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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| Format: | Article |
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Dove Medical Press
2020-10-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/etoposide-amorphous-nanopowder-for-improved-oral-bioavailability-formu-peer-reviewed-article-IJN |
| _version_ | 1818429631711150080 |
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| 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 |
| collection | DOAJ |
| 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 |
| first_indexed | 2024-12-14T15:20:35Z |
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| id | doaj.art-4338ebaf18774aaeabcc14a3e3838d1d |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-12-14T15:20:35Z |
| publishDate | 2020-10-01 |
| publisher | Dove Medical Press |
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| series | International Journal of Nanomedicine |
| spelling | doaj.art-4338ebaf18774aaeabcc14a3e3838d1d2022-12-21T22:56:10ZengDove Medical PressInternational Journal of Nanomedicine1178-20132020-10-01Volume 157601761357847Etoposide Amorphous Nanopowder for Improved Oral Bioavailability: Formulation Development, Optimization, in vitro and in vivo EvaluationWang YWang SXu YWang PLi SLiu LLiu MJin XYue 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 enhancementhttps://www.dovepress.com/etoposide-amorphous-nanopowder-for-improved-oral-bioavailability-formu-peer-reviewed-article-IJNetoposideamorphous nanopowderoral absorptionpoor aqueous solubilitybioavailability enhancement |
| spellingShingle | 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 International Journal of Nanomedicine etoposide amorphous nanopowder oral absorption poor aqueous solubility bioavailability enhancement |
| title | 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_short | 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 |
| topic | etoposide amorphous nanopowder oral absorption poor aqueous solubility bioavailability enhancement |
| url | https://www.dovepress.com/etoposide-amorphous-nanopowder-for-improved-oral-bioavailability-formu-peer-reviewed-article-IJN |
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