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

被引:3
作者
Rao, Qianru [1 ]
Xu, Yujie [1 ]
Wang, Xiaorong [2 ]
Luo, Hang [3 ,4 ]
Li, Haoqi [3 ,4 ]
Xiong, Jingyuan [3 ,4 ]
Gao, Huile [2 ]
Cheng, Guo [1 ]
机构
[1] Sichuan Univ, West China Univ Hosp 2, Key Lab Birth Defects & Related Dis Women & Child, Maternal & Child Nutr Ctr,Minist Educ,Lab Mol Tra, Chengdu, Peoples R China
[2] Sichuan Univ, West China Sch Pharm, Key Lab Drug Targeting & Drug Delivery Syst, Educ Minist, Chengdu, Peoples R China
[3] Sichuan Univ, Hlth Food Evaluat Res Ctr, West China Sch Publ Hlth, Chengdu, Peoples R China
[4] Sichuan Univ, West China Hosp 4, Chengdu, Peoples R China
来源
SUSMAT | 2024年 / 4卷 / 04期
基金
中国国家自然科学基金;
关键词
hypothalamus; intranasal delivery; nanoparticles; neurokinin receptor 3; BLOOD-BRAIN-BARRIER; NEUROKININ B; ELECTROSTATIC REPULSION; ANISOTROPIC HYDROGEL; RECEPTOR; NEURONS; KISSPEPTIN; MODEL; PERMEABILITY; SECRETION;
D O I
10.1002/sus2.222
中图分类号
O6 [化学];
学科分类号
0703 ;
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 strategy. This system could overcome the primary obstacles in drug delivery for hypothalamus-related diseases. Under the guidance of a modified (Trp7, beta-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 nanoparticles 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 nanoparticles (S@ANP + NAC) to increase mucosal solubility and intranasal delivery efficiency. In vivo evaluations showed that S@ANP + NAC could effectively target 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. A multifunctional nanocarrier system (S@ANP) was constructed to directly target the hypothalamic neurokinin receptor 3 (NK3R) via an intranasal delivery strategy. Under the guidance of a modified NKA peptide (NKA-C), composite S@ANP could bypass the blood-brain barrier and penetrate hypothalamic cells with a substantial loading capacity upon intranasal administration. As a result, this intranasal nanoparticle drug delivery system has the potential to serve as a potential strategy for precision therapy for hypothalamic disorders. image
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页数:12
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