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

- S-TEL-PEG-CNPs offered sustained in vitro drug release in simulated vaginal fluid (pH ~ 4.2)
- S-TEL-PEG-CNPs reduced affinity for cervicovaginal mucus in comparison to CNPs alone.
- S-TEL-PEG-CNPs induced higher extent of apoptosis and endocytosis in cervical cancer, HeLa cells.

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 IC50 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 100 nm. In conclusion, S-TEL-PEG-CNPs warrant further in vivo tumour regression study to scale up the technology for clinical translation.

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