title: Transdermal enhancement effect and mechanism of iontophoresis for non-steroidal anti-inflammatory drugs.
abstract: Iontophoresis is an important approach to improve transdermal drug delivery. However, The transdermal enhancement mechanism of iontophoresis was not well known. The relationship between the physicochemical properties of drugs and the transdermal enhancement effect of iontophoresis was revealed in this study. Non-steroidal anti-inflammatory drugs (NSAIDs) were used as the models, including aspirin, ibuprofen and indomethacin. Their oil-water partition coefficients were measured. The carbomer-based hydrogels of them were prepared. Iontophoresis significantly enhanced in vitro transdermal delivery across the rat skins. Strong lipophilicity could lead to high permeation of drugs. However, the dissociation extent (indicated as pKa) of drugs was the key factor to determine the transdermal enhancement effect of iontophoresis. The more dissociation the drugs were, the higher the transdermal enhancement effect of iontophoresis. The drug-loaded hydrogels combined with iontophoresis improved the treatment of rat raw's inflammatory syndrome. Iontophoresis significantly improved the drugs penetrating into the hypodermis, dermis and epidermis, more deeply than the application of drugs alone according to the experimental result of 5-carboxylfluorescein hydrogels. Iontophoresis led to the unordered arrangement of skin intercellular lipids, the significantly increased flowability and loose stratum corneum structure. Iontophoresis is a promising approach to improve transdermal drug delivery with safety and high efficiency.
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, PR China; Department of Graduates, Anhui Medical University, Hefei 230001, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zuo
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, PR China; Pharmaceutical College of Henan University, Kaifeng 475004, PR China; Department of Pharmacy, Bengbu Medical College, Bengbu 233030, PR China. Electronic address: dulina@188.com.
authors.forename: Lina
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors.forename: Miao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, PR China; Pharmaceutical College of Henan University, Kaifeng 475004, PR China.
authors.forename: Boming
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, PR China; Department of Pharmacy, Bengbu Medical College, Bengbu 233030, PR China.
authors.forename: Weinan
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, PR China; Department of Graduates, Anhui Medical University, Hefei 230001, PR China; Pharmaceutical College of Henan University, Kaifeng 475004, PR China; Department of Pharmacy, Bengbu Medical College, Bengbu 233030, PR China. Electronic address: jinyg@bmi.ac.cn.
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Jin
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry; D001241:Aspirin / Q000008:administration & dosage / Q000737:chemistry; D002351:Carrageenan; D004058:Diffusion; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D005528:Foot / Q000473:pathology; D007052:Ibuprofen / Q000008:administration & dosage / Q000737:chemistry; D066298:In Vitro Techniques; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry; D007478:Iontophoresis; D008297:Male; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism; D014867:Water / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014867:Water; D002351:Carrageenan; D020003:1-Octanol; D001241:Aspirin; D007052:Ibuprofen; D007213:Indomethacin
keywords: Dissociation; Iontophoresis; Non-steroidal anti-inflammatory drugs; Oil-water partition coefficients; Transdermal drug delivery