Drug Delivery ( IF 6 ) Pub Date : 2023-09-05 , DOI: 10.1080/10717544.2023.2254530 Shimaa A Elbanna 1 , Heba M K Ebada 2 , Ossama Y Abdallah 1 , Marwa M Essawy 3, 4 , Hend M Abdelhamid 3, 4 , Hebatallah S Barakat 1
Abstract
Oral cancer is one of the leading causes of death worldwide. Oral precancerous lesions (OPL) are the precursors of oral cancer, with varying degrees of progression. Tetrahydrocurcumin (THC) is a major metabolite of curcumin with superior anticancer properties against various types of cancer. However, THC’s clinical outcome is limited by its poor aqueous solubility. Herein, we developed novel mucoadhesive biopolymer-based composite sponges for buccal delivery of THC, exploiting nanotechnology and mucoadhesion for efficient prevention and treatment of oral cancer. Firstly, THC-nanocrystals (THC-NC) were formulated and characterized for subsequent loading into mucoadhesive composite sponges. The anticancer activity of THC-NC was assessed on a human tongue squamous carcinoma cell line (SCC-4). Finally, the chemopreventive activity of THC-NC loaded sponges (THC-NC-S) was examined in DMBA-induced hamster OPL. The selected THC-NC exhibited a particle size of 532.68 ± 13.20 nm and a zeta potential of −46.08 ± 1.12 mV. Moreover, THC-NC enhanced the anticancer effect against SCC-4 with an IC50 value of 80 µg/mL. THC-NC-S exhibited good mucoadhesion properties (0.24 ± 0.02 N) with sustained drug release, where 90% of THC was released over 4 days. Furthermore, THC-NC-S had a magnificent potential for maintaining high chemopreventive activity, as demonstrated by significant regression in the dysplasia degree and a decline in cyclin D1 (control: 40.4 ± 12.5, THC-NC-S: 12.07 ± 5.2), culminating in significant amelioration after 25 days of treatment. Conclusively, novel THC-NC-S represent a promising platform for local therapy of OPL, preventing their malignant transformation into cancer.
中文翻译:
新型四氢姜黄素集成粘膜粘附纳米复合材料κ-卡拉胶/黄原胶海绵:有效局部治疗口腔癌和癌前病变的策略
摘要
口腔癌是全世界导致死亡的主要原因之一。口腔癌前病变(OPL)是口腔癌的前兆,具有不同程度的进展。四氢姜黄素(THC)是姜黄素的主要代谢物,对多种癌症具有卓越的抗癌特性。然而,THC 的临床效果因其水溶性差而受到限制。在此,我们开发了新型粘膜粘附生物聚合物复合海绵,用于口腔输送 THC,利用纳米技术和粘膜粘附有效预防和治疗口腔癌。首先,对 THC 纳米晶体 (THC-NC) 进行配制和表征,以便随后将其装载到粘膜粘附复合海绵中。THC-NC 的抗癌活性在人舌鳞状癌细胞系 (SCC-4) 上进行了评估。最后,在 DMBA 诱导的仓鼠 OPL 中检查了 THC-NC 负载海绵 (THC-NC-S) 的化学预防活性。所选THC-NC的粒径为532.68±13.20 nm,zeta电位为-46.08±1.12 mV。此外,THC-NC 增强了对 SCC-4 的抗癌作用,IC50 值为 80 µg/mL。THC-NC-S 表现出良好的粘膜粘附特性 (0.24 ± 0.02 N) 和持续的药物释放,其中 90% 的 THC 在 4 天内释放。此外,THC-NC-S 具有维持高化学预防活性的巨大潜力,不典型增生程度的显着消退和细胞周期蛋白 D1 的下降证明了这一点(对照:40.4 ± 12.5,THC-NC-S:12.07 ± 5.2),治疗25天后,病情明显改善。总之,新型 THC-NC-S 代表了 OPL 局部治疗的一个有前景的平台,可防止其恶性转化为癌症。