Release mechanism studies on TFu nanoparticles-in-microparticles system

This study was aimed at developing a nanoparticles-in-microparticles delivery system for N3-O-toluyl-5-fluorouracil (TFu), a new and potential antitumor prodrug of 5-fluorouracil (5-Fu), and intended to improve the release properties, bioavailability and therapeutic efficacy. TFu nanoparticles-in-microparticles system (TFu-NiMS), was prepared by ionotropic gelation technique, and the formulation and manufacture parameters were optimized concerning the drug encapsulation efficiency. TFu-NiMS was characterized according to particle size, zeta potential, drug entrapment efficiency, drug loading and physical stability, respectively. The effects of various factors on drug release and in vitro release characteristics of TFu from NiMS were investigated and the release mechanisms were also explored. The optimum formulation was found to be relatively uniform in size (350.5 ± 12.6 nm) with a positive zeta potential (13.4 ± 0.9 mV). The drug entrapment efficiency and loading were (75.58 ± 3.25%) and (10.19 ± 0.24%), respectively. The in vitro release behavior of TFu from NiMS followed the Weibull or Ritger–Peppas kinetic equation and could be better expressed by the following equations: ln ln[1/(1 − Q/100)] = 0.5577 ln t − 0.3377, r = 0.9768 and ln Q = 0.5059 ln t + 3.881, r = 0.9759, respectively. TFu-NiMS presented controlled release properties in comparison with TFu solutions and the release properties of TFu from NiMS were fit a combination of diffusion controlled drug release and matrix dissolution mechanism. The TFu-NiMS were valued to develop as a practical preparation for oral or i.v. administration.