Mashaqbeh Hadeia, Hamed Rania, Obaidat Rana, Hmedat Ali, Aburayya Raffa, Hijazi Sara, Akkam Yazan
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Yarmouk University, Irbid, Jordan.
Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.
J Biomater Sci Polym Ed. 2025 Jul 3:1-30. doi: 10.1080/09205063.2025.2524059.
Hydrogel-based drug delivery technologies have garnered considerable interest in the biomedical field, aiming to overcome the challenges associated with conventional treatments. This investigation reports a novel injectable hydrogel composed of non-chemically modified hyaluronic acid and κ-carrageenan, crosslinked using a Fe(III)-ethylenediaminetetraacetic acid (EDTA) complex for the delivery of a chemotherapeutic agent. The system exhibits shear-thinning behavior, possessing both appropriate rheological and drug-release properties, thereby eliminating the need for chemical or thermoresponsive additives. This study examines this system in the context of chemotherapeutic delivery, providing a novel approach to achieving biocompatibility, structural flexibility, injectability, and prolonged release properties. The developed hydrogels were evaluated for their ability to deliver the model drug daunorubicin (DNR). Physicochemical characterizations of hydrogels, including FTIR, DSC, and SEM analysis, were carried out. Furthermore, the rheological properties, release, swelling, degradation, and cytotoxicity of the developed hydrogels were evaluated. Homopolymer hydrogels of metal ion crosslinked HA, KCG, and hybrid hydrogels of HA-KCG were developed and evaluated. All studied hydrogels can control DNR release; compared to homopolymer hydrogels, the HA-KCG hybrid hydrogels showed a better swelling ratio, a slower degradation rate, and a higher capability to prolong DNR release over 16 days. In addition, the evaluated hydrogels exhibit shear-thinning properties and diverse viscoelastic properties, as well as enhanced DNR cytotoxic activities. Overall, Injectable self-healing hydrogels of HA and KCG interpenetrating polymer networks (IPNs) produced by metal ionic crosslinking were successfully created, exhibiting shear-thinning ability and thixotropic properties, making them a potential candidate for localized chemotherapeutic drug delivery.
基于水凝胶的药物递送技术在生物医学领域引起了广泛关注，旨在克服传统治疗方法所带来的挑战。本研究报告了一种新型可注射水凝胶，它由非化学改性的透明质酸和κ-卡拉胶组成，通过铁（III）-乙二胺四乙酸（EDTA）络合物交联，用于递送化疗药物。该系统表现出剪切变稀行为，具有合适的流变学和药物释放特性，从而无需化学或热响应添加剂。本研究在化疗药物递送的背景下对该系统进行了研究，提供了一种实现生物相容性、结构灵活性、可注射性和长效释放特性的新方法。对所制备的水凝胶递送模型药物柔红霉素（DNR）的能力进行了评估。对水凝胶进行了包括傅里叶变换红外光谱（FTIR）、差示扫描量热法（DSC）和扫描电子显微镜（SEM）分析在内的物理化学表征。此外，还评估了所制备水凝胶的流变学性质、释放、溶胀、降解和细胞毒性。制备并评估了金属离子交联透明质酸（HA）、κ-卡拉胶（KCG）的均聚物水凝胶以及HA-KCG杂化水凝胶。所有研究的水凝胶都能控制DNR的释放；与均聚物水凝胶相比，HA-KCG杂化水凝胶表现出更好的溶胀率、更慢的降解速率以及在16天内更高的延长DNR释放的能力。此外，所评估的水凝胶表现出剪切变稀特性和多样的粘弹性特性，以及增强的DNR细胞毒性活性。总体而言，成功制备了通过金属离子交联产生的HA和KCG互穿聚合物网络（IPN）的可注射自愈合水凝胶，其具有剪切变稀能力和触变性，使其成为局部化疗药物递送潜在候选物。
