Bijukumar Divya, Choonara Yahya E, Kumar Pradeep, du Toit Lisa C, Pillay Viness
a Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand , Parktown , South Africa.
Pharm Dev Technol. 2016 Nov;21(7):875-886. doi: 10.3109/10837450.2015.1073742. Epub 2015 Aug 10.
The purpose of this study was to develop an electro-responsive co-polymeric (ERP) implantable gel from polyethylene glycol (PEG), sodium polystyrene sulphonate (NaPss), polyvinyl alcohol (PVA), and diethyl acetomidomalonate (DAA) for electro-liberation of the model drug diclofenac sodium. Various physicochemical and physicomechanical characterization tests were undertaken on the synthesized drug-free gel (ERP G1) and drug-loaded gel (ERP G2). The ability of the gel to release diclofenac sodium following electrical stimulation was evaluated using a galvanostat while Molecular Mechanics (MM) simulations were performed to elucidate the experimental mechanisms. A stable electro-active gel exhibiting superior cycling stability was produced with desirable rheological properties, rigidity (BHN = 35.4 N ± 0.33 N/mm; resilience = 10.91 ± 0.11%), thermal properties (T ≈ 70 °C; T ≈ 200 °C) and homogeneous morphology. "ON-OFF" pursatile gradual drug release (37-94% from t-t ) kinetics was observed upon applying electric stimulation intermittently, indicating that drug release from the gel was electrically controlled. Overall, the galvanometric and MM evaluation ascertained the suitability of the PEG/NaPss/PVA ERP-Gel for application as a subcutaneously injectable drug delivery implant.
本研究的目的是由聚乙二醇(PEG)、聚苯乙烯磺酸钠(NaPss)、聚乙烯醇(PVA)和二乙乙酰氨基丙二酸酯(DAA)开发一种用于模型药物双氯芬酸钠电释放的电响应共聚物(ERP)可植入凝胶。对合成的无药凝胶(ERP G1)和载药凝胶(ERP G2)进行了各种物理化学和物理机械表征测试。使用恒电流仪评估凝胶在电刺激后释放双氯芬酸钠的能力,同时进行分子力学(MM)模拟以阐明实验机制。制备出了一种具有优异循环稳定性的稳定电活性凝胶,其具有理想的流变学性质、硬度(布氏硬度=35.4 N±0.33 N/mm;回弹性=10.91±0.11%)、热性质(T≈70°C;T≈200°C)和均匀形态。间歇性施加电刺激时观察到“开-关”可控的逐渐药物释放(t-t时间段内释放37-94%)动力学,表明凝胶中的药物释放是受电控制的。总体而言,电流测定和MM评估确定了PEG/NaPss/PVA ERP凝胶作为皮下注射药物递送植入物应用的适用性。