Chitosan-Alginate Nanoparticles as a Novel Delivery System for Linamarin

Abstract

Nanoparticulate delivery of naturally occurring therapeutic agents provide a new insight towards prevention and therapy for diseases like cancer. Linamarin, found in cassava has been proven as a drug candidate for cancer due to its cyanogenic property. This study dealt with developing a nanoparticulate system using chitosan and alginate to deliver linamarin. Chitosan-alginate nanoparticles were prepared by a two-step method composed of ionotropic pre-gelation of an alginate core followed by chitosan polyelectrolyte complexation. They were characterized using Fourier transform infrared spectroscopy (FT-IR), Transmission electron microscopy (TEM), Scanning electron microscopy (SEM), particle size analyzer, and thermogravimetric analysis (TGA). Then the in-vitro release profiles were studied at pH 7.4 and pH 2 and kinetically modeled. Cytotoxicity was assayed against MCF-7 breast cancer cell line. After the incorporation of linamarin, the particle size was 70.64 ± 5.54 nm and zeta potential was -30.10 ± 2.21 mV. The encapsulation efficiency was 57.67 ± 5.32%. The SEM and TEM images demonstrated that the linamarin loaded chitosanalginate nanoparticles had spherical and homogeneous shapes. Successful loading was evidenced by FT-IR and TGA data. In-vitro release studies and kinetic analysis data demonstrated the controlled release behavior at pH 7.4 and pH 2. The overall cumulative percentage release after 120 h was about 72% at pH 7.4 and 88% at pH 2 and it became significantly higher (91%) in the presence of linamarase enzyme. All three experimental conditions exhibited anomalous transport mechanism. Dose dependent cytotoxicity was observed where 50% cell viability was exhibited after 48 h at lower drug concentrations (100 µg mL-1≥) while 48 % cell viability was observed after 24 h at higher drug concentrations (200 µg mL-1). The IC50 value of linamarin loaded chitosan-alginate nanoparticles at 48 h was 80 µg mL-1. In vitro cytotoxicity results revealed that when linamarin was loaded into chitosan-alginate nanoparticles, it was delivered and internalized more effectively than free linamarin. The formulated linamarin loaded chitosan-alginate nanoparticles have the potential to be developed into a nutraceutical as a novel candidate for cancer prevention and therapy.