Characterization and antitumor efficacy of poly(L-lactid acid)-based etoposide-loaded implants

Etoposide is widely used in the chemotherapy of a variety of malignancies. But the strong lipophilicity, poor bioavailability, and severe side effects of etoposide limit its clinical application. The aim of this study was to develop sustained-release etoposide-loaded implants and evaluate antitumor...

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Main Authors: Li Gao, Chuanqi Xie, Yuzhi Du, Xiaodong Wang, Erkang Xuan, Xiuxiu Liu, Yang Zhao, Jianjian Xu, Lan Luo
Format: Article
Language:English
Published: Taylor & Francis Group 2017-01-01
Series:Drug Delivery
Subjects:
Online Access:http://dx.doi.org/10.1080/10717544.2017.1321063
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author Li Gao
Chuanqi Xie
Yuzhi Du
Xiaodong Wang
Erkang Xuan
Xiuxiu Liu
Yang Zhao
Jianjian Xu
Lan Luo
author_facet Li Gao
Chuanqi Xie
Yuzhi Du
Xiaodong Wang
Erkang Xuan
Xiuxiu Liu
Yang Zhao
Jianjian Xu
Lan Luo
author_sort Li Gao
collection DOAJ
description Etoposide is widely used in the chemotherapy of a variety of malignancies. But the strong lipophilicity, poor bioavailability, and severe side effects of etoposide limit its clinical application. The aim of this study was to develop sustained-release etoposide-loaded implants and evaluate antitumor activity of the implants after intratumoral implantation. We prepared the implants containing etoposide, poly(L-lactid acid) and polyethylene glycol 4000 by the direct compression method. The implants were characterized regarding drug-excipient compatibility, content uniformity, morphology, sterility, in vitro, and in vivo release profiles. Then the antitumor activity of the implants was tested in xenograft model of A549 human non-small cell lung cancer. SEM images displayed smooth surface of the implant and indicated that etoposide was homogeneously dispersed in the polymeric matrix. The results of content uniformity met the requirements of the Chinese Pharmacopoeia. Both in vitro and in vivo release profiles of the implants were characterized by high burst release followed by sustained release of etoposide. Intratumoral implantation of etoposide-loaded implants could efficiently delay the tumor growth. Furthermore, increasing the dose of implants led to higher tumor suppression rate without adding systemic toxicity. These results indicated that etoposide-loaded implants have significant antitumor efficacy in xenograft model without dose-limiting side effects and they possess a strong potential to be used as an intratumoral chemotherapy option for lung cancer treatment.
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spelling doaj.art-f24ac935554c4fe693b8dc792ce4eb7b2022-12-21T18:12:09ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642017-01-0124176577410.1080/10717544.2017.13210631321063Characterization and antitumor efficacy of poly(L-lactid acid)-based etoposide-loaded implantsLi Gao0Chuanqi Xie1Yuzhi Du2Xiaodong Wang3Erkang Xuan4Xiuxiu Liu5Yang Zhao6Jianjian Xu7Lan Luo8State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing UniversityAnhui Zhongren Science and Technology Co., LtdSchool of Biological and Medical Engineering, Hefei University of TechnologyAnhui Zhongren Science and Technology Co., LtdAnhui Zhongren Science and Technology Co., LtdSchool of Biological and Medical Engineering, Hefei University of TechnologyThe Second People’s Hospital of HefeiSchool of Biological and Medical Engineering, Hefei University of TechnologyState Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing UniversityEtoposide is widely used in the chemotherapy of a variety of malignancies. But the strong lipophilicity, poor bioavailability, and severe side effects of etoposide limit its clinical application. The aim of this study was to develop sustained-release etoposide-loaded implants and evaluate antitumor activity of the implants after intratumoral implantation. We prepared the implants containing etoposide, poly(L-lactid acid) and polyethylene glycol 4000 by the direct compression method. The implants were characterized regarding drug-excipient compatibility, content uniformity, morphology, sterility, in vitro, and in vivo release profiles. Then the antitumor activity of the implants was tested in xenograft model of A549 human non-small cell lung cancer. SEM images displayed smooth surface of the implant and indicated that etoposide was homogeneously dispersed in the polymeric matrix. The results of content uniformity met the requirements of the Chinese Pharmacopoeia. Both in vitro and in vivo release profiles of the implants were characterized by high burst release followed by sustained release of etoposide. Intratumoral implantation of etoposide-loaded implants could efficiently delay the tumor growth. Furthermore, increasing the dose of implants led to higher tumor suppression rate without adding systemic toxicity. These results indicated that etoposide-loaded implants have significant antitumor efficacy in xenograft model without dose-limiting side effects and they possess a strong potential to be used as an intratumoral chemotherapy option for lung cancer treatment.http://dx.doi.org/10.1080/10717544.2017.1321063etoposideimplantpoly(l-lactid acid)sustained releaseintratumoral chemotherapy
spellingShingle Li Gao
Chuanqi Xie
Yuzhi Du
Xiaodong Wang
Erkang Xuan
Xiuxiu Liu
Yang Zhao
Jianjian Xu
Lan Luo
Characterization and antitumor efficacy of poly(L-lactid acid)-based etoposide-loaded implants
Drug Delivery
etoposide
implant
poly(l-lactid acid)
sustained release
intratumoral chemotherapy
title Characterization and antitumor efficacy of poly(L-lactid acid)-based etoposide-loaded implants
title_full Characterization and antitumor efficacy of poly(L-lactid acid)-based etoposide-loaded implants
title_fullStr Characterization and antitumor efficacy of poly(L-lactid acid)-based etoposide-loaded implants
title_full_unstemmed Characterization and antitumor efficacy of poly(L-lactid acid)-based etoposide-loaded implants
title_short Characterization and antitumor efficacy of poly(L-lactid acid)-based etoposide-loaded implants
title_sort characterization and antitumor efficacy of poly l lactid acid based etoposide loaded implants
topic etoposide
implant
poly(l-lactid acid)
sustained release
intratumoral chemotherapy
url http://dx.doi.org/10.1080/10717544.2017.1321063
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