Preparation of naringenin-loaded solid lipid nanoparticles lyophilized powder and its pharmacokinetics after pulmonary delivery to rats

Yan-Sheng YAO

ABSTRACT

Objective:

To prepare naringenin-loaded solid lipid nanoparticles (NRG-SLN) lyophilized powder, and investigate its physicochemical properties and release characteristics, then to investigate the pharmacokinetic characteristics in rats after pulmonary delivery.

Methods:

NRG-SLN were prepared by solvent emulsification-evaporation method, the formulation was optimized by orthogonal design, with encapsulation efficiency as reference, and the measurements of particle size, morphology, Zeta potential, the polydispersity index (PDI) and in vitro drug release behavior were performed. To screen the best lyoprotectants in appearance, color, and redispersibility as indexes the differential scanning calorimetry (DSC) was used to analyze its material phase of the drug in nanoparticles. The study on pulmonary pharmacokinetics in rats was carried out by pulmonary instillation.

Results:

The NRG-SLN assumed a spherical shape with an even distribution of diameter and particle size of (97.69±2.84) nm, the PDI was 0.207±0.010, Zeta potential was (-26.20±0.45) mV, entrapment efficiency was (81.09±1.37)%, and drug loading was (8.30±0.04)% (n=3). Mannitol (5%) was the best protective agent for lyophilized powder of NRG-SLNs. The characterization indicated that the drug to amorphous state dispersed in a lipid. In vitro dissolution experiments showed NRG-SLN compared with pure drugs had obviously sustained release. After pulmonary administration to rats, the pharmacokinetic parameters of NRG-SLN and solution were as follows Cmax (163.00±23.05) and (269.00±35.34) ng/mL, AUC0-t (929.32±190.28) and (3 390.23±533.68) ng∙h/mL, t1/2 (5.13±0.23) and (18.93±7.90) h, MRT (7.19±0.44) and (23.29±9.27) h.

Conclusion:

The technique of preparing NRG-SLN by solvent emulsification-evaporation has small particle size, high entrapment efficiency, and good stability, and the process is simple. Compared with the naringenin solution, the SLN show the sustained-release characteristics and can significantly improve the bioavailability after pulmonary administration.