title: Fast release of lipophilic agents from circulating PEG-PDLLA micelles revealed by in vivo forster resonance energy transfer imaging.
abstract: Understanding the in vivo behavior of nanoparticles is critical for the translation of nanomedicine from laboratory research to clinical trials. In this work, in vivo Forster resonance energy transfer (FRET) imaging was employed to monitor the release of hydrophobic molecules from circulating poly(ethylene glycol)-poly( D, L-lactic acid) (PEG-PDLLA) micelles. A lipophilic FRET pair (DiIC(18) and DiOC(18)) was physically entrapped into micelle cores by mimicking the loading of hydrophobic drugs. The FRET efficiency was found significantly reduced within 15 min after intravenous injection, implying that DiIC(18) and DiOC(18) quickly escaped from the circulating micelles. FRET spectroscopy studies further demonstrated that alpha- and beta-globulins were major factors for the observed fast release, while gamma-globulins, albumin, and red blood cells played minor roles. These results provide useful information for developing blood-stable micelles to deliver hydrophobic drugs to the target site via prolonged circulation and extravasation from the vascular system.
authors.affiliation: Department of Chemistry, Weldon School of Biomedical Engineering, and Oncological Sciences Center, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Chen
authors.forename: Sungwon
authors.initials: S
authors.lastname: Kim
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wang
authors.forename: Philip S
authors.initials: PS
authors.lastname: Low
authors.forename: Kinam
authors.initials: K
authors.lastname: Park
authors.forename: Ji-Xin
authors.initials: JX
authors.lastname: Cheng
mesh_terms: D000510:Alpha-Globulins / Q000737:chemistry; D000818:Animals; D001609:Beta-Globulins / Q000737:chemistry; D001703:Biophysics / Q000379:methods; D002417:Cattle; D004337:Drug Carriers / Q000737:chemistry; D004912:Erythrocytes / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D036103:Nanotechnology; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry; D013050:Spectrometry, Fluorescence
chemical_list: D000510:Alpha-Globulins; D001609:Beta-Globulins; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D012709:Serum Albumin; C499774:polyethylene glycol-polylactide-polyethylene glycol; D011092:Polyethylene Glycols