title: A comparison of changes to doxorubicin pharmacokinetics, antitumor activity, and toxicity mediated by PEGylated dendrimer and PEGylated liposome drug delivery systems.
abstract: 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).
  
  
  BACKGROUND
  In this manuscript, three different doxorubicin preparations are compared and preliminary evidence suggests that dendrimer-doxorubicin displays similar antitumor efficacy to PEGylated liposomal doxorubicin, but with lower systemic toxicity.
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Kaminskas
authors.forename: Victoria M
authors.initials: VM
authors.lastname: McLeod
authors.forename: Brian D
authors.initials: BD
authors.lastname: Kelly
authors.forename: Gian
authors.initials: G
authors.lastname: Sberna
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Boyd
authors.forename: Mark
authors.initials: M
authors.lastname: Williamson
authors.forename: David J
authors.initials: DJ
authors.lastname: Owen
authors.forename: Christopher J H
authors.initials: CJ
authors.lastname: Porter
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D002279:Carcinoma 256, Walker / Q000188:drug therapy; D050091:Dendrimers / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D007958:Leukocyte Count; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D012965:Sodium Chloride; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D050091:Dendrimers; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D012965:Sodium Chloride; D004317:Doxorubicin