Treatment of experimental brain metastasis with MTO-liposomes: impact of fluidity and LRP-targeting on the therapeutic result

Item Type:	Article
Title:	Treatment of experimental brain metastasis with MTO-liposomes: impact of fluidity and LRP-targeting on the therapeutic result
Creators Name:	Orthmann, A. and Zeisig, R. and Suess, R. and Lorenz, D. and Lemm, M. and Fichtner, I.
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.
Keywords:	Brain Metastases, LRP, Targeting, Transcytosis, Uptake, Animals, Mice
Source:	Pharmaceutical Research
ISSN:	0724-8741
Publisher:	Springer
Volume:	29
Number:	7
Page Range:	1949-1959
Date:	July 2012
Official Publication:	https://doi.org/10.1007/s11095-012-0723-7
PubMed:	View item in PubMed

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