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