低分子量半乳糖化脂肪酰壳聚糖的制备及其形成胶束的性质研究  

Synthesis and Micelle-forming Properties of Low Molecular Weight Galactosylated Fatty Acyl Chitosan

作　　者：石春勤[1] 王晓明[1] 胡巧红[1,2] 谢智林[1] 

机构地区：[1]广东药学院药剂系,广州510006 [2]广东药学院临床药学系,广州510006

出　　处：《中国现代应用药学》2012年第12期1101-1107,共7页Chinese Journal of Modern Applied Pharmacy

基　　金：广东省科技计划项目(2009B030801346);广东省自然科学基金项目(8151022401000021);广东药学院师资队伍建设经费资助

摘　　要：目的制备具有主动肝靶向作用的低分子量半乳糖化脂肪酰壳聚糖聚合物胶束材料并进行结构表征,对其形成的胶束特性进行研究。方法以甲磺酸为溶剂及反应介质,利用脂肪酰氯(棕榈酰氯及月桂酰氯)与壳聚糖的OH进行酰化反应制备具有不同碳链长度及取代度的脂肪酰壳聚糖,再利用EDC.HCl活化乳糖酸,与所得的脂肪酰壳聚糖的2位氨基反应制备半乳糖化脂肪酰壳聚糖。用红外光谱、1H核磁共振谱对其结构进行表征及取代度的计算,并考察其溶解性能;制备其聚合物胶束,测定临界胶束浓度(CMC)和粒径。结果壳聚糖脂肪酰化的反应条件为20℃、1 h,半乳糖化反应的条件为30℃、24 h;壳聚糖棕榈酰化及月桂酰化反应中酰氯/壳聚糖的合适摩尔比分别为2∶1～8∶1、2∶1～10∶1。此条件下制得的脂肪酰壳聚糖及半乳糖化脂肪酰壳聚糖在二甲基亚砜(DMSO)中有较好的溶解性能;红外光谱、1H核磁共振光谱结果表明,成功合成了半乳糖化脂肪酰壳聚糖;脂肪酰基的取代度范围为0.28～1.13 mol,胶束的CMC约为0.39×10 2～2.82×10 2mg·mL-1,粒径大小119.8～546.0 nm。结论成功制备低分子量半乳糖化脂肪酰壳聚糖聚合物胶束材料。相同碳链长度条件下,脂肪酰氯与壳聚糖摩尔比越大,脂肪酰基的取代度越大,所得胶束的CMC及粒径越小;相同脂肪酰氯与壳聚糖摩尔比时,制得的半乳糖化脂肪酰壳聚糖的粒径小于脂肪酰壳聚糖的粒径。OBJECTIVE To synthesis a series of low molecular weight galactosylated fatty acyl chitosan as novel polymeric mieellar materials for hepatoeyte-targeting, and characterize their structures and properties of polymeric micelles. METHODS Using methanesulfonic acid as reaction medium, fatty acyl chitosans （F-CTS） with different chain length and degree of substitution （DS） of fatty acyl group were synthesized by the reactions between hydroxyl groups of chitosan and fatty aeyl chloride （palmitoyl chloride and lauroyl chloride）. Galactosylated fatty acyl chitosans （GF-CTS） were synthesized by reactions of lactobionic acid and 2-amino of F-CTS under the activation of 1-ethyl-3-（3-dimethylaminopropyl） carbodiimide hydrochloride （EDC.HC1）. The structure and DS were confirmed by IR and 1H-NMR. The critical micellar concentration （CMC） of F-CTS and GF-CTS were determined, and the particle sizes of polymeric micelles formed were measured. RESULTS F-CTS was synthesized by reaction of chitosan and chloride at 20 ℃ for 1 hour. Then GF-CTS was synthesized by reaction of lactobionic acid and F-CTS at 30 ℃ for 24 hours. The appropriate molar ratio of palmitoyl chloride （or lauroyl chloride） to chitosan was in the range of 2 ： 1-8 ： 1 （or 2 ： 1-10 ： 1）. DS of fatty acyl group ranged from 0.28 mol to 1.13 mol, GF-CTS and F-CTS were soluble in DMSO. The CMC and particle size of polymeric micelles formed were about 0.39x10-2-2.82×10-2 mg·mL^-1 and 119.8-546.0 nm, respectively. CONCLUSION Galactosylated fatty acyl chitosans （GF-CTS） are successfully synthesized. The DS of fatty acyl group and micellar properties changed regularly with the aliphatic chain length and molar ratio of chloride to chitosan. With the increase of molar ratio, the DS of fatty acyl group increased, but the CMC and micelle size decreased. With same molar ratio, the micelle size of F-CTS is bigger than that of GF-CTS.

关 键 词：低分子量壳聚糖 半乳糖化 脂肪酰 聚合物胶束 取代度 

分 类 号：R943.42[医药卫生—药剂学]