Sharma Anjali, Jyoti Kiran, Bansal Vikas, Jain Upendra Kumar, Bhushan Bharat, Madan Jitender
Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Panjab 140307, India.
Department of Pharmaceutical Chemistry, Hindu College of Pharmacy, Sonepat, Haryana, India.
Mater Sci Eng C Mater Biol Appl. 2017 Mar 1;72:69-76. doi: 10.1016/j.msec.2016.11.048. Epub 2016 Nov 15.
Soluble telmisartan and telmisartan were loaded in to poly (ethylene-glycol) grafted chitosan nanoparticles (S-TEL-PEG-CNPs and TEL-PEG-CNPs) for targeting cervical cancer through non-invasive, intravaginal route. The mean particle size of S-TEL-PEG-CNPs was measured to be 23.4±5.9-nm significantly (P<0.05) higher than 16.2±3.2-nm of TEL-PEG-CNPs. In contrast, the zeta-potential (-21.5±4.6-mV) of S-TEL-PEG-CNPs was insignificantly (P>0.05) different from -23.8±3.7-mV of TEL-PEG-CNPs. In addition, S-TEL-PEG-CNPs exhibited higher percent mucoadhesiveness (40.2%) in comparison (P<0.05) to 31.4% of TEL-PEG-CNPs, although it was lower than CNPs (100%). S-TEL-PEG-CNPs displayed significantly (P<0.01) higher dissolution of drug, 92.5% in comparison to 31.6% from TEL-PEG-CNPs up to 24h. Furthermore, S-TEL-PEG-CNPs exhibited superior cytotoxicity, apoptosis and cellular uptake, analyzed in human cervical cancer, HeLa cells. The IC of S-TEL-PEG-CNPs was measured to be 22.3-μM significantly (P<0.05) lower than 40.1-μM of TEL-PEG-CNPs. S-TEL-PEG-CNPs induced higher extent of apoptosis (P<0.05) in HeLa cells as compared to TEL-PEG-CNPs, owing to higher diffusion of drug across biological membrane. Finally, quantitative and qualitative cellular uptake assay confirmed the greater endocytosis of S-TEL-PEG-CNPs in HeLa cells due to diffusion, amorphization, hydrophilicity, and submicron size particularly, below 100nm. In conclusion, S-TEL-PEG-CNPs warrant further in vivo tumour regression study to scale up the technology for clinical translation.
将可溶性替米沙坦和替米沙坦负载于聚乙二醇接枝壳聚糖纳米粒（S-TEL-PEG-CNPs和TEL-PEG-CNPs）中，通过无创的阴道途径靶向宫颈癌。测得S-TEL-PEG-CNPs的平均粒径为23.4±5.9纳米，显著（P<0.05）高于TEL-PEG-CNPs的16.2±3.2纳米。相比之下，S-TEL-PEG-CNPs的zeta电位（-21.5±4.6毫伏）与TEL-PEG-CNPs的-23.8±3.7毫伏无显著差异（P>0.05）。此外，与TEL-PEG-CNPs的31.4%相比，S-TEL-PEG-CNPs表现出更高的黏膜黏附百分比（40.2%）（P<0.05），尽管它低于壳聚糖纳米粒（100%）。S-TEL-PEG-CNPs的药物溶出度显著更高（P<0.01），在24小时内为92.5%，而TEL-PEG-CNPs为31.6%。此外，在人宫颈癌HeLa细胞中分析发现，S-TEL-PEG-CNPs表现出更强的细胞毒性、凋亡作用和细胞摄取。测得S-TEL-PEG-CNPs的半数抑制浓度为22.3微摩尔，显著（P<0.05）低于TEL-PEG-CNPs的40.1微摩尔。由于药物在生物膜上的扩散性更高，与TEL-PEG-CNPs相比，S-TEL-PEG-CNPs在HeLa细胞中诱导的凋亡程度更高（P<0.05）。最后，定量和定性细胞摄取试验证实，由于扩散、无定形化、亲水性和亚微米尺寸（特别是低于100纳米），S-TEL-PEG-CNPs在HeLa细胞中的内吞作用更强。总之，S-TEL-PEG-CNPs有待进一步进行体内肿瘤消退研究，以扩大该技术用于临床转化的规模。
