探索纳米载体以提高卡的生物可用性:通过系统表征和毒性评估以及药理和2D透性回报的旅程
Cláudia Sofia Machado1, Miguel Pinto1,2,3, Brandon Aguiar1,2,3
1CIQUP-IMS─Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, R. Campo Alegre s/n, 4169-007 Porto, Portugal.
ACS applied materials & interfaces
|October 21, 2024
概括
恩塔卡是帕金森病的药物,面临着生物可用性挑战. 将其封装在纳米粒子 (PLGA NPs) 和纳米结构脂质载体 (NLC) 中,改善了其特性和透性,为药物输送提供了有前途的替代方案.
科学领域:
- 药理学 药理学是指药理学的学科.
- 纳米技术纳米技术
- 药物运输 药物运输 药物运输
背景情况:
- 甲基转移酶抑制剂 (iCOMT),像恩塔卡一样,治疗帕金森病的症状,但患有短半衰期和不良的口服生物可用性.
- 基于纳米的药物输送系统提供解决方案,克服传统药物的局限性.
研究的目的:
- 将恩塔卡封装成以PEG为基础的聚乳-协同甘油酸 (PLGA) 纳米颗粒 (NP) 和以PEG为基础的纳米结构脂质载体 (NLC).
- 评估开发的纳米配方的物理化学性质,稳定性,粘素相互作用,细胞毒性,COMT抑制和透性.
主要方法:
- 恩塔卡被封装使用纳米沉 (PLGA NPs) 和溶剂乳化/蒸发 (NLCs).
- 纳米配方的特点是尺寸,泽塔潜力 (ZP) 和不同pH值的稳定性.
- 在HepG2,SH-SY5Y和Caco-2细胞系中评估了细胞毒性.
- 使用3-BTD探针测量了COMT抑制,并在Caco-2和共同培养模型中评估了透性.
主要成果:
- 两种纳米配方都实现了200nm以下的尺寸,ZP值接近-30mV,并表现出良好的稳定性.
- 纳米配方与粘膜相互作用,表明具有良好的透潜力.
- 溶解型PLGANP没有表现出细胞毒性,而NLC在HepG2细胞中表现出一些细胞毒性.
- 这两种纳米配方都保留了COMT抑制活性,并增强了跨细胞屏障的卡透性.
结论:
- 在PLGA NP和NLC中封装恩塔卡可以改善其物理化学特性和透性.
- 这些纳米配方代表了一种可行的策略,以克服恩塔卡的局限性,以提高治疗疗效.
- 对这些纳米载体系统的进一步研究有望改善帕金森病治疗.
相关概念视频
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01:23Mechanisms of Drug Absorption: Paracellular, Transcellular, and Vesicular Transport
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