Liposome mediated delivery of biologicals to the brain as a novel therapeutic strategy for Alzheimer’s disease

Prof. Dr. U. Müller1), University Heidelberg/Germany

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Professor Dr. Ulrike MüllerUniversity of Heidelberg, Institute for Pharmacy and Molecular Biotechnology (IPMB), Im Neuenheimer Feld 364, 69120 Heidelberg, Germany

People involved

Lara Kilian (PhD fellow sponsored by the PRC) - University Heidelberg, Germany

Tanja Roeder (PhD fellow sponsored by the PRC) - University Heidelberg, Germany


The blood-brain barrier (BBB) is a very selective biological barrier protecting the brain. It is formed by endothelial cells of microvessels being characterized by extremely tight junctions and high expression of export proteins. It is impermeable for macromolecules including biologicals. However, biologicals are of highest interest for the therapy of Alzheimer´s disease.1) A promising option to overcome the BBB with macromolecules is the use of colloidal drug carrier systems, for example liposomes2) or solid lipid nanoparticles, which are surface-modified to recognize specific binding sites at the BBB and with subsequent internalization and transcytosis across the barrier. Surface modifications are achieved by coupling such nanocarriers to antibodies against receptors at the BBB, cell penetrating peptides (CPPs), or (fragments of) apolipoproteins. Only very few data are available with macromolecules despite a very urgent clinical need for Alzheimer’s disease, as all clinical trials with conventional drugs have failed so far.

Therefore, we aim to use liposome-mediated drug delivery for the transfer of macromolecules across the BBB. We expect to conduct proof-of-principle experiments to deliver biologicals across the BBB. Importantly, our preliminary data support the feasibility of this approach to deliver biologicals via intravenous injection of liposomal formulations to the brain, which represents an entirely novel treatment approach for Alzheimer’s disease.

Benefit for the community

Due to the modular nature of this project optimized delivery systems may in the future be applied to other biologicals or nucleic acids.

Visit the supervisors lab


Müller UC, Deller T, Korte M, 2017
Not just amyloid: physiological functions of the amyloid precursor protein family
Nat. Rev. Neurosci. 18, 281-298
Helm F, Fricker G, 2015
Liposomal conjugates for drug delivery to the central nervous system
Pharmaceutics 7, 27-42
Publications derived from the project:
Bold CS, Baltissen D, Ludewig S, Back MK, Just J, Kilian L, Erdinger S, Banicevic M, Rehra L, Almouhanna F, Nigri M, Wolfer DP, Spilger R, Rohr K, Kann O, Buchholz CJ, von Engelhardt J, Korte M, Müller UC, 2022
APPsα Rescues Tau-Induced Synaptic Pathology
J. Neurosci. 42, 5782-5802
Baltissen D, Bold CS, Rehra L, Banićević M, Fricke J, Just J, Ludewig S, Buchholz CJ, Korte M, Müller UC, 2023
APPsα rescues CDK5 and GSK3β dysregulation and restores normal spine density in Tau transgenic mice
Front. Cell Neurosci. 17, 1106176
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