Topical Delivery of Four Neuroprotective Ingredients by Ethosome-Gel: Synergistic Combination for Treatment of Oxaliplatin-Induced Peripheral Neuropathy

Hong-mei Lin,1,* Long-fei Lin,2,* Ming-yi Sun,3 Jia Liu,3 Qing Wu3 1Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 2Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 1...

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Autores principales:	Lin HM, Lin LF, Sun MY, Liu J, Wu Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	hydroxysafflor yellow a icariin epimedin b 3 4-dihydroxybenzoic acid (da) oxaliplatin-induced neuropathy ethosomes gel Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/33e1cc42f9044504971f4eaf0a0bba54
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spelling	oai:doaj.org-article:33e1cc42f9044504971f4eaf0a0bba542021-12-02T13:12:07ZTopical Delivery of Four Neuroprotective Ingredients by Ethosome-Gel: Synergistic Combination for Treatment of Oxaliplatin-Induced Peripheral Neuropathy1178-2013https://doaj.org/article/33e1cc42f9044504971f4eaf0a0bba542020-05-01T00:00:00Zhttps://www.dovepress.com/topical-delivery-of-four-neuroprotective-ingredients-by-ethosome-gel-s-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Hong-mei Lin,1,* Long-fei Lin,2,* Ming-yi Sun,3 Jia Liu,3 Qing Wu3 1Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 2Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, People’s Republic of China; 3Department of TCM Pharmaceutics, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing WuDepartment of TCM Pharmaceutics, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of ChinaTel +86 10 84738603Fax +86 10 84738611Email qwu@vip.sina.comBackground: Peripheral neuropathy is a common and painful side effect that occurs in patients with cancer induced by Oxaliplatin (OXL). The neurotoxicity correlates with the damage of dorsal root ganglion (DRG) neurons and Schwann cells (SCs). Hydroxysafflor yellow A (HSYA), icariin, epimedin B and 3, 4-dihydroxybenzoic acid (DA) are the main neuroprotective ingredients identified in Wen-Luo-Tong (WLT), a traditional Chinese medicinal topical compound. The purpose of this study was to prepare and evaluate the efficacy of an ethosomes gel formulation loaded with a combination of HSYA, icariin, epimedin B and DA. However, the low LogP value, poor solubility and macromolecule are several challenges for topical delivery of these drugs.Methods: Ethosomes were prepared by the single-step injection technique. Particle size, entrapment efficiency and in vitro drug deposition studies were determined to select the optimum ethosomes. The optimized ethosomes were further incorporated into carbopol to obtain a gel. The rheological properties, morphology, in vitro drug release, in vitro gel application and skin distribution of the ethosomes gels were studied. A rat model of oxaliplatin-induced neuropathy was established to assess the therapeutic efficacy of the ethosomes gel.Results: Seventy percent (v/v) ethanol, cinnamaldehyde and Phospholipon 90G were employed to develop ethosomes a carrier system. This system had a high entrapment efficiency, carried large amounts of HSYA, epimedin B, DA and icarrin, and penetrated deep into the epidermis and dermis. The optimized ethosomes had the maximum deposition of icariin, HSYA, epimedin B and relative higher amount of DA in epidermis (2.00± 0.13 μg/cm2, 5.72± 0.75 μg/cm2, 1.97± 0.27 μg/cm2 and 9.25± 1.21 μg/cm2, respectively). 0.5% carbopol 980 was selected to develop the ethosomes gel with desirable viscoelasticity and spreadability, which was suitable for topical application. The mechanical allodynia and hyperalgesia induced by OXL in rats were significantly reduced after the new ethosomes gel was applied to rats compared to model group.Conclusion: Based on our findings, the ethosomes gel delivery system provided a new formulation for the topical delivery of HSYA, icariin, epimedin B and DA to counteract OXL-induced peripheral neuropathy.Keywords: hydroxysafflor yellow A, icariin, epimedin B, 3, 4-dihydroxybenzoic acid, DA, oxaliplatin-induced neuropathy, ethosomes gelLin HMLin LFSun MYLiu JWu QDove Medical Pressarticlehydroxysafflor yellow aicariinepimedin b34-dihydroxybenzoic acid (da)oxaliplatin-induced neuropathyethosomes gelMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 3251-3266 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	hydroxysafflor yellow a icariin epimedin b 3 4-dihydroxybenzoic acid (da) oxaliplatin-induced neuropathy ethosomes gel Medicine (General) R5-920
