Intranasal delivery of paeoniflorin nanocrystals for brain targeting

作     者：Chaoyin Wu Benyue Li Yi Zhang Tingting Chen Chuangrong Chen Wei Jiang Qi Wang Tongkai Chen Chaoyin Wu;Benyue Li;Yi Zhang;Tingting Chen;Chuangrong Chen;Wei Jiang;Qi Wang;Tongkai Chen

作者机构：Institute of Clinical PharmacologyGuangzhou University of Chinese MedicineGuangzhou 510405China Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Science and Technology DepartmentGuangzhou University of Chinese MedicineGuangzhou 510006China Department of RadiologySun Yet-sen Memorial HospitalSun Yet-sen UniversityGuangzhou 510120China 

出 版 物：《Asian Journal of Pharmaceutical Sciences》 (亚洲药物制剂科学（英文）)

年 卷 期：2020年第15卷第3期

页      面：326-335页

核心收录：

学科分类：100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1002[医学-临床医学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：the Guangdong Provincial Natural Science Foundation of China(2018A030310623) the Guangdong Provincial Medical Scientific Research Foundation of China(A2019027) the Guangzhou Science Technology and Innovation Commission Technology Research Projects(201805010005) 

主　　题：Intranasal delivery Nanocrystals Paeoniflorin Brain targeting Neuroprotective effect 

摘      要：Paeoniflorin(PA) is an anti-Parkinson Chinese medicine with inferior bioavailability and difficulty in delivery to the brain. This research is to develop an efficacious PA nanocrystal formulation(PA-NCs) that is suitable for intranasal administration to treat Parkinson’s disease(PD). PA-NCs were fabricated through an antisolvent precipitation method using TPGS as the stabilizer. The rod-shaped PA-NCs had particle size of 139.6 ± 1.3 nm and zeta potential of-23.2 ± 0.529 mV. A molecular dynamics simulation indicated that van der Waals forces are the primary drivers of interactions between PA and TPGS. In the ex vivo nasal mucosa permeation assay, the cumulative drug release at 24 h was 87.14% ± 5.34%,which was significantly higher than that of free PA. PA-NCs exhibited substantially improved cellular uptake as well as permeability on Calu-3 cells as compared to PA alone. FRET imaging analysis demonstrated that intact NCs could be internalized into Calu-3 ***, PA-NCs conferred desirable protective effect against MPP+-induced SH-SY5Y cellular damage. Pharmacokinetic studies revealed a higher PA concentration in the brain following intranasal delivery of PA-NCs. In summary, the intranasal administration of PANCs is a promising treatment strategy for PD.