基于席夫碱键的可注射糖肽水凝胶的制备及性能

以氧化葡聚糖(ODEX)和聚赖氨酸-聚乙二醇-聚赖氨酸(PLL₂₄-PEG-PLL₂₅)三嵌段聚合物为前驱体, 通过ODEX中的醛基与PLL中的氨基之间的席夫碱键反应, 制备了ODEX/PLL₂₄-PEG-PLL₂₅水凝胶. 研究了其凝胶强度、 降解时间及对阿霉素(DOX)释放量的影响. 结果表明, 随着ODEX中醛基密度的增加, 凝胶强度逐渐增大, 最大强度为3100 Pa. 流变学研究结果表明, 由于ODEX中的醛基与DOX中的氨基存在席夫碱键作用, 导致凝胶强度从2160 Pa降至1730 Pa. 降解实验结果表明, ODEX/PLL₂₄-PEG-PLL₂₅水凝胶具有较长的降解时间, 最长时间达到29 d. 药物释放结果表明, ODEX/PLL₂₄-PEG-PLL₂₅水凝胶具有酶促降解释放药物的性能. 在Elastase溶液中, ODEX/PLL₂₄-PEG-PLL₂₅水凝胶所载DOX累积释放量达到最大值74.35%. 结果表明, ODEX/PLL₂₄-PEG-PLL₂₅水凝胶具有进一步应用于体内局部药物传输的潜力.

Fabrication and Characterization of Injectable Polysaccharide-polypeptide Hydrogel Based on Schiff’s Base†

The purpose of gel is applied to body with no toxic. Based on dextran, oxidized dextran( ODEX) with the different oxidation extent was prepared. At the same time, the tri-block polymers poly ( lysine )-polyethylene glycol-poly( lysine) ( PLL24-PEG-PLL25 ) was synthesized, which becomes hydrogels through the reaction between the dextran aldehyde groups and the poly-L-lysine amino groups via Schiff’ s base formation. The storage modulus, degradation time of gel, and release of doxorubicin ( DOX ) were characterized. The results showed that gel strength increased gradually with the increasing density of aldehyde in ODEX, and the maximum storage modulus was 3100 Pa. The rheological test indicates that the storage modulus was reduced from 2160 Pa to 1730 Pa, due to the Schiff’ s effect between ODEX aldehyde group and DOX amine group. The gel had a long degradation time up to 29 d. Drug release studies showed that DOX released from carrier gel was triggered by the enzyme. In Elastase solution, DOX release rate had reached up to 74. 35%. The findings reveal that the hydrogel have promising applications in drug delivery in vivo.