Surface-functionalized niosomes using a folic acid-chitosan conjugate for delivery of capecitabine in breast cancer: In vitro and in vivo characterization.

Abstract

In this study, capecitabine (CAP) niosomes were prepared using the thin-film hydration method with Span 60 and cholesterol as key excipients and the formulation was optimized using a 32 factorial design. The synthesized folic acid-chitosan (FA-CS) conjugate was used to functionalize the niosome surface. An optimized formulation, after preliminary evaluation, was characterized for compatibility, XRD, NMR, in vitro drug release, cytotoxicity and cellular uptake, and in vivo bioavailability. Optimized niosomes achieved a particle size (PS) of 241.8 nm, a zeta potential of -22.9 mV, and an entrapment efficiency of 93.05%. After FA-CS functionalization, the PS increased to 272.9 nm, and the zeta potential shifted to 14 mV. FA-CS functionalized niosomes presented sustained drug release, attaining 86.31% cumulative drug release of CAP over 24 h. Successful CAP loading and FA-CS functionalization were confirmed by FTIR, XRD and NMR analysis, revealing significant crystalline changes. MTT assay showed 3.24- and 1.24-fold greater cytotoxicity than CAP and CAP niosomes, respectively, whereas cellular uptake increased 1.77-fold with FA-CS functionalized CAP niosomes, representing effective drug delivery. The in vivo bioavailability study of FA-CS functionalized niosomes showed a 3.18-fold increased Cmax and an 11.63-fold increase in AUC of CAP. Minimal changes in PS and maintained entrapment efficiency, along with Zeta potential, PDI and drug content during the stability study indicated the formulation's stability. In conclusion, enhanced cellular uptake and sustained delivery of CAP in cancer therapy were achieved using FA-CS functionalized niosomes, which displayed favourable physicochemical properties, effective drug release and enhanced effectiveness.