In vivo survival and organ uptake of loaded carrier rat erythrocytes.
Rat RBCs loaded with 125I-CA by hypotonic dialysis and isotonic resealing were evaluated as a carrier system. Loaded RBCs stored at 4 degrees C remained unlysed (90% survival) allowing release of encapsulated 125I-CA for up to 4 days. Thereafter, cellular lysis increased significantly. IP-injected loaded RBCs reached the maximum level (50%) in circulation at 24 h post-injection. Circulating loaded RBCs showed a half-life of 8-10 days, which was advantageous for carrier function. In contrast to IP-injected free CA, which remained in circulation for only a short time, encapsulated CA showed significant levels in circulation up to 10 days post-injection. The profile of organ uptake with time is essentially not altered for loaded with respect to native cells, being higher the removal of loaded cells and mainly localized in spleen. Nevertheless, liver is the organ with highest elimination capacity for both native and loaded cells, showing its maximum at 24 h post-injection. Concomitantly, the concentration of 125I-CA in all organs studied was highest at this time. These data demonstrate that rat loaded RBCs can potentially be used as a carrier system for long-term dissemination of drug into the organism, with specially increased delivery to the spleen. They also support the use of the rat as an experimental model for biochemical and pharmacological studies in these therapeutic systems.
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Alcalá de Henares, Madrid, Spain.
F J
FJ
Alvarez
A
A
Herráez
J C
JC
Murciano
J A
JA
Jordán
J C
JC
Díez
M C
MC
Tejedor
D000818:Animals; D002860:Chromium Radioisotopes / Q000097:blood / Q000493:pharmacokinetics; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004905:Erythrocyte Aging; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes / Q000097:blood / Q000493:pharmacokinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014018:Tissue Distribution
D002860:Chromium Radioisotopes; D004337:Drug Carriers; D007457:Iodine Radioisotopes