College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA.
Biomater Sci. 2022 Aug 9;10(16):4492-4507. doi: 10.1039/d2bm00022a.
Applicability of hydrogels as drug delivery systems is on the rise due to their highly tunable degree of polymeric crosslinking to attain varying rates of payload release. Sustaining the release of therapeutic payloads at certain physiological sites has been the need of the hour to treat disorders such as peritoneal or pleural malignancies. These disorders can be targeted intracavitary administration of hydrogels, providing localized therapy. In this study, a gelatin methacrylate (GelMa) hydrogel with tunable physicochemical traits is developed and characterized. A hydrogel-based depot system was curated using GelMa as backbone, a photo-initiator (lithium phenyl-2,4,6-trimethylbenzoylphosphinate) and a chemical crosslinker (,-methylenebisacrylamide). Hydrogels were optimized using a 2 factorial design, by testing for their gelling time, injectability, viscosity change, elasticity, bio-adhesion, swelling-index, degradation, release, and biocompatibility. Gelling time for hydrogel formulations was found to be <60 seconds with gelling being achieved in as fast as 24 seconds. Bio-adhesion studies revealed that formulations with higher concentrations of both crosslinkers had more adhesion to guinea pig lung tissues. Hydrogels with higher swelling showcased a more sustained release. Biocompatibility studies for hydrogel formulations was done by evaluating formulation performance in MTT, live/dead, and apoptosis assays performed using non-malignant Human embryonic kidney cells (HEK-293). The optimized hydrogel formulations were biocompatible, yielding >90% cellular viability over 72 hours. This delivery system prototype may be used to deliver potent chemotherapeutics locally, reducing off target effects and improving therapeutic benefits.
水凝胶作为药物传递系统的应用由于其高度可调的聚合物交联程度而不断增加，以达到不同的载药释放率。在某些生理部位维持治疗性载药的释放一直是治疗腹膜或胸膜恶性肿瘤等疾病的迫切需要。这些疾病可以通过腔内给予水凝胶来靶向治疗，提供局部治疗。在这项研究中，开发并表征了一种具有可调节理化特性的甲基丙烯酸明胶（GelMa）水凝胶。使用 GelMa 作为骨干，光引发剂（苯甲酰膦酸二苯基酯）和化学交联剂（N,N’-亚甲基双丙烯酰胺），构建了一种基于水凝胶的储存库系统。通过测试凝胶时间、可注射性、粘度变化、弹性、生物附着力、溶胀指数、降解、释放和生物相容性，使用 2 因子设计优化了水凝胶。水凝胶配方的凝胶时间发现<60 秒，最快在 24 秒内凝胶化。生物附着力研究表明，两种交联剂浓度较高的配方对豚鼠肺组织的附着力更强。具有较高溶胀度的水凝胶表现出更持续的释放。通过评估非恶性人胚肾细胞（HEK-293）中进行的 MTT、死活和细胞凋亡测定中配方的性能，对水凝胶配方进行了生物相容性研究。优化后的水凝胶配方具有生物相容性，在 72 小时内细胞活力>90%。这种输送系统原型可用于局部递送电化疗药物，减少脱靶效应并提高治疗效果。
