title: Soluble telmisartan bearing poly (ethylene glycol) conjugated chitosan nanoparticles augmented drug delivery, cytotoxicity, apoptosis and cellular uptake in human cervical cancer cells.
abstract: 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 IC50of 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.
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Panjab 140307, India.
authors.forename: Anjali
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Panjab 140307, India.
authors.forename: Kiran
authors.initials: K
authors.lastname: Jyoti
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Panjab 140307, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Bansal
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Panjab 140307, India.
authors.forename: Upendra Kumar
authors.initials: UK
authors.lastname: Jain
authors.affiliation: Department of Pharmaceutical Chemistry, Hindu College of Pharmacy, Sonepat, Haryana, India.
authors.forename: Bharat
authors.initials: B
authors.lastname: Bhushan
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Panjab 140307, India. Electronic address: jitenderpharmacy@gmail.com.
authors.forename: Jitender
authors.initials: J
authors.lastname: Madan
mesh_terms: D000959:Antihypertensive Agents / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000737:chemistry* / Q000633:toxicity; D001565:Benzoates / Q000737:chemistry* / Q000633:toxicity; D002152:Calorimetry, Differential Scanning; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005260:Female; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D000077333:Telmisartan; D013696:Temperature; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology; D014961:X-Ray Diffraction
chemical_list: D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D004337:Drug Carriers; D011092:Polyethylene Glycols; D048271:Chitosan; D000077333:Telmisartan
keywords: Apoptosis and cellular uptake; Cervical cancer; Cytotoxicity; Intravaginal route; Poly (ethylene-glycol) grafted chitosan nanoparticles; Soluble telmisartan