Enhanced oral absorption of 20(S)-protopanaxadiol by self-assembled liquid crystalline nanoparticles containing piperine: in vitro and in vivo studies
Xin Jin,1,2 Zhen-hai Zhang,1 E Sun,1 Xiao-bin Tan,1 Song-lin Li,3 Xu-dong Cheng,4 Ming You,4 Xiao-bin Jia11Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, People's Republic of China; 2College of Pharmacy, Nanj...
Guardado en:
| Autores principales: | , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/6160780f1e754eaaa2ae5c258a5d83da |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:6160780f1e754eaaa2ae5c258a5d83da |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:6160780f1e754eaaa2ae5c258a5d83da2021-12-02T02:10:35ZEnhanced oral absorption of 20(S)-protopanaxadiol by self-assembled liquid crystalline nanoparticles containing piperine: in vitro and in vivo studies1176-91141178-2013https://doaj.org/article/6160780f1e754eaaa2ae5c258a5d83da2013-02-01T00:00:00Zhttp://www.dovepress.com/enhanced-oral-absorption-of-20s-protopanaxadiol-by-self-assembled-liqu-a12188https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Xin Jin,1,2 Zhen-hai Zhang,1 E Sun,1 Xiao-bin Tan,1 Song-lin Li,3 Xu-dong Cheng,4 Ming You,4 Xiao-bin Jia11Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, People's Republic of China; 2College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China; 3Department of Pharmaceutical Analysis and Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, People's Republic of China; 4ALG Bioscience Co, Ltd, Suzhou, People's Republic of ChinaBackground: 20(S)-protopanaxadiol (PPD), similar to several other anticancer agents, has low oral absorption and is extensively metabolized. These factors limit the use of PPD for treatment of human diseases.Methods: In this study, we used cubic nanoparticles containing piperine to improve the oral bioavailability of PPD and to enhance its absorption and inhibit its metabolism. Cubic nanoparticles loaded with PPD and piperine were prepared by fragmentation of glyceryl monoolein (GMO)/poloxamer 407 bulk cubic gel and verified using transmission electron microscopy and differential scanning calorimetry. We evaluated the in vitro release of PPD from these nanoparticles and its absorption across the Caco-2 cell monolayer model, and subsequently, we examined the bioavailability and metabolism of PPD and its nanoparticles in vivo.Results: The in vitro release of PPD from these nanoparticles was less than 5% at 12 hours. PPD-cubosome and PPD-cubosome loaded with piperine (molar ratio PPD/piperine, 1:3) increased the apical to basolateral permeability values of PPD across the Caco-2 cell monolayer from 53% to 64%, respectively. In addition, the results of a pharmacokinetic study in rats showed that the relative bioavailabilities of PPD-cubosome [area under concentration–time curve (AUC)0–∞ ] and PPD-cubosome containing piperine (AUC0–∞) compared to that of raw PPD (AUC0–∞) were 166% and 248%, respectively.Conclusion: The increased bioavailability of PPD-cubosome loaded with piperine is due to an increase in absorption and inhibition of metabolism of PPD by cubic nanoparticles containing piperine rather than because of improved release of PPD. The cubic nanoparticles containing piperine may be a promising oral carrier for anticancer drugs with poor oral absorption and that undergo extensive metabolism by cytochrome P450.Keywords: 20(S)-protopanaxadiol, cubosome, piperine, Caco-2 cell monolayer, bioavailability, metabolitesJin XZhang ZHSun ETan XBLi SLCheng XDYou MJia XBDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 641-652 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine (General) R5-920 |
| spellingShingle |
Medicine (General) R5-920 Jin X Zhang ZH Sun E Tan XB Li SL Cheng XD You M Jia XB Enhanced oral absorption of 20(S)-protopanaxadiol by self-assembled liquid crystalline nanoparticles containing piperine: in vitro and in vivo studies |
| description |
