Angiopep-2-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) polymersomes for dual-targeting drug delivery to glioma in rats
Fei Lu,1,2 Zhiyong Pang,2,3 Jingjing Zhao,2 Kai Jin,4 Haichun Li,2 Qiang Pang,2 Long Zhang,2 Zhiqing Pang2 1Department of Pharmacy, Xianju People’s Hospital, Xianju, Zhejiang, 2Department of Pharmaceutics, Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pha...
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doaj-014376443db64db6a24101d330ab65632020-11-24T20:43:09ZengDove Medical PressInternational Journal of Nanomedicine1178-20132017-03-01Volume 122117212731902Angiopep-2-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) polymersomes for dual-targeting drug delivery to glioma in ratsLu FPang ZZhao JJin KLi HPang QZhang LPang ZFei Lu,1,2 Zhiyong Pang,2,3 Jingjing Zhao,2 Kai Jin,4 Haichun Li,2 Qiang Pang,2 Long Zhang,2 Zhiqing Pang2 1Department of Pharmacy, Xianju People’s Hospital, Xianju, Zhejiang, 2Department of Pharmaceutics, Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, 3Chongyang Center for Disease Control and Prevention, Xianning, Hubei, 4School of Life Science, Fudan University, Shanghai, People’s Republic of China Abstract: The blood–brain barrier is a formidable obstacle for glioma chemotherapy due to its compact structure and drug efflux ability. In this study, a dual-targeting drug delivery system involving Angiopep-2-conjugated biodegradable polymersomes loaded with doxorubicin (Ang-PS-DOX) was developed to exploit transport by the low-density lipoprotein receptor-related protein 1 (LRP1), which is overexpressed in both blood–brain barrier and glioma cells. The polymersomes (PS) were prepared using a thin-film hydration method. The PS were loaded with doxorubicin using the pH gradient method (Ang-PS-DOX). The resulting PS were uniformly spherical, with diameters of ~135 nm and with ~159.9 Angiopep-2 molecules on the surface of each PS. The drug-loading capacity and the encapsulation efficiency for doxorubicin were 7.94%±0.17% and 95.0%±1.6%, respectively. Permeability tests demonstrated that the proton diffusion coefficient across the PS membrane was far slower than that across the liposome membrane, and the common logarithm value was linearly dependent on the dioxane content in the external phase. Compared with PS-DOX, Ang-PS-DOX demonstrated significantly higher cellular uptake and stronger cytotoxicity in C6 cells. In vivo pharmacokinetics and brain distribution experiments revealed that Ang-PS-DOX achieved a more extensive distribution and more abundant accumulation in glioma cells than PS-DOX. Moreover, the survival time of glioma-bearing rats treated with Ang-PS-DOX was significantly prolonged compared with those treated with PS-DOX or a solution of free doxorubicin. These results suggested that Ang-PS-DOX can target glioma cells and enhance chemotherapeutic efficacy. Keywords: Angiopep-2, dual targeting, biodegradable polymersomes, doxorubicin, glioma treatmenthttps://www.dovepress.com/angiopep-2-conjugated-polyethylene-glycol-co-polye-caprolactone-polyme-peer-reviewed-article-IJNAngiopep-2dual targetingbiodegradable polymersomesdoxorubicinglioma treatment |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lu F Pang Z Zhao J Jin K Li H Pang Q Zhang L Pang Z |
spellingShingle |
Lu F Pang Z Zhao J Jin K Li H Pang Q Zhang L Pang Z Angiopep-2-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) polymersomes for dual-targeting drug delivery to glioma in rats International Journal of Nanomedicine Angiopep-2 dual targeting biodegradable polymersomes doxorubicin glioma treatment |
author_facet |
Lu F Pang Z Zhao J Jin K Li H Pang Q Zhang L Pang Z |
author_sort |
Lu F |
title |
Angiopep-2-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) polymersomes for dual-targeting drug delivery to glioma in rats |
title_short |
Angiopep-2-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) polymersomes for dual-targeting drug delivery to glioma in rats |
title_full |
Angiopep-2-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) polymersomes for dual-targeting drug delivery to glioma in rats |
title_fullStr |
Angiopep-2-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) polymersomes for dual-targeting drug delivery to glioma in rats |
title_full_unstemmed |
Angiopep-2-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) polymersomes for dual-targeting drug delivery to glioma in rats |
title_sort |
angiopep-2-conjugated poly(ethylene glycol)-co-poly(ε-caprolactone) polymersomes for dual-targeting drug delivery to glioma in rats |
publisher |
Dove Medical Press |
series |
International Journal of Nanomedicine |
issn |
1178-2013 |
publishDate |
2017-03-01 |
description |
Fei Lu,1,2 Zhiyong Pang,2,3 Jingjing Zhao,2 Kai Jin,4 Haichun Li,2 Qiang Pang,2 Long Zhang,2 Zhiqing Pang2 1Department of Pharmacy, Xianju People’s Hospital, Xianju, Zhejiang, 2Department of Pharmaceutics, Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, 3Chongyang Center for Disease Control and Prevention, Xianning, Hubei, 4School of Life Science, Fudan University, Shanghai, People’s Republic of China Abstract: The blood–brain barrier is a formidable obstacle for glioma chemotherapy due to its compact structure and drug efflux ability. In this study, a dual-targeting drug delivery system involving Angiopep-2-conjugated biodegradable polymersomes loaded with doxorubicin (Ang-PS-DOX) was developed to exploit transport by the low-density lipoprotein receptor-related protein 1 (LRP1), which is overexpressed in both blood–brain barrier and glioma cells. The polymersomes (PS) were prepared using a thin-film hydration method. The PS were loaded with doxorubicin using the pH gradient method (Ang-PS-DOX). The resulting PS were uniformly spherical, with diameters of ~135 nm and with ~159.9 Angiopep-2 molecules on the surface of each PS. The drug-loading capacity and the encapsulation efficiency for doxorubicin were 7.94%±0.17% and 95.0%±1.6%, respectively. Permeability tests demonstrated that the proton diffusion coefficient across the PS membrane was far slower than that across the liposome membrane, and the common logarithm value was linearly dependent on the dioxane content in the external phase. Compared with PS-DOX, Ang-PS-DOX demonstrated significantly higher cellular uptake and stronger cytotoxicity in C6 cells. In vivo pharmacokinetics and brain distribution experiments revealed that Ang-PS-DOX achieved a more extensive distribution and more abundant accumulation in glioma cells than PS-DOX. Moreover, the survival time of glioma-bearing rats treated with Ang-PS-DOX was significantly prolonged compared with those treated with PS-DOX or a solution of free doxorubicin. These results suggested that Ang-PS-DOX can target glioma cells and enhance chemotherapeutic efficacy. Keywords: Angiopep-2, dual targeting, biodegradable polymersomes, doxorubicin, glioma treatment |
topic |
Angiopep-2 dual targeting biodegradable polymersomes doxorubicin glioma treatment |
url |
https://www.dovepress.com/angiopep-2-conjugated-polyethylene-glycol-co-polye-caprolactone-polyme-peer-reviewed-article-IJN |
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