{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T09:03:14Z","timestamp":1777971794290,"version":"3.51.4"},"reference-count":119,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:00:00Z","timestamp":1620345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Membranes"],"abstract":"<jats:p>Transdermal drug delivery (TDD) presents many advantages compared to other conventional routes of drug administration, yet its full potential has not been achieved. The administration of drugs through the skin is hampered by the natural barrier properties of the skin, which results in poor permeation of most drugs. Several methods have been developed to overcome this limitation. One of the approaches to increase drug permeation and thus to enable TDD for a wider range of drugs consists in the use of chemical permeation enhancers (CPEs), compounds that interact with skin to ultimately increase drug flux. Amino acid derivatives show great potential as permeation enhancers, as they exhibit high biodegradability and low toxicity. Here we present an overview of amino acid derivatives investigated so far as CPEs for the delivery of hydrophilic and lipophilic drugs across the skin, focusing on the structural features which promote their enhancement capacity.<\/jats:p>","DOI":"10.3390\/membranes11050343","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T22:36:24Z","timestamp":1620426984000},"page":"343","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Current Status of Amino Acid-Based Permeation Enhancers in Transdermal Drug Delivery"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1459-0905","authenticated-orcid":false,"given":"Rui","family":"Pereira","sequence":"first","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, Rua do Campo Alegre s\/n, 4169-007 Porto, Portugal"}]},{"given":"Sandra G.","family":"Silva","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, Rua do Campo Alegre s\/n, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6931-1355","authenticated-orcid":false,"given":"Marina","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0736-2835","authenticated-orcid":false,"given":"Salette","family":"Reis","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8967-6642","authenticated-orcid":false,"given":"M. Lu\u00edsa do","family":"Vale","sequence":"additional","affiliation":[{"name":"LAQV-REQUIMTE, Departamento de Qu\u00edmica e Bioqu\u00edmica, Faculdade de Ci\u00eancias, Universidade do Porto, Rua do Campo Alegre s\/n, 4169-007 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jconrel.2012.09.017","article-title":"Approaches for breaking the barriers of drug permeation through transdermal drug delivery","volume":"164","author":"Alexander","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nrd1304","article-title":"Current status and future potential of transdermal drug delivery","volume":"3","author":"Prausnitz","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0928-0987(01)00167-1","article-title":"Novel mechanisms and devices to enable successful transdermal drug delivery","volume":"14","author":"Barry","year":"2001","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1038\/nbt.1504","article-title":"Transdermal drug delivery","volume":"26","author":"Prausnitz","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2340\/00015555741214","article-title":"A Domain Mosaic Model of the Skin Barrier","volume":"74","author":"Forslind","year":"1994","journal-title":"Acta Derm. Venereol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0163-7827(02)00028-0","article-title":"Structure of the skin barrier and its modulation by vesicular formulations","volume":"42","author":"Bouwstra","year":"2003","journal-title":"Prog. Lipid Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"139","DOI":"10.2174\/1566523217666170510151540","article-title":"Recent Advances in Skin Penetration Enhancers for Transdermal Gene and Drug Delivery","volume":"17","author":"Amjadi","year":"2017","journal-title":"Curr. Gene Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.ejps.2013.05.005","article-title":"Microneedles for intradermal and transdermal drug delivery","volume":"50","author":"McCrudden","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.addr.2011.01.012","article-title":"Nanoparticles and microparticles for skin drug delivery","volume":"63","author":"Prow","year":"2011","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"89","DOI":"10.4155\/tde.15.94","article-title":"Recent advances in peptides for enhancing transdermal macromolecular drug delivery","volume":"7","author":"Ruan","year":"2016","journal-title":"Ther. Deliv."