Strategier för transport till hjärnan av peptider och proteiner som läkemedel: Nanopartiklars roll för ett ökat upptag över blod-hjärnbarriären.

Tidsperiod: 2011-01-01 till 2013-12-31

Projektledare: Margareta Hammarlund-Udenaes

Finansiär: Vetenskapsrådet

Bidragstyp: Projektbidrag

Budget: 3 090 000 SEK

Peptides and proteins are objects of great interest as potential new medicines for the treatment of central nervous system (CNS) disorders. However, the transport into the brain is minute due to the blood-brain barrier (BBB). Nanocarriers are promising candidates to improve the delivery.We recently presented a key new concept and associated methods, describing CNS delivery of low molecular weight drugs, and believe that this concept could also govern the understanding of peptide and protein delivery to the brain. The concept has created much attention, as shown for example by the election of the main applicant as the Chair of the Gordon conference on ?Barriers of the CNS? in 2014. Thus, the purpose of the research is to develop concepts and furthering understanding of the transport of large molecules across the BBB in health and disease, with focus on the role of nanocarriers in enhancing the uptake.The nanocarrier delivery of opioid peptide DAMGO is presently studied. Proteins are chosen in the starting phase in relation to the choice of nanocarriers, to be produced by international collaborators. Methods will be microdialysis sampling of free peptide/protein in rat brain, with LC-MS/MS or ELISA analyses. The new MALDI-TOF IMS technique will be used to measure peptides/proteins and effect markers. The importance of the project lies in furthering understanding of large molecular transport to the brain and thereby possible new treatments for CNS diseases.