Nano-scaffolds for enhanced in-vitro and in-vivo anti-VEGFR drug delivery.

Abstract

Background: Sorafenib (SB) is a receptor tyrosine kinase inhibitor, currently marketed as an oral dosage form. However, due to severe irritation of the gastrointestinal tract, the drug is facing decreased acceptability as a therapeutic agent.

Objectives: This study aimed to develop nano-scaffolds to increase the drug loading capacity and decrease the adverse drug reactions of SB.

Method: Polymers used for the preparation of nano-scaffolds were polylactic co-glycolic acid (PLGA), ethyl cellulose (EC) and polyvinyl alcohol which was used as a surfactant. A range of different formulations was designed using 12.5 mg and 25 mg of EC, while the concentration of the PLGA was kept constant throughout the study. All formulations with or without the drug were characterized for size by dynamic light scattering (DLS), scanning electron microscopy, differential scanning calorimetry, hemolysis assay, cell viability assay, apoptotic assay and in-vivo evaluation.

Results: DLS results showed the minimum nano-scaffold size of 252.8 ± 12 nm, which was increased by increasing the concentration of polymer and drug. The physicochemical assessment showed the presence of minor interactions between the polymeric system and SB. The cell viability assay showed the minimum cell viability at 50.66 ± 0.13 % at a maximum concentration of SB-loaded formulations, whereas the presence of apoptotic bodies confirmed these results.

Conclusion: The in-vitro and in-vivo evaluation showed the safety profile of the polymeric PLGA/EC in the absence of drug content. Therefore, the fabricated system may be used as a carrier system for SB and can further be included in tumor model studies.