In vivo Functional Evaluation of Increased Brain Delivery of the Opioid Peptide DAMGO by Glutathione-PEGylated Liposomes

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Fältnamn	Indikatorer	Metadata
000		03493naa a2200421 4500
001		oai:DiVA.org:uu-267583
003		SwePub
008		151124s2016 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2675832 URI
024	7	a https://doi.org/10.1007/s11095-015-1774-32 DOI
040		a (SwePub)uu
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Lindqvist, Annika,d 1983-u Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab,Translational PKPD4 aut0 (Swepub:uu)annbo297
245	1 0	a In vivo Functional Evaluation of Increased Brain Delivery of the Opioid Peptide DAMGO by Glutathione-PEGylated Liposomes
264		c 2015-08-15
264	1	b Springer Science and Business Media LLC,c 2016
338		a print2 rdacarrier
520		a Purpose:The purpose of this study was to evaluate formulation factors causing improvement in brain delivery of a small peptide after encapsulation into a targeted nanocarrier in vivo.Methods:The evaluation was performed in rats using microdialysis, which enabled continuous sampling of the released drug in both the brain (striatum) and blood. Uptake in brain could thereby be studied in terms of therapeutically active, released drug.Results:We found that encapsulation of the peptide DAMGO in fast-releasing polyethylene glycol (PEG)ylated liposomes, either with or without the specific brain targeting ligand glutathione (GSH), doubled the uptake of DAMGO into the rat brain. The increased brain delivery was observed only when the drug was encapsulated into the liposomes, thus excluding any effects of the liposomes themselves on the blood-brain barrier integrity as a possible mechanism. The addition of a GSH coating on the liposomes did not result in an additional increase in DAMGO concentrations in the brain, in contrast to earlier studies on GSH coating. This may be caused by differences in the characteristics of the encapsulated compounds and the composition of the liposome formulations. Conclusions:We were able to show that encapsulation into PEGylated liposomes of a peptide with limited brain delivery could double the drug uptake into the brain without using a specific brain targeting ligand.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Farmaceutiska vetenskaper0 (SwePub)301012 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Pharmaceutical Sciences0 (SwePub)301012 hsv//eng
653		a Brain delivery
653		a liposomes
653		a blood-brain barrier
653		a microdialysis
653		a opioid peptide
653		a Farmakokinetik och läkemedelsterapi
653		a Pharmacokinetics and Drug Therapy
700	1	a Rip, Jaap4 aut
700	1	a van Kregten, Joan4 aut
700	1	a Gaillard, Pieter J4 aut
700	1	a Hammarlund-Udenaes, Margaretau Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab,Translational PKPD4 aut0 (Swepub:uu)marghamm
710	2	a Uppsala universitetb Institutionen för farmaceutisk biovetenskap4 org
773	0	t Pharmaceutical researchd : Springer Science and Business Media LLCg 33:1, s. 177-185q 33:1<177-185x 0724-8741x 1573-904X
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-267583
856	4 8	u https://doi.org/10.1007/s11095-015-1774-3

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