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研究制备了一种双pH敏感型载多柔比星(DOX)纳米粒,以期实现DOX肿瘤定位释放。利用pH敏感化学键腙键将聚乙烯亚胺(PEI)和DOX化学连接,合成材料PEI-DOX(PD)。PD与pH敏感材料羧甲基壳聚糖(CMCS)静电相互作用形成双pH敏感载DOX纳米粒CMCS/PD(CPD)。通过核磁共振氢谱确证PD结构。采用透射电镜及动态光散射粒径电位分析仪考察CPD的理化性质。通过不同pH条件下粒径与Zeta电位变化和体外释放实验考察CPD双pH敏感性。PD核磁图谱表明其成功合成。CPD呈球形或类球形,平均粒径和Zeta电位分别为(164.1±4.90)nm,-(13.0±1.56)m V。当pH由7.4降低至5.0时,CPD粒径与电位发生显著变化,表明CMCS可pH响应性与PD解离;在pH 5.0时,CPD体外累积释放为(51.22±1.48)%,显著高于pH 7.4时[(26.24±0.49)%,P<0.05],表明DOX的释放具有pH敏感性。该研究表明CPD具有双pH敏感性,为pH敏感肿瘤定位释放纳米载体的制备提供一种新思路。
A double pH-sensitive DOX-loaded nanoparticle was prepared in order to achieve DOX tumor localization and release. Polyethylenimine (PEI) and DOX were chemically linked to PEI-DOX (PD) by pH-sensitive chemical bond hydrazone bond. PD and pH sensitive material carboxymethyl chitosan (CMCS) electrostatically interact to form double pH sensitive DOX loaded nanoparticles CMCS / PD (CPD). PD structure was confirmed by 1H NMR. The physical and chemical properties of CPD were investigated by transmission electron microscopy and dynamic light scattering particle size analyzer. The pH-sensitivity of CPD was investigated by the changes of particle size and Zeta potential and in vitro release under different pH conditions. PD NMR showed its successful synthesis. The CPDs were spherical or spheroidal with the mean diameter and Zeta potential of (164.1 ± 4.90) nm and - (13.0 ± 1.56) mV, respectively. When the pH was decreased from 7.4 to 5.0, the particle size and potential of CPD changed significantly, indicating that CMCS could dissociate pH response from PD. The cumulative release of CPD in vitro was (51.22 ± 1.48)% at pH 5.0, which was significantly higher than pH 7.4 [(26.24 ± 0.49)%, P <0.05], indicating that DOX release is pH-sensitive. This study shows that CPD has dual pH sensitivity and provides a new idea for the preparation of pH-sensitive tumor localization release nanocarriers.