PMID- 7562001
OWN - NLM
STAT- MEDLINE
DCOM- 19951121
LR  - 20190909
IS  - 0167-594X (Print)
IS  - 0167-594X (Linking)
VI  - 24
IP  - 2
DP  - 1995
TI  - Tissue distribution of methotrexate following administration as a solution and as 
      a magnetic microsphere conjugate in rats bearing brain tumors.
PG  - 143-52
AB  - A novel magnetic microsphere-methotrexate (MM-MTX) drug delivery system was 
      synthesized and evaluated in rats bearing rat glioma-2 (RG-2) tumors. 
      Methotrexate was linked to the surface of the magnetic particle via an 
      aminohexanol linker that would release free drug following hydrolysis. Male 
      Fischer 344 rats bearing RG-2 tumors were administered 3 mg/kg of methotrexate 
      (MTX) either as MM-MTX or as a solution (MTX-S) over 5 min. A 6000 gauss magnetic 
      field was applied for 15 min from the end of MM-MTX administrations. Serial 
      sacrifices were conducted at 15 min, 30 min and 45 min after drug 
      administrations, organs collected, and analyzed for total MTX by a radioassay. At 
      all times, MTX right brain (ipsilateral), brain tumor, and left brain 
      concentrations were approximately 3.5 to 5-fold greater in the MM-MTX group 
      compared to the MTX-S group. MTX concentrations in all other organs were less 
      following administration of MM-MTX than MTX-S except in lung at 30 and 45 min. 
      The targeting efficacy, an index for site-specificity, for both MM-MTX and MTX-S 
      were similar and indicated some enhancement in MTX localization in brain tumor. 
      Confocal and conventional light microscopic analyses demonstrated a diffuse 
      distribution of MM-MTX in tumor consistent with extravascular uptake, whereas a 
      predominant capillary distribution of MM-MTX was observed in normal brain. 
      Following 45 min, the animals treated with MM-MTX died possibly due to 
      redistribution of particles to the lung. This toxicity was dose-dependent. High 
      brain MTX concentrations coupled with extravascular uptake of MM-MTX provide a 
      basis for further investigations with this novel drug delivery system.
FAU - Devineni, D
AU  - Devineni D
AD  - Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
FAU - Klein-Szanto, A
AU  - Klein-Szanto A
FAU - Gallo, J M
AU  - Gallo JM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Neurooncol
JT  - Journal of neuro-oncology
JID - 8309335
RN  - 0 (Solutions)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Animals
MH  - Brain Neoplasms/*metabolism
MH  - Disease Models, Animal
MH  - *Drug Delivery Systems
MH  - Evaluation Studies as Topic
MH  - Glioma/*metabolism
MH  - Magnetics
MH  - Male
MH  - Methotrexate/administration & dosage/*pharmacokinetics
MH  - Microspheres
MH  - Rats
MH  - Rats, Inbred F344
MH  - Solutions
MH  - Tissue Distribution
EDAT- 1995/01/01 00:00
MHDA- 1995/01/01 00:01
CRDT- 1995/01/01 00:00
PHST- 1995/01/01 00:00 [pubmed]
PHST- 1995/01/01 00:01 [medline]
PHST- 1995/01/01 00:00 [entrez]
AID - 10.1007/BF01078484 [doi]
PST - ppublish
SO  - J Neurooncol. 1995;24(2):143-52. doi: 10.1007/BF01078484.