Rational Design of Thermosensitive Hydrogel to Deliver Nanocrystals with Intranasal Administration for Brain Targeting in Parkinson’s Disease
Yun Tan,
Yao Liu,
Yujing Liu,
Rui Ma,
Jingshan Luo,
Huijie Hong,
Xiaojia Chen,
Shengpeng Wang,
Chuntai Liu,
Yi Zhang,
Tongkai Chen
Affiliations
Yun Tan
Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China
Yao Liu
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
Yujing Liu
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
Rui Ma
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
Jingshan Luo
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
Huijie Hong
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China
Xiaojia Chen
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China
Shengpeng Wang
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China
Chuntai Liu
Key Laboratory of Materials Processing and Mold, Ministry of Education, Zhengzhou University, Zhengzhou 450002, China
Yi Zhang
Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China
Tongkai Chen
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
Mitochondrial dysfunction is commonly detected in individuals suffering from Parkinson’s disease (PD), presenting within the form of excessive reactive oxygen species (ROS) generation as well as energy metabolism. Overcoming this dysfunction within brain tissues is an effective approach to treat PD, while unluckily, the blood-brain barrier (BBB) substantially impedes intracerebral drug delivery. In an effort to improve the delivery of efficacious therapeutic drugs to the brain, a drug delivery platform hydrogel (MAG-NCs@Gel) was designed by complexing magnolol (MAG)-nanocrystals (MAG-NCs) into the noninvasive thermosensitive poly(N-isopropylacrylamide) (PNIPAM) with self-gelation. The as-prepared MAG-NCs@Gel exhibited obvious improvements in drug solubility, the duration of residence with the nasal cavity, and the efficiency of brain targeting, respectively. Above all, continuous intranasal MAG-NCs@Gel delivery enabled MAG to cross the BBB and enter dopaminergic neurons, thereby effectively alleviating the symptoms of MPTP-induced PD. Taking advantage of the lower critical solution temperature (LCST) behavior of this delivery platform increases its viscoelasticity in nasal cavity, thus improving the efficiency of MAG-NCs transit across the BBB. As such, MAG-NCs@Gel represented an effective delivery platform capable of normalizing ROS and adenosine triphosphate (ATP) in the mitochondria of dopaminergic neurons, consequently reversing the mitochondrial dysfunction and enhancing the behavioral skills of PD mice without adversely affecting normal tissues.
