Enhanced Percutaneous Delivery of Methotrexate Using Micelles Prepared with Novel Cationic Amphipathic Material

Yun-Chun Zhao,1 Hai-Li Zheng,2 Xiao-Rong Wang,1 Xiao-Ling Zheng,1 Yue Chen,1 Wei-Dong Fei,1 Yong-Quan Zheng,1 Wen-Xi Wang,2 Cai-Hong Zheng1 1Pharmacy Department, Zhejiang University, Women’s Hospital, School of Medicine, Hangzhou, People’s Republic of China; 2College of Pharmaceu...

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Autores principales:	Zhao YC, Zheng HL, Wang XR, Zheng XL, Chen Y, Fei WD, Zheng YQ, Wang WX, Zheng CH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	n n-dimethyl-(n′ n′-di-stearoyl-1-ethyl)1 3-diaminopropane methotrexate micelle percutaneous delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/ccf42e3550874637868436d78a5f713f
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spelling	oai:doaj.org-article:ccf42e3550874637868436d78a5f713f2021-12-02T09:36:58ZEnhanced Percutaneous Delivery of Methotrexate Using Micelles Prepared with Novel Cationic Amphipathic Material1178-2013https://doaj.org/article/ccf42e3550874637868436d78a5f713f2020-05-01T00:00:00Zhttps://www.dovepress.com/enhanced-percutaneous-delivery-of-methotrexate-using-micelles-prepared-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yun-Chun Zhao,1 Hai-Li Zheng,2 Xiao-Rong Wang,1 Xiao-Ling Zheng,1 Yue Chen,1 Wei-Dong Fei,1 Yong-Quan Zheng,1 Wen-Xi Wang,2 Cai-Hong Zheng1 1Pharmacy Department, Zhejiang University, Women’s Hospital, School of Medicine, Hangzhou, People’s Republic of China; 2College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, People’s Republic of ChinaCorrespondence: Cai-Hong ZhengZhejiang University, Women’s Hospital, School of Medicine, 1 Xueshi Road, Hangzhou 310006, People’s Republic of ChinaTel +86-0571-89991730Email chzheng@zju.edu.cnWen-Xi WangCollege of Pharmaceutical Science, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou 310014, People’s Republic of ChinaTel +86-0571-88320320Email yjw@zjut.edu.cnBackground: Methotrexate (MTX) is an antiproliferative drug widely used to treat inflammatory diseases and autoimmune diseases. The application of percutaneous administration is hindered due to its poor transdermal penetration. To reduce side effects and enhanced percutaneous delivery of MTX, novel methotrexate (MTX)-loaded micelles prepared with a amphiphilic cationic material, N,N-dimethyl-(N′,N′-di-stearoyl-1-ethyl)1,3-diaminopropane (DMSAP), was designed.Materials and Methods: DMSAP was synthesized via three steps using simple chemical agents. H nuclear magnetic resonance and mass spectroscopy were used to confirm the successful synthesis of DMSAP. A safe and non-toxic phosphatidylcholine, soybean phosphatidylcholine (SPC), was added to DMSAP at different ratios to form P/D-micelles. Then, MTX-entrapped micelles (M/P/D-micelles) were prepared by electrostatic adsorption. The physicochemical properties and blood stability of micelles were examined thoroughly. In addition, the transdermal potential of the micelles was evaluated by permeation experiments.Results: In aqueous environments, DMSAP conjugates could self-assemble spontaneously into micelles with a low critical micelle concentration (CMC) of 0.056 mg/mL. Stable, spherical MTX-entrapped micelles (M/P/D-micelles) with a size of 100– 120 nm and high zeta potential of +36.26 mV were prepared. In vitro permeation studies showed that M/P/D-micelles exhibited superior skin permeability and deposition of MTX in the epidermis and dermis compared with that of free MTX.Conclusion: These special novel cationic M/P/D-micelles can enhance the permeability of MTX and are expected to be a promising percutaneous delivery system for therapy skin diseases.Keywords: N N-dimethyl-(N′ N′-di-stearoyl-1-ethyl)1, 3-diaminopropane, methotrexate, micelle, percutaneous deliveryZhao YCZheng HLWang XRZheng XLChen YFei WDZheng YQWang WXZheng CHDove Medical Pressarticlenn-dimethyl-(n′n′-di-stearoyl-1-ethyl)13-diaminopropanemethotrexatemicellepercutaneous deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 3539-3550 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	n n-dimethyl-(n′ n′-di-stearoyl-1-ethyl)1 3-diaminopropane methotrexate micelle percutaneous delivery Medicine (General) R5-920