Xin Jin,1,2 Zhen-hai Zhang,1 E Sun,1 Xiao-bin Tan,1 Song-lin Li,3 Xu-dong Cheng,4 Ming You,4 Xiao-bin Jia11Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, People's Republic of China; 2College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China; 3Department of Pharmaceutical Analysis and Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, People's Republic of China; 4ALG Bioscience Co, Ltd, Suzhou, People's Republic of ChinaBackground: 20(S)-protopanaxadiol (PPD), similar to several other anticancer agents, has low oral absorption and is extensively metabolized. These factors limit the use of PPD for treatment of human diseases.Methods: In this study, we used cubic nanoparticles containing piperine to improve the oral bioavailability of PPD and to enhance its absorption and inhibit its metabolism. Cubic nanoparticles loaded with PPD and piperine were prepared by fragmentation of glyceryl monoolein (GMO)/poloxamer 407 bulk cubic gel and verified using transmission electron microscopy and differential scanning calorimetry. We evaluated the in vitro release of PPD from these nanoparticles and its absorption across the Caco-2 cell monolayer model, and subsequently, we examined the bioavailability and metabolism of PPD and its nanoparticles in vivo.Results: The in vitro release of PPD from these nanoparticles was less than 5% at 12 hours. PPD-cubosome and PPD-cubosome loaded with piperine (molar ratio PPD/piperine, 1:3) increased the apical to basolateral permeability values of PPD across the Caco-2 cell monolayer from 53% to 64%, respectively. In addition, the results of a pharmacokinetic study in rats showed that the relative bioavailabilities of PPD-cubosome [area under concentration–time curve (AUC)0–∞ ] and PPD-cubosome containing piperine (AUC0–∞) compared to that of raw PPD (AUC0–∞) were 166% and 248%, respectively.Conclusion: The increased bioavailability of PPD-cubosome loaded with piperine is due to an increase in absorption and inhibition of metabolism of PPD by cubic nanoparticles containing piperine rather than because of improved release of PPD. The cubic nanoparticles containing piperine may be a promising oral carrier for anticancer drugs with poor oral absorption and that undergo extensive metabolism by cytochrome P450.Keywords: 20(S)-protopanaxadiol, cubosome, piperine, Caco-2 cell monolayer, bioavailability, metabolites |
| format |
article |
| author |
Jin X Zhang ZH Sun E Tan XB Li SL Cheng XD You M Jia XB |
| author_facet |
Jin X Zhang ZH Sun E Tan XB Li SL Cheng XD You M Jia XB |
| author_sort |
Jin X |
| title |
Enhanced oral absorption of 20(S)-protopanaxadiol by self-assembled liquid crystalline nanoparticles containing piperine: in vitro and in vivo studies |
| title_short |
Enhanced oral absorption of 20(S)-protopanaxadiol by self-assembled liquid crystalline nanoparticles containing piperine: in vitro and in vivo studies |
| title_full |
Enhanced oral absorption of 20(S)-protopanaxadiol by self-assembled liquid crystalline nanoparticles containing piperine: in vitro and in vivo studies |
| title_fullStr |
Enhanced oral absorption of 20(S)-protopanaxadiol by self-assembled liquid crystalline nanoparticles containing piperine: in vitro and in vivo studies |
| title_full_unstemmed |
Enhanced oral absorption of 20(S)-protopanaxadiol by self-assembled liquid crystalline nanoparticles containing piperine: in vitro and in vivo studies |
| title_sort |
enhanced oral absorption of 20(s)-protopanaxadiol by self-assembled liquid crystalline nanoparticles containing piperine: in vitro and in vivo studies |
| publisher |
Dove Medical Press |
| publishDate |
2013 |
| url |
https://doaj.org/article/6160780f1e754eaaa2ae5c258a5d83da |
| work_keys_str_mv |
AT jinx enhancedoralabsorptionof20sprotopanaxadiolbyselfassembledliquidcrystallinenanoparticlescontainingpiperineinvitroandinvivostudies AT zhangzh enhancedoralabsorptionof20sprotopanaxadiolbyselfassembledliquidcrystallinenanoparticlescontainingpiperineinvitroandinvivostudies AT sune enhancedoralabsorptionof20sprotopanaxadiolbyselfassembledliquidcrystallinenanoparticlescontainingpiperineinvitroandinvivostudies AT tanxb enhancedoralabsorptionof20sprotopanaxadiolbyselfassembledliquidcrystallinenanoparticlescontainingpiperineinvitroandinvivostudies AT lisl enhancedoralabsorptionof20sprotopanaxadiolbyselfassembledliquidcrystallinenanoparticlescontainingpiperineinvitroandinvivostudies AT chengxd enhancedoralabsorptionof20sprotopanaxadiolbyselfassembledliquidcrystallinenanoparticlescontainingpiperineinvitroandinvivostudies AT youm enhancedoralabsorptionof20sprotopanaxadiolbyselfassembledliquidcrystallinenanoparticlescontainingpiperineinvitroandinvivostudies AT jiaxb enhancedoralabsorptionof20sprotopanaxadiolbyselfassembledliquidcrystallinenanoparticlescontainingpiperineinvitroandinvivostudies |
| _version_ |
1718402650995687424 |