Local drug delivery using poly(lactic-co-glycolic acid) nanoparticles in thermosensitive gels for inner ear disease treatment

被引:27
作者
Kim, Dong-Hyun [1 ]
Nguyen, Thu Nhan [1 ]
Han, Young-Min [1 ]
Tran, Phuong [1 ]
Rho, Jinhyung [2 ]
Lee, Jae-Young [1 ]
Son, Hwa-Young [2 ]
Park, Jeong-Sook [1 ]
机构
[1] Chungnam Natl Univ, Coll Pharm, 99 Daehak Ro, Daejeon 34134, South Korea
[2] Chungnam Natl Univ, Coll Vet Med, Daejeon, South Korea
基金
新加坡国家研究基金会;
关键词
Inner ear drug delivery; intratympanic administration; thermosensitive gel; PLGA nanoparticles; dexamethasone; PLGA NANOPARTICLES; IN-VITRO; SUSTAINED-RELEASE; MENIERES-DISEASE; DEXAMETHASONE; STABILITY; SKIN; BIOAVAILABILITY; MICROSPHERES; SCAFFOLDS;
D O I
10.1080/10717544.2021.1992041
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Intratympanic (IT) therapies have been explored to address several side effects that could be caused by systemic administration of steroids to treat inner ear diseases. For effective drug delivery to the inner ear, an IT delivery system was developed using poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and thermosensitive gels to maintain sustained release. Dexamethasone (DEX) was used as a model drug. The size and zeta potential of PLGA NPs and the gelation time of the thermosensitive gel were measured. In vitro drug release was studied using a Franz diffusion cell. Cytotoxicity of the formulations was investigated using SK-MEL-31 cells. Inflammatory responses were evaluated by histological observation of spiral ganglion cells and stria vascularis in the mouse cochlea 24 h after IT administration. In addition, the biodistribution of the formulations in mouse ears was observed by fluorescence imaging using coumarin-6. DEX-NPs showed a particle size of 150.0 +/- 3.2 nm in diameter and a zeta potential of -18.7 +/- 0.6. The DEX-NP-gel showed a gelation time of approximately 64 s at 37 degrees C and presented a similar release profile and cytotoxicity as that for DEX-NP. Furthermore, no significant inflammatory response was observed after IT administration. Fluorescence imaging results suggested that DEX-NP-gel sustained release compared to the other formulations. In conclusion, the PLGA NP-loaded thermosensitive gel may be a potential drug delivery system for the inner ear.
引用
收藏
页码:2268 / 2277
页数:10
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