","unstructured":"Bruschi, M.L. (2015). Mathematical models of drug release. Strategies to Modify the Drug Release from Pharmaceutical Systems, Elsevier."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1111\/ijd.14107","article-title":"Effective permeation of 2.5 and 5% lidocaine hydrochloride in human skin using iontophoresis technique","volume":"57","author":"Manjunatha","year":"2018","journal-title":"Int. J. Dermatol."},{"key":"ref_57","first-page":"139","article-title":"Local anaesthetics as antibacterial agents: Effects on cellular respiration and the leakage of cytoplasmic constituents","volume":"37","author":"Bazaz","year":"1983","journal-title":"Microbios"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1093\/infdis\/121.6.597","article-title":"Antimicrobial activity of local anesthetics: Lidocaine and procaine","volume":"121","author":"Schmidt","year":"1970","journal-title":"J. Infect. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/j.1348-0421.1994.tb01803.x","article-title":"Lidocaine hydrochloride and acetylsalicylate kill bacteria by disrupting the bacterial membrane potential in different ways","volume":"38","author":"Ohsuka","year":"1994","journal-title":"Microbiol. Immunol."},{"key":"ref_60","first-page":"1","article-title":"Determination of minimum inhibitory concentrations (MICs) of antibacterial agents by broth dilution","volume":"9","author":"Hasselmann","year":"2003","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1099\/jmm.0.47339-0","article-title":"Analysis of the antimicrobial activity of local anaesthetics used for dental analgesia","volume":"57","author":"Pelz","year":"2008","journal-title":"J. Med. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1093\/bja\/81.3.444","article-title":"Antibacterial activity of lidocaine in mixtures with Diprivan","volume":"81","author":"Gajraj","year":"1998","journal-title":"Br. J. Anaesth."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"166S","DOI":"10.1097\/00000539-199802001-00165","article-title":"Growth inhibition of Staphylococcus aureus by propofol\/lidocaine admixture","volume":"86","author":"Driver","year":"1998","journal-title":"Anesth. Analg."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1089\/sur.2007.036","article-title":"Local anesthetics as antimicrobial agents: A review","volume":"9","author":"Johnson","year":"2008","journal-title":"Surg. Infect."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/9\/870\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:09:26Z","timestamp":1760177366000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/9\/870"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,12]]},"references-count":64,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["pharmaceutics12090870"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics12090870","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,12]]}}}