Development and optimization of ifosfamide nanostructured lipid carriers for oral delivery using response surface methodology

The research focuses on the development and optimization of ifosfamide nanostructured lipid carriers for oral delivery with the application of response surface methodology. The objectives of the study were to develop a formulation for ifosfamide to be delivered orally, overcome the instability of the drug in acidic environment during oral administration, to sustain the release, drug leakage during storage and low loading capacity. A modified solvent diffusion method in aqueous system was applied to prepare nanostructured lipid nanoparticles. Hydrophilic polymers such as chitosan and sodium alginate were used as coating materials. Glycerol mono oleate and oleic acid were used as solid and liquid lipid, respectively. Poloxamer is used as stabilizers. The central composite rotatable design consisting of three-factored factorial design with three levels was used in this study. The physiochemical characterization included evaluation of surface morphology, particle size and surface charge of the drug in the delivery system. The in vitro drug release, entrapment and drug loading efficiency and as well as the storage stability were evaluated. The results showed that the optimal formulation was composed of drug/lipid ratio of 1:3, organic/aqueous phase ratio of 1:10 and concentration of surfactant of 1 % w/v. Ifosfamide nanostructured lipid carrier under the optimized conditions gave rise to the entrapment efficiency of 77 %, drug loading of 6.14 %, mean diameter of 223 nm and zeta potential value of -25 mV. Transmission electron microscopy analysis showed spherical particles. The in vitro experiment proved that ifosfamide from the delivery system released gradually over the period of 72 h. Sodium alginate cross-linked chitosan nanostructured lipid carrier demonstrated enhanced stability of ifosfamide, high entrapment efficiency and sustained release.