TY - JOUR
T1 - Conjugating an anticancer drug onto thiolated hyaluronic acid by acid liable hydrazone linkage for its gelation and dual stimuli-response release
AU - Fu, Chaoping
AU - Li, Hailiang
AU - Li, Nannan
AU - Miao, Xiangwan
AU - Xie, Minqiang
AU - Du, Wenjun
AU - Zhang, Li Ming
N1 - Funding Information:
This work was supported by the Opening Project of Guangdong Key Laboratory of New Drug Design and Evaluation (2011A060901014-004), the 973 Program of China (2015CB755500), the National Natural Science Foundation of China ( 21074152 , 51273216 , J1103305 ) and the Natural Science Foundation of Guangdong Province ( S2013010012549 ).
Publisher Copyright:
© 2015 Elsevier Ltd. All rights reserved.
PY - 2015/9/5
Y1 - 2015/9/5
N2 - A prodrug gelation strategy was developed for the sustained and dual stimuli-response release of doxorubicin hydrochloride (DOX·HCl), a commonly used anticancer drug. For this purpose, the chemical conjugation of DOX·HCl onto thiolated hyaluronic acid (HA) was carried out by an acid liable hydrazone linkage and verified by 1H NMR analyses. When exposed to the air, such a polysaccharide conjugate showed unique self-gelation ability in aqueous solution. The gelation time and extent depended mainly on the content of thiol groups on thiolated HA. The resultant hydrogel exhibited a dominant elastic response and a thixotropic property. In particular, it could release sustainably conjugated DOX·HCl in dual pH- and reduction-responsive modes. The cumulative drug release was found to be significantly accelerated under the conditions mimicking the intracellular environments of cancer cells. The in vitro cytotoxicity assays for the human nasopharyngeal carcinoma CNE2 cells treated with various release media confirmed the effectiveness of this conjugate hydrogel for cancer cell inhibition.
AB - A prodrug gelation strategy was developed for the sustained and dual stimuli-response release of doxorubicin hydrochloride (DOX·HCl), a commonly used anticancer drug. For this purpose, the chemical conjugation of DOX·HCl onto thiolated hyaluronic acid (HA) was carried out by an acid liable hydrazone linkage and verified by 1H NMR analyses. When exposed to the air, such a polysaccharide conjugate showed unique self-gelation ability in aqueous solution. The gelation time and extent depended mainly on the content of thiol groups on thiolated HA. The resultant hydrogel exhibited a dominant elastic response and a thixotropic property. In particular, it could release sustainably conjugated DOX·HCl in dual pH- and reduction-responsive modes. The cumulative drug release was found to be significantly accelerated under the conditions mimicking the intracellular environments of cancer cells. The in vitro cytotoxicity assays for the human nasopharyngeal carcinoma CNE2 cells treated with various release media confirmed the effectiveness of this conjugate hydrogel for cancer cell inhibition.
KW - Cancer cell inhibition
KW - Chemical conjugation
KW - Doxorubicin hydrochloride
KW - Gelation Stimuli-responsive release
KW - Thiolated hyaluronic acid
UR - http://www.scopus.com/inward/record.url?scp=84928812499&partnerID=8YFLogxK
U2 - 10.1016/j.carbpol.2015.04.024
DO - 10.1016/j.carbpol.2015.04.024
M3 - Article
C2 - 26005152
AN - SCOPUS:84928812499
SN - 0144-8617
VL - 128
SP - 163
EP - 170
JO - Carbohydrate Polymers
JF - Carbohydrate Polymers
ER -