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

中文翻译：

---

脂肪酸-肽-生物共轭胶束纳米载体作为 L-天冬酰胺酶的新传递系统：多标准优化、表征和药代动力学研究

通过将脂肪酸的羧基与酶的赖氨酸的NH 2 基团偶联来制备l-天冬酰胺酶-脂肪酸生物缀合物。在这项研究中，通过加入具有这种两亲结构的表面活性剂来改变 l-天冬酰胺酶的理化性质。胶束纳米载体的制备过程通过系统的多标准优化方法在粒径和酶活性方面进行了优化。最终粒径、PDI 和酶活性分别为 387.6 ± 9.8 nm、0.341 ± 0.031 和 92.1 ± 1.3%。结果处于最佳状态。此外，结果表明，与天然酶相比，优化的配方更能抵抗蛋白水解，在不同的 pH 值（6.5 至 10）下更稳定，并且血浆半衰期更长（56.8 小时）。还，药代动力学研究数据证实了胶束纳米载体在循环中的寿命。该方法可作为一种合适的方法，为治疗相关疾病提供一种新的L-天冬酰胺酶制剂。图形概要