IEDDA 클릭 반응을 이용한 생체직교성 히알루론산계 약물 전달 하이드로겔 제조 연구

Abstract

In this work, we developed injectable hydrogels derived from hyaluronic acid (HA) modified with norbornene (Nb) and a cross-linker composed of polyethylene glycol (PEG) with tetrazine (Tz) functional groups. The hydrogels exhibited high biocompatibility and rapid absorption. The porosity of the hydrogels was created through the release of nitrogen gas as a by-product during the cross-linking reaction known as inverse electron demand Diels-Alder (IEDDA). By adjusting the molar ratio of HA-Nb and PEG-DTz (Nb:Tz = 10:2.5 10:5, 10:10), we could control the porosity, gelation time, mechanical strength, and swelling properties of the hydrogels. The gelation process was quick, taking less than 100 seconds, which suggests the potential for their use as injectable drug delivery systems. The hydrogels exhibited rapid swelling and high swelling ratios due to the presence of PEG chains and a highly porous structure. They effectively encapsulated curcumin, with an encapsulation efficiency of approximately 99%, and released the curcumin in a controlled manner. The cytotoxicity evaluation conducted on HEK-293 cells demonstrated no harmful effects of the PEG-DTz cross-linker, HA-Nb, and resulting hydrogels. Overall, these absorbent hydrogels, fabricated from HA-Nb and the IEDDA clickable cross-linker, hold great promise as biocompatible drug carriers for injectable drug delivery applications.