Essa Divesha, Choonara Yahya E, Kondiah Pierre P D, Pillay Viness
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.
Polymers (Basel). 2020 Aug 21;12(9):1882. doi: 10.3390/polym12091882.
Poor circulation stability and inadequate cell membrane penetration are significant impediments in the implementation of nanocarriers as delivery systems for therapeutic agents with low bioavailability. This research discusses the fabrication of a biocompatible poly(lactide-co-glycolide) (PLGA) based nanocarrier with cationic and hydrophilic surface properties provided by natural polymer chitosan and coating polymer polyethylene glycol (PEG) for the entrapment of the hydrophobic drug disulfiram. The traditional emulsification solvent evaporation method was compared to a microfluidics-based method of fabrication, with the optimisation of the parameters for each method, and the PEGylation densities on the experimental nanoparticle formulations were varied. The size and surface properties of the intermediates and products were characterised and compared by dynamic light scattering, scanning electron microscopy and X-ray diffraction, while the thermal properties were investigated using thermogravimetric analysis and differential scanning calorimetry. Results showed optimal particle properties with an intermediate PEG density and a positive surface charge for greater biocompatibility, with nanoparticle surface characteristics shielding physical interaction of the entrapped drug with the exterior. The formulations prepared using the microfluidic method displayed superior surface charge, entrapment and drug release properties. The final system shows potential as a component of a biocompatible nanocarrier for poorly soluble drugs.
循环稳定性差和细胞膜穿透性不足是纳米载体作为低生物利用度治疗药物递送系统应用中的重大障碍。本研究讨论了一种基于生物相容性聚(丙交酯 - 乙交酯)(PLGA)的纳米载体的制备,该纳米载体具有由天然聚合物壳聚糖和包衣聚合物聚乙二醇(PEG)提供的阳离子和亲水表面性质,用于包载疏水性药物双硫仑。将传统的乳化溶剂蒸发法与基于微流控的制备方法进行了比较,对每种方法的参数进行了优化,并改变了实验纳米颗粒制剂上的聚乙二醇化密度。通过动态光散射、扫描电子显微镜和X射线衍射对中间体和产物的尺寸及表面性质进行了表征和比较,同时使用热重分析和差示扫描量热法研究了热性质。结果表明,具有中等聚乙二醇密度和正表面电荷的纳米颗粒具有最佳的颗粒性质,具有更高的生物相容性,纳米颗粒表面特性可屏蔽包载药物与外部的物理相互作用。使用微流控方法制备的制剂表现出优异的表面电荷、包封率和药物释放性质。最终系统显示出作为难溶性药物生物相容性纳米载体组件的潜力。