Development And Optimization Of 5-Fluorouracil Loaded Nanosponges Gel Using Box–Behnken Design

Abstract

5-Fluorouracil (5-FU) is an important antimetabolite drug widely used in the treatment of various cancers. However, conventional topical delivery of 5-FU may be associated with rapid drug release and limited control over drug residence at the site of application. Nanosponges provide a porous polymeric carrier system capable of incorporating drug molecules and modulating their release. The present study was undertaken to formulate and optimize 5-FU loaded nanosponges and develop them into a topical gel formulation for controlled drug delivery. A Box–Behnken experimental design was employed to investigate the effect of formulation variables on entrapment efficiency and particle size. The prepared nanosponges were evaluated for particle size, zeta potential, polydispersity index and entrapment efficiency. The optimized nanosponge formulation was incorporated into a gel and evaluated for physicochemical properties, homogeneity, grittiness, spreadability, extrudability, viscosity, content uniformity, in-vitro drug release and skin irritancy. The optimized formulation F13 exhibited an entrapment efficiency of 90.25% and particle size of 121.80 nm. The predicted values for particle size and entrapment efficiency were 122.58 nm and 87.75%, respectively. The optimized formulation showed a zeta potential of −38.45 mV, indicating a suitably charged nanosponge surface. The in-vitro drug release study of F13 nanosponges gel demonstrated a gradual release pattern, with cumulative drug release of 48.72 ± 1.03% at 4 h, 74.86 ± 1.24% at 8 h, 86.72 ± 1.37% at 12 h and 92.48 ± 1.42% at 24 h. The formulation also showed satisfactory physicochemical characteristics and was suitable for further evaluation. The findings demonstrate that the Box–Behnken design was useful for optimization of 5-FU loaded nanosponges. The optimized F13 formulation exhibited high drug entrapment, nanosized particles and prolonged drug release. Incorporation of the optimized nanosponges into a gel provided a promising approach for controlled topical delivery of 5-FU