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

被引：16
作者：
Sharma, Anjali [1 ]
Jyoti, Kiran [1 ]
Bansal, Vikas [1 ]
Jain, Upendra Kumar [1 ]
Bhushan, Bharat [2 ]
Madan, Jitender [1 ]
机构：
[1] Chandigarh Coll Pharm, Dept Pharmaceut, Mohali 140307, Panjab, India
[2] Hindu Coll Pharm, Dept Pharmaceut Chem, Sonepat, Haryana, India
来源：
MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS | 2017年 / 72卷
关键词：
Cervical cancer; Intravaginal route; Soluble telmisartan; Poly (ethylene-glycol) grafted chitosan nano-particles; Cytotoxicity; Apoptosis and cellular uptake; ACTIVATED RECEPTOR-GAMMA; IN-VITRO; RELEASE; PARTICLES; TARGET; MUCUS;
D O I：
10.1016/j.msec.2016.11.048
中图分类号：
TB3 [工程材料学]; R318.08 [生物材料学];
学科分类号：
0805 ; 080501 ; 080502 ;
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 IC50 of S-TEL-PEG-CNPs was measured to be 223-mu m significantly (P < 0.05) lower than 40.1-mu M 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. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码：69 / 76
页数：8
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