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通过甘露糖基化聚乳酸-羟基乙酸共聚物纳米粒联合多奈哌齐和美金刚用于鼻内给药:表征及临床前研究

Combining donepezil and memantine via mannosylated PLGA nanoparticles for intranasal delivery: Characterization and preclinical studies.

作者信息

Handa Mayank, Sanap Sachin Nashik, Bhatta Rabi Sankar, Patil Gajanan Pratap, Ghose Suchetana, Singh Dhirendra Pratap, Shukla Rahul

机构信息

Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research-Raebareli, Lucknow 226002, India.

Pharmaceutics and Pharmacokinetics Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.

出版信息

Biomater Adv. 2023 Nov;154:213663. doi: 10.1016/j.bioadv.2023.213663. Epub 2023 Oct 16.

Abstract

The current work is focused on developing mannose-coated PLGA nanoparticles for delivering Donepezil and Memantine in one dosage form. The formulated nanoparticles were prepared using a simple emulsification technique. The final coated NPs exhibited 179.4 nm size and - 33.1 mV zeta potential and spherical shape. The concentration of IN-administrated MEM and DPZ mannose coated NPs in brain was ~573 and 207 ng/mL respectively. This amount accounts for 3 times more in comparison to uncoated NPs administered via intranasal and peroral routes. The plasma concentration of coated NPs administered via the intranasal route was various times less in comparison to other groups. In the field of pharmacodynamics, the administration of coated NPs via the IN route has shown superior efficacy in comparison to other groups in various investigations involving neurobehavioral assessments, gene expression analyses and biochemical estimations. The findings indicate that the IN route may be a potential avenue for delivering therapeutic agents using nanoparticles to treat neurological illnesses. This approach shows promise as a viable alternative to traditional dose forms and administration methods.

摘要

当前的工作集中于开发甘露糖包被的聚乳酸-羟基乙酸共聚物纳米颗粒,用于以单一剂型递送多奈哌齐和美金刚。所制备的纳米颗粒采用简单的乳化技术制备。最终包被的纳米颗粒尺寸为179.4纳米,zeta电位为-33.1毫伏,呈球形。经鼻给药的美金刚和多奈哌齐甘露糖包被纳米颗粒在脑中的浓度分别约为573和207纳克/毫升。与经鼻和口服途径给药的未包被纳米颗粒相比,该量多出3倍。与其他组相比,经鼻途径给药的包被纳米颗粒的血浆浓度低数倍。在药效学领域,在涉及神经行为评估、基因表达分析和生化测定的各种研究中,经鼻途径给药的包被纳米颗粒与其他组相比显示出更高的疗效。研究结果表明,经鼻途径可能是使用纳米颗粒递送治疗剂以治疗神经疾病的潜在途径。这种方法有望成为传统剂型和给药方法的可行替代方案。

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