<p>Design And Characterisation Of Novel Sorafenib-Loaded Carbon Nanotubes With Distinct Tumour-Suppressive Activity In Hepatocellular Carcinoma</p>

Abstract

PurposeOver 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®), 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.Materials and methodsSorafenib 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).ResultsThe 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.ConclusionOur 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.

Synthesis and Characterization of Chitosan-Based Nanodelivery Systems to Enhance the Anticancer Effect of Sorafenib Drug in Hepatocellular Carcinoma and Colorectal Adenocarcinoma Cells

“…A band at 679 cm −1 in SF-CS nanoparticles is attributed to C-Cl stretching of the SF drug. This observation is similar to that of previous works [41,42]. Figure 9b shows the FTIR spectrum of CS with several bands at 3195, 2828, 1630, 1539, 1063, and 1011 cm −1 and these bands are observed in Figure 9c when the SF drug was incorporated with CS.…”

Poly(3-Hydroxybutyrate)-Based Nanoparticles for Sorafenib and Doxorubicin Anticancer Drug Delivery

“…The 1430–1625 cm −1 region is where the numerous aromatic stretching C=C vibrations are present, and the overlapping of these bands are also noticeable in the spectra of the composite sample. The presence of sorafenib is confirmed by the absorption band at 1505 cm −1 , which corresponds to the disubstituted pyridine ring (stretching vibration of the C=N bond) [ 36 ].…”

“…Korsmeyer et al (1983) [ 36 ] described the following semi-empirical equation: Qd = ktn where ‘k’ is the diffusion kinetic rate constant that is determined by the geometric and structural properties of the drug-release system and ‘n’ is the diffusion exponent. By substituting the diffusion term in Equation (1) with this simplified Equation (2), Equation (1) can be transferred to: where ‘ k b ’ is the initial burst constant, ‘ θ b ’ is the contribution of initial burst release over total mass drug release, ‘ k r ’ is the rate of degradation–relaxation constant, ‘ k d ’ is the diffusion kinetic constant and ‘ t max ’ is the time to achieve a maximum rate of drug release or the time to achieve 50% of release from the polymer degradation.…”

Topical Nano-Vesicular Spanlastics of Celecoxib: Enhanced Anti-Inflammatory Effect and Down-Regulation of TNF-α, NF-кB and COX-2 in Complete Freund’s Adjuvant-Induced Arthritis Model in Rats

“…The grid was left to dry at ambient temperature before the examination. 26,36 Preparation of Carbopol Gel of the Selected Celecoxib-Loaded Spanlastics and Niosomes…”