پديدآورندگان :
Alavizadeh Seyedeh Hoda Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran, Alavizadehh@mums.ac.ir , Rahnamaei Rahchamandi Seyedeh Yasaman Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran , Gheybi Fatemeh Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran , Jaafari Mahmoud Reza Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
كليدواژه :
Cisplatin , Carbon nanohorn , Cancer , Surface modification
چكيده فارسي :
Aim and Background: Cisplatin (CDDP) application as a widely used chemotherapeutic is associated with severe dose-related adverse effects including nephrotoxicity, and hematological toxicities. Though nanotechnology using advanced vehicles greatly improved carrier accumulation within the tumor, anti-tumor efficacy of cisplatin nanostructures is still limited due to insufficient availability. Herein, carbon nanohorns (CNH) platforms with surface modification were developed for cisplatin tumor delivery. Methods: Two different carbon nanohorn formulations with physical and chemical modification including PEG-CNH and CNH-GA were fabricated to improve surface features and drug loading. Complete particle characterization was performed and 24, 48 and 72 h in vitro cytotoxicity studies, in vivo assessment, biodistribution and histological analysis were investigated and compared to free drug using C26 tumor engrafted BALB/c mice. Results and discussion: The diameters of PEG-CNH and CNH-GA were 250 and 312 nm with PDI of 0.24 and 0.22 and cisplatin concentration of 1.3 and 0.96 mg/ml, respectively. The modified platforms showed significant toxicity on C26 cells. Following CNH platforms i.v administration, cisplatin plasma concentration was significantly increased compared to free cisplatin. Animal received PEG-modified platform showed the longest survival and greatly reduced tumor size and drug accumulation within kidneys. Conclusion: Modified CNH platforms with proper particulate features improved cisplatin loading and led to an increase in BALB/c mice survival time and a decrease in the tumor size