巯基壳聚糖的合成及其眼用纳米粒的研究

【作者】 朱铉； 李福男； 苏美琴；

【机构】 厦门大学药学院；

【摘要】 壳聚糖(Chitosan,CS)经巯基化改造后所得巯基壳聚糖(Thiolated chitosan,TCS),其水溶性、黏附性等大大提高,同时具有在体凝胶特性,更有利于其眼用新剂型的开发。而纳米粒(NPs)具有助溶性、控释性、眼部损伤低及可实现靶向性等优点,作为眼用制剂有广阔的应用前景。本研究利用N,N-二甲基甲酰胺(DMF)代替水作为反应介质,将反应分成两步进行,从而大大提高反应效率,使巯基结合率从231.51±15.52提高到1411.01±4.02μmol/g(每克的CS结合的巯基量),为后续实验的开展做了充分准备。之后选用另一种生物材料海藻酸钠(Sodium alginate,SA)与CS/TCS为膜材制备纳米粒,对该纳米粒处方进行了优化,并比较了CS改造前后在粒径、ζ电位、形态、黏附性及对药物的释放性的差异,TCS-SA纳米粒各方面性能均优于CS纳米粒,更有利于眼用药物的治疗。MTT实验结果表明了合成的TCS对HCE细胞几乎没有毒性,说明其用于眼部治疗的安全性。细胞摄取实验从细胞水平充分显示TCS-SA纳米粒较CS-SA纳米粒在眼部药物传递方面的优越性。通过对比FITC溶液、包载FITC的CS/TCS-SA纳米粒的在体角膜透过性实验,进一步确证纳米粒能增加FITC的角膜透过量,并且经过巯基化修饰后的TCS-SA纳米粒的药物角膜透过率比未修饰的CS-SA纳米粒高,显示了TCS-SA纳米粒眼部传递系统的优越性。更多还原

【Abstract】 Study found that Chitosan(CS) after being thiolated to thiolated chitosan(TCS),the water solubility and mucoadhesive ability of TCS are much better than CS,besides,TCS displays gelling properties in situ at physiological pH,all these properties are beneficial to the development of ophthalmic preparation.Nanoparticles for its solubility,control release ability,low eye injure and the target activity,has an extensive applied foreground as a ocular drug delivery system.We explored a new method to synthesize TCS,aimed at obtaining more effective and greater thiol group immobilization.we split the single-step reaction into two steps.Compared with the one-step method,we obtained much higher thiol group immobilization in the polymer,at 231.51 ± 15.52 versus 1411.01 ± 4.02 μmol/g.The study used another biological material Sodium alginate(SA) to prepare NPs with CS/TCS.Both the materials display good biocompatibility,biodegradable and mucoadhesive properties,which were useful for ocular nanoparticle drug delivery.The study also optimized the preparation,and compared the differents of CS/TCS-SA NPs in size,zeta potential,morphology,mucoadhesive properties and drug release,all these came out that TCS-SA NPs was much better than CS-SA NPs for ocular treatment.The results of MTT assay indicate that TCS has low toxicity towards HCE cells,an essential requirement for any material intended for use in biomedical applications.And the cell uptake study was demonstrated that the intracellular uptake of TCS-SA NPs was significantly greater than that of CS-SA NPs.This may be further confirmation that TCS-SA NPs are more adhesive and thus more effective as a potential system for ocular drug delivery,compared with CS-SA NPs.After comparing in vivo corneal permeation ability of FITC solution and FITC-loaded CS/TCS-SA NPs,we further confirmed that NPs can increase the permeation of FITC,and,TCS-SA NPs exhibited much better permeation ability than CS-SA NPs,which was more effective as a potential system for ocular drug delivery.更多还原