TY - JOUR
T1 - Distribution and fate of free and liposome-encapsulated [3H]nor-muramyl dipeptide and [3H]muramyl tripeptide phosphatidylethanolamine in mice
AU - Fogler, W. E.
AU - Wade, R.
AU - Brundish, D. E.
AU - Fidler, I. J.
N1 - Copyright:
Copyright 2004 Elsevier B.V., All rights reserved.
PY - 1985
Y1 - 1985
N2 - The pharmacokinetics and metabolism of i.v. administered free (unencapsulated) or liposome-encapsulated hydrophilic [3H]-labeled nor-muramyl dipeptide (nor-MDP) and lipophilic [3H]-labeled muramyl tripeptide phosphatidylethanolamine (MTP-PE) were evaluated. In addition we also examined the distribution and fate of these immunomodulators subsequent to intranasal (i.n.) administration. Unique patterns of circulatory clearance, organ distribution, metabolism, and excretion were observed for each of the four preparations. Nor-MDP in saline was rapidly cleared from the circulation and excreted in the urine as intact molecules. MTP-PE dissolved in saline was cleared from the circulation at a slow rate and found within various organs as intact MTP-PE, lyso-MTP-PE, and MDP. Following the i.v. administration of nor-MDP or MTP-PE in liposomes, patterns of clearance and organ distribution corresponded to that of liposome distribution, i.e., the reticuloendothelial system. Extensive dissociation of hydrophilic nor-MDP from the carrier liposomes occurred, and the immunomodulator was recovered in the urine. In contrast, MTP-PE entrapped in liposomes was retained in target organs for the duration of the study. The i.n. instillation of radiolabeled nor-MDP or MTP-PE was associated with the accumulation of these immunomodulators in the brain. Our results demonstrate the feasibility of targeting hydrophilic and lipophilic immunomodulators to cells of the macrophage-histiocyte series.
AB - The pharmacokinetics and metabolism of i.v. administered free (unencapsulated) or liposome-encapsulated hydrophilic [3H]-labeled nor-muramyl dipeptide (nor-MDP) and lipophilic [3H]-labeled muramyl tripeptide phosphatidylethanolamine (MTP-PE) were evaluated. In addition we also examined the distribution and fate of these immunomodulators subsequent to intranasal (i.n.) administration. Unique patterns of circulatory clearance, organ distribution, metabolism, and excretion were observed for each of the four preparations. Nor-MDP in saline was rapidly cleared from the circulation and excreted in the urine as intact molecules. MTP-PE dissolved in saline was cleared from the circulation at a slow rate and found within various organs as intact MTP-PE, lyso-MTP-PE, and MDP. Following the i.v. administration of nor-MDP or MTP-PE in liposomes, patterns of clearance and organ distribution corresponded to that of liposome distribution, i.e., the reticuloendothelial system. Extensive dissociation of hydrophilic nor-MDP from the carrier liposomes occurred, and the immunomodulator was recovered in the urine. In contrast, MTP-PE entrapped in liposomes was retained in target organs for the duration of the study. The i.n. instillation of radiolabeled nor-MDP or MTP-PE was associated with the accumulation of these immunomodulators in the brain. Our results demonstrate the feasibility of targeting hydrophilic and lipophilic immunomodulators to cells of the macrophage-histiocyte series.
UR - http://www.scopus.com/inward/record.url?scp=0022360699&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0022360699&partnerID=8YFLogxK
M3 - Article
C2 - 4008926
AN - SCOPUS:0022360699
SN - 0022-1767
VL - 135
SP - 1372
EP - 1377
JO - Journal of Immunology
JF - Journal of Immunology
IS - 2
ER -