Hodaei Mahboobeh, Varshosaz Jaleh
Department of Pharmaceutics, Novel Drug Delivery Systems Research Centre, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Pharm Dev Technol. 2022 Sep;27(7):773-784. doi: 10.1080/10837450.2022.2119249. Epub 2022 Sep 8.
Oxaliplatin (OXP) is the typical treatment for colorectal cancer. Combining chemotherapeutic drugs can reduce drug resistance and side effects. In the present study, the co-delivery of OXP with Hesperetin (HSP), a natural anti-cancer flavonoid, by nanoliposomes was studied against HT-29 colon cancer cells. Cationic Okra gum (COG) was synthesized to coat nanoliposomes. The successful synthesis of COG was confirmed by NMR spectroscopy. Liposomes were prepared by thin film hydration technique. Formulations containing 0.5, 1, and 2 mg·ml COG, had particle sizes ranging from 145 to 175 nm and zeta potentials for uncoated and coated formulations changed between -29 and -0.403 mV. Coated liposomes released 98 and 66% of HSP and OXP, respectively during 24 h pH-dependently. Cationic Okra gum enhanced the physical stability of the liposomes for about 30 days. The composite liposomes containing OXP and HSP at final concentrations of 1.125 and 125 µM, respectively could generate significant cytotoxicity at 48 h in comparison to each drug alone. Extracted drug-target interactions from the STITCH database, showed that Catalase (CAT) is the common target between OXP and HSP drugs. Measurement of the CAT activity may be used as an indicator to investigate the mechanism of action of these drugs in subsequent experiments.
奥沙利铂(OXP)是结直肠癌的典型治疗药物。联合使用化疗药物可以降低耐药性和副作用。在本研究中,通过纳米脂质体研究了奥沙利铂与天然抗癌类黄酮橙皮素(HSP)共同递送对HT-29结肠癌细胞的作用。合成了阳离子秋葵胶(COG)来包覆纳米脂质体。通过核磁共振光谱证实了COG的成功合成。采用薄膜水化技术制备脂质体。含有0.5、1和2mg·ml COG的制剂,粒径范围为145至175nm,未包覆和包覆制剂的zeta电位在-29至-0.403mV之间变化。包覆脂质体在24小时内分别以pH依赖的方式释放了98%的HSP和66%的OXP。阳离子秋葵胶可提高脂质体的物理稳定性约30天。与单独使用每种药物相比,最终浓度分别为1.125和125µM的含有OXP和HSP的复合脂质体在48小时时可产生显著的细胞毒性。从STITCH数据库中提取的药物-靶点相互作用表明,过氧化氢酶(CAT)是OXP和HSP药物的共同靶点。在后续实验中,测量CAT活性可作为研究这些药物作用机制的指标。