Evaluation of in-vitro cytotoxic effect of 5-FU loaded-chitosan nanoparticles against spheroid models

Taylor Smith, Kevin Affram, Errol Bulumko, Edward Agyare

Division of Basic Sciences, College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida, USA

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Purpose: The studies investigate the anticancer activity of 5-fluorouracil (5-FU)-hyaluronidase (Hase) enzyme-loaded chitosan nanoparticles (5-FUChnps) using three-dimensional (3D) spheroid HCT-116 culture. Hase-loaded nanoparticles (Chnps) have recently been used to improve the efficacy of chemotherapeutic drugs for cancer treatment. It has been found that administration of Hase improves tumor vessel densities and increase perfusion within tumor.

Methods: Particle size and zeta potential of the nanoparticles were determined using a particle size analyzer while Fourier transform infrared (FTIR) was used to investigate the interactions among the various components making up the chitosan nanoparticles. Cytotoxic effects of 5-FU and 5FUchnps against dimensional (2D) and 3D spheroid cultures were assessed using trypan blue assay.

Results: Low molecular weight chitosan (ChiL) nanoparticle size was determined to between 215 to 670 nm while medium molecular weight chitosan (ChiM) nanoparticle size ranged from 151 to 778 nm. All 5FUChnps exhibited a zeta potential value ranging from +4 to +37 mV. Among the 16 formulations prepared, formulation #7 (5-FUChnps7) was selected for the in-vitro cytotoxic studies based on its high 5-FU entrapment efficiency (59%). 5FUchnps treated 3D HCT-116 culture exhibited significant growth inhibition compared with 5-FU treated groups. Further, spheroids with significant growth inhibition exhibited high spheroid volume and non-spherical shapes.

Conclusion: 5-FUChnps were significantly cytotoxic to the 3D HCT-116 cultures than that of the free 5-FU. Chnps proved to have the ability to deliver and improve the anticancer activity of 5-FU in 3D HCT-116 culture studies.

J Nat Sci, 4(10):e535, 2018

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