温度/pH双重响应型壳聚糖纳米药物载体的制备及性能

Preparation and properties of temperature and pH sensitive chitosan nanoparticles as drug delivery system

环境响应型纳米颗粒是一种能够随外界环境刺激信号(如温度、pH值和光等)的变化而发生快速改变,同时在结构、性质上发生突变的功能性复合物材料。温度/pH敏感纳米药物载体作为一种新兴的药物缓释体系受到了越来越多的关注。研究采用温敏型单体N-异丙基丙烯酰胺(NIPAm)和含有阴离子基团的单体2-丙烯酰胺基-2-甲基丙磺酸(AMPS)自由基共聚,制备温度敏感型聚合物poly(NIPAm-co-AMPS),利用其表面的阴离子与壳聚糖质子化氨基间的静电相互作用形成纳米颗粒。通过动态光散射仪(DLS)及扫描电镜(SEM)对粒径及其形貌进行表征,考察了浓度、pH值、质量比对壳聚糖纳米颗粒粒径的影响,并研究了其稳定性、温度、pH值响应性及生物相容性。实验结果表明,浓度为0.2mg/mL、聚合物pH值为6、质量比为3∶2时,可以形成粒径大小200nm左右的纳米颗粒,常温放置72h、pH值=3~6条件下体系稳定,34~38℃之间纳米颗粒的粒径发生突变。所制备的壳聚糖纳米颗粒毒性等级0~1级,符合生物医用材料的基本要求。该纳米颗粒在药物控释及基因载体等领域有广泛的应用前景。

Environment-responsive nanoparticle is a kind of functional composite material of which the structure and property can be quickly changed with the stimulation signal(such as temperature,pH and light)of the ex-ternal environment.As new drug delivery system9the thermo/pH-sensitive nano drug carrier has received more and more attention.In this paper,thermo-sensitive functional polymer poly(NIPAm-co-AMPS)was prepared by means of radical polymerization,using thermo-sensitive N-isopropyl acrylamide(NIPAM)and anionic mon-omer2-acrylamide-2-methyl propane sulfonic acid(AMPS)as monomers.Nanoparticles were formed by elec-trostatic interactions between the anionic on the surface of polymer and the protonated amino groups of chi-tosan.The particle size and morphology were characterized by dynamic light scattering(DLS)and scanning e-lectron microscope(SEM)9and the effect of concentration,pH and mass ratio on the particle size of chitosan nanoparticles was investigated.The stability9temperature9pH response and biocompatibility were also studied.The results showed that when the concentration was0.2mg/mL,pH of polymer was6and the mass ratio was3:2,the nanoparticles with the size of about200nm can be formed.The nanoparticles can be stable at room temperature for more than72h with the pH of3-6.The particle size of nanoparticles changed sharply between34to38°C.In addition9the results showed that the toxicity of prepared CS NPs was grade0-19which was in accordance with the basic requirements of biomedical materials.It has broad application prospects in the field of drug controlled release and gene delivery.