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Vasyuchenko, E.P., Orekhov, P.S., Armeev, G.A., and Bozdaganyan, M.E. (2021). CPE-DB: An Open Database of Chemical Penetration Enhancers. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010066"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/S0169-409X(02)00121-7","article-title":"New insights into skin structure: Scratching the surface","volume":"54","author":"Menon","year":"2002","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.addr.2012.12.002","article-title":"Modeling the human skin barrier-Towards a better understanding of dermal absorption Preface","volume":"65","author":"Hansen","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_14","unstructured":"Tekade, R.K. (2019). Chapter 15\u2014Cutaneous and Transdermal Drug Delivery: Techniques and Delivery Systems. Advances in Pharmaceutical Product Development and Research, Basic Fundamentals of Drug Delivery, Academic Press."},{"key":"ref_15","first-page":"10","article-title":"The Lipid Organisation in Human Stratum Corneum and Model Systems","volume":"4","author":"Bouwstra","year":"2010","journal-title":"Open Dermatol. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1046\/j.1523-1747.2003.12359.x","article-title":"Barrier function of the skin: \u201cLa raison d\u2019\u00eatre\u201d of the epidermis","volume":"121","author":"Madison","year":"2003","journal-title":"J. Invest. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0168-3659(98)00187-4","article-title":"Chemical enhancement of percutaneous absorption in relation to stratum corneum structural alterations","volume":"59","author":"Suhonen","year":"1999","journal-title":"J. Control. Release"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1159\/000231523","article-title":"Barrier Functions of Human Skin: A Holistic View","volume":"22","author":"Menon","year":"2009","journal-title":"Skin Pharmacol. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1016\/j.bbamem.2006.06.021","article-title":"The skin barrier in healthy and diseased state","volume":"1758","author":"Bouwstra","year":"2006","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.chemphyslip.2018.09.017","article-title":"State of the art in Stratum Corneum research: The biophysical properties of ceramides","volume":"216","author":"Schmitt","year":"2018","journal-title":"Chem. Phys. Lipids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"119960","DOI":"10.1016\/j.ijpharm.2020.119960","article-title":"Application of the human stratum corneum lipid-based mimetic model in assessment of drug-loaded nanoparticles for skin administration","volume":"591","author":"Moniz","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1111\/j.1600-0625.2008.00786.x","article-title":"The skin: An indispensable barrier","volume":"17","author":"Proksch","year":"2008","journal-title":"Exp. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Benson, H.A., and Wattkinson, A.C. (2012). Skin Structure, Function, and Permeation. Topical and Transdermal Drug Delivery: Principles and Practice, Jonhn Wiley & Sons Inc.","DOI":"10.1002\/9781118140505.ch1"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0168-3659(02)00321-8","article-title":"Modeling skin permeability to hydrophilic and hydrophobic solutes based on four permeation pathways","volume":"86","author":"Mitragotri","year":"2003","journal-title":"J. Control. Release"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.1016\/S0169-409X(02)00113-8","article-title":"Drug delivery routes in skin: A novel approach","volume":"54","author":"Barry","year":"2002","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_26","unstructured":"Grumezescu, A.M. (2018). Nanoparticles influence in skin penetration of drugs in vitro and in vivo characterization. Nanostructures for the Engineering of Cells, Tissues and Organs, William Andrew."},{"key":"ref_27","first-page":"1","article-title":"Transfollicular drug delivery: Current perspectives","volume":"5","author":"Verma","year":"2016","journal-title":"Res. Rep. Transdermal Drug Deliv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/0168-3659(87)90066-6","article-title":"Mode of action of penetration enhancers in human skin","volume":"6","author":"Barry","year":"1987","journal-title":"J. Control. Release"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1615\/CritRevTherDrugCarrierSyst.v17.i6.20","article-title":"Enhancement of transdermal drug delivery: Chemical and physical approaches","volume":"17","author":"Asbill","year":"2000","journal-title":"Crit. Rev. Ther. Drug Carrier Syst."