title: Targeted drug delivery crossing cytoplasmic membranes of intended cells via ligand-grafted sterically stabilized liposomes.
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.
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois, Chicago, IL 60612-7231, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
authors.forename: Eunjung
authors.initials: E
authors.lastname: Jeon
authors.forename: Bao-Shiang
authors.initials: BS
authors.lastname: Lee
authors.forename: Hayat
authors.initials: H
authors.lastname: Onyuksel
authors.forename: Zaijie Jim
authors.initials: ZJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D016466:CHO Cells; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008024:Ligands; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D018847:Opioid Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013237:Stereoisomerism
chemical_list: D008024:Ligands; D008081:Liposomes; D018847:Opioid Peptides; D012710:Serum Albumin, Bovine; C030058:dermorphin