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Long-circulating and target-specific distributions of cyanine 5.5-labeled hyaluronic acid nanoparticles in mouse organs during 28 days after a single administration
2018
Yun, T.S., Chungbuk National University, Cheongju, Republic of Korea | Chunmei Lin, Jilin Agricultural University, Changchun, Republic of Korea | Yon, J.M., Chungbuk National University, Cheongju, Republic of Korea | Park, S.G., Chungbuk National University, Cheongju, Republic of Korea | Gwon, L.W., Chungbuk National University, Cheongju, Republic of Korea | Lee, J.G., Chungbuk National University, Cheongju, Republic of Korea | Baek, I.J., University of Ulsan College of Medicine, Seoul, Republic of Korea | Nahm, S.S., Konkuk University, Seoul, Republic of Korea | Lee, B.J., Chungbuk National University, Cheongju, Republic of Korea | Yun, Y.W., Chungbuk National University, Cheongju, Republic of Korea | Nam, S.Y., Chungbuk National University, Cheongju, Republic of Korea
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.
Show more [+] Less [-]Temporal and subcellular distributions of Cy5.5-labeled hyaluronic acid nanoparticles in mouse organs during 28 days as a drug carrier
2017
Lin, C., Jilin Agricultural University, Changchun, China | Kim, S.B., Chungbuk National University, Cheongju, Republic of Korea | Yon, J.M., Chungbuk National University, Cheongju, Republic of Korea | Park, S.G., Chungbuk National University, Cheongju, Republic of Korea | Gwon, L.W., Chungbuk National University, Cheongju, Republic of Korea | Lee, J.G., Chungbuk National University, Cheongju, Republic of Korea | Baek, I.J., Asan Medical Center and University of Ulsan, Seoul, Republic of Korea | Lee, B.J., Chungbuk National University, Cheongju, Republic of Korea | Yun, Y.W., Chungbuk National University, Cheongju, Republic of Korea | Nam, S.Y., Chungbuk National University, Cheongju, Republic of Korea
Temporal and subcellular distributions of hyaluronic acid (HA) as a degradable nanoparticle (NP) in animals were investigated to determine if HA-NP could be utilized as an appropriate drug delivery system. After mice were intravenously injected with 5 mg/kg of Cy5.5-labeled HA-NP sized 350-400 nm or larger HA-polymers, the fluorescence intensity was measured in all homogenized organs from 0.5 h to 28 days. HA-NP was greatly detected in spleen, liver and kidney until day 28, while it was maintained at low levels in other organs. HA-polymer was observed at low levels in all organs. HA-NP quantities in spleen and liver were reduced until day 3, but increased sharply between days 3 and 7, then decreased again, while their HA-polymers were maintained at low levels until day 28. In kidneys, both HA-NP and HA-polymer showed high levels after 0.5 h of administration, but steadily decreased until day 28. According to ultrastructural analyses, HA-NP was engulfed in Kupffer cells of liver and macrophages of spleen and kidney at day 1 and was accumulated in the cytoplasm of kidney tubular cells at day 7. Overall, these findings suggest that HA-NP could be considered a desirable drug carrier in the liver, kidney, or spleen.
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