Polymer Laboratory, Chemistry Department, Faculty of Science, Mansoura University, ET-35516 Mansoura, Egypt.
Int J Pharm. 2010 Aug 16;395(1-2):132-41. doi: 10.1016/j.ijpharm.2010.05.032. Epub 2010 May 24.
Design of appropriate inhaled carriers with adequate aerodynamic properties, drug release, biodegradation and evasion of macrophage uptake is a major challenge for controlled release pulmonary drug delivery. In this study, PEG graft copolymerized onto N-phthaloyl chitosan (NPHCs) was synthesized then characterized using FTIR, EA, DSC and 2D-XRD. The resulting PEG-g-NPHCs copolymers were self-assembled into drug-loaded nanoparticles and encapsulated in respirable/swellable sodium alginate semi-IPN hydrogel microspheres as novel biodegradable carriers for controlled release pulmonary drug delivery. The developed nano-/microspheres carrier systems were formed via spray drying followed by ionotropic crosslinking in mild aqueous medium. The size of the developed self-assembled nanoparticles and the microspheres was measured using dynamic light scattering and laser diffraction, respectively. Morphology, moisture content, in vitro biodegradation and dynamic swelling studies were also investigated for the developed carriers. A model protein was entrapped and the in vitro release profiles were determined in PBS, pH 7.4 at 37 degrees C. A dry powder aerosolization study was conducted using a Next Generation Impactor (NGI). The developed microspheres had suitable aerodynamic diameters (1.02-2.63 microm) and an excellent fine particle fraction, FPF of 31.52%. The microspheres showed also a very fast initial swelling within the first 2 min and started to enzymatically degrade within the first 2h. Moreover, the microspheres entrapped up 90% of the model drug and showed promising in vitro sustained release profiles as compared to the control formulation.
设计具有适当空气动力学特性、药物释放、生物降解和逃避巨噬细胞摄取的合适吸入载体，是控制释放肺部药物输送的主要挑战。在这项研究中，将聚乙二醇接枝到 N-邻苯二甲酰壳聚糖（NPHCs）上，然后使用傅里叶变换红外光谱（FTIR）、元素分析（EA）、差示扫描量热法（DSC）和二维 X 射线衍射（2D-XRD）进行表征。得到的 PEG-g-NPHCs 共聚物自组装成载药纳米粒子，并封装在可吸入/可溶胀的海藻酸钠半互穿网络水凝胶微球中，作为新型可生物降解载体用于控制释放肺部药物输送。通过喷雾干燥，然后在温和的水介质中离子交联，形成所开发的纳米/微球载体系统。使用动态光散射和激光衍射分别测量所开发的自组装纳米粒子和微球的粒径。还研究了形态、水分含量、体外生物降解和动态溶胀研究。包封了一种模型蛋白，并在 PBS（pH 7.4，37°C）中测定了体外释放曲线。使用下一代撞击器（NGI）进行干粉雾化研究。所开发的微球具有合适的空气动力学直径（1.02-2.63 微米）和出色的微细颗粒分数（FPF）为 31.52%。微球在最初的 2 分钟内表现出非常快的初始膨胀，并在最初的 2 小时内开始酶降解。此外，与对照制剂相比，微球包封了高达 90%的模型药物，表现出有前途的体外持续释放曲线。
