Fatty acid-peptide-bioconjugated micellar nanocarrier as a new delivery system for l-asparaginase: multi-criteria optimization, characterization, and pharmacokinetic study

l -Asparaginase-fatty acid bioconjugate was prepared by coupling the carboxyl group of fatty acids to NH 2 groups of lysine of the enzyme. In this study, the physicochemical properties of l -asparaginase were modified by incorporating surfactant with this amphiphilic structure. The preparation process of micellar nanocarrier was optimized by a systematic multi-criteria optimization approach in terms of particle size and enzyme activity. The final particle size, PDI, and enzyme activity were 387.6 ± 9.8 nm, 0.341 ± 0.031, and 92.1 ± 1.3%, respectively. Results are in an optimum condition. Furthermore, results showed that the optimized formulation is more resistant to proteolysis, is more stable at different pH (6.5 to 10), and has prolonged plasma half-life (56.8 h) in comparison to the native enzyme. Also, the longevity in the circulation by micellar nanocarriers was confirmed by the data on the pharmacokinetic study. This method can be used as a suitable method to provide a new formulation of l -asparaginase for the treatment of related diseases. Graphical abstract