Intranasal administration of in silico designed Rivastigmine mucoadhesive nanoparticles ameliorates scopolamine-induced Alzheimer’s symptoms in mice: Pharmacokinetic and pharmacodynamic evidences

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics Pub Date : 2025-04-30 DOI:10.1016/j.ijpharm.2025.125635

Vinni Kalra, Om Silakari, Ashok Kumar Tiwary

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Abstract

The low oral bioavailability (36 %) of rivastigmine tartrate (RT), and the inconspicuous pharmacological target site has necessitated the need to explore alternative routes of delivery for effective management of Alzheimer’s disease (AD). The current study aimed to develop in silico designed polymeric nanoparticles (NPs) for the intranasal delivery of RT. Eudragit RL 100 (EDRL) was selected as mucoadhesive polymer because of its optimum binding affinity with RT and nasal mucin. These NPs were prepared using spray drying method by utilizing QbD approach. Yield, particle size, zeta potential, entrapment efficiency and drug loading were optimized using central composite design. Furthermore, the TEM and SEM analysis of RT-EDRL NPs, respectively, revealed the particle size in the range of 50–100 nm and their spherical shape. The in vitro and ex vivo release profiles revealed sustained drug release from RT-EDRL NPs as compared to RT solution. The intranasal administration of optimized NPs exhibited higher RT concentration in mice brain as compared to other routes.

Higher direct transport percentage (DTP %) and drug targeting efficiency (DTE %) indicated direct transport of RT to the brain through the nose and was better than that observed after application of transdermal patch. The neuroprotective potential conferred by intranasal administration of in silico designed NPs in scopolamine induced amnesia mice seems to be a potential brain targeted delivery system for effective management of AD.

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鼻内给药硅设计的利瓦斯汀黏附纳米颗粒改善东莨菪碱诱导的小鼠阿尔茨海默病症状：药代动力学和药效学证据

酒石酸利瓦斯汀（RT）的低口服生物利用度（36%）和不明显的药理学靶点使得有必要探索有效治疗阿尔茨海默病（AD）的替代给药途径。目前的研究目的是开发硅设计的聚合物纳米颗粒（NPs）用于鼻内给药。Eudragit RL 100 （EDRL）被选为黏附聚合物，因为它与RT和鼻黏液具有最佳的结合亲和力。利用QbD方法，采用喷雾干燥法制备NPs。采用中心复合设计对收率、粒径、zeta电位、包封效率和载药量进行优化。对RT-EDRL NPs进行了TEM和SEM分析，发现其粒径在50 ~ 100 nm之间，呈球形。体外和离体释放谱显示，与RT溶液相比，RT- edrl NPs的药物持续释放。与其他途径相比，经鼻给药优化的NPs在小鼠脑内显示出更高的RT浓度。更高的直接转运率（DTP %）和药物靶向效率（DTE %）表明RT经鼻直接转运至脑，且优于透皮贴剂。在东莨菪碱诱导的健忘症小鼠中，经鼻给药硅设计的NPs具有神经保护潜力，似乎是一种潜在的有效管理AD的脑靶向递送系统。

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来源期刊

International Journal of Pharmaceutics 医学-药学

CiteScore

10.70

自引率

8.60%

发文量

951

审稿时长

72 days

期刊介绍： The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.