Chen Yan, Mohanraj Vellore J, Wang Fang, Benson Heather A E
School of Pharmacy, Curtin University of Technology, GPO Box U1987, Perth, Western Australia.
AAPS PharmSciTech. 2007 Nov 30;8(4):E98. doi: 10.1208/pt0804098.
The purpose of this study was to examine the effect of charge ratio on the formation and properties of the chitosan (CS)-dextran sulfate (DS) nanoparticles developed for the delivery of water-soluble small and large molecules, including proteins. Rhodamine 6G (R6G) and bovine serum albumin (BSA) were chosen as model molecules. CS-DS nanoparticles were formulated by a complex coacervation process under mild conditions. The influence of formulation and process variables, including the charge ratio of the 2 ionic polymers, on particle size, zeta potential, and nanoparticle entrapment of R6G and BSA was studied. The in vitro release of R6G and BSA was also evaluated, and the integrity of BSA in the release fraction was assessed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Depending on the concentration and charge ratio of DS and CS, nanoparticles with varied size (>or=244 nm) and zeta potential (-47.1-60 mV) were obtained. High entrapment efficiency (98%) was achieved for both R6G and BSA when the charge ratio of the 2 ionic polymers was greater than 1.12. The release of both R6G and BSA from nanoparticles was based on the ion-exchange mechanism. BSA showed much slower continuous release for up to 7 days while still maintaining its integrity for an extended period. The CS-DS nanoparticles developed based on the modulation of charge ratio show promise as a system for controlled delivery of both small and large molecules, including proteins.
本研究的目的是考察电荷比对为递送包括蛋白质在内的水溶性小分子和大分子而制备的壳聚糖(CS)-硫酸葡聚糖(DS)纳米粒的形成及性质的影响。选择罗丹明6G(R6G)和牛血清白蛋白(BSA)作为模型分子。CS-DS纳米粒通过温和条件下的复凝聚法制备。研究了配方和工艺变量(包括两种离子聚合物的电荷比)对粒径、zeta电位以及R6G和BSA纳米粒包封率的影响。还评估了R6G和BSA的体外释放情况,并使用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳评估释放组分中BSA的完整性。根据DS和CS的浓度及电荷比,可获得尺寸各异(≥244 nm)且zeta电位不同(-47.1至60 mV)的纳米粒。当两种离子聚合物的电荷比大于1.12时,R6G和BSA的包封率均达到较高水平(98%)。R6G和BSA从纳米粒中的释放均基于离子交换机制。BSA在长达7天的时间内持续释放速度慢得多,同时在较长时间内仍保持其完整性。基于电荷比调控制备的CS-DS纳米粒有望成为一种用于控制递送包括蛋白质在内的小分子和大分子的体系。