Application of Box-Behnken experimental design for the formulation and optimisation of selenomethionine-loaded chitosan nanoparticles coated with zein for oral delivery

• Published in: International journal of pharmaceutics 2018-11, Vol.551 (1-2), p.257-269
• Main Authors: Vozza, Giuliana, Danish, Minna, Byrne, Hugh J., Frías, Jesús M., Ryan, Sinéad M.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Box-Behnken design; Caco-2 Cells; Cell Survival - drug effects; Chitosan; Chitosan - administration & dosage; Chitosan - chemistry; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Compounding; Drug Liberation; Humans; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Oral delivery; Selenomethionine; Selenomethionine - administration & dosage; Selenomethionine - chemistry; Zein; Zein - administration & dosage; Zein - chemistry
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2018.08.050

The above graphic depicts the formulation methodology used to produce selenomethionine loaded chitosan nanoparticles, coated with zein, for in vitro assessment. Briefly, to produce the nanoparticles, chitosan was protonated by dissolving in acidic buffer (pH 3), then crosslinked with ionised tripolyphosphate and selenomethionine in NaOH (0.1 M). Zein coating was then employed to coat the nanoparticles and purification was achieved by removing unencapsulated formulation components through ultracentrifugation. [Display omitted] Selenomethionine is an essential amino acid with a narrow therapeutic index and susceptibility to oxidation. Here it was encapsulated into a nanoparticle composed of chitosan cross-linked with tripolyphosphate for oral delivery. The formulation was optimised using a three-factor Box-Behnken experimental design. The chitosan:tripolyphosphate ratio, chitosan solvent pH, and drug load concentration were independently varied. The dependent variables studied were encapsulation efficiency, particle size, polydispersity index and zeta potential. For optimisation, encapsulation efficiency and zeta potential were maximised, particle diameter was set to 300 nm and polydispersity index was minimised. A 0.15 mg/mL concentration of selenomethionine, chitosan solvent pH of 3, and chitosan:tripolyphosphate ratio of 6:1 yielded optimum nanoparticles of size 187 ± 58 nm, polydispersity index 0.24 ± 0.01, zeta potential 36 ± 6 mV, and encapsulation efficiency of 39 ± 3%. Encapsulation efficiency was doubled to 80 ± 1.5% by varying pH of the ionotropic solution components and by subsequent coating of the NPs with zein, increasing NP diameter to 377 ± 47 nm, whilst retaining polydispersity index and zeta potential values. Selenomethionine-entrapped nanoparticles were not cytotoxic to intestinal and liver cell lines. Accelerated thermal stability studies indicated good stability of the nanoparticles under normal storage conditions (23 °C). In simulated gastrointestinal and intestinal fluid conditions, 60% cumulative release was obtained over 6 h.