Etoposide Amorphous Nanopowder for Improved Oral Bioavailability: Formulation Development, Optimization, in vitro and in vivo Evaluation

Yue Wang, Shuhang Wang, Yingju Xu, Ping Wang, Sukai Li, Lu Liu, Mengyan Liu, Xiangqun Jin School of Pharmacy, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Xiangqun Jin Tel +86-138-4409-0377Fax +86-431-8561-9662Email jinxq@jlu.edu.cnIntroduction: Etoposide refers t...

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Autores principales:	Wang Y, Wang S, Xu Y, Wang P, Li S, Liu L, Liu M, Jin X
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	etoposide amorphous nanopowder oral absorption poor aqueous solubility bioavailability enhancement Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/4338ebaf18774aaeabcc14a3e3838d1d
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spelling	oai:doaj.org-article:4338ebaf18774aaeabcc14a3e3838d1d2021-12-02T11:14:05ZEtoposide Amorphous Nanopowder for Improved Oral Bioavailability: Formulation Development, Optimization, in vitro and in vivo Evaluation1178-2013https://doaj.org/article/4338ebaf18774aaeabcc14a3e3838d1d2020-10-01T00:00:00Zhttps://www.dovepress.com/etoposide-amorphous-nanopowder-for-improved-oral-bioavailability-formu-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yue Wang, Shuhang Wang, Yingju Xu, Ping Wang, Sukai Li, Lu Liu, Mengyan Liu, Xiangqun Jin School of Pharmacy, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Xiangqun Jin Tel +86-138-4409-0377Fax +86-431-8561-9662Email jinxq@jlu.edu.cnIntroduction: Etoposide refers to a derivative of podophyllotoxin, which plays an important role in the treatment of cancer due to its prominent anti-tumor effect. As a BCS IV drug, etoposide exhibits insufficient aqueous solubility and permeability, thereby limiting its oral absorption. To enhance the oral bioavailability of etoposide, this study developed an amorphous nanopowder.Methods: Based on preliminary screening and experimental design, the stabilizer and preparation process of etoposide nanosuspension were explored. Subsequently, using a Box–Behnken design, the effects of independent factors (ultrasonication time, ratio of two phases and stabilizer concentration) on response variables (particle size and polydispersity index) were studied, and then the formulation was optimized. Finally, nanosuspension was further freeze dried with 1% of mannitol resulting in the formation of etoposide amorphous nanopowder.Results: The optimized etoposide nanopowder showed as spherical particles with an average particle size and polydispersity index of 211.7 ± 10.4 nm and 0.125 ± 0.028. X-ray powder diffraction and differential scanning calorimetry confirmed the ETO in the nanopowder was amorphous. Compared with coarse powder and physical mixture, etoposide nanopowder achieved significantly enhanced saturated solubility and dissolution in various pH environments. The Cmax and AUC0–t of etoposide nanopowder after oral administration in rats were respectively 2.21 and 2.13 times higher than the crude etoposide suspension. Additionally, the Tmax value of nanopowder was 0.25 h, compared with 0.5 h of reference group.Discussion: In the present study, the optimized amorphous nanopowder could significantly facilitate the dissolution and oral absorption of etoposide and might act as an effective delivery method to enhance its oral bioavailability.Keywords: etoposide, amorphous nanopowder, oral absorption, poor aqueous solubility, bioavailability enhancementWang YWang SXu YWang PLi SLiu LLiu MJin XDove Medical Pressarticleetoposideamorphous nanopowderoral absorptionpoor aqueous solubilitybioavailability enhancementMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 7601-7613 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	etoposide amorphous nanopowder oral absorption poor aqueous solubility bioavailability enhancement Medicine (General) R5-920
spellingShingle	etoposide amorphous nanopowder oral absorption poor aqueous solubility bioavailability enhancement Medicine (General) R5-920 Wang Y Wang S Xu Y Wang P Li S Liu L Liu M Jin X Etoposide Amorphous Nanopowder for Improved Oral Bioavailability: Formulation Development, Optimization, in vitro and in vivo Evaluation
description	Yue Wang, Shuhang Wang, Yingju Xu, Ping Wang, Sukai Li, Lu Liu, Mengyan Liu, Xiangqun Jin School of Pharmacy, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Xiangqun Jin Tel +86-138-4409-0377Fax +86-431-8561-9662Email jinxq@jlu.edu.cnIntroduction: Etoposide refers to a derivative of podophyllotoxin, which plays an important role in the treatment of cancer due to its prominent anti-tumor effect. As a BCS IV drug, etoposide exhibits insufficient aqueous solubility and permeability, thereby limiting its oral absorption. To enhance the oral bioavailability of etoposide, this study developed an amorphous nanopowder.Methods: Based on preliminary screening and experimental design, the stabilizer and preparation process of etoposide nanosuspension were explored. Subsequently, using a Box–Behnken design, the effects of independent factors (ultrasonication time, ratio of two phases and stabilizer concentration) on response variables (particle size and polydispersity index) were studied, and then the formulation was optimized. Finally, nanosuspension was further freeze dried with 1% of mannitol resulting in the formation of etoposide amorphous nanopowder.Results: The optimized etoposide nanopowder showed as spherical particles with an average particle size and polydispersity index of 211.7 ± 10.4 nm and 0.125 ± 0.028. X-ray powder diffraction and differential scanning calorimetry confirmed the ETO in the nanopowder was amorphous. Compared with coarse powder and physical mixture, etoposide nanopowder achieved significantly enhanced saturated solubility and dissolution in various pH environments. The Cmax and AUC0–t of etoposide nanopowder after oral administration in rats were respectively 2.21 and 2.13 times higher than the crude etoposide suspension. Additionally, the Tmax value of nanopowder was 0.25 h, compared with 0.5 h of reference group.Discussion: In the present study, the optimized amorphous nanopowder could significantly facilitate the dissolution and oral absorption of etoposide and might act as an effective delivery method to enhance its oral bioavailability.Keywords: etoposide, amorphous nanopowder, oral absorption, poor aqueous solubility, bioavailability enhancement
format	article
author	Wang Y Wang S Xu Y Wang P Li S Liu L Liu M Jin X
author_facet	Wang Y Wang S Xu Y Wang P Li S Liu L Liu M Jin X
author_sort	Wang Y
title	Etoposide Amorphous Nanopowder for Improved Oral Bioavailability: Formulation Development, Optimization, in vitro and in vivo Evaluation
title_short	Etoposide Amorphous Nanopowder for Improved Oral Bioavailability: Formulation Development, Optimization, in vitro and in vivo Evaluation
title_full	Etoposide Amorphous Nanopowder for Improved Oral Bioavailability: Formulation Development, Optimization, in vitro and in vivo Evaluation
title_fullStr	Etoposide Amorphous Nanopowder for Improved Oral Bioavailability: Formulation Development, Optimization, in vitro and in vivo Evaluation
title_full_unstemmed	Etoposide Amorphous Nanopowder for Improved Oral Bioavailability: Formulation Development, Optimization, in vitro and in vivo Evaluation
title_sort	etoposide amorphous nanopowder for improved oral bioavailability: formulation development, optimization, in vitro and in vivo evaluation
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/4338ebaf18774aaeabcc14a3e3838d1d
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_version_	1718396106446995456

Etoposide Amorphous Nanopowder for Improved Oral Bioavailability: Formulation Development, Optimization, in vitro and in vivo Evaluation

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