Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Center for Chemistry and Biomedicine, Innrain 80/82, 6020 Innsbruck, Austria.
Int J Pharm. 2012 Oct 15;436(1-2):120-6. doi: 10.1016/j.ijpharm.2012.05.073. Epub 2012 Jun 7.
The aim of this study was to investigate the influence of molar mass of thiolated polymers (thiomers) on their in situ gelling properties. Chitosan-thioglycolic acid (chitosan-TGA) and pectin-cysteine (pectin-Cys) of increasing molar mass were chosen to produce in situ gels in combination with carbamide peroxide. Low molar mass chitosan (2 kDa) was prepared by oxidative degradation with NaNO(2), whereas pectin was depolymerized by heat treatment. Thiomers, displaying 1271-1616 μmol (chitosan-TGA) and 305-403 μmol (pectin-Cys) free thiol groups per gram polymer, were synthesized via amide bond formation mediated by a carbodiimide. The results showed that a reduction of molar mass combined with increased concentrations of both cationic chitosan-TGA and anionic pectin-Cys leads to higher final viscosities and to a higher relative increase in viscosity within 60 min and 180 min, respectively. Using this method, the dynamic viscosity of a very low molar mass chitosan-TGA (2 kDa) could be increased 100,000-fold within 60 min and 390,000-fold within 180 min. In view of these in situ gelling properties carbohydrate thiomers might be useful for various pharmaceutical applications such as vehicle for drug delivery or as wound dressing material.
本研究旨在探讨巯基化聚合物（硫醇聚合物）的分子量对其原位凝胶性能的影响。选择了分子量逐渐增加的壳聚糖-硫代乙醇酸（chitosan-TGA）和果胶-半胱氨酸（pectin-Cys）与过氧尿素结合形成原位凝胶。低分子量壳聚糖（2 kDa）通过用 NaNO₂氧化降解制备，而果胶则通过热处理解聚。硫醇聚合物通过碳二亚胺介导的酰胺键形成合成，每克聚合物显示 1271-1616 μmol（chitosan-TGA）和 305-403 μmol（pectin-Cys）游离巯基。结果表明，分子量的降低加上阳离子壳聚糖-TGA 和阴离子果胶-Cys 的浓度增加，分别导致最终粘度更高和在 60 分钟和 180 分钟内相对粘度增加更高。使用这种方法，非常低分子量的 chitosan-TGA（2 kDa）的动态粘度在 60 分钟内增加了 100,000 倍，在 180 分钟内增加了 390,000 倍。鉴于这些原位凝胶性能，碳水化合物硫醇聚合物可能对各种药物应用有用，例如药物输送载体或伤口敷料材料。
