具有近红外光控释功能的邻苯二酚改性壳聚糖基可注射生物黏合剂的制备及性能

Preparation and Properties of Catechol Modified Chitosan-based Injectable Biological Adhesives with Near-infrared-light-controlled Release Behavior

在制备邻苯二酚基团改性壳聚糖(CS-pC)的基础上,将CS-pC乙酸水溶液与β-甘油磷酸钠(β-GP)水溶液混合形成可注射溶胶,该溶胶加热至体温附近(37°C)时发生溶胶-凝胶转化,得到无细胞毒性且有优良抗菌和黏附性能的水凝胶(CS-pC/β-GP).该水凝胶黏附在猪皮上的临界剥离强度可达4.9 kPa,是纯壳聚糖(CS)基水凝胶临界剥离强度(0.6 kPa)的8倍.进一步在CS-pC/β-GP溶胶形成过程中加入水溶性药物盐酸多西环素(DH)和近红外光热剂金纳米棒(AuNR),即可以形成具有近红外光控释功能的CSpC/β-GP/DH/AuNR水凝胶,其负载的DH在808 nm近红外激光照射下的释放速率是无光照下的6倍.本工作为开发高效可注射型多功能邻苯二酚改性壳聚糖基生物黏合剂提供了新思路.

Chitosan(CS)hydrogel based adhesives have good biocompatibility,but poor adhesive property.In this paper,catechol modified chitosan(CS-pC)was synthesized by modifying CS with 3,4-dihydroxybenzoic acid.The mass ratio of catechol group of CS-pC is 14.4%.When the CS-pC acetic acid aqueous solution and the aqueous solution ofβ-glycerol phosphate disodium salt(β-GP)is mixed,an injectable CS-pC/β-GP sol is formed,which can be transformed into CS-pC/β-GP hydrogel under heating.The sol-gel transition time decreases exponentially with the increase of the temperature,and is around seven minutes at 37°C.The CS-pC/β-GP hydrogel has good biocompatibility,showing no cytotoxicity to Hela cells,MCF-7 cell,as well as 293T cells.It has excellent antibacterial properties on killing Escherichia coli and Staphylococcus aureus.It is noted that the CS-pC/β-GP hydrogel has brilliant adhesion property.The CS-pC/β-GP hydrogel can adhere to the porcine skin tightly. The critical peel strength is up to 4.9 kPa, eight times higher than that of the hydrogel prepared fromunmodified CS (0.6 kPa). Furthermore, the water-soluble drug doxycycline hydrochloride (DH) and near-infrared(NIR) photothermal agent gold nanorods (AuNR) can be loaded into the CS-pC/β-GP sol to form an injectable CSpC/β-GP/DH/AuNR sol, which can also be transformed into CS-pC/β-GP/DH/AuNR hydrogel rapidly at 37 °C.The strong NIR photothermal conversion effect of the loaded AuNR offers the hydrogel a remarkable NIR lightcontrolled release function. The release rate of the loaded DH will increase six times under the irradiation of808 nm NIR laser, which indicates that the CS-pC/β-GP/DH/AuNR hydrogel adhesive can also achieve acontrolled wound healing. This work provides a new way for the development of safe, high-performance, andmultifunctional injectable catechol modified chitosan based biological adhesives.