PMID- 9067330
OWN - NLM
STAT- MEDLINE
DCOM- 19970411
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 280
IP  - 3
DP  - 1997 Mar
TI  - The role of tumor-associated macrophages in the delivery of liposomal doxorubicin 
      to solid murine fibrosarcoma tumors.
PG  - 1406-14
AB  - Murine fibrosarcoma tumors arising from subcutaneous inoculation of FSa-N cells 
      exhibit 4-fold higher tumor-associated macrophage (TAM) levels than those from 
      the FSa-R line. These solid tumors were used to assess the role of TAMs in the 
      accumulation of liposomal anticancer drugs. Two liposomal formulations of 
      doxorubicin were investigated: a conventional formulation composed of 
      distearoylphosphatidylcholine (DSPC) and cholesterol and a sterically stabilized 
      liposomal formulation composed of DSPC/cholesterol/poly (ethylene 
      glycol)-modified distearoylphosphatidyethanolamine (PEG-PE). Circulating 
      concentrations of PEG-PE containing liposomes 24 h after i.v. administration were 
      3-fold greater than those observed after administration of conventional 
      liposomes. No differences were observed in drug retention or tumor (FSa-R or 
      FSa-N) drug and liposomal lipid delivery when comparisons were made between 
      different liposomal formulations. However, tumor doxorubicin concentrations were 
      increased as much as 4-fold for liposomal formulations relative to free drug. 
      Further, there was a 1.5- to 2-fold increase in doxorubicin delivery to 
      TAM-enriched FSa-N tumors compared with FSa-R tumors. Fluorescence microscopy 
      studies revealed a poor correlation between CD11b (Mac-1) positive cells (TAMs) 
      and the appearance of doxorubicin fluorescence. These results suggest that uptake 
      of liposomal drugs by TAMs does not account for the enhanced accumulation of 
      liposomal drugs in solid tumors. Rather, the increased tumor drug delivery may be 
      related to alternative TAM-mediated processes that increase tumor vascular 
      permeability. Therapeutic studies demonstrated that increased tumor drug uptake 
      observed for the liposomal doxorubicin formulations led to marginal improvements 
      in antitumor activity, and it is suggested that much of the drug delivered in 
      liposomal form is not biologically available.
FAU - Mayer, L D
AU  - Mayer LD
AD  - Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada.
FAU - Dougherty, G
AU  - Dougherty G
FAU - Harasym, T O
AU  - Harasym TO
FAU - Bally, M B
AU  - Bally MB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Drug Carriers)
RN  - 0 (Liposomes)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/*administration & dosage/therapeutic use
MH  - Doxorubicin/*administration & dosage/blood/pharmacokinetics/therapeutic use
MH  - Drug Carriers
MH  - Female
MH  - Fibrosarcoma/*drug therapy/metabolism
MH  - Liposomes
MH  - Macrophages/*physiology
MH  - Mice
MH  - Mice, Inbred C3H
EDAT- 1997/03/01 00:00
MHDA- 1997/03/01 00:01
CRDT- 1997/03/01 00:00
PHST- 1997/03/01 00:00 [pubmed]
PHST- 1997/03/01 00:01 [medline]
PHST- 1997/03/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1997 Mar;280(3):1406-14.