Shahzad Khurram, Raza Muhammad Asim, Hussain Abrar, Ko Kyong-Cheol, Jeong Hyeon-Jin, Seralathan Kamala-Kannan, Han Sung Soo, Park Sang Hyun
Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute, Jeongeup 56212, Republic of Korea; Radiation Science, University of Science and Technology, Daejeon 34113, Republic of Korea.
School of Chemical Engineering, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea.
Int J Biol Macromol. 2025 May;308(Pt 3):142256. doi: 10.1016/j.ijbiomac.2025.142256. Epub 2025 Mar 27.
Hydrogels are widely employed in drug delivery, gene delivery, tissue engineering, and wound healing applications. However, many organic crosslinkers used in hydrogel fabrication exhibit poor water solubility, low biodegradation rates, and toxicity, limiting their biomedical utility. In this study, we developed a simple, cost-effective, and rapid method for synthesizing self-crosslinked carboxymethyl chitosan-based hydrogel (CMCH HG) using N-(3-Dimethylaminopropyl)-N-ethylcarbodiimide (EDC) and N-Hydroxysuccinimide (NHS) chemistry instead of toxic organic crosslinkers. To enhance physicochemical properties, we prepared composites of self-crosslinked hydrogel with gelatin (CMCH/GL HG) and 6-arm polyethylene glycol amine-functionalized graphene oxide (CMCH/GL/PEG-GO HG). The fabrication and physicochemical characteristics of the self-crosslinked hydrogel and its composites were verified through analytical and spectroscopic techniques. The in-vitro drug release study using berberine chloride demonstrated that CMCH/GL/PEG-GO HG released only 30 % of the drug in the first 12 h and a total of 39 % after 96 h. Due to controlled drug release, excellent antioxidant activities, anticancer properties, biodegradability, and minimal toxicity, the composite of self-crosslinked carboxymethyl chitosan hydrogel with gelatin and graphene oxide represents a promising candidate as a drug carrier at tumor sites to minimize off-target effects of chemotherapy.
水凝胶广泛应用于药物递送、基因递送、组织工程和伤口愈合等领域。然而，许多用于水凝胶制备的有机交联剂表现出较差的水溶性、低生物降解率和毒性，限制了它们在生物医学方面的应用。在本研究中，我们开发了一种简单、经济高效且快速的方法，使用N-(3-二甲氨基丙基)-N-乙基碳二亚胺（EDC）和N-羟基琥珀酰亚胺（NHS）化学方法，而非有毒的有机交联剂，来合成自交联的羧甲基壳聚糖基水凝胶（CMCH HG）。为了增强物理化学性质，我们制备了自交联水凝胶与明胶的复合材料（CMCH/GL HG）以及六臂聚乙二醇胺功能化氧化石墨烯的复合材料（CMCH/GL/PEG-GO HG）。通过分析和光谱技术验证了自交联水凝胶及其复合材料的制备和物理化学特性。使用盐酸小檗碱进行的体外药物释放研究表明，CMCH/GL/PEG-GO HG在最初12小时内仅释放了30%的药物，96小时后总共释放了39%。由于药物释放可控、具有出色的抗氧化活性、抗癌特性、生物可降解性和最小毒性，自交联羧甲基壳聚糖水凝胶与明胶和氧化石墨烯的复合材料有望成为肿瘤部位的药物载体，以最大限度地减少化疗的脱靶效应。