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1080\/17425247.2020.1713087","article-title":"Permeation enhancers in transdermal drug delivery: Benefits and limitations","volume":"17","year":"2020","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"23","DOI":"10.2174\/1567201052772915","article-title":"Transdermal drug delivery: Penetration enhancement techniques","volume":"2","author":"Benson","year":"2005","journal-title":"Curr. Drug. Deliv."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/0168-3659(91)90115-T","article-title":"Lipid-Protein-Partitioning theory of skin penetration enhancement","volume":"15","author":"Barry","year":"1991","journal-title":"J. Control. Release"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Dragicevic, N., and Maibach, H.I. (2015). Penetration Enhancers and Their Mechanism Studied on a Molecular Level. Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement: Modification of the Stratum Corneum, Springer.","DOI":"10.1007\/978-3-662-47039-8"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"118920","DOI":"10.1016\/j.ijpharm.2019.118920","article-title":"Solubility-physicochemical-thermodynamic theory of penetration enhancer mechanism of action","volume":"575","author":"Haq","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1517\/17425247.2014.875528","article-title":"Skin permeabilization for transdermal drug delivery: Recent advances and future prospects","volume":"11","author":"Schoellhammer","year":"2014","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"90","DOI":"10.3390\/pharmaceutics7030090","article-title":"Transdermal Delivery of Drugs with Microneedles\u2014Potential and Challenges","volume":"7","author":"Ita","year":"2015","journal-title":"Pharmaceutics"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Dragicevic, N., and Maibach, H.I. (2016). Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement: Nanocarriers, Springer.","DOI":"10.1007\/978-3-662-47862-2"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1208\/s12249-018-0977-4","article-title":"Influence of a Combination of Chemical Enhancers and Iontophoresis on In Vitro Transungual Permeation of Nystatin","volume":"19","author":"Monti","year":"2018","journal-title":"AAPS PharmSciTech"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"R7","DOI":"10.1016\/0378-5173(89)90310-4","article-title":"Essential oils as novel human skin penetration enhancers","volume":"57","author":"Williams","year":"1989","journal-title":"Int. J. Pharm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0378-5173(95)04108-7","article-title":"Modes of action of terpene penetration enhancers in human skin; Differential scanning calorimetry, small-angle X-ray diffraction and enhancer uptake studies","volume":"127","author":"Cornwell","year":"1996","journal-title":"Int. J. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Chen, J., Jiang, Q.-D., Chai, Y.-P., Zhang, H., Peng, P., and Yang, X.-X. (2016). Natural Terpenes as Penetration Enhancers for Transdermal Drug Delivery. Molecules, 21.","DOI":"10.3390\/molecules21121709"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Dragicevic, N., and Maibach, H.I. (2015). Terpenes and Essential Oils as Skin Penetration Enhancers. Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement: Modification of the Stratum Corneum, Springer.","DOI":"10.1007\/978-3-662-47039-8"},{"key":"ref_43","unstructured":"Walters, K., and Hadgraft, J. (1993). Water: The most natural penetration enhancer. Pharmaceutical Skin Penetration Enhancement, Marcel Dekker."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dragicevic, N., and Maibach, H.I. (2015). Urea and Derivatives as Penetration Enhancers. Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement: Modification of the Stratum Corneum, Springer.","DOI":"10.1007\/978-3-662-47039-8"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1001\/archderm.1982.01650190028013","article-title":"Enhanced percutaneous penetration with 1-dodecylazacycloheptan-2-one","volume":"118","author":"Stoughton","year":"1982","journal-title":"Arch. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.bbamem.2017.01.029","article-title":"Influence of the penetration enhancer isopropyl myristate on stratum corneum lipid model membranes revealed by neutron diffraction and 2H NMR experiments","volume":"1859","author":"Eichner","year":"2017","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Dragicevic, N., and Maibach, H.I. (2015). Pyrrolidones as Penetration Enhancers. Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement: Modification of the Stratum Corneum, Springer.","DOI":"10.1007\/978-3-662-47039-8"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1208\/s12248-013-9518-y","article-title":"Structure Activity Relationships in Alkylammonium C12-Gemini Surfactants Used as Dermal Permeation Enhancers","volume":"15","author":"Silva","year":"2013","journal-title":"AAPS J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.ejpb.2015.02.024","article-title":"Novel serine-based gemini surfactants as chemical permeation enhancers of local anesthetics: A comprehensive study on structure\u2013activity relationships, molecular dynamics and dermal delivery","volume":"93","author":"Teixeira","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Dragicevic, N., and Maibach, H.I. (2015). Ethanol and Other Alcohols: Old Enhancers, Alternative Perspectives. Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement: Modification of the Stratum Corneum, Springer.","DOI":"10.1007\/978-3-662-47039-8"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Dragicevic, N., and Maibach, H.I. (2015). Fatty Alcohols, Fatty Acids, and Fatty Acid Esters as Penetration Enhancers. Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement: Modification of the Stratum Corneum, Springer.","DOI":"10.1007\/978-3-662-47039-8"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/jps.2600800109","article-title":"Enhancement of Propranolol Hydrochloride and Diazepam Skin Absorption In Vitro: Effect of Enhancer Lipophilicity","volume":"80","author":"Hori","year":"1991","journal-title":"J. Pharm. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0168-3659(01)00439-4","article-title":"Comparison of the effect of fatty alcohols on the permeation of melatonin between porcine and human skin","volume":"77","author":"Andega","year":"2001","journal-title":"J. Control. Release"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1023\/A:1015822312426","article-title":"Oleic acid: Its effects on stratum corneum in relation to (trans) dermal drug delivery","volume":"7","author":"Francoeur","year":"1990","journal-title":"Pharm. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2","DOI":"10.4103\/0975-7406.92724","article-title":"Status of surfactants as penetration enhancers in transdermal drug delivery","volume":"4","author":"Som","year":"2012","journal-title":"J. Pharm. Bioall. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1023\/A:1015990222731","article-title":"New Alkyl N, N-Dialkyl-Sustituted Amino Acetates as Transdermal Penetration Enhancers","volume":"6","author":"Wong","year":"1989","journal-title":"Pharm. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1023\/A:1015824100788","article-title":"N-dimethylamino acetate and azone enhance drug penetration across human, snake, and rabbit skin","volume":"8","author":"Hirvonen","year":"1991","journal-title":"Pharm. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1023\/A:1018914806761","article-title":"\u03b5-Aminocaproic Acid Esters as Transdermal Penetration Enhancing Agents","volume":"10","year":"1993","journal-title":"Pharm. Res."},{"key":"ref_59","first-page":"325","article-title":"Esters of omega-amino acids as flexible penetration enhancers","volume":"49","author":"Hrabalek","year":"1994","journal-title":"Pharmazie"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1016\/S0960-894X(03)00409-8","article-title":"L-Serine and glycine based ceramide analogues as transdermal permeation enhancers: Polar head size and hydrogen bonding","volume":"13","author":"Holas","year":"2003","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1007\/s11095-008-9780-3","article-title":"Dimethylamino acid esters as biodegradable and reversible transdermal permeation enhancers: Effects of linking chain length, chirality and polyfluorination","volume":"26","author":"Novotny","year":"2009","journal-title":"Pharm. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1002\/jps.2600820221","article-title":"Facilitated Transport of Two Model Steroids by Esters and Amides of Clofibric Acid","volume":"82","author":"Mlchniak","year":"1993","journal-title":"J. Pharm. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3810\/psm.2011.09.1923","article-title":"Dimethyl sulfoxide: An effective penetration enhancer for topical administration of NSAIDs","volume":"39","author":"Marren","year":"2011","journal-title":"Phys. Sportsmed."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1016\/j.bbamem.2009.08.015","article-title":"Enhancement of transdermal drug delivery via synergistic action of chemicals","volume":"1788","author":"Karande","year":"2009","journal-title":"Biochim. Biophys. Acta-Biomembr."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.ijpharm.2013.02.040","article-title":"Skin penetration enhancers","volume":"447","author":"Lane","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.addr.2003.10.025","article-title":"Penetration enhancers","volume":"56","author":"Williams","year":"2004","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5381","DOI":"10.1016\/j.bmc.2003.09.034","article-title":"Synthetic ceramide analogues as skin permeation enhancers: Structure-activity relationships","volume":"11","author":"Dolezal","year":"2003","journal-title":"Bioorg. Med. