Intranasal tetrandrine temperature-sensitive in situ hydrogels for the treatment of microwave-induced brain injury

• Published in: International journal of pharmaceutics Vol. 583; p. 119384
• Main Authors: Zhang, Lihua, Pang, Lulu, Zhu, Siqing, Ma, Jinqiu, Li, Ruiteng, Liu, Yijing, Zhu, Lin, Zhuang, Xiaomei, Zhi, Weijia, Yu, Xiang, Du, Lina, Zuo, Hongyan, Jin, Yiguang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.06.2020
• Subjects: Administration, Intranasal; Administration, Oral; Animals; Behavior, Animal - drug effects; Benzylisoquinolines - administration & dosage; Benzylisoquinolines - chemistry; Benzylisoquinolines - metabolism; Blood-brain barrier (BBB); Blood-Brain Barrier - metabolism; Brain - drug effects; Brain - metabolism; Brain - pathology; Brain - physiopathology; Brain Injuries - drug therapy; Brain Injuries - etiology; Brain Injuries - metabolism; Brain Injuries - psychology; Brain targeting; Calcium Channel Blockers - administration & dosage; Calcium Channel Blockers - chemistry; Calcium Channel Blockers - metabolism; Calcium Channels - drug effects; Calcium Channels - genetics; Calcium Channels - metabolism; Delayed-Action Preparations; Disease Models, Animal; Drug Compounding; Drug Liberation; Hydrogels; In situ hydrogels; Intranasal administration; Male; Microwave; Microwaves; Poloxamer - chemistry; Rats, Wistar; Stimuli Responsive Polymers - chemistry; Temperature; Temperature-sensitive; Tissue Distribution; Viscosity; Microwave; Brain targeting; Intranasal administration; In situ hydrogels; Temperature-sensitive; Blood-brain barrier (BBB)
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2020.119384

[Display omitted] •Intranasal tetradrine temperature-sensitive in-situ gels are prepared to treat microwave-induced brain damage.•The therapeutic mechanism depends on the blockage of calcium channels.•The gels have obvious brain-targeting effect with the higher brain targeting index. The brain is the most sensitive organ to microwave radiation. However, few effective drugs are available for the treatment of microwave-induced brain injury due to the poor drug permeation into the brain. Here, intranasal tetrandrine (TET) temperature-sensitive in situ hydrogels (ISGs) were prepared with poloxamers 407 and 188. Its characteristics were evaluated, including rheological properties, drug release in vitro, and mucosal irritation. The pharmacodynamics and brain-targeting effects were also studied. The highly viscous ISGs remained in the nasal cavity for a long time with the sustained release of TET and no obvious ciliary toxicity. Intranasal temperature-sensitive TET ISGs markedly improved the spatial memory and spontaneous exploratory behavior induced by microwave with the Morris water maze (MWM) and the open field test (OFT) compared to the model. The ISGs alleviated the microwave-induced brain damage and inhibited the certain mRNA expressions of calcium channels in the brain. Intranasal temperature-sensitive TET ISGs was rapidly absorbed with a shorter Tmax (4.8 h) compared to that of oral TET (8.4 h). The brain targeting index of intranasal temperature-sensitive TET ISGs was as 2.26 times as that of the oral TET. Intranasal temperature-sensitive TET ISGs are a promising brain-targeted medication for the treatment of microwave-induced brain injury.