pH敏感白藜芦醇长循环脂质体的制备及其初步体外表征

Preparation and evaluation of PEG-modified pH-sensitive resveratrol liposomes

目的:制备pH敏感白藜芦醇长循环脂质体并对其性质进行评价。方法:合成膜材二硬脂酸磷脂酰乙醇胺-聚乙二醇2000(m PEG2000-DSPE),并通过薄层色谱(TLC)及氢谱(1H-NMR)进行表征;采用薄膜分散法制备普通白藜芦醇脂质体(LP-RSV)和pH敏感白藜芦醇脂质体(pH-LP-RSV),后插入法制备pH敏感白藜芦醇长循环脂质体(PEG-pH-LP-RSV)及普通白藜芦醇长循环脂质体(PEG-LP-RSV),对脂质体的粒径、Zeta电位、外貌形态、包封率及体外释放等理化性质进行研究;用MTT法考察PEG-pH-LP-RSV与PEGLP-RSV的细胞毒性差别。结果:成功合成膜材m PEG2000-DSPE。所制备的脂质体粒径均在150 nm以下,包封率均大于80%;脂质体形态为均匀的球形或近球形;体外pH敏感性实验及体外释放试验表明PEG-pHLP-RSV具有明显的pH敏感性;体外细胞毒性实验表明PEG-pH-LP-RSV的毒性明显高于普通的RSV脂质体。结论:本实验所制得的pH敏感白藜芦醇长循环脂质体粒径分布均一,包封率较高,且具有明显的pH刺激响应性,具有很好的应用前景。

Objective ： To prepare and Methods： mPEG2ooo-DSPE was synthesized and characterize PEG2000-modified pH-sensitive resveratrol liposomes. characterized by TLC and ^1H-NMR. The LP-RSV and pH-LP-RSV were prepared using the film dispersion method, and the PEG-pH-LP-RSV and PEG-LP-RSV were prepared using the post-insertion method. Their sizes, Zeta potential, morphous, encapsulation efficiency, in vitro pH sensitive property and release rate of RSV from PEG-pH-LP-RSV were investigated. Results： DSPE-PEG^000 was successfully synthesized. The particle size of the liposomes prepared in this experiment was 150 nm or less, and the RSV encap- sulation efficiency was more than 80%. The liposomes were spherical or ellipsoidal shape. In vitro pH sensitive analyses and the release study revealed that PEG-pH-LP-RSV had pH sensitivity. The cytotoxity of PEG-pH-LP-RSV was higher than PEG-LP-RSV. Conclusion： PEG-pH-LP-RSV has been successfully prepared. It has an obvious pH stimuli-responsiveness and higher cytotoxity than non-pH sensitive liposomes, providing the basis for further in- vestigation of its anti-tumor effect.