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.2174\/0929867054864822","article-title":"Amphiphilic Transdermal Permeation Enhancers: Structure-Activity Relationships","volume":"12","author":"Zbytovska","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s40204-019-0114-9","article-title":"Effect of permeation enhancers on in vitro release and transdermal delivery of lamotrigine from Eudragit \u00aeRS100 polymer matrix-type drug in adhesive patches","volume":"8","author":"Jafri","year":"2019","journal-title":"Prog. Biomater."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s11095-009-9985-0","article-title":"Efficiency of Fatty Acids as Chemical Penetration Enhancers: Mechanisms and Structure Enhancement Relationship","volume":"27","author":"Ibraim","year":"2010","journal-title":"Pharm. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4688","DOI":"10.1073\/pnas.0501176102","article-title":"Design principles of chemical penetration enhancers for transdermal drug delivery","volume":"102","author":"Karande","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.jconrel.2010.02.015","article-title":"Multicomponent chemical enhancer formulations for transdermal drug delivery: More is not always better","volume":"144","author":"Arora","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_73","unstructured":"Ghosh, T.K., Pfister, W.R., and Yum, S. (1997). Chemical means of transdermal drug permeation enhancement. Transdermal and Topical Drug Delivery Systems, Informa Health Care."},{"key":"ref_74","first-page":"305","article-title":"Skin absorption enhancers","volume":"9","author":"Williams","year":"1992","journal-title":"Crit. Rev. Ther. Drug Carrier Syst."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jconrel.2006.07.001","article-title":"Insights into synergistic interactions in binary mixtures of chemical permeation enhancers for transdermal drug delivery","volume":"115","author":"Karande","year":"2006","journal-title":"J. Control. Release"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1365-2133.1968.tb11979.x","article-title":"The mechanism of water binding in stratum corneum","volume":"80","author":"Middleton","year":"1968","journal-title":"Br. J. Dermatol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Dragicevic, N., and Maibach, H.I. (2015). Amino Acid-Based Transdermal Penetration Enhancers. Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement: Modification of the Stratum Corneum, Springer.","DOI":"10.1007\/978-3-662-47039-8"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/cbdd.12008","article-title":"Cell-penetrating Peptides as a Novel Transdermal Drug Delivery System","volume":"80","author":"Nasrollahi","year":"2012","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_79","unstructured":"Dragicevic, N., and Maibach, H.I. (2015). Peptide-Mediated Transdermal Drug Delivery. Penetration Enhancement: Modification of the Stratum Corneum, Springer."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1166\/jbn.2010.1158","article-title":"Transdermal delivery enhanced by antimicrobial peptides","volume":"6","author":"Kim","year":"2010","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1039\/C7NJ04025C","article-title":"Novel mono, di and tri-fatty acid esters bearing secondary amino acid ester head groups as transdermal permeation enhancers","volume":"42","author":"Rambharose","year":"2018","journal-title":"New J. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Dahlizar, S., Futaki, M., Okada, A., Yatomi, C., Todo, H., and Sugibayashi, K. (2018). Combined Use of N-Palmitoyl-Glycine-Histidine Gel and Several Penetration Enhancers on the Skin Permeation and Concentration of Metronidazole. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10040163"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"119031","DOI":"10.1016\/j.ijpharm.2020.119031","article-title":"Novel skin permeation enhancers based on amino acid ester ionic liquid: Design and permeation mechanism","volume":"576","author":"Zheng","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_84","first-page":"87","article-title":"Transdermal drug delivery: Efficacy and potential applications of the penetration enhancer Azone","volume":"6","author":"Wiechers","year":"1990","journal-title":"Drug Des. Deliv."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0378-5173(91)90053-Q","article-title":"Transdermal permeability and skin accumulation of amino acids","volume":"72","author":"Ruland","year":"1991","journal-title":"Int. J. Pharm."