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载药温敏凝胶纳米系统经鼻递送至脑：增强大鼠的抗癫痫活性。

Thermoresponsive Gel-loaded Oxcarbazepine Nanosystems for Nose- To-Brain Delivery: Enhanced Antiepileptic Activity in Rats.

机构信息

Department of Pharmaceutics & Pharmaceutical Technology, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt.

Department of Pharmacy practices, Alexandria University Hospitals, Alexandria University, Alexandria, Egypt.

出版信息

Pharm Res. 2023 Jul;40(7):1835-1852. doi: 10.1007/s11095-023-03552-7. Epub 2023 Jun 23.

DOI:10.1007/s11095-023-03552-7
PMID:37353628
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10421799/
Abstract

BACKGROUND

Oxcarbazepine (OXC) is a frequently prescribed antiepileptic drug for managing focal and generalized seizures. Its therapeutic benefits are limited by its dose-dependent side effects. Nose-to-brain delivery is a novel route for improving the efficacy of antiepileptics. Drug encapsulation in mucoadhesive nanoparticles offers even more advantages for the nasal route.

OBJECTIVE

The study aimed to develop oxcarbazepine-loaded chitosan nanoparticles (OXC-NP) added to a mucoadhesive thermo-reversible gel for intranasal delivery and enhancement of antiepileptic activity.

METHODS

The formulation was optimized based on entrapment efficiency, polydispersity index, particle size, zeta potential, and in vitro release analysis. The therapeutic efficacy of OXC-NP was assessed in an epileptic rat model and compared to intranasal OXC and oral OXC.

RESULTS

The optimized OXC-NPs with chitosan exhibited particle size, zeta potential, and entrapment efficiency of 189 nm, + 31.4 mV ± 2.5 and 97.6% ± 0.14, respectively. The release of OXC was prolonged, reaching 47.1% after 6 h and 55% after 24 h. Enhanced antiepileptic activity of OXC-NP was manifested as decreased seizure score and prolonged survival. Halting of hippocampal TNF-α and IL-6 together with upregulated IL-10 could explain its anti-inflammatory mechanisms.

CONCLUSIONS

Intranasal OXC-NP-loaded in situ gel represents a promising formulation for enhanced antiepileptic potential achieved at low drug concentrations.

摘要

背景

奥卡西平（OXC）是一种常用于治疗局灶性和全面性癫痫发作的抗癫痫药物。但其治疗效果受到剂量相关副作用的限制。鼻腔给药是提高抗癫痫药物疗效的一种新途径。将药物包封在黏附性纳米粒中为鼻腔给药提供了更多优势。

目的

本研究旨在开发奥卡西平载壳聚糖纳米粒（OXC-NP），并添加到黏附性热可逆凝胶中，用于经鼻腔给药，增强抗癫痫活性。

方法

根据包封效率、多分散指数、粒径、Zeta 电位和体外释放分析对制剂进行优化。在癫痫大鼠模型中评估 OXC-NP 的治疗效果，并与经鼻腔给予 OXC 和口服 OXC 进行比较。

结果

用壳聚糖优化的 OXC-NP 粒径、Zeta 电位和包封效率分别为 189nm、+31.4mV±2.5 和 97.6%±0.14。OXC 的释放得到了延长，6 小时后达到 47.1%，24 小时后达到 55%。OXC-NP 增强抗癫痫活性的表现为癫痫发作评分降低和生存时间延长。阻断海马 TNF-α和 IL-6，同时上调 IL-10 可以解释其抗炎机制。

结论

载 OXC-NP 的原位鼻腔凝胶代表了一种有前途的制剂，可在低药物浓度下实现增强的抗癫痫潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78a/10421799/0a335d8d7723/11095_2023_3552_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78a/10421799/63bd4833a23c/11095_2023_3552_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78a/10421799/013868069567/11095_2023_3552_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78a/10421799/9485e4ee1424/11095_2023_3552_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78a/10421799/152626e0242b/11095_2023_3552_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78a/10421799/eaaf2b07399a/11095_2023_3552_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78a/10421799/36caae68da01/11095_2023_3552_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78a/10421799/0a335d8d7723/11095_2023_3552_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78a/10421799/63bd4833a23c/11095_2023_3552_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78a/10421799/013868069567/11095_2023_3552_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78a/10421799/9485e4ee1424/11095_2023_3552_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78a/10421799/152626e0242b/11095_2023_3552_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78a/10421799/eaaf2b07399a/11095_2023_3552_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78a/10421799/36caae68da01/11095_2023_3552_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c78a/10421799/0a335d8d7723/11095_2023_3552_Fig7_HTML.jpg

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