University of Innsbruck, Institute of Pharmacy, Department of Pharmaceutical Technology, Innrain 20-82, 6020 Innsbruck, Austria; Massachusetts Institute of Technology, Koch Institute for Integrative Cancer Research at MIT, Langer Lab, 77 Massachussets Ave, Cambridge, MA 02139, USA.
University of Innsbruck, Institute of Pharmacy, Department of Pharmaceutical Technology, Innrain 20-82, 6020 Innsbruck, Austria; Division of Pharmaceutical Sciences, Faculty of Pharmacy, Thammasat University, Rangsit campus, Phahonyothin Rd., Khlong Luang, Pathumthani 12120, Thailand.
Int J Biol Macromol. 2019 Feb 15;123:1204-1210. doi: 10.1016/j.ijbiomac.2018.11.186. Epub 2018 Nov 19.
This study aimed to investigate the properties of modified hyaluronic acid in terms of rheological properties, enzymatic degradation and mucoadhesiveness.
Hyaluronic acid (HA) was chemically modified with sulfhydryl ligand cysteine ethyl ester (C) in order to immobilize sulfhydryl groups on the polymeric backbone. MTT assay was performed to evaluate the safety of hyaluronic acid-cysteine ethyl ester (HAC). Rheological and enzymatic degradation studies were accomplished by preparing hydrogels of HA and HAC, respectively. HA served as control. Enzymes such as lysozyme, amylase and hyaluronidase were chosen to perform degradation studies. To study mucoadhesiveness, hydrogels of HA and HAC, respectively, were mixed with mucus and evaluated by rheology.
MTT assay indicated no toxicity at all. The rheological assay showed 2.2-fold increase in gelling properties in case of HAC in comparison to HA. Furthermore, it could be shown that HAC was degraded by amylase to a lesser extent of 11.5-fold than HA. After 2 h, HA showed a higher degradation by lysozyme with 67.97% than HAC. Adhesion studies exhibited a 2.17-fold higher mucoadhesion of HAC with mucus compared to HA.
These results will open the door for high efficient drug delivery systems based on hydrogels for mucosal application.
本研究旨在研究经巯基配体半胱氨酸乙酯（C）化学修饰的透明质酸（HA）的流变性能、酶降解和黏膜黏附特性。
为了在聚合物主链上固定巯基，HA 被化学修饰为带有巯基配体半胱氨酸乙酯（C）。通过 MTT 测定法评估透明质酸-半胱氨酸乙酯（HAC）的安全性。通过分别制备 HA 和 HAC 的水凝胶来完成流变和酶降解研究。HA 用作对照。选择溶菌酶、淀粉酶和透明质酸酶等酶进行降解研究。为了研究黏膜黏附性，分别将 HA 和 HAC 的水凝胶与黏液混合，并通过流变学进行评估。
MTT 测定法表明 HAC 完全没有毒性。流变学测定表明，与 HA 相比，HAC 的凝胶性能增加了 2.2 倍。此外，结果表明 HAC 被淀粉酶降解的程度比 HA 低 11.5 倍。2 小时后，HA 对溶菌酶的降解率为 67.97%，高于 HAC。黏附研究表明，与 HA 相比，HAC 与黏液的黏附性高 2.17 倍。
这些结果将为基于用于黏膜应用的水凝胶的高效药物输送系统开辟道路。