spellingShingle	hydroxysafflor yellow a icariin epimedin b 3 4-dihydroxybenzoic acid (da) oxaliplatin-induced neuropathy ethosomes gel Medicine (General) R5-920 Lin HM Lin LF Sun MY Liu J Wu Q Topical Delivery of Four Neuroprotective Ingredients by Ethosome-Gel: Synergistic Combination for Treatment of Oxaliplatin-Induced Peripheral Neuropathy
description	Hong-mei Lin,1,* Long-fei Lin,2,* Ming-yi Sun,3 Jia Liu,3 Qing Wu3 1Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China; 2Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, People’s Republic of China; 3Department of TCM Pharmaceutics, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing WuDepartment of TCM Pharmaceutics, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, People’s Republic of ChinaTel +86 10 84738603Fax +86 10 84738611Email qwu@vip.sina.comBackground: Peripheral neuropathy is a common and painful side effect that occurs in patients with cancer induced by Oxaliplatin (OXL). The neurotoxicity correlates with the damage of dorsal root ganglion (DRG) neurons and Schwann cells (SCs). Hydroxysafflor yellow A (HSYA), icariin, epimedin B and 3, 4-dihydroxybenzoic acid (DA) are the main neuroprotective ingredients identified in Wen-Luo-Tong (WLT), a traditional Chinese medicinal topical compound. The purpose of this study was to prepare and evaluate the efficacy of an ethosomes gel formulation loaded with a combination of HSYA, icariin, epimedin B and DA. However, the low LogP value, poor solubility and macromolecule are several challenges for topical delivery of these drugs.Methods: Ethosomes were prepared by the single-step injection technique. Particle size, entrapment efficiency and in vitro drug deposition studies were determined to select the optimum ethosomes. The optimized ethosomes were further incorporated into carbopol to obtain a gel. The rheological properties, morphology, in vitro drug release, in vitro gel application and skin distribution of the ethosomes gels were studied. A rat model of oxaliplatin-induced neuropathy was established to assess the therapeutic efficacy of the ethosomes gel.Results: Seventy percent (v/v) ethanol, cinnamaldehyde and Phospholipon 90G were employed to develop ethosomes a carrier system. This system had a high entrapment efficiency, carried large amounts of HSYA, epimedin B, DA and icarrin, and penetrated deep into the epidermis and dermis. The optimized ethosomes had the maximum deposition of icariin, HSYA, epimedin B and relative higher amount of DA in epidermis (2.00± 0.13 μg/cm2, 5.72± 0.75 μg/cm2, 1.97± 0.27 μg/cm2 and 9.25± 1.21 μg/cm2, respectively). 0.5% carbopol 980 was selected to develop the ethosomes gel with desirable viscoelasticity and spreadability, which was suitable for topical application. The mechanical allodynia and hyperalgesia induced by OXL in rats were significantly reduced after the new ethosomes gel was applied to rats compared to model group.Conclusion: Based on our findings, the ethosomes gel delivery system provided a new formulation for the topical delivery of HSYA, icariin, epimedin B and DA to counteract OXL-induced peripheral neuropathy.Keywords: hydroxysafflor yellow A, icariin, epimedin B, 3, 4-dihydroxybenzoic acid, DA, oxaliplatin-induced neuropathy, ethosomes gel
format	article
author	Lin HM Lin LF Sun MY Liu J Wu Q
author_facet	Lin HM Lin LF Sun MY Liu J Wu Q
author_sort	Lin HM
title	Topical Delivery of Four Neuroprotective Ingredients by Ethosome-Gel: Synergistic Combination for Treatment of Oxaliplatin-Induced Peripheral Neuropathy
title_short	Topical Delivery of Four Neuroprotective Ingredients by Ethosome-Gel: Synergistic Combination for Treatment of Oxaliplatin-Induced Peripheral Neuropathy
title_full	Topical Delivery of Four Neuroprotective Ingredients by Ethosome-Gel: Synergistic Combination for Treatment of Oxaliplatin-Induced Peripheral Neuropathy
title_fullStr	Topical Delivery of Four Neuroprotective Ingredients by Ethosome-Gel: Synergistic Combination for Treatment of Oxaliplatin-Induced Peripheral Neuropathy
title_full_unstemmed	Topical Delivery of Four Neuroprotective Ingredients by Ethosome-Gel: Synergistic Combination for Treatment of Oxaliplatin-Induced Peripheral Neuropathy
title_sort	topical delivery of four neuroprotective ingredients by ethosome-gel: synergistic combination for treatment of oxaliplatin-induced peripheral neuropathy
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/33e1cc42f9044504971f4eaf0a0bba54
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Topical Delivery of Four Neuroprotective Ingredients by Ethosome-Gel: Synergistic Combination for Treatment of Oxaliplatin-Induced Peripheral Neuropathy

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