Surface modified methotrexate loaded erythrocytes for enhanced macrophage uptake.
The unique property of macrophages to distinguish between 'mature self' and 'senescent self' was applied for the enhanced macrophage uptake upon loading drugs into erythrocytes and provoking environment within which it gets translated into senescent cells. Two different approaches were applied one by depleting the sialic acid from the surface of cells and another by inducing hemichrome formation in the cells. Erythrocytes encapsulation of methotrexate was carried out by preswell dilution technique. Surface modification of erythrocytes was performed using desialation and hemichrome induction by treating with trypsin (Tt) and phenylhydrazine (PhT) respectively. Desialation technique was optimized in terms of concentration of trypsin, incubation temperature and time period. Both of these surface modified erythrocytes were characterized for in vitro macrophage uptake. In vivo organ localization was assessed by recording amount of drug present in different organs. The macrophage uptake of both surface modified erythrocytes was enhanced by almost 3-5 and 5-6 times with Tt and PhT cells, respectively. These new surface modified carriers are found to be excellent candidate for enhanced macrophage uptake and anticipated to be useful for any RES tumors.
Mishra
P R
PR
Department of Pharmaceutical Sciences, Dr. H.S. Gour University, Sagar, MP, India.
Jain
N K
NK
D000818:Animals; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism*; D008727:Methotrexate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D010659:Phenylhydrazines / Q000494:pharmacology; D051381:Rats; D014018:Tissue Distribution; D014357:Trypsin / Q000494:pharmacology
D004337:Drug Carriers; D010659:Phenylhydrazines; C030299:phenylhydrazine; D014357:Trypsin; D019158:N-Acetylneuraminic Acid; D008727:Methotrexate