Synthesis, characterization, and biological evaluation of poly(L-γ-glutamyl-glutamine)-paclitaxel nanoconjugate
Sang Van1, Sanjib K Das1, Xinghe Wang1, Zhongling Feng1, Yi Jin1, Zheng Hou1, Fu Chen1, Annie Pham1, Nan Jiang1, Stephen B Howell2, Lei Yu11Nitto Denko Technical Corporation, Oceanside, CA, USA; 2Moores Cancer Center, University of California, La Jolla, San Diego, CA, USAAbstract: The purpose of thi...
Guardado en:
| Autores principales: | , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2010
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/bec6bb1b91d248ef89860edcb294f1a1 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:bec6bb1b91d248ef89860edcb294f1a1 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:bec6bb1b91d248ef89860edcb294f1a12021-12-02T02:44:04ZSynthesis, characterization, and biological evaluation of poly(L-γ-glutamyl-glutamine)-paclitaxel nanoconjugate1176-91141178-2013https://doaj.org/article/bec6bb1b91d248ef89860edcb294f1a12010-10-01T00:00:00Zhttp://www.dovepress.com/synthesis-characterization-and-biological-evaluation-of-polyl-gamma-gl-a5483https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Sang Van1, Sanjib K Das1, Xinghe Wang1, Zhongling Feng1, Yi Jin1, Zheng Hou1, Fu Chen1, Annie Pham1, Nan Jiang1, Stephen B Howell2, Lei Yu11Nitto Denko Technical Corporation, Oceanside, CA, USA; 2Moores Cancer Center, University of California, La Jolla, San Diego, CA, USAAbstract: The purpose of this study was to develop a novel, highly water-soluble poly(L-γ-glutamyl-glutamine)-paclitaxel nanoconjugate (PGG-PTX) that would improve the therapeutic index of paclitaxel (PTX). PGG-PTX is a modification of poly(L-glutamic acid)-paclitaxel conjugate (PGA-PTX) in which an additional glutamic acid has been added to each glutamic side chain in the polymer. PGG-PTX has higher water-solubility and faster dissolution than PGA-PTX. Unlike PGA-PTX, PGG-PTX self-assembles into nanoparticles, whose size remains in the range of 12–15 nm over the concentration range from 25 to 2,000 µg/mL in saline. Its critical micellar concentration in saline was found to be ~25 µg/mL. The potency of PGG-PTX when tested in vitro against the human lung cancer H460 cell line was comparable to other known polymer-PTX conjugates. However, PGG-PTX possesses lower toxicity compared with PGA-PTX in mice. The maximum tolerated dose of PGG-PTX was found to be 350 mg PTX/kg, which is 2.2-fold higher than the maximum tolerated dose of 160 mg PTX/kg reported for the PGA-PTX. This result indicates that PGG-PTX was substantially less toxic in vivo than PGA-PTX.Keywords: nanoconjugates, poly(L-glutamic acid), poly(L-γ-glutamyl-glutamine)-paclitaxel, nanoparticles, anticancer Sang VanSanjib K DasXinghe Wanget alDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2010, Iss default, Pp 825-837 (2010) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine (General) R5-920 |
| spellingShingle |
Medicine (General) R5-920 Sang Van Sanjib K Das Xinghe Wang et al Synthesis, characterization, and biological evaluation of poly(L-γ-glutamyl-glutamine)-paclitaxel nanoconjugate |
| description |
Sang Van1, Sanjib K Das1, Xinghe Wang1, Zhongling Feng1, Yi Jin1, Zheng Hou1, Fu Chen1, Annie Pham1, Nan Jiang1, Stephen B Howell2, Lei Yu11Nitto Denko Technical Corporation, Oceanside, CA, USA; 2Moores Cancer Center, University of California, La Jolla, San Diego, CA, USAAbstract: The purpose of this study was to develop a novel, highly water-soluble poly(L-γ-glutamyl-glutamine)-paclitaxel nanoconjugate (PGG-PTX) that would improve the therapeutic index of paclitaxel (PTX). PGG-PTX is a modification of poly(L-glutamic acid)-paclitaxel conjugate (PGA-PTX) in which an additional glutamic acid has been added to each glutamic side chain in the polymer. PGG-PTX has higher water-solubility and faster dissolution than PGA-PTX. Unlike PGA-PTX, PGG-PTX self-assembles into nanoparticles, whose size remains in the range of 12–15 nm over the concentration range from 25 to 2,000 µg/mL in saline. Its critical micellar concentration in saline was found to be ~25 µg/mL. The potency of PGG-PTX when tested in vitro against the human lung cancer H460 cell line was comparable to other known polymer-PTX conjugates. However, PGG-PTX possesses lower toxicity compared with PGA-PTX in mice. The maximum tolerated dose of PGG-PTX was found to be 350 mg PTX/kg, which is 2.2-fold higher than the maximum tolerated dose of 160 mg PTX/kg reported for the PGA-PTX. This result indicates that PGG-PTX was substantially less toxic in vivo than PGA-PTX.Keywords: nanoconjugates, poly(L-glutamic acid), poly(L-γ-glutamyl-glutamine)-paclitaxel, nanoparticles, anticancer |
| format |
article |
| author |
Sang Van Sanjib K Das Xinghe Wang et al |
| author_facet |
Sang Van Sanjib K Das Xinghe Wang et al |
| author_sort |
Sang Van |
| title |
Synthesis, characterization, and biological evaluation of poly(L-γ-glutamyl-glutamine)-paclitaxel nanoconjugate |
| title_short |
Synthesis, characterization, and biological evaluation of poly(L-γ-glutamyl-glutamine)-paclitaxel nanoconjugate |
| title_full |
Synthesis, characterization, and biological evaluation of poly(L-γ-glutamyl-glutamine)-paclitaxel nanoconjugate |
| title_fullStr |
Synthesis, characterization, and biological evaluation of poly(L-γ-glutamyl-glutamine)-paclitaxel nanoconjugate |
| title_full_unstemmed |
Synthesis, characterization, and biological evaluation of poly(L-γ-glutamyl-glutamine)-paclitaxel nanoconjugate |
| title_sort |
synthesis, characterization, and biological evaluation of poly(l-γ-glutamyl-glutamine)-paclitaxel nanoconjugate |
| publisher |
Dove Medical Press |
| publishDate |
2010 |
| url |
https://doaj.org/article/bec6bb1b91d248ef89860edcb294f1a1 |
| work_keys_str_mv |
AT sangvan synthesischaracterizationandbiologicalevaluationofpolylampgammaglutamylglutaminepaclitaxelnanoconjugate AT sanjibkdas synthesischaracterizationandbiologicalevaluationofpolylampgammaglutamylglutaminepaclitaxelnanoconjugate AT xinghewang synthesischaracterizationandbiologicalevaluationofpolylampgammaglutamylglutaminepaclitaxelnanoconjugate AT etal synthesischaracterizationandbiologicalevaluationofpolylampgammaglutamylglutaminepaclitaxelnanoconjugate |
| _version_ |
1718402187077353472 |