title: Myristic acid-conjugated polyethylenimine for brain-targeting delivery: in vivo and ex vivo imaging evaluation.
abstract: To investigate the potential of myristic acid (MC) to mediate brain delivery of polyethylenimine (PEI) as a gene delivery system, a covalent conjugate (MC-PEI) of MC, and PEI was synthesized. A near-infrared fluorescence probe, IR820 was conjugated to MC-PEI to explore its in vivo distribution after intravenous (i.v.) administration in mice. The brain targeting ability of MC-PEI was evaluated by near-infrared fluorescence imaging and analyzed semiquantitatively by fluorescence intensity, respectively. Significant NIR fluorescent signal was detected in the brain 12 h after i.v. administration and further confirmed by imaging the whole brain and brain slices. Semiquantitative results from fluorescence intensity further supported the successful brain delivery of MC-PEI which led to a very significant increase ( approximately 200%) in the brain uptake after i.v. injection in comparison with unmodified PEI. The capability of MC-PEI to condense DNA was further confirmed using agarose gel retardation assay, indicating its potential for gene delivery. The significant in vivo and ex vivo results suggest that MC-PEI is a promising brain-targeting drug delivery system, especially for gene delivery.
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing, P.R. China.
authors.forename: Qinggang
authors.initials: Q
authors.lastname: Meng
authors.forename: Mei
authors.initials: M
authors.lastname: Yu
authors.forename: Bing
authors.initials: B
authors.lastname: Gu
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Changyou
authors.initials: C
authors.lastname: Zhan
authors.forename: Cao
authors.initials: C
authors.lastname: Xie
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhou
authors.forename: Weiyue
authors.initials: W
authors.lastname: Lu
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D018014:Gene Transfer Techniques; D007208:Indocyanine Green / Q000031:analogs & derivatives / Q000737:chemistry; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D009226:Myristates / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D019814:Myristic Acid / Q000737:chemistry*; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D013050:Spectrometry, Fluorescence; D019265:Spectroscopy, Near-Infrared
chemical_list: D004337:Drug Carriers; C541053:IR 820; D009226:Myristates; D019814:Myristic Acid; D011094:Polyethyleneimine; D007208:Indocyanine Green