TY - JOUR
T1 - Doxorubicin loading and eluting characteristics of bioresorbable hydrogel microspheres
T2 - In vitro study
AU - Weng, Lihui
AU - Le, Hung C.
AU - Lin, Jingying
AU - Golzarian, Jafar
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/5/16
Y1 - 2011/5/16
N2 - Non-bioresorbable drug eluting microspheres are being increasingly used for the treatment of unresectable liver tumors, whereas bioresorbable microspheres have not received much attention. In this study, bioresorbable microspheres prepared from chitosan and carboxymethyl cellulose were loaded with doxorubicin (Doxo) via ion-exchange interactions with carboxylic groups in the microspheres. With a 25-40% decrease in the microsphere size depending on their size ranges, the microspheres could load a maximum of 0.3-0.7 mg Doxo/mg dry spheres. As confirmed by confocal microscopy, Doxo was mainly concentrated in the outer 20 ± 5 μm surface layer of the microspheres. The loaded microspheres were stable in aqueous dispersions without aggregation for a prolonged period of time but degradable in a lysozyme solution. Furthermore, the loaded microspheres exhibited a noticeable pH-sensitive behavior with accelerated release of Doxo in acidic environment due to the protonation of carboxylic groups in the microspheres. Compared to commercial non-resorbable drug eluting beads, the loaded bioresorbable microspheres showed a sustained release manner in phosphate buffered saline (PBS). The release data were fitted to an empirical relationship, which reveals a non-Fickian transport mechanism (n = 0.55-0.59). These results demonstrate that the bioresorbable microspheres are promising as attractive carriers for Doxo.
AB - Non-bioresorbable drug eluting microspheres are being increasingly used for the treatment of unresectable liver tumors, whereas bioresorbable microspheres have not received much attention. In this study, bioresorbable microspheres prepared from chitosan and carboxymethyl cellulose were loaded with doxorubicin (Doxo) via ion-exchange interactions with carboxylic groups in the microspheres. With a 25-40% decrease in the microsphere size depending on their size ranges, the microspheres could load a maximum of 0.3-0.7 mg Doxo/mg dry spheres. As confirmed by confocal microscopy, Doxo was mainly concentrated in the outer 20 ± 5 μm surface layer of the microspheres. The loaded microspheres were stable in aqueous dispersions without aggregation for a prolonged period of time but degradable in a lysozyme solution. Furthermore, the loaded microspheres exhibited a noticeable pH-sensitive behavior with accelerated release of Doxo in acidic environment due to the protonation of carboxylic groups in the microspheres. Compared to commercial non-resorbable drug eluting beads, the loaded bioresorbable microspheres showed a sustained release manner in phosphate buffered saline (PBS). The release data were fitted to an empirical relationship, which reveals a non-Fickian transport mechanism (n = 0.55-0.59). These results demonstrate that the bioresorbable microspheres are promising as attractive carriers for Doxo.
KW - Bioresorbable
KW - Doxorubicin
KW - Hydrogel microspheres
KW - Ion exchange
UR - http://www.scopus.com/inward/record.url?scp=79955032169&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955032169&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2011.02.058
DO - 10.1016/j.ijpharm.2011.02.058
M3 - Article
C2 - 21382461
AN - SCOPUS:79955032169
SN - 0378-5173
VL - 409
SP - 185
EP - 193
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -