title: Use of lipolanthionine peptide, a toll-like receptor 2 inhibitor, enhances transdermal delivery efficiency.
abstract: The transdermal delivery system (TDS) is able to obtain a systemic therapeutic effect by administration through the skin, which has low side effects and is able to maintain a sustained blood concentration. However, due to the barrier presented by the stratum corneum, numerous drugs have poor percutaneous permeability. Therefore, the improvement of skin permeability is key to TDS. The main method of promoting transdermal absorption is through the usage of penetration enhancers. Dimethyl sulfoxide (DMSO) is a commonly used penetration enhancer, which has anti‑inflammatory analgesic effects and is able to penetrate the skin. Retinoic acid (RA) and lipolanthionine peptide (LP) may also benefit the permeation efficiency of TDS. Therefore, the present study examined the function of DMSO, RA and LP as penetration enhancers in TDS. Firstly, the optimum concentration of DMSO was confirmed by detecting the expression of the LacZ gene in vitro. Secondly, different combinations of LP, RA and DMSO were applied to mouse skin to analyze the penetration enhancer combination with the greatest efficacy. All the animals were divided into five groups: The RA + LP + DMSO + pORF‑LacZ group, the RA + DMSO + pORF‑LacZ group, the LP + DMSO + pORF‑LacZ group, the DMSO + pORF-LacZ group and the control group. Skin was soaked in combinations of LP, RA and DMSO for seven days and then the pORF‑LacZ plasmids were daubed onto the skin once daily three days. On the 11th day, all the animals were sacrificed by cervical dislocation and the skin and blood samples were collected. The blood samples were used to detect the expression of the LacZ gene by quantitative polymerase chain reaction and the skin samples were used to detect the expression of claudin‑4 and zonula occluden‑1 (ZO‑1) proteins by immunohistochemistry and western blot analysis. The results demonstrated that the combination of LP, RA and DMSO exhibited the greatest transdermal delivery efficiency, which verified that RA and LP were able to increase the penetration effects. Following treatment with LP, the symptoms of dermal edema were relieved and the capillaries contracted, which suggested that LP was a safe and effective penetration enhancer able to reduce the side‑effects caused by DMSO. The present study provides a guideline for the synthesis of novel penetration enhancers.
authors.affiliation: Department of Plastic Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Plastic Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, P.R. China.
authors.forename: Da-Lie
authors.initials: DL
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Liuzhou Worker's Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, P.R. China.
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Pan
authors.affiliation: Department of Plastic Surgery, Liuzhou Worker's Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, P.R. China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Yang
authors.affiliation: Department of Plastic Surgery, Liuzhou Worker's Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, P.R. China.
authors.forename: Jia-Bao
authors.initials: JB
authors.lastname: Shou
authors.affiliation: Department of Rehabilitation Medicine, Liuzhou Worker's Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, P.R. China.
authors.forename: Ju-Hua
authors.initials: JH
authors.lastname: Wu
authors.affiliation: Department of Plastic Surgery, Liuzhou Worker's Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, P.R. China.
authors.forename: Qing-Long
authors.initials: QL
authors.lastname: Mao
authors.affiliation: Department of Plastic Surgery, Liuzhou Worker's Hospital, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D062506:Claudin-4 / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects*; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D062506:Claudin-4; D010455:Peptides; D051195:Toll-Like Receptor 2; D062826:Zonula Occludens-1 Protein; D014212:Tretinoin; D004121:Dimethyl Sulfoxide