Biocompatible, injectable and self-healable MOF-based anti-freezing eutectogels for higher encapsulation and sustained release of the anticancer drug curcumin†

Nildhara Parsana, Hiral Ukani, Dharmveer Singh Chauhan, Omar El Seoud, Sanjay Mehra, Arvind Kumar, Naina Raje and Naved Malek
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Abstract

Inspired by the antifreeze proteins found in the blood of Trematomus borchgrevtnki, a fish from the Antarctic Ocean, herein we developed metal organic framework (MOF) based ‘waterless’ eutectogels with impermeable nano-domains as antifreeze “soft” materials. The eutectogels were successfully developed through dissolving sodium alginate and ZIF-8, a known MOF, within deep eutectic solvents (DESs) prepared from the environmentally benign biocompatible cryoprotectants glucose and fructose as the HBDs and choline chloride as the HBA. The structural integrity of ZIF-8 and DES was preserved during the eutectogel formation and so also their properties. The eutectogels showcased notable attributes, including antifreeze properties, self-healing capabilities, injectability, adhesiveness, substantial drug loading capacity (∼75 000 and ∼71 000 fold higher curcumin than in water) and efficient sustained drug release behaviour. Moreover, the eutectogel also demonstrated antibacterial and antioxidant attributes, along with hemocompatibility evidenced by hemolysis levels below 2%. Furthermore, the eutectogel exhibited biocompatibility even at very high concentrations (50 mg mL−1). Leveraging on its robust colloidal forces and an environmentally benign composition, the studied eutectogel proves its suitability not just for pharmaceutical applications but also for high-performance applications that prioritize ecological sustainability.

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基于 MOF 的生物相容性、可注射性和自愈性抗冻共晶凝胶,用于提高抗癌药物姜黄素的封装和持续释放率†。
受南极海洋鱼类 Trematomus borchgrevtnki 血液中抗冻蛋白的启发,我们在此开发了基于金属有机框架(MOF)的 "无水 "共晶凝胶,这种凝胶具有不透水的纳米域,可作为抗冻 "软 "材料。海藻酸钠和 ZIF-8(一种已知的 MOF)在深共晶溶剂(DES)中溶解,而深共晶溶剂(DES)是以对环境无害的生物相容性低温保护剂葡萄糖和果糖为 HBD,氯化胆碱为 HBA 制成的。在形成共晶凝胶的过程中,ZIF-8 和 DES 的结构完整性得以保持,因此它们的性能也得以保持。共晶凝胶具有显著的特性,包括防冻性、自愈合能力、可注射性、粘附性、巨大的载药量(姜黄素的载药量比水高出 75 000 倍和 71 000 倍)以及高效的持续释药行为。此外,共晶凝胶还具有抗菌和抗氧化特性,溶血水平低于 2%,证明其具有血液相容性。此外,即使在浓度非常高(50 毫克毫升/升)的情况下,共晶凝胶也能表现出生物相容性。所研究的共晶凝胶具有强大的胶体作用力和对环境无害的成分,这证明它不仅适用于制药应用,还适用于优先考虑生态可持续性的高性能应用。
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