title: Lymphatic trafficking kinetics and near-infrared imaging using star polymer architectures with controlled anionic character.
abstract: Targeted lymphatic delivery of nanoparticles for drug delivery and imaging is primarily dependent on size and charge. Prior studies have observed increased lymphatic uptake and retentions of over 48 h for negatively charged particles compared to neutral and positively charged particles. We have developed new polymeric materials that extend retention over a more pharmaceutically relevant 7-day period. We used whole body fluorescence imaging to observe in mice the lymphatic trafficking of a series of anionic star poly-(6-O-methacryloyl-D-galactose) polymer-NIR dye (IR820) conjugates. The anionic charge of polymers was increased by modifying galactose moieties in the star polymers with succinic anhydride. Increasing anionic nature was associated with enhanced lymphatic uptake up to a zeta potential of ca.-40 mV; further negative charge did not affect lymphatic uptake. Compared to the 20% acid-conjugate, the 40-90% acid-star-polymer conjugates exhibited a 2.5- to 3.5-fold increase in lymphatic uptake in both the popliteal and iliac nodes. The polymer conjugates exhibited node half-lives of 2-20 h in the popliteal nodes and 19-114 h in the deeper iliac nodes. These polymer conjugates can deliver drugs or imaging agents with rapid lymphatic uptake and prolonged deep-nodal retention; thus they may provide a useful vehicle for sustained intralymphatic drug delivery with low toxicity.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS, USA.
authors.forename: Taryn R
authors.initials: TR
authors.lastname: Bagby
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Duan
authors.forename: Shuang
authors.initials: S
authors.lastname: Cai
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Yang
authors.forename: Sharadvi
authors.initials: S
authors.lastname: Thati
authors.forename: Cory
authors.initials: C
authors.lastname: Berkland
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Aires
authors.forename: M Laird
authors.initials: ML
authors.lastname: Forrest
mesh_terms: D000818:Animals; D000838:Anions / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005453:Fluorescence; D005690:Galactose / Q000008:administration & dosage / Q000737:chemistry; D006207:Half-Life; D007272:Injections, Intralymphatic; D007700:Kinetics; D008196:Lymph / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D061848:Optical Imaging / Q000379:methods; D010316:Particle Size; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013387:Succinic Anhydrides / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000838:Anions; D003692:Delayed-Action Preparations; D011108:Polymers; D013387:Succinic Anhydrides; C031801:succinic anhydride; D005690:Galactose