Myristic acid-conjugated polyethylenimine for brain-targeting delivery: in vivo and ex vivo imaging evaluation.
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.
Meng
Qinggang
Q
School of Pharmacy, China Pharmaceutical University, Nanjing, P.R. China.
Yu
Mei
M
Gu
Bing
B
Li
Jin
J
Liu
Yu
Y
Zhan
Changyou
C
Xie
Cao
C
Zhou
Jianping
J
Lu
Weiyue
W
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
D004337:Drug Carriers; C541053:IR 820; D009226:Myristates; D019814:Myristic Acid; D011094:Polyethyleneimine; D007208:Indocyanine Green