RT Journal Article
SR Electronic
T1 Body Distribution of Free, Liposomal and Nanoparticle-Associated Mitoxantrone in B16-Melanoma-Bearing Mice
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 232
OP 237
VO 280
IS 1
A1 R. Reszka
A1 P. Beck
A1 I. Fichtner
A1 M. Hentschel
A1 J. Richter
A1 J. Kreuter
YR 1997
UL http://jpet.aspetjournals.org/content/280/1/232.abstract
AB B16-melanoma-bearing mice were treated with four different formulations containing equivalent doses of the highly effective antineoplastic drug mitoxantrone. The formulations were: A mitoxantrone solution, a negatively charged liposome preparation (small unilamellar vesicles), a14C-labeled polybutylcyanoacrylate- (PBCA) nanoparticle suspension, and a suspension of poloxamine 1508-coated14C-PBCA-nanoparticles. After 1, 4 and 24 hr, three animals of each group were killed and the mitoxantrone concentrations in the blood, tumor, liver, spleen, heart and bone marrow were determined using an high performance liquid chromatography technique. Additionally, the concentrations of PBCA particles in the same tissues were measured by scintillation counting to compare the mitoxantrone distribution with the corresponding PBCA nanoparticle distribution. Each formulation led to a different body distribution profile of the drug. Liposomes drastically increased the blood level of mitoxantrone even after 24 hr, although free drug was cleared quickly. Liposomes also raised the concentration in the liver and spleen, but not the drug level in the tumor. PBCA-nanoparticles considerably increased the mitoxantrone concentrations in tumor, heart and spleen. However, the increase in tumor concentrations was not statistically significant due to the high variability. Nevertheless, the tumor growth was reduced significantly (P < .05) compared to both, the liposome and the solution preparation. The nanoparticle polymer concentrations did not completely mirror those of the drug concentrations. Especially in the heart, where no nanoparticle polymer radioactivity was found, the particle concentration did not completely correspond to the mitoxantrone concentration, revealing that a part of the drug was lost from the particles. These pharmacokinetic results correspond to parallel therapeutic effects obtained with mitoxantrone-loaded nanoparticles and liposomes in the B16 melanoma. The American Society for Pharmacology and Experimental Therapeutics