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通过环碳酸酯开环反应合成的基于葵花油多元醇-聚氨酯纳米粒子中奥氮平的持续释放。

Sustained delivery of olanzapine from sunflower oil-based polyol-urethane nanoparticles synthesised through a cyclic carbonate ring-opening reaction.

机构信息

Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.

Department of Polymer, Faculty of Chemistry and Petroleum Sciences, Shahid Beheshti University, Tehran, Iran.

出版信息

IET Nanobiotechnol. 2019 Sep;13(7):703-711. doi: 10.1049/iet-nbt.2018.5440.

Abstract

The forefront horizon of biomedical investigations in recent decades is parcelling-up and delivery of drugs to achieve controlled/targeted release. In this regard, developing green-based delivery systems for a spatiotemporal controlling therapeutic agent have drawn a lot of attention. A facile route based on cyclic carbonate ring-opening reaction has been utilised to synthesise a bio-based polyol-containing urethane bond [polyol-urethane (POU)] as a nanoparticulate drug delivery system of olanzapine in order to enhance its bioavailability. After characterisation, the nanoparticles were also estimated for in vitro release, toxicity, and pharmacokinetic studies. As olanzapine has shown poor bioavailability and permeability in the brain, the sustained release of olanzapine from the designed carriers could enhance pharmacokinetic effectiveness. POU in the aqueous solution formed micelles with a hydrophobic core and embedded olanzapine under the influence of its hydrophobic nature. Drug release from the nanoparticles (90 ± 0.43 nm in diameter) indicated a specific pattern with initial burst release, and then a sustained release behaviour (82 ± 3% after 168 h), by the Higuchi-based release mechanism. Pharmacokinetics assessments of POU-olanzapine nanoparticles were carried in male Wistar rats through intravenous administration. The obtained results paved a way to introduce the POU as an efficient platform to enhance the bioavailability of olanzapine in therapeutic methods.

摘要

近几十年来,生物医学研究的前沿方向是将药物分割并递送到特定位置,以实现控制/靶向释放。在这方面,开发用于时空控制治疗剂的基于绿色的递药系统引起了广泛关注。我们利用基于环状碳酸酯开环反应的简易路线合成了一种生物基多元醇型含脲键的聚氨酯(POU),作为奥氮平的纳米颗粒药物递送系统,以提高其生物利用度。在进行特征描述后,还对纳米颗粒进行了体外释放、毒性和药代动力学研究。由于奥氮平在大脑中的生物利用度和通透性较差,因此从设计的载体中持续释放奥氮平可以增强药代动力学效果。POU 在水溶液中形成具有疏水性内核的胶束,并在其疏水性的影响下嵌入奥氮平。纳米颗粒(直径 90 ± 0.43nm)的药物释放表现出特定的模式,即初始突释,然后是持续释放行为(168 小时后释放 82 ± 3%),遵循 Higuchi 释放机制。通过静脉注射在雄性 Wistar 大鼠中对 POU-奥氮平纳米颗粒进行了药代动力学评估。所得结果为 POU 作为提高奥氮平治疗方法生物利用度的有效平台铺平了道路。

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