Targeted drug delivery crossing cytoplasmic membranes of intended cells via ligand-grafted sterically stabilized liposomes.
J Control Release
; 110(3): 505-13, 2006 Feb 21.
Article
in En
| MEDLINE
| ID: mdl-16356575
ABSTRACT
In this study, we tested whether sterically stabilized liposomes (SSL) with surface ligands specific for the mu opioid receptor (MOR) can actively target MOR-expressing cells. Dermorphin, a selective MOR agonist, was conjugated to DSPE-PEG(3400) to obtain DSPE-PEG(3400)-dermorphin. Dermorphin-grafted SSL (dermorphin-SSL) was prepared by thin-film rehydration-extrusion and post-insertion method. DSPE-PEG(3400)-dermorphin and dermorphin-SSL retained the affinity to MOR as determined by receptor binding assay using [(3)H]DAMGO, whereas plain SSL without surface ligands showed no binding to the receptor. Cellular uptake of cholesteryl BODIPY encapsulated dermorphin-SSL was studied by microplate spectrofluorometry as well as fluorescent and confocal microscopy. Significant fluorescence signal was observed inside CHO-hMOR cells after the treatment with dermorphin-SSL, indicative of MOR-mediated endocytosis. In contrast, no uptake of dermorphin-SSL was found in naive CHO cells or CHO-hDOR cells that lack MOR. Taken together, these results demonstrate that dermorphin-SSL delivery system is capable of targeting intracellular components of MOR-expressing cells. Such a system may be applied to carry pharmaceutical agents to achieve region-specific delivery of analgesics and/or to attenuate side effects associated with opioids.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Membrane
/
Drug Delivery Systems
/
Liposomes
Limits:
Animals
/
Humans
Language:
En
Journal:
J Control Release
Journal subject:
FARMACOLOGIA
Year:
2006
Document type:
Article
Affiliation country:
United States