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Abstract
The intranasal drug administration has attracted great interest as a non-invasive route allowing targeted delivery of drugs directly to the brain. However, one of the main issues in nasal drug administration is mucociliary clearance. Hyaluronate (HA) has been widely used as a mucoadhesive excipient for ocular, rectal, and vaginal delivery. Here, FG loop peptide (FGL) was conjugated to HA for improving enzymatic stability and delivery efficiency from the nose to the brain. The successful conjugation of FGL to aldehyde modified HA was confirmed by gel permeation chromatography (GPC) and 1H nuclear magnetic resonance (NMR). The outstanding enzymatic stability of HA-FGL conjugate was also corroborated by the GPC. The HA-FGL conjugate showed enhanced binding affinity onto nasal epithelial cells. In addition, in vivo nose-to-brain delivery of HA-FGL conjugate could be visualized by using an IVIS imaging system and fluorescence microscopy. Finally, in vivo therapeutic effect of HA-FGL conjugate was successfully confirmed by histological analysis, transferase-mediated uridine 5-triphosphate-biotin nick end-labeling (TUNEL) assay, immunofluorescent staining, transmission electron microscopy (TEM), and rotarod tests in hypoxic-ischemic encephalopathy model animals.

Author information

Kim YS1, Sung DK2, Kim H3, Kong WH4, Kim YE5, Hahn SK6.
1
Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, Republic of Korea.
2
Department of Pediatrics, Samsung Medical Center, School of Medicine, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea.
3
Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, Republic of Korea; PHI Biomed Co., 175 Yeoksam-ro, Gangnam-gu, Seoul 06247, Republic of Korea.
4
Advanced Bio Convergence Center, Pohang Techno Park 394 Jigok-ro, Nam-gu, Pohang 37668, Gyeoungbuk, Republic of Korea.
5
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea.
6
Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, Republic of Korea; PHI Biomed Co., 175 Yeoksam-ro, Gangnam-gu, Seoul 06247, Republic of Korea. Electronic address: skhanb@postech.ac.kr.