Pharmacokinetics and biodistribution of methotrexate conjugated to mannosyl human serum albumin.
The superior efficacy of mannosylated neoglycoprotein-conjugated methotrexate, compared with free drug, in eliminating the parasite burden in both the in-vitro macrophage model and in-vivo mouse model of visceral leishmaniasis has been demonstrated previously. In the present study it was found that: (i) methotrexate conjugated to mannosyl human serum albumin (Man-HSA) was taken up rapidly by the liver and spleen, whereas the free drug was taken up by the kidney; (ii) uptake of the conjugate was ten-fold more efficient in liver macrophages (Kupffer cells) than in hepatocytes; (iii) most of the drug conjugate reached the lysosomes of Kupffer cells; and (iv) the active drug was released in the lysosomes of macrophages to act on Leishmania parasites.
Sett
R
R
Indian Institute of Chemical Biology, Calcutta.
Sarkar
H S
HS
Das
P K
PK
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D066298:In Vitro Techniques; D007898:Leishmaniasis, Visceral / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008358:Mannose / Q000378:metabolism*; D008727:Methotrexate / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D012709:Serum Albumin / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution
D012709:Serum Albumin; D008358:Mannose; D008727:Methotrexate