可注射改性羧甲基纤维素水凝胶的制备及性能

Preparation and Properties of Injectable Carboxymethyl Cellulose Based Hydrogels

对羧甲基纤维素(CMC)进行巯基接枝改性,制备了羧甲基纤维素衍生物(CMC-SH),采用溶解氧或H2O2氧化巯基(-SH)形成双硫键(-S-S-)的方法,化学交联制备了CMC-SH10、CMC-SH20和CMC-SH30系列可注射羧甲基纤维素基水凝胶,并对水凝胶的流变学性能以及在37℃的磷酸盐缓冲溶液(PBS)中的溶胀率、降解行为、体外药物释放行为进行了研究。结果表明,系列CMC-SH水凝胶具有较好的流变学性能,CMC-SH30水凝胶的储能模量(G′)和屈服应力(τ)分别达到2873Pa和9328Pa;在37℃的PBS溶液中,系列水凝胶均能快速达到溶胀平衡,8h溶胀率介于22~29之间;均具有较好的稳定性,13d降解率为28%~48%;药物模型牛血清蛋白(BSA)5d的累积释放率为45%~59%,对BSA具有较好的控释能力。总体而言,前驱体浓度越高,CMC-SH水凝胶的综合性能越好,系列水凝胶均具有较好的综合性能,其中CMC-SH30水凝胶的综合性能更好,有望应用于中短期蛋白类等大分子药物传输领域。

Thiolated carboxymethyl cellulose(CMC-SH)was synthesized with sodium carboxymethyl cellulose(CMC)utilizing sulfydryl grafting,and a series of injectable carboxymethyl cellulose based hydrogels(CMC-SH10,CMC-SH20,and CMC-SH30 hydrogels)were prepared using thiolated carboxymethyl cellulose as precursor through chemical cross-linking via disulfide bonds by the oxidation of dissolved oxygen or H2 O2.The rheological properties,swelling ratio,degradation behavior,and in vitro drug release behavior of CMC-SH hydrogels were investigated.The results show that the series of CMC-SH hydrogels exhibit appropriate rheological properties,the storage modulus(G')and the yield stress(τ)of CMC-SH30 hydrogel are 2873 Pa and 9328 Pa,respectively.All hydrogels exhibit the fast swelling rate,high swelling ratio,good stability,and sustained drug controlled release ability.In PBS solution(pH7.4)at 37℃,the swelling ratio of the series of CMC-SH hydrogels ranges from 22 to 29 after incubating 8 h,the degradation percentage ranges from 28%to 48%after 13 d,and the in vitro cumulative release percentage of BSA from drug-loaded hydrogels ranges from 45%to 59%after 5 d.Overall,the series of injectable CMC-SH hydrogels exhibit a good comprehensive performance,and the comprehensive performances of CMC-SH hydrogels are improved with the increasing of the concentration of precursor solution,and the comprehensive performances of CMC-SH30 hydrogel are better than those of CMC-SH10 and CMC-SH20,signifying that these hydrogels could be potentially used in the fields of short-and medium-term macromolecular drug(such as protein,etc.)delivey.