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Thi Phuc LeThi Phuc Le
충남대학교
J. Control. Release, Feb 20 2025, S0168-3659(25)00173-7 | https://doi.org/10.1016/j.jconrel.2025.02.060
Injectable polyplex-loaded glycol chitosan thermogel for efficient and safe inner ear gene delivery
Thi Phuc Le a,1, Le Thi Thuy b,c,1, Sheng Jin d,1, Sun-Ae Shin d,e,f, Ah-Ra Lyu d,e,f, Yong-Ho Park d,e,f, Joon Sig Choi b, Kang Moo Huh a,g
aDepartment of Polymer Science and Engineering, Chungnam National University, Daejeon 34134, South Korea
bDepartment of Biochemistry, Chungnam National University, Daejeon 34134, South Korea
cDepartment of Biochemistry and Molecular Biology, Faculty of Biology, VNU University of Science, Thanh Xuan, 334 Nguyen Trai, Hanoi, Viet Nam
dDepartment of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, South Korea
eDepartment of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University and Chungnam National University Hospital, Daejeon 35015, South Korea
fBrain Research Institute, College of Medicine, Chungnam National University, Daejeon 35015, South Korea
gDepartment of Materials Science and Engineering, Chungnam National University, Daejeon 34134, South Korea
1These three authors contributed equally to this work.
Correspondence to: Yong-Ho Park, Joon Sig Choi, Kang Moo Huh
aDepartment of Polymer Science and Engineering, Chungnam National University, Daejeon 34134, South Korea
bDepartment of Biochemistry, Chungnam National University, Daejeon 34134, South Korea
cDepartment of Biochemistry and Molecular Biology, Faculty of Biology, VNU University of Science, Thanh Xuan, 334 Nguyen Trai, Hanoi, Viet Nam
dDepartment of Medical Science, College of Medicine, Chungnam National University, Daejeon 35015, South Korea
eDepartment of Otolaryngology-Head and Neck Surgery, College of Medicine, Chungnam National University and Chungnam National University Hospital, Daejeon 35015, South Korea
fBrain Research Institute, College of Medicine, Chungnam National University, Daejeon 35015, South Korea
gDepartment of Materials Science and Engineering, Chungnam National University, Daejeon 34134, South Korea
1These three authors contributed equally to this work.
Correspondence to: Yong-Ho Park, Joon Sig Choi, Kang Moo Huh
Abstract
Gene therapy has emerged as a promising approach for treating inner ear disorders, such as hearing loss and balance impairments, which require precise and efficient delivery mechanisms. This study introduces a dual-component delivery system combining RH-PAMAM G2 dendrimer-based polyplexes with hexanoyl glycol chitosan (HGC) thermogel to enhance gene delivery to the inner ear. The RH-PAMAM G2 dendrimers, modified with histidine and arginine, demonstrated high DNA binding affinity, low cytotoxicity, and effective cellular uptake, facilitating stable plasmid DNA (pDNA) transfection in HEI-OC1 auditory cells. Encapsulating these polyplexes within the HGC thermogel, an injectable and thermosensitive hydrogel, resulted in a supportive matrix that protects against premature clearance and provides sustained gene release upon intratympanic administration. In vivo studies in a mouse model confirmed substantial gene expression in the cochlear tissues, with widespread distribution in regions including the spiral ganglion and organ of Corti, compared to polyplexes alone. The HGC thermogel also exhibited favorable biocompatibility, with no observed inflammation or adverse effects in the middle ear tissues. This novel polyplex-HGC thermogel system demonstrates potential as a safe, efficient injectable gene delivery platform, offering a significant advance in gene therapy for inner ear disorders.
논문정보
- Research article
- 2025년 02월 (BRIC 등록일 2025-02-25)
- 국내(교신)+국외 연구진
- 바이오·의료융합 > 바이오소재
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