Pharmacokinetics of gonadotropin-releasing hormone and stimulation of luteinizing hormone secretion after single dose administration of GnRH incorporated into liposomes.
The properties of liposomes as a carrier for sustained release of gonadotropin-releasing hormone (GnRH) was investigated. A mixture of egg-phosphatidylcholine/egg-phosphatidic acid, binding GnRH with high capacity, was used for preparation of GnRH-carrier liposomes, which were of the multilamellar type in most experiments. As test animals we used rabbits and pigs, the last mentioned for checking the LH4 response to GnRH-injections, which was via the i.m. route throughout in this investigation. By measuring the kinetics of removal of GnRH from the injection site and by following the GnRH invasion into the circulation, it was demonstrated that GnRH release from liposomal depots is strongly slowed down, compared with injections of the free hormone. Further, plasma levels of GnRH were detectable up to 8 h generally, sometimes up to 20 h after injection. However, a considerable portion of GnRH bound to multilamellar liposomes was released so slowly in our case, that the concentration decreased even below the RIA detection limit. This appears clearly from our kinetic data. For this reason the resorption of GnRH from liposomes seems to be less efficient than after i.m. injections of the free hormone. With pigs also the LH response to the injection of GnRH-liposomes was relatively poor. Apparently, biological activity is missing with very low GnRH concentrations. The results furnish good information on how to modify the liposome carrier in order to produce preparations with changed rates of GnRH release.
Schäfer
H
H
Central Institute of Isotope and Radiation Research, Academy of Agricultural Sciences of the GDR.
Schmidt
W
W
Berger
H
H
Bergfeld
J
J
D000818:Animals; D007273:Injections, Intramuscular; D008081:Liposomes; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D009919:Orchiectomy; D010906:Pituitary Hormone-Releasing Hormones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D011817:Rabbits; D013268:Stimulation, Chemical; D013552:Swine
D008081:Liposomes; D010906:Pituitary Hormone-Releasing Hormones; D007986:Luteinizing Hormone