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Impact of Molecular Weight on Lymphatic Drainage of a Biopolymer-Based Imaging Agent
Department of Pharmaceutical Chemistry, University of Kansas, 2095 Constant Ave, Lawrence, KS 66047, USA
Division of Dermatology, Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA
* Author to whom correspondence should be addressed.
Received: 7 March 2012; in revised form: 23 April 2012 / Accepted: 8 May 2012 / Published: 23 May 2012
Abstract: New lymphatic imaging technologies are needed to better assess immune function and cancer progression and treatment. Lymphatic uptake depends mainly on particle size (10–100 nm) and charge. The size of carriers for imaging and drug delivery can be optimized to maximize lymphatic uptake, localize chemotherapy to lymphatic metastases, and enable visualization of treatment deposition. Toward this end, female BALB/c mice were injected subcutaneously in the hind footpad or forearm with a series of six different molecular weight hyaluronan (HA) near-infrared dye (HA-IR820) conjugates (ca. 5–200 nm). Mice were imaged using whole body fluorescent imaging over two weeks. HA-IR820 fluorescence was clearly visualized in the draining lymphatic capillaries, and in the popliteal and iliac or axillary lymph nodes. The 74-kDa HA-IR820 had the largest lymph node area-under-the-curve. In contrast to prior reports, mice bearing limb tumors exhibited three-fold longer retention of 74-kDa HA-IR820 in the popliteal node compared to mice without tumors. HA conjugate kinetics and disposition can be specifically tailored by altering their molecular weight. The specific lymphatic uptake and increased nodal retention of HA conjugates indicate significant potential for development as a natural biopolymer for intralymphatic drug delivery and imaging.
Keywords: lymphatic imaging; hyaluronan; fluorescence; nanoparticle; tumor metastasis
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MDPI and ACS Style
Bagby, T.R.; Cai, S.; Duan, S.; Thati, S.; Aires, D.J.; Forrest, L. Impact of Molecular Weight on Lymphatic Drainage of a Biopolymer-Based Imaging Agent. Pharmaceutics 2012, 4, 276-295.
Bagby TR, Cai S, Duan S, Thati S, Aires DJ, Forrest L. Impact of Molecular Weight on Lymphatic Drainage of a Biopolymer-Based Imaging Agent. Pharmaceutics. 2012; 4(2):276-295.
Bagby, Taryn R.; Cai, Shuang; Duan, Shaofeng; Thati, Sharadvi; Aires, Daniel J.; Forrest, Laird. 2012. "Impact of Molecular Weight on Lymphatic Drainage of a Biopolymer-Based Imaging Agent." Pharmaceutics 4, no. 2: 276-295.