Synthesis and Evaluation of β-cyclodextrin Based Nanosponges of 5-Fluorouracil Using Ultrasound Assisted Method

Abstract

5-Fluorouracil (5-FU) is mostly used in the treatment of stomach cancer. After intravenous injection of 5-FU, it is rapidly distributed and eliminated with an apparent terminal half-life of 8-20 min. It is poorly absorbed after oral administration with an extremely variable bioavailability. Hence, this study has been made to synthesize 5-FU nanosponges (NS) to increase its accumulation in gastric tumors by the help of an enhanced permeability retention effect (EPR) and decrease its systemic side effects. On the other hand, 5-FU is sparingly soluble in water so its dissolution can be increased by incorporation in nanosponges as nanoparticles.CD-nanosponges were prepared by crosslinking β-CD with diphenylcarbonate (DPC) using ultrasound assisted technique. 5-FU was incorporated with NS by freeze drying, and the phase solubility study, complexation efficiency (CE) entrapment efficiency were performed. Also, the particle morphology was studied using SEM and AFM. The in-vitro release of 5-FU from the prepared nanosponges was carried out in 0.1N HCl.5-FU nanosponges particle size was in the nano size. The optimum formula showed a particle size of (405.46±30) nm, with a polydispersity index (PDI) (0.328±0.002) and a negative zeta potential (-18.75±1.8). Also the drug entrapment efficiency varied with the CD: DPC molar ratio from 15.6 % to 30%. The SEM and AFM showed crystalline and porous nature of the nanosponges. The in vitro drug release study of the selected formula 5-FUNS2 exhibited the fastest dissolution rate which is 56% in the first hr.Different molar ratios of (cyclodextrin to crosslinker) (CD: DPC) has a proficient effect on complexation efficiency (CE), apparent stability constant (Kst) and entrapment efficiency of 5-FU. 5-FUNS2 with (1:4) molar ratio showed the best result of CE, Kst and entrapment efficiency. 5-FUNS2 gave a higher release rate than the 5-FU-βCD inclusion complex and 5-FU solution. Surface morphology of the prepared nanosponges by SEM, AFM indicate that nanosized and highly porous nanosponges was obtained. The overall results suggest that cyclodextrin nanosponges could be a promising 5-FU delivery system utilizing the suitable formula.