Continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth

Xiaonan Guo,1,* Xiaoshuang Zhu,1,* Dakan Liu,1 Yubin Gong,1 Jing Sun,2 Changxian Dong1 1Department of Hemangioma and Vascular Malformation, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Pharmacy, Second Military Medical University, Sha...

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Autores principales:	Guo XN, Zhu XS, Liu DK, Gong YB, Sun J, Dong CX
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	propranolol liposomes microsphere controlled release hemangioma Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/74f2fe4a38a149468b5fdba50f39cadc
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spelling	oai:doaj.org-article:74f2fe4a38a149468b5fdba50f39cadc2021-12-02T07:46:15ZContinuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth1178-2013https://doaj.org/article/74f2fe4a38a149468b5fdba50f39cadc2017-09-01T00:00:00Zhttps://www.dovepress.com/continuous-delivery-of-propranolol-from-liposomes-in-microspheres-sign-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiaonan Guo,1,* Xiaoshuang Zhu,1,* Dakan Liu,1 Yubin Gong,1 Jing Sun,2 Changxian Dong1 1Department of Hemangioma and Vascular Malformation, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: To reduce the adverse effects and high frequency of administration of propranolol to treat infantile hemangioma, we first utilized propranolol-loaded liposomes-in-microsphere (PLIM) as a novel topical release system to realize sustained release of propranolol.Methods: PLIM was developed from encapsulating propranolol-loaded liposomes (PLs) in microspheres made of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) copolymers (PLGA-PEG-PLGA). The release profile of propranolol from PLIM was evaluated, and its biological activity was investigated in vitro using proliferation assays on hemangioma stem cells (HemSCs). Tumor inhibition was studied in nude mice bearing human subcutaneous infantile hemangioma.Results: The microspheres were of desired particle size (~77.8 µm) and drug encapsulation efficiency (~23.9%) and achieved sustained drug release for 40 days. PLIM exerted efficient inhibition of the proliferation of HemSCs and significantly reduced the expression of two angiogenesis factors (vascular endothelial growth factor-A [VEGF-A] and basic fibroblast growth factor [bFGF]) in HemSCs. Notably, the therapeutic effect of PLIM in hemangioma was superior to that of propranolol and PL in vivo, as reflected by significantly reduced hemangioma volume, weight, and microvessel density. The mean hemangioma weight of the PLIM-treated group was significantly lower than that of other groups (saline =0.28 g, propranolol =0.21 g, PL =0.13 g, PLIM =0.03 g; PLIM vs saline: P<0.001, PLIM vs propranolol: P<0.001, PLIM vs PL: P<0.001). The mean microvessel density of the PLIM-treated group was significantly lower than that of other groups (saline =40 vessels/mm2, propranolol =31 vessels/mm2, PL =25 vessels/mm2, PLIM =11 vessels/mm2; PLIM vs saline: P<0.001, PLIM vs propranolol: P<0.01, PLIM vs PL: P<0.05).Conclusion: Our findings show that PLIM is a very promising approach to locally and efficiently deliver propranolol to the hemangioma site leading to a significant inhibition of infantile hemangioma. Keywords: propranolol, liposomes, microsphere, controlled release, hemangiomaGuo XNZhu XSLiu DKGong YBSun JDong CXDove Medical Pressarticlepropranololliposomesmicrospherecontrolled releasehemangiomaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 6923-6936 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	propranolol liposomes microsphere controlled release hemangioma Medicine (General) R5-920
spellingShingle	propranolol liposomes microsphere controlled release hemangioma Medicine (General) R5-920 Guo XN Zhu XS Liu DK Gong YB Sun J Dong CX Continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth
description	Xiaonan Guo,1,* Xiaoshuang Zhu,1,* Dakan Liu,1 Yubin Gong,1 Jing Sun,2 Changxian Dong1 1Department of Hemangioma and Vascular Malformation, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 2Department of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Purpose: To reduce the adverse effects and high frequency of administration of propranolol to treat infantile hemangioma, we first utilized propranolol-loaded liposomes-in-microsphere (PLIM) as a novel topical release system to realize sustained release of propranolol.Methods: PLIM was developed from encapsulating propranolol-loaded liposomes (PLs) in microspheres made of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) copolymers (PLGA-PEG-PLGA). The release profile of propranolol from PLIM was evaluated, and its biological activity was investigated in vitro using proliferation assays on hemangioma stem cells (HemSCs). Tumor inhibition was studied in nude mice bearing human subcutaneous infantile hemangioma.Results: The microspheres were of desired particle size (~77.8 µm) and drug encapsulation efficiency (~23.9%) and achieved sustained drug release for 40 days. PLIM exerted efficient inhibition of the proliferation of HemSCs and significantly reduced the expression of two angiogenesis factors (vascular endothelial growth factor-A [VEGF-A] and basic fibroblast growth factor [bFGF]) in HemSCs. Notably, the therapeutic effect of PLIM in hemangioma was superior to that of propranolol and PL in vivo, as reflected by significantly reduced hemangioma volume, weight, and microvessel density. The mean hemangioma weight of the PLIM-treated group was significantly lower than that of other groups (saline =0.28 g, propranolol =0.21 g, PL =0.13 g, PLIM =0.03 g; PLIM vs saline: P<0.001, PLIM vs propranolol: P<0.001, PLIM vs PL: P<0.001). The mean microvessel density of the PLIM-treated group was significantly lower than that of other groups (saline =40 vessels/mm2, propranolol =31 vessels/mm2, PL =25 vessels/mm2, PLIM =11 vessels/mm2; PLIM vs saline: P<0.001, PLIM vs propranolol: P<0.01, PLIM vs PL: P<0.05).Conclusion: Our findings show that PLIM is a very promising approach to locally and efficiently deliver propranolol to the hemangioma site leading to a significant inhibition of infantile hemangioma. Keywords: propranolol, liposomes, microsphere, controlled release, hemangioma
format	article
author	Guo XN Zhu XS Liu DK Gong YB Sun J Dong CX
author_facet	Guo XN Zhu XS Liu DK Gong YB Sun J Dong CX
author_sort	Guo XN
title	Continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth
title_short	Continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth
title_full	Continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth
title_fullStr	Continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth
title_full_unstemmed	Continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth
title_sort	continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/74f2fe4a38a149468b5fdba50f39cadc
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Continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth

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