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0378-5173(93)90321-6","article-title":"In vitro permeation of human skin by multipolar ions","volume":"99","author":"Sznitowska","year":"1993","journal-title":"Int. J. Pharm."},{"key":"ref_87","unstructured":"Fix, J.A., and Pogany, S.A. (1988). Lysine Esters Used as Absorption Enhancing Agents. (EP-0162747), Patent No."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1007\/s11095-006-9782-y","article-title":"Synthesis and Enhancing Effect of Transkarbam 12 on the Transdermal Delivery of Theophylline, Clotrimazole, Flobufen, and Griseofulvin","volume":"23","author":"Holas","year":"2006","journal-title":"Pharm. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1023\/A:1018980905312","article-title":"Synthesis and enhancing effect of dodecyl 2-(N,N-dimethylamino) propionate on the transepidermal delivery of indomethacin, clonidine, and hydrocortisone","volume":"10","author":"Rytting","year":"1993","journal-title":"Pharm. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ijpharm.2003.09.018","article-title":"The interaction of the penetration enhancer DDAIP with a phospholipid model membrane","volume":"271","author":"Wolka","year":"2004","journal-title":"Int. J. Pharm."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jconrel.2012.11.003","article-title":"Amino acid derivatives as transdermal permeation enhancers","volume":"165","author":"Roh","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1002\/jps.2600840522","article-title":"n-pentyl N-acetylprolinate. A new skin penetration enhancer","volume":"84","author":"Harris","year":"1995","journal-title":"J Pharm Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1021\/js9600787","article-title":"In Vitro Evaluation of a Series of N-Dodecanoyl-L-Amino Acid Methyl Esters as Dermal Penetration Enhancers","volume":"85","author":"Fincher","year":"1996","journal-title":"J. Pharm. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0378-5173(99)00300-2","article-title":"Synthesis and evaluation of N-acetylprolinate esters\u2014novel skin penetration enhancers","volume":"192","author":"Tenjarla","year":"1999","journal-title":"Int. J. Pharm."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.ijpharm.2014.08.002","article-title":"Lysine-based surfactants as chemical permeation enhancers for dermal delivery of local anesthetics","volume":"474","author":"Teixeira","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.ijpharm.2017.06.083","article-title":"Pharmaceutical versatility of cationic niosomes derived from amino acid-based surfactants: Skin penetration behavior and controlled drug release","volume":"529","author":"Muzzalupo","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1002\/jps.2600730831","article-title":"Increased Skin Permeability for Lipophilic Molecules","volume":"73","author":"Cooper","year":"1984","journal-title":"J. Pharm. Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.ejps.2003.12.009","article-title":"Ceramide analogue 14S24 ((S)-2-tetracosanoylamino-3-hydroxypropionic acid tetradecyl ester) is effective in skin barrier repair in vitro","volume":"21","author":"Holas","year":"2004","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1023\/A:1015845632280","article-title":"Evidence that oleic acid exists in a separate phase within stratum corneum lipids","volume":"8","author":"Ongpipattanakul","year":"1991","journal-title":"Pharm Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"14617","DOI":"10.1038\/s41598-019-51226-5","article-title":"Esters of terpene alcohols as highly potent, reversible, and low toxic skin penetration enhancers","volume":"9","author":"Paraskevopoulos","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0168-3659(97)00168-5","article-title":"In vitro percutaneous absorption enhancement of a lipophilic drug tamoxifen by terpenes","volume":"51","author":"Gao","year":"1998","journal-title":"J. Control. Release"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1081\/DDC-100102251","article-title":"Influence of drug lipophilicity on terpenes as penetration enhancers","volume":"25","author":"Godwin","year":"1999","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1002\/jps.10160","article-title":"Terpenes in propylene glycol as skin-penetration enhancers: Permeation and partition of haloperidol, fourier transform infrared spectroscopy, and differential scanning calorimetry","volume":"91","author":"Vaddi","year":"2002","journal-title":"J. Pharm. Sci."