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Lymphatic trafficking kinetics and near-infrared imaging using star polymer architectures with controlled anionic character
Bagby, Taryn Rochelle Cai, Shuang Duan, Shaofeng Yang, Qiuhong Thati, Sharadvi Berkland, Cory J. Aires, Daniel J. Forrest, M. Laird
Bagby, Taryn Rochelle
Cai, Shuang
Duan, Shaofeng
Yang, Qiuhong
Thati, Sharadvi
Berkland, Cory J.
Aires, Daniel J.
Forrest, M. Laird
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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 hrs 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 to 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 to 20 hrs in the popliteal nodes and 19 to 114 hrs 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.
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This is the published version. Copyright Elsevier
Date
2012-04-22
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Elsevier
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Keywords
Lymphatics, imaging, polymer trafficking
Citation
Bagby, Taryn R. et al. "Lymphatic trafficking kinetics and near-infrared imaging using star polymer architectures with controlled anionic character." Eur J Pharm Sci. 2012 Aug 30; 47(1): 287–294.
http://dx.doi.org/10.1016/j.ejps.2012.04.016