title: Probing in vivo trafficking of polymer/DNA micellar nanoparticles using SPECT/CT imaging.
abstract: Successful translation of nonviral gene delivery to therapeutic applications requires detailed understanding of in vivo trafficking of the vehicles. This report compares the pharmacokinetic and biodistribution profiles of polyethylene glycol-b-polyphosphoramidate (PEG-b-PPA)/DNA micellar nanoparticles after administration through intravenous infusion, intrabiliary infusion, and hydrodynamic injection using single photon emission computed tomography/computed tomography (SPECT/CT) imaging. Nanoparticles were labeled with (111)In using an optimized protocol to retain their favorable physicochemical properties. Quantitative imaging analysis revealed different in vivo trafficking kinetics for PEG-b-PPA/DNA nanoparticles after different routes of administration. The intrabiliary infusion resulted in the highest liver uptake of micelles compared with the other two routes. Analysis of intrabiliary infusion by the two-compartment pharmacokinetic modeling revealed efficient retention of micelles in the liver and minimal micelle leakage from the liver to the blood stream. This study demonstrates the utility of SPECT/CT as an effective noninvasive imaging modality for the characterization of nanoparticle trafficking in vivo and confirms that intrabiliary infusion is an effective route for liver-targeted delivery of DNA-containing nanoparticles.
authors.affiliation: Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA.
authors.forename: Rajesh R
authors.initials: RR
authors.lastname: Patil
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.forename: Sangeeta R
authors.initials: SR
authors.lastname: Banerjee
authors.forename: Yong
authors.initials: Y
authors.lastname: Ren
authors.forename: Derek
authors.initials: D
authors.lastname: Leong
authors.forename: Xuan
authors.initials: X
authors.lastname: Jiang
authors.forename: Martin
authors.initials: M
authors.lastname: Pomper
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tsui
authors.forename: Dara L
authors.initials: DL
authors.lastname: Kraitchman
authors.forename: Hai-Quan
authors.initials: HQ
authors.lastname: Mao
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D004247:DNA / Q000737:chemistry*; D005260:Female; D018014:Gene Transfer Techniques; D007262:Infusions, Intravenous; D008099:Liver; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010957:Plasmids / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: D008823:Micelles; D011092:Polyethylene Glycols; D004247:DNA