[Lani]

what the future may hold:
Pharm Res. 2012 Mar 8. [Epub ahead of print]
Treatment of Experimental Brain Metastasis with MTO-Liposomes: Impact of Fluidity and LRP-Targeting on the Therapeutic Result.
Orthmann A, Zeisig R, Süss R, Lorenz D, Lemm M, Fichtner I.
Source
Experimental Pharmacology, Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125, Berlin-Buch, Germany.
Abstract
PURPOSE:
To test targeted liposomes in an effort to improve drug transport across cellular barriers into the brain.
METHODS:
Therefore we prepared Mitoxantrone (MTO) entrapping, rigid and fluid liposomes, equipped with a 19-mer angiopeptide as ligand for LDL lipoprotein receptor related protein (LRP) targeting.
RESULTS:
Fluid, ligand bearing liposomes showed in vitro the highest cellular uptake and transcytosis and were significantly better than the corresponding ligand-free liposomes and rigid, ligand-bearing vesicles. Treatment of mice, transplanted with human breast cancer cells subcutaneously and into the brain, with fluid membrane liposomes resulted in a significant reduction in the tumor volume by more than 80% and in a clear reduction in drug toxicity. The improvement was mainly depended on liposome fluidity while the targeting contributed only to a minor degree. Pharmacokinetic parameters were also improved for liposomal MTO formulations in comparison to the free drug. So the area under the curve was increased and t(1/2) was extended for liposomes.
CONCLUSION:
Our data show that it is possible to significantly improve the therapy of brain metastases if MTO-encapsulating, fluid membrane liposomes are used instead of free MTO. This effect could be further enhanced by fluid, ligand bearing liposomes.
PMID: 22399388