Faculty of Pharmacy, Philadelphia University, P.O. Box 1, Amman 19392, Jordan.
Faculty of Pharmacy, Isra University, P.O. Box 33, Amman 11622, Jordan.
Molecules. 2022 Dec 30;28(1):306. doi: 10.3390/molecules28010306.
This work aimed to develop a new one-pot and readily scaled-up formulation capable of retaining 5-fluorouracil and prolonging its release to obtain a site-specific medication delivery for the potential treatment of colorectal cancer. Six polymer-based formulations were successfully produced using a thermal bulk polymerization method and loaded with 5-fluorouracil, which is a chemotherapeutic agent used in the treatment of colorectal carcinoma. The pellets produced were characterized by measuring the glass transition temperature, tensile strength, Young's modulus, and tensile elongation at break. Studies on in vitro swelling and release were carried out in phosphate-buffered saline to evaluate the behaviour of the developed system. The Young's modulus, glass transition temperature, and tensile strength all increased significantly as the crosslinker concentration increased, but the fracture strain value reduced significantly. The in vitro swelling profile of the produced formulations was significantly reduced by increasing crosslinking density. Less than 27% cumulative drug release was achieved for all formulations after 5 h of starting the release study. The highest cumulative drug release reached after 24 h was 69%. The developed drug delivery system demonstrated the ability to delay the release of 5-fluorouracil in upper gastrointestinal tract-mimicking conditions, while permitting its release in a controlled way afterward, which makes it promising for the potential delivery of 5-fluorouracil to the colon.
本工作旨在开发一种新的一锅法和可规模化的制剂，以保留 5-氟尿嘧啶并延长其释放时间，从而实现针对结直肠肿瘤的局部给药治疗。采用热本体聚合方法成功制备了 6 种基于聚合物的制剂，并负载 5-氟尿嘧啶，5-氟尿嘧啶是一种用于治疗结直肠癌的化疗药物。通过测量玻璃化转变温度、拉伸强度、杨氏模量和拉伸断裂伸长率来表征所制备的微丸。在磷酸盐缓冲盐水中进行体外溶胀和释放研究，以评估所开发系统的行为。随着交联剂浓度的增加，杨氏模量、玻璃化转变温度和拉伸强度都显著增加，而断裂应变值显著降低。通过增加交联密度，显著降低了所制备制剂的体外溶胀曲线。在开始释放研究 5 小时后，所有制剂的累积药物释放均低于 27%。在 24 小时后达到的最高累积药物释放率为 69%。所开发的药物传递系统在模拟上胃肠道条件下能够延迟 5-氟尿嘧啶的释放，而随后能够以受控的方式释放，这使其有望将 5-氟尿嘧啶递送到结肠。
