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原位热-电响应型黏胶用于生物活性物质的控制释放。

In situ thermo-co-electroresponsive mucogel for controlled release of bioactive agent.

机构信息

Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.

Department of Neurology, Division of Neurosciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.

出版信息

Int J Pharm. 2019 Mar 25;559:255-270. doi: 10.1016/j.ijpharm.2019.01.044. Epub 2019 Jan 26.

Abstract

The purpose of this work was to develop an in situ thermosensitive electro-responsive mucoadhesive gel loaded with bioactive agent (nanocomposite) meant for nose to brain delivery in a controllable manner when electric stimulation is applied. Nanocomposite was developed using a combinatorial blending of chitosan, hydroxypropylmethylcellulose, pluronic F127 and polyaniline which was then loaded with BCNU-Nano-co-Plex (the bioactive agent). The nanocomposite was a liquid at room temperature but formed an in situ mucogel at a temperature of 27.5 ± 0.5 °C. Furthermore, the nanocomposite possessed a redox element which makes it responsive to electrical stimulation (ES). The stimuli responsiveness enabled the formulation to release the bioactive agent when electrical potential was applied and demonstrated a desired 10.28% release of nanoparticles per application cycle. The results further revealed pore formation within the formulation which accommodated the loaded nanoparticles. The release profile also demonstrated a pulsatile release of the bioactive material when subjected to ES. This formulation may therefore be useful as a nose to brain drug delivery system that can be modulated to deliver bioactive agents to the brain via electro-actuation in an "on-off" drug release kinetics by means of an external ES for a controlled nose-to-brain delivery.

摘要

这项工作的目的是开发一种原位热敏电响应型黏附凝胶,用于以可控的方式将生物活性药物(纳米复合物)递送至鼻腔至脑部,当施加电刺激时。纳米复合物是通过壳聚糖、羟丙基甲基纤维素、泊洛沙姆 F127 和聚苯胺的组合混合制备的,然后负载 BCNU-Nano-co-Plex(生物活性药物)。纳米复合物在室温下为液体,但在 27.5°C±0.5°C 的温度下形成原位黏膜凝胶。此外,纳米复合物具有氧化还原元素,使其对电刺激(ES)有响应。这种刺激响应使配方在施加电势能时释放生物活性药物,并在每个应用周期中表现出所需的 10.28%的纳米颗粒释放。结果进一步揭示了制剂内的孔形成,以容纳负载的纳米颗粒。释放曲线还表明,当受到 ES 时,生物活性物质呈脉冲式释放。因此,该制剂可用作鼻腔至脑部药物递送系统,可通过外部 ES 进行电触发调节,以“开-关”药物释放动力学将生物活性剂递送至脑部,从而实现对脑部的受控鼻腔递药。

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