Impact of Molecular Weight on Lymphatic Drainage of a Biopolymer-Based Imaging Agent

Pharmaceutics

Taryn R. Bagby²  Shuang Cai²  Shaofeng Duan²  Sharadvi Thati²  Daniel J. Aires¹ 

[1] Division of Dermatology, Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA;Department of Pharmaceutical Chemistry, University of Kansas, 2095 Constant Ave, Lawrence, KS 66047, USA;

关键词: lymphatic imaging;    hyaluronan;    fluorescence;    nanoparticle;    tumor metastasis;   

DOI  :  10.3390/pharmaceutics4020276

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.