Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2H7, Canada; College of Pharmacy, Taibah University, Medina, 42353, Saudi Arabia.
Carbohydr Polym. 2021 Mar 1;255:117332. doi: 10.1016/j.carbpol.2020.117332. Epub 2020 Nov 4.
To fabricate a mucoadhesive hydrogel with superior properties for local delivery of cisplatin (CDDP) to colorectal cancer, a hardcore bottle-brush polymer (HCBBP) was developed through grafting of poly(acrylic acid) (PAA) on cellulose nanocrystals (CNC) at 6, 9 and 12 CNC:PAA w/w ratios. The developed materials were characterized by acid-base titrations, FT-IR, electron microscopy, muco-rheological behaviour in the presence of mucin, in vitro drug release and anticancer activity against human HCT-116 colorectal cancer cells. The results showed CNC-g-PAA9 to have superior rheological behavior in the presence of mucin compared to CNC and other gels under study indicating beneficial mucoadhesive characteristics. CNC-g-PAA9:CDDP complex showed slow CDDP release causing a significant increase in IC of the drug (> 3-fold) against HCT116 cells. The developed CNC-PAA9 hydrogel showed no intrinsic cytotoxicity on its own. The results point to a great promise for CNC-g-PAA9 as mucoadhesive hydrogels for local platinum delivery in colorectal cancer.
为了制备一种具有优异性能的用于局部递送顺铂（CDDP）的黏附性水凝胶，通过在纤维素纳米晶体（CNC）上接枝聚丙烯酸（PAA），在 6、9 和 12 CNC：PAA w/w 比下开发了一种硬核刷型聚合物（HCBBP）。所开发的材料通过酸碱滴定、FT-IR、电子显微镜、存在粘蛋白时的粘膜流变行为、体外药物释放和对人 HCT-116 结肠直肠癌细胞的抗癌活性进行了表征。结果表明，与 CNC 和其他研究中的凝胶相比，CNC-g-PAA9 在存在粘蛋白时具有优越的流变行为，表明具有有益的黏附特性。CNC-g-PAA9：CDDP 复合物表现出缓慢的 CDDP 释放，导致药物对 HCT116 细胞的 IC 显著增加（>3 倍）。所开发的 CNC-PAA9 水凝胶本身没有内在的细胞毒性。结果表明，CNC-g-PAA9 作为用于结直肠癌细胞局部铂类药物递送的黏附性水凝胶具有很大的应用前景。
