title: Solubilization of flurbiprofen into aptamer-modified PEG-PLA micelles for targeted delivery to brain-derived endothelial cells in vitro.
abstract: Novel aptamer-functionalized polyethylene glycol-polylactic acid (PEG-PLA) (APP) micelles were developed with the objective to target the transferrin receptor on brain endothelial cells. Flurbiprofen, a potential drug for therapeutic management of Alzheimer's disease (AD), was loaded into the APP micelles using the co-solvent evaporation method. Results indicated that 9.03% (w/w) of flurbiprofen was entrapped in APP with good retention capacity in vitro. Targeting potential of APPs was investigated using the transferring receptor-expressing murine brain endothelial bEND5 cell line. APPs significantly enhanced surface association of micelles to bEND5 cells as quantified by fluorescence spectroscopy. Most importantly, APPs significantly enhanced intracellular flurbiprofen delivery when compared to unmodified micelles. These results suggest that APP micelles may offer an effective strategy to deliver therapeutically effective flurbiprofen concentrations into the brain for AD patients.
authors.affiliation: Division of Pharmaceutical Sciences, James L. Winkle College of Pharmacy, University of Cincinnati , Cincinnati, OH , USA and.
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Mu
authors.forename: Nimita
authors.initials: N
authors.lastname: Dave
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Pankaj
authors.initials: P
authors.lastname: Desai
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pauletti
authors.forename: Shuhua
authors.initials: S
authors.lastname: Bai
authors.forename: Jiukuan
authors.initials: J
authors.lastname: Hao
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000378:metabolism; D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000378:metabolism; D005480:Flurbiprofen / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052157:Aptamers, Nucleotide; D004337:Drug Carriers; D008823:Micelles; D011990:Receptors, Transferrin; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; D005480:Flurbiprofen