},{"key":"ref_104","first-page":"81","article-title":"Effect of various vehicles on skin permeation of ondansetron hydrochloride, and their mechanism of permeation enhancement","volume":"4","author":"Takada","year":"2009","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/0378-5173(92)90251-V","article-title":"Surfactant effects in percutaneous absorption I. Effects on the transdermal flux of methyl nicotinate","volume":"87","author":"Ashton","year":"1992","journal-title":"Int. J. Pharm."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0378-5173(02)00554-9","article-title":"The enhancement effect of surfactants on the penetration of lorazepam through rat skin","volume":"250","author":"Nokhodchi","year":"2003","journal-title":"Int. J. Pharm."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s11743-998-0057-8","article-title":"Gemini Surfactants","volume":"1","author":"Rosen","year":"1998","journal-title":"J. Surfactants Deterg."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"685","DOI":"10.3109\/03639049309062975","article-title":"Effect of Cationic Surfactants on the Transdermal Permeation of Ionized Indomethacin","volume":"19","author":"Tan","year":"1993","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.crci.2004.02.009","article-title":"Amino acid-based surfactants","volume":"7","author":"Infante","year":"2004","journal-title":"C. R. Chim."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"13652","DOI":"10.1021\/acs.langmuir.8b02627","article-title":"Partition of Glutamic Acid-Based Single-Chain and Gemini Amphiphiles into Phospholipid Membranes","volume":"34","author":"Zhang","year":"2018","journal-title":"Langmuir"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.colsurfb.2009.03.017","article-title":"Physicochemical and toxicological properties of novel amino acid-based amphiphiles and their spontaneously formed catanionic vesicles","volume":"72","author":"Brito","year":"2009","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1002\/ejoc.201201396","article-title":"Synthesis of Gemini Surfactants and Evaluation of Their Interfacial and Cytotoxic Properties: Exploring the Multifunctionality of Serine as Headgroup","volume":"9","author":"Silva","year":"2013","journal-title":"Eur. J. Org. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.ijpharm.2012.12.034","article-title":"Skin accumulation and penetration of a hydrophilic compound by a novel gemini surfactant, sodium dilauramidoglutamide lysine","volume":"443","author":"Hikima","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1248\/cpb.c17-00965","article-title":"Design of a Topically Applied Gel Spray Formulation with Ivermectin Using a Novel Low Molecular Weight Gelling Agent, Palmitoyl-Glycine-Histidine, to Treat Scabies","volume":"66","author":"Dahlizar","year":"2018","journal-title":"Chem. Pharm. Bull."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.ijpharm.2012.10.035","article-title":"Ionic liquids as ingredients in topical drug delivery systems","volume":"441","author":"Dobler","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1039\/b907462g","article-title":"Ionic liquid-assisted transdermal delivery of sparingly soluble drugs","volume":"46","author":"Moniruzzaman","year":"2010","journal-title":"Chem. Commun."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"8162","DOI":"10.1021\/acs.jpcb.7b06231","article-title":"Unveiling the Interaction between Fatty-Acid-Modified Membrane and Hydrophilic Imidazolium-Based Ionic Liquid: Understanding the Mechanism of Ionic Liquid Cytotoxicity","volume":"121","author":"Kundu","year":"2017","journal-title":"J. Phys. Chem. B"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"3660","DOI":"10.1021\/acssuschemeng.0c03419","article-title":"Design and Characterization of Fatty Acid-Based Amino Acid Ester as a New \u201cGreen\u201d Hydrophobic Ionic Liquid for Drug Delivery","volume":"8","author":"Moshikur","year":"2020","journal-title":"ACS Sustain. Chem. Eng."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ejpb.2019.03.004","article-title":"Enhancement of water solubility of poorly water-soluble drugs by new biocompatible N-acetyl amino acid N-alkyl cholinium-based ionic liquids","volume":"137","author":"Jesus","year":"2019","journal-title":"Eur. J. Pharm. Biopharm."}],"container-title":["Membranes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0375\/11\/5\/343\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:58:04Z","timestamp":1760162284000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0375\/11\/5\/343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,7]]},"references-count":119,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["membranes11050343"],"URL":"https:\/\/doi.org\/10.3390\/membranes11050343","relation":{},"ISSN":["2077-0375"],"issn-type":[{"value":"2077-0375","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,7]]}}}