Trummer Ronny, Rangsimawong Worranan, Sajomsang Warayuth, Kumpugdee-Vollrath Mont, Opanasopit Praneet, Tonglairoum Prasopchai
Faculty of Pharmaceutical and Chemical Engineering, Beuth Hochschule für Technik Berlin, University of Applied Sciences 13353 Berlin Germany.
Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University Nakhon Pathom 73000 Thailand
RSC Adv. 2018 Jun 22;8(41):22967-22973. doi: 10.1039/c8ra03069c. eCollection 2018 Jun 21.
Polymeric nanocarriers were prepared a dialysis method using three chitosan derivatives, -benzyl-,-succinyl chitosan (BSCT), -naphthyl-,-succinyl chitosan (NSCT), and -octyl--succinyl chitosan (OSCT) and were coordinated to cisplatin. The nanocarrier properties and cytotoxicity on the human carcinoma cells, HN22 (head and neck), were investigated. In addition, intracellular cisplatin accumulation, apoptosis induction and toxicity on renal cells were also evaluated. The findings revealed that the succinyl groups of the polymers were perfectly deprotonated and bound with cisplatin by co-ordinate bonds at pH 8.5. Among the derivatives, BSCT exhibited the highest cisplatin loading and release in simulated physiological medium. The cytotoxicities on HN22 cells of cisplatin-loaded BSCT nanocarriers were lower than that of free cisplatin, however, they presented a greater percentage of early apoptosis in HN22 cells and could decrease cisplatin induced renal cell death. In conclusion, the BSCT self-assembly nanocarrier might be a cisplatin carrier for sustained release, which provides prolonged antitumour treatment and reduced nephrotoxicity.
使用三种壳聚糖衍生物,即苄基-、琥珀酰壳聚糖(BSCT)、萘基-、琥珀酰壳聚糖(NSCT)和辛基-、琥珀酰壳聚糖(OSCT),通过透析法制备了聚合物纳米载体,并使其与顺铂配位。研究了纳米载体的性质以及对人癌细胞HN22(头颈癌)的细胞毒性。此外,还评估了细胞内顺铂的积累、凋亡诱导以及对肾细胞的毒性。研究结果表明,聚合物的琥珀酰基团在pH 8.5时完全去质子化,并通过配位键与顺铂结合。在这些衍生物中,BSCT在模拟生理介质中表现出最高的顺铂负载量和释放量。负载顺铂的BSCT纳米载体对HN22细胞的细胞毒性低于游离顺铂,然而,它们在HN22细胞中呈现出更高比例的早期凋亡,并且可以减少顺铂诱导的肾细胞死亡。总之,BSCT自组装纳米载体可能是一种用于持续释放的顺铂载体,可提供延长的抗肿瘤治疗并降低肾毒性。