Preparation of lactoferrin-modified nanostructured lipid carriers and evaluation of its brain targeting efficiency / 中国药学杂志

ABSTRACT

OBJECTIVE: To construct receptor-mediated lactoferrin-modified curcumin-loaded nanostructured lipid carriers (Lf-Cur-NLCs) and investigate its in vitro physicochemical properties and in vivo brain targeting efficiency. METHODS: Cur-NLCs were prepared by melt-emulsification method, and then lactoferrin(Lf) was adsorbed onto the surface of Cur-NLCs via electrostatic interaction to form Lf-Cur-NLCs. Lf-Cur-NLCs with different concentrations of Lf were characterized in terms of shape, diameter, Zeta potential, serum stability and in vitro release of Lf-Cur-NLCs in saline containing 1% Tween 80. Additionally, Lf-NLCs labeled with NIRD-15, a fluorescent imaging agent, were prepared with Lf at concentrations of 0.5, 1.5 and 2.0 mg · mL-1 (marked for Lf1, -NLC, Lf3-NLC, and Lf4-NLC, respectively). After iv injection in mice, living animal imaging system was used to observe the fluorescence intensity of NIRD-15 in the living animals and isolated organs to evaluate the brain targeting of Lf-NLCs. RESULTS: Cur-NLCs were spherical with average particle size of(187.5 ±4.7) nm and Zeta potential of(- 23.7 ± 2.9) mV. The average diameter of Lf-Cur-NLCs with spherical shape was between 167.8-299.9 nm. The Zeta potential was between -26.87 - -13.03 mV. When the concentration of Lf was 2.0 mg · mL-1 and the incubated time was 6 h, the adsorption of Lf at the surface of the Cur-NLCs was saturated. Lf-Cur-NLCs were stable in serum, and the release of Cur from Lf-Cur-NLCs was slowed down. Compared with NLCs, there was a strong fluorescence in the brain after iv injection of Lf-NLCs, indicating that Lf-NLCs were more effective than NLCs in brain targeting, while Lf3-NLCs were the most effective one. CONCLUSION: Lf-NLCs are constructed successfully for brain targeting via electrostatic adsorption. The established process avoids chemical synthesis in the targeting drug delivery system design. However, the ability of brain targeting of the carriers is related with the amount of Lf.