Bone marrow targeted liposomal drug delivery systems

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2011
Baki, Mert
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Homing is the process that stem cells move to their own stem cell niches under the influence of chemokines like stromal-derived factor-1α (SDF-1α) upon bone marrow transplantation (BMT). There is a need for increasing homing efficiency after BMT since only 10-15% of the transplanted cells can home to their own niches and a limited amount of donor marrow can be transplanted. In this study, we aimed to develop and characterize bone marrow targeted liposomal SDF-1α delivery system prepared by extrusion method. Alendronate conjugation was chosen to target the liposomes to bone marrow microenvironment, particularly the endosteal niche. Optimization studies were conducted with the model protein (-lactoglobulin). 200 nm sized 5% pegylated DPPC:Cho (2:0.5) liposomes were chosen for targeted SDF-1α loaded large unilamellar liposomes (LUVs). DSPE-PEG2000-Carboxylic Acid was conjugated with alendronate via carbodiimide chemistry for preparing targeted liposomes. Alendronate (ALE) conjugation was shown by FT-IR and the conjugation efficiency was found 34.5±4.6 %. 5%ALE-PEG/LUV200 encapsulated 48.3 ± 0.3% of SDF-1α and released 44.10.9% after 24h, with a similar profile as 5%PEG/LUV200 and 2.5%ALE-PEG/LUV200. 5%ALE-PEG/LUV200 had more negative potential (-21.9 mV) and significantly higher affinity to hydroxyapatite than 5%PEG/LUV200 and 2.5%ALE-PEG/LUV200. Migration assays conducted with human mesenchymal stem cells showed that SDF-1α released (24.4 ng/ml) from the liposomes in 24 hours increased the chemotactic activity of these cells. SDF-1 loaded 5%ALE-PEG/LUV200, reported for the first time in literature, has potential as an effective vehicle for improving homing efficiency and thereby permitting successful BMT from young donors. Additionally, this system could also be considered for treating large and difficult bone fractures with recruitment of host stem cells. However, further studies including migration assays with human hematopoietic stem cells and in-vivo distribution of the liposomal system are suggested.
Liposomes.
http://etd.lib.metu.edu.tr/upload/12613251/index.pdf
https://hdl.handle.net/11511/20567
Graduate School of Natural and Applied Sciences, Thesis

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Citation Formats
M. Baki, “Bone marrow targeted liposomal drug delivery systems,” M.S. - Master of Science, Middle East Technical University, 2011.
METU IIS - Integrated Information Service open@metu.edu.tr