spellingShingle	n n-dimethyl-(n′ n′-di-stearoyl-1-ethyl)1 3-diaminopropane methotrexate micelle percutaneous delivery Medicine (General) R5-920 Zhao YC Zheng HL Wang XR Zheng XL Chen Y Fei WD Zheng YQ Wang WX Zheng CH Enhanced Percutaneous Delivery of Methotrexate Using Micelles Prepared with Novel Cationic Amphipathic Material
description	Yun-Chun Zhao,1 Hai-Li Zheng,2 Xiao-Rong Wang,1 Xiao-Ling Zheng,1 Yue Chen,1 Wei-Dong Fei,1 Yong-Quan Zheng,1 Wen-Xi Wang,2 Cai-Hong Zheng1 1Pharmacy Department, Zhejiang University, Women’s Hospital, School of Medicine, Hangzhou, People’s Republic of China; 2College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, People’s Republic of ChinaCorrespondence: Cai-Hong ZhengZhejiang University, Women’s Hospital, School of Medicine, 1 Xueshi Road, Hangzhou 310006, People’s Republic of ChinaTel +86-0571-89991730Email chzheng@zju.edu.cnWen-Xi WangCollege of Pharmaceutical Science, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou 310014, People’s Republic of ChinaTel +86-0571-88320320Email yjw@zjut.edu.cnBackground: Methotrexate (MTX) is an antiproliferative drug widely used to treat inflammatory diseases and autoimmune diseases. The application of percutaneous administration is hindered due to its poor transdermal penetration. To reduce side effects and enhanced percutaneous delivery of MTX, novel methotrexate (MTX)-loaded micelles prepared with a amphiphilic cationic material, N,N-dimethyl-(N′,N′-di-stearoyl-1-ethyl)1,3-diaminopropane (DMSAP), was designed.Materials and Methods: DMSAP was synthesized via three steps using simple chemical agents. H nuclear magnetic resonance and mass spectroscopy were used to confirm the successful synthesis of DMSAP. A safe and non-toxic phosphatidylcholine, soybean phosphatidylcholine (SPC), was added to DMSAP at different ratios to form P/D-micelles. Then, MTX-entrapped micelles (M/P/D-micelles) were prepared by electrostatic adsorption. The physicochemical properties and blood stability of micelles were examined thoroughly. In addition, the transdermal potential of the micelles was evaluated by permeation experiments.Results: In aqueous environments, DMSAP conjugates could self-assemble spontaneously into micelles with a low critical micelle concentration (CMC) of 0.056 mg/mL. Stable, spherical MTX-entrapped micelles (M/P/D-micelles) with a size of 100– 120 nm and high zeta potential of +36.26 mV were prepared. In vitro permeation studies showed that M/P/D-micelles exhibited superior skin permeability and deposition of MTX in the epidermis and dermis compared with that of free MTX.Conclusion: These special novel cationic M/P/D-micelles can enhance the permeability of MTX and are expected to be a promising percutaneous delivery system for therapy skin diseases.Keywords: N N-dimethyl-(N′ N′-di-stearoyl-1-ethyl)1, 3-diaminopropane, methotrexate, micelle, percutaneous delivery
format	article
author	Zhao YC Zheng HL Wang XR Zheng XL Chen Y Fei WD Zheng YQ Wang WX Zheng CH
author_facet	Zhao YC Zheng HL Wang XR Zheng XL Chen Y Fei WD Zheng YQ Wang WX Zheng CH
author_sort	Zhao YC
title	Enhanced Percutaneous Delivery of Methotrexate Using Micelles Prepared with Novel Cationic Amphipathic Material
title_short	Enhanced Percutaneous Delivery of Methotrexate Using Micelles Prepared with Novel Cationic Amphipathic Material
title_full	Enhanced Percutaneous Delivery of Methotrexate Using Micelles Prepared with Novel Cationic Amphipathic Material
title_fullStr	Enhanced Percutaneous Delivery of Methotrexate Using Micelles Prepared with Novel Cationic Amphipathic Material
title_full_unstemmed	Enhanced Percutaneous Delivery of Methotrexate Using Micelles Prepared with Novel Cationic Amphipathic Material
title_sort	enhanced percutaneous delivery of methotrexate using micelles prepared with novel cationic amphipathic material
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/ccf42e3550874637868436d78a5f713f
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Enhanced Percutaneous Delivery of Methotrexate Using Micelles Prepared with Novel Cationic Amphipathic Material

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