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Design And Characterisation Of Novel Sorafenib-Loaded Carbon Nanotubes With Distinct Tumour-Suppressive Activity In Hepatocellular Carcinoma.
- Source :
-
International journal of nanomedicine [Int J Nanomedicine] 2019 Oct 29; Vol. 14, pp. 8445-8467. Date of Electronic Publication: 2019 Oct 29 (Print Publication: 2019). - Publication Year :
- 2019
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Abstract
- Purpose: Over the past 30 years, no consistent survival benefits have been recorded for anticancer agents of advanced hepatocellular carcinoma (HCC), except for the multikinase inhibitor sorafenib (Nexavar <superscript>®</superscript> ), which clinically achieves only ~3 months overall survival benefit. This modest benefit is attributed to limited aqueous solubility, slow dissolution rate and, consequently, limited absorption from the gastrointestinal tract. Thus, novel formulation modalities are in demand to improve the bioavailability of the drug to attack HCC in a more efficient manner. In the current study, we aimed to design a novel sorafenib-loaded carbon nanotubes (CNTs) formula that is able to improve the therapeutic efficacy of carried cargo against HCC and subsequently investigate the antitumour activity of this formula.<br />Materials and Methods: Sorafenib was loaded on functionalized CNTs through physical adsorption, and an alginate-based method was subsequently applied to microcapsulate the drug-loaded CNTs (CNTs-SFN). The therapeutic efficacy of the new formula was estimated and compared to that of conventional sorafenib, both in vitro (against HepG2 cells) and in vivo (in a DENA-induced HCC rat model).<br />Results: The in vitro MTT anti-proliferative assay revealed that the drug-loaded CNTs formula was at least two-fold more cytotoxic towards HepG2 cells than was sorafenib itself. Moreover, the in vivo animal experiments proved that our innovative formula was superior to conventional sorafenib at all assessed end points. Circulating AFP-L3% was significantly decreased in the CNTs-SFN-MCs-treated group (14.0%) in comparison to that of the DENA (40.3%) and sorafenib (38.8%) groups. This superiority was further confirmed by Western blot analysis and immunofluorescence assessment of some HCC-relevant biomarkers.<br />Conclusion: Our results firmly suggest the distinctive cancer-suppressive nature of CNTs-SFN-MCs, both against HepG2 cells in vitro and in a DENA-induced HCC rat model in vivo, with a preferential superiority over conventional sorafenib.<br />Competing Interests: The authors report no conflicts of interest in this work.<br /> (© 2019 Elsayed et al.)
- Subjects :
- Animals
Antineoplastic Agents blood
Antineoplastic Agents pharmacokinetics
Antineoplastic Agents pharmacology
Antineoplastic Agents therapeutic use
Biomarkers, Tumor metabolism
Body Weight drug effects
Carcinoma, Hepatocellular pathology
Cell Proliferation drug effects
Drug Compounding
Hep G2 Cells
Humans
Hydrogen-Ion Concentration
Liver drug effects
Liver pathology
Liver Neoplasms pathology
Male
Nanotubes, Carbon ultrastructure
Niacinamide pharmacology
Rats, Wistar
Sorafenib blood
Sorafenib pharmacokinetics
Sorafenib pharmacology
Spectroscopy, Fourier Transform Infrared
Static Electricity
Carcinoma, Hepatocellular drug therapy
Drug Design
Liver Neoplasms drug therapy
Nanotubes, Carbon chemistry
Sorafenib therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1178-2013
- Volume :
- 14
- Database :
- MEDLINE
- Journal :
- International journal of nanomedicine
- Publication Type :
- Academic Journal
- Accession number :
- 31754301
- Full Text :
- https://doi.org/10.2147/IJN.S223920