Long-circulating and target-specific distributions of cyanine 5.5-labeled hyaluronic acid nanoparticles in mouse organs during 28 days after a single administration

Yun, Tae Sik; Lin, Chunmei; Yon, Jung-Min; Park, Seul Gi; Gwon, Lee Wha; Lee, Jong-Geol; Baek, In-Jeoung; Nahm, Sang-Seop; Lee, Beom Jun; Yun, Young Won; Nam, Sang-Yoon

doi:2018.58.4.183

Korean J Vet Res > Volume 58(4); 2018 > Article

Original Article

Korean Journal of Veterinary Research 2018;58(4):183-192.
DOI: https://doi.org/10.14405/kjvr.2018.58.4.183 Published online February 1, 2019.

Long-circulating and target-specific distributions of cyanine 5.5-labeled hyaluronic acid nanoparticles in mouse organs during 28 days after a single administration

Tae Sik Yun¹, Chunmei Lin², Jung-Min Yon¹, Seul Gi Park¹, Lee Wha Gwon¹, Jong-Geol Lee¹, In-Jeoung Baek³, Sang-Seop Nahm⁴, Beom Jun Lee¹, Young Won Yun¹, Sang-Yoon Nam¹

¹College of Veterinary Medicine and Veterinary Medical Center, Chungbuk National University
²College of Chinese Medicinal Materials, Jilin Agricultural University
³Asan Institute for Life Sciences, University of Ulsan College of Medicine
⁴College of Veterinary Medicine, Konkuk University

Abstract

Although hyaluronic acid (HA) has been developed as a nanoparticle (NP; 320-400 nm) for a drug delivery system, the tissue targeting efficacy and the pharmacokinetics of HA-NPs are not yet fully understood. After a dose of 5 mg/kg of cyanine 5.5-labeled HA-NPs or HA-polymers was intravenously administrated into mice, the fluorescence was measured from 0.5 h to 28 days. The HA-NPs fluorescence was generally stronger than that of HA-polymers, which was maintained at a high level over 7 days in vivo, after which it gradually decreased. Upon ex vivo imaging, liver, spleen, kidney, lung, testis and sublingual gland fluorescences were much higher than that of other organs. The fluorescence of HA-NPs in the liver, spleen and kidney was highest at 30 min, where it was generally maintained until 4 h, while it drastically decreased at 1 day. However, the fluorescence in the liver and spleen increased sharply at 7 days relative to 3 days, then decreased drastically at 14 days. Conversely, the fluorescence of HA-polymers in the lymph node was higher than that of HA-NPs. The results presented herein may have important clinical implications regarding the safety of as self-assembled HA-NPs, which can be widely used in biomedical applications.

Key Words: drug delivery systems, hyaluronic acid, nanoparticles, tissue distribution, toxicokinetics