TY - JOUR
T1 - A comparison of changes to doxorubicin pharmacokinetics, antitumour activity, and toxicity mediated by PEGylated dendrimer and PEGylated liposome drug delivery systems
AU - Kaminskas, Lisa
AU - McLeod, Victoria
AU - Kelly, Brian
AU - Sberna, Gian
AU - Boyd, Benjamin
AU - Williamson, Mark
AU - Owen, D
AU - Porter, Christopher
PY - 2012
Y1 - 2012
N2 - The pharmacokinetics, biodistribution, and antitumor efficacy of three doxorubicin formulations (doxorubicin in saline, conjugated to a polylysine dendrimer, and encapsulated within a stealth liposome) were investigated in Walker 256 tumor-bearing rats. Liposomal and dendrimer-based delivery systems resulted in more prolonged plasma exposure of total doxorubicin when compared to administration of doxorubicin in saline, although concentrations of free doxorubicin remained low in both cases. Biodistribution profiles revealed enhanced accumulation of dendrimer- and liposome-associated doxorubicin in tumors when compared to doxorubicin alone, although all three doxorubicin formulations reduced tumor growth to a similar extent. Markers of systemic toxicity (spleen weight, white blood cell counts, body weight, and cardiotoxicity) were more pronounced in rats that received doxorubicin and liposomal doxorubicin when compared to dendrimer-doxorubicin. The data provide preliminary evidence that dendrimer-doxorubicin displays similar antitumor efficacy to PEGylated liposomal doxorubicin, but with lower systemic toxicity (resulting from reduced drug exposure to nontarget organs).
AB - The pharmacokinetics, biodistribution, and antitumor efficacy of three doxorubicin formulations (doxorubicin in saline, conjugated to a polylysine dendrimer, and encapsulated within a stealth liposome) were investigated in Walker 256 tumor-bearing rats. Liposomal and dendrimer-based delivery systems resulted in more prolonged plasma exposure of total doxorubicin when compared to administration of doxorubicin in saline, although concentrations of free doxorubicin remained low in both cases. Biodistribution profiles revealed enhanced accumulation of dendrimer- and liposome-associated doxorubicin in tumors when compared to doxorubicin alone, although all three doxorubicin formulations reduced tumor growth to a similar extent. Markers of systemic toxicity (spleen weight, white blood cell counts, body weight, and cardiotoxicity) were more pronounced in rats that received doxorubicin and liposomal doxorubicin when compared to dendrimer-doxorubicin. The data provide preliminary evidence that dendrimer-doxorubicin displays similar antitumor efficacy to PEGylated liposomal doxorubicin, but with lower systemic toxicity (resulting from reduced drug exposure to nontarget organs).
UR - http://www.sciencedirect.com/science/article/pii/S1549963411001857
U2 - 10.1016/j.nano.2011.05.013
DO - 10.1016/j.nano.2011.05.013
M3 - Article
VL - 8
SP - 103
EP - 111
JO - Nanomedicine: Nanotechnology, Biology and Medicine
JF - Nanomedicine: Nanotechnology, Biology and Medicine
SN - 1549-9634
IS - 1
ER -