Search

Yue Sun,1 Lingjun Li,1 Huichao Xie,2 Yuzhen Wang,1 Shuang Gao,1 Li Zhang,1 Fumin Bo,1 Shanjing Yang,1 Anjie Feng1 1College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, People’s Republic of China; 2School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of ChinaCorrespondence: Lingjun Li Email sdzyylilingjun@163.comBackground: Paeonol (PAE) is a potential central neuroprotective agent with poor water solubility and rapid metabolism in vivo. The key to improve the clinical application of PAE in the treatment of neurodegenerative diseases is to improve the brain delivery of it. The purpose of this study was to construct a paeonol-solid lipid nanoparticles-in situ gel (PAE-SLNs-ISG) drug delivery system based on nose-brain transport pathway.Materials and Methods: In this study, the stability of PAE in simulated biological samples was studied firstly in order to clarify the reasons for low oral bioavailability. Paeonol-solid lipid nanoparticles (PAE-SLNs) were prepared by high-temperature emulsification–low-temperature curing combined with ultrasound. The PAE-SLNs-ISG drug delivery system was constructed, and related formulation optimization, preparation characterization, cell evaluation and in vivo evaluation were performed.Results: The metabolic mechanism of PAE incubated in the liver microsomes metabolic system was in accordance with the first-order kinetics, and the half-life was 0.23 h. PAE-SLNs were polyhedral or spherical particles with good dispersion and the particle size was 166.79 nm ± 2.92 nm. PAE-SLNs-ISG solution was a Newtonian fluid with a viscosity of 44.36 mPa · S ± 2.89 mPa · S. The viscosity of PAE-SLNs-ISG gel was 1542.19 mPa · S ± 19.30 mPa · S, and the rheological evaluation showed that the gel was a non-Newtonian pseudoplastic fluid with shear thinning, thixotropy and yield