Search: onr:"swepub:oai:DiVA.org:uu-191593" >
Enhanced Brain Deli...
Enhanced Brain Delivery of the Opioid Peptide DAMGO in Glutathione PEGylated Liposomes : A Microdialysis Study
-
- Lindqvist, Annika (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Translational PKPD
-
Rip, Jaap (author)
-
Gaillard, Pieter J (author)
-
show more...
-
- Björkman, Sven (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Translational PKPD
-
- Hammarlund-Udenaes, Margareta (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Translational PKPD
-
show less...
-
(creator_code:org_t)
- 2012-09-14
- 2013
- English.
-
In: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 10:5, s. 1533-1541
- Related links:
-
https://urn.kb.se/re...
-
show more...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- Glutathione PEGylated (GSH-PEG) liposomes were evaluated for their ability to enhance and prolong blood-to-brain drug delivery of the opioid peptide DAMGO (H-Tyr-d-Ala-Gly-MePhe-Gly-ol). An intravenous loading dose of DAMGO followed by a 2 h constant rate infusion was administered to rats, and after a washout period of 1 h, GSH-PEG liposomal DAMGO was administered using a similar dosing regimen. DAMGO and GSH-PEG liposomal DAMGO were also administered as a 10 min infusion to compare the disposition of the two formulations. Microdialysis made it possible to determine free DAMGO in brain and plasma, while the GSH-PEG liposomal encapsulated DAMGO was measured with regular plasma sampling. The antinociceptive effect of DAMGO was determined with the tail-flick method. All samples were analyzed using liquid chromatography–tandem mass spectrometry. The short infusion of DAMGO resulted in a fast decline of the peptide concentration in plasma with a half-life of 9.2 ± 2.1 min. Encapsulation in GSH-PEG liposomes prolonged the half-life to 6.9 ± 2.3 h. Free DAMGO entered the brain to a limited extent with a steady state ratio between unbound drug concentrations in brain interstitial fluid and in blood (Kp,uu) of 0.09 ± 0.04. GSH-PEG liposomes significantly increased the brain exposure of DAMGO to a Kp,uu of 0.21 ± 0.17 (p < 0.05). By monitoring the released, active substance in both blood and brain interstitial fluid over time, we were able to demonstrate that GSH-PEG liposomes offer a promising platform for enhancing and prolonging the delivery of drugs to the brain.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- drug delivery
- nanocarrier
- liposomes
- blood-brain barrier
- microdialysis
- pharmacokinetics
- antinociception
- opioid peptide
- Farmakokinetik och läkemedelsterapi
- Pharmacokinetics and Drug Therapy
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database