Construction of an intranasal drug delivery system with hypothalamus-targeting nanoparticles  

作　　者：Qianru Rao Yujie Xu Xiaorong Wang Hang Luo Haoqi Li Jingyuan Xiong Huile Gao Guo Cheng 

机构地区：[1]Laboratory of Molecular Translational Medicine,Center for Translational Medicine,Key Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University),Ministry of Education,Maternal&Child Nutrition Center,West China Second University Hospital,Sichuan University,Chengdu,China [2]Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry,West China School of Pharmacy,Sichuan University,Chengdu,China [3]Healthy Food Evaluation Research Center,West China School of Public Health and West China Fourth Hospital,Sichuan University,Chengdu,China

出　　处：《SusMat》2024年第4期65-76,共12页可持续发展材料（英文）

基　　金：National Natural Science Foundation of China,Grant/Award Numbers:82173512,82304135。

摘　　要：Dysfunction of the hypothalamus is associated with endocrine imbalances,growth abnormalities,and reproductive disorders.However,there is a lack of targeted treatment strategies focused on the hypothalamus.In this study,we constructed a multifunctional nanocarrier system(S@ANP)to directly target the hypothalamic neurokinin receptor 3(NK3R)via an intranasal delivery strat-egy.This system could overcome the primary obstacles in drug delivery for hypothalamus-related diseases.Under the guidance of a modified(Trp7,β-Ala8)-neurokinin A(4-10)peptide with cysteine,nanoparticles encapsulated with SB222200,an NK3R inhibitor,were found to readily penetrate hypothalamic cells with substantial loading capacity,encapsulation efficiency,and sustained release in vitro.Moreover,intranasal delivery represents an optimal delivery strategy that allows for a significant reduction in oral dosage and enables nanoparti-cles to bypass the blood-brain barrier and target relevant parts of the brain.The mucolytic agent N-acetyl-L-cysteine(NAC)was loaded into the nanopar-ticles(S@ANP+NAC)to increase mucosal solubility and intranasal delivery efficiency.In vivo evaluations showed that S@ANP+NAC could effectively tar-get the hypothalamus and modulate NK3R-regulated hypothalamic functions in mice.Due to its high hypothalamic targeting efficiency and low toxicity,this intranasal nanoparticle drug delivery system may serve as a potential strategy for precision therapy of hypothalamic disorders.

关 键 词：HYPOTHALAMUS intranasal delivery NANOPARTICLES neurokinin receptor 3 

分 类 号：TB383[一般工业技术—材料科学与工程]