Preparation of an efficient and safe polymeric-magnetic nanoparticle delivery system for sorafenib in hepatocellular carcinoma

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Abstract

Aims:

Superparamagnetic iron oxide nanoparticles (SPIONs), as drug delivery vehicles, offer to eliminate the concerns associated with hydrophobic anti-cancer agents. The current study was intended to fabricate a SPION based delivery system for sorafenib that can simultaneously enable targeted delivery of sorafenib and expand its therapeutic index against hepatocellular carcinoma (HCC).

Main methods:

Co-precipitation and physical entrapment methods were employed for the synthesis of sorafenib loaded PVA coated SPIONs. Physicochemical characterizations were done using TEM, XRD, FTIR, Raman spectra and VSM measurements. The superior activity of nanoconjugate was demonstrated by AO/EB staining, FACS, immunofluorescence and Western blot. The safety of the sorafenib conjugated nanoparticles were verified in Wistar rats.

Key findings:

The synthesized nanoparticles were in the size range of 5-15 nm. The adsorption of PVA to the SPIONs and the conjugation of sorafenib to the nanocarrier were confirmed by XRD, FTIR and Raman spectra analyses. VSM study ascertained the superparamagnetic nature of the nanoconjugate. Cellular uptake studies suggested its efficient entrapment in HepG2 cells. MTT assay showed that the cytotoxicity of sorafenib loaded PVA/SPIONs was comparable or higher than free sorafenib. The activation of apoptosis and autophagy pathways in HepG2 by the nanoconjugate was evidenced. Acute toxicity testing in Wistar rats supported the safe administration of the nanoconjugate and established its localization in animal tissues by Perl's Prussian Blue reaction.

Significance:

The novel combination of sorafenib with PVA/SPIONs showed better anticancer efficiency than free sorafenib demonstrative of its potential in cancer chemotherapy.

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