Soluble telmisartan bearing poly (ethylene glycol) conjugated chitosan nanoparticles augmented drug delivery, cytotoxicity, apoptosis and cellular uptake in human cervical cancer cells

摘要

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 24 h. Furthermore, S-TEL-PEG-CNPs exhibited superior cytotoxicity, apoptosis and cellular uptake, analyzed in human cervical cancer, HeLa cells. The IC_(50) 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 submi-cron size particularly, below 100 nm. In conclusion, S-TEL-PEG-CNPs warrant further in vivo tumour regression study to scale up the technology for clinical translation.