兽用抗虫药碘醚柳胺新型纳米冻干粉的制备及安全性评价OA

[Objective]To overcome the poor water solubility of the veterinary drug rafoxanide(RFN),and to enhance its application effectiveness and operational convenience in intensive farming systems.[Method]First,novel rafoxanide nanoparticles(RFN-NPs)were prepared using monomethoxy polyeth-ylene glycol-polylactic acid-glycolic acid copolymer(mPEG-PLGA)as the carrier.Using particle size,polydispersity index(PDI),encapsulation efficiency,and drug loading capacity as evaluation indicators,the effects of the organic solvent volume ratio(acetone/dichloromethane),polyvinyl alco-hol(PVA)mass fraction,oil-to-water phase volume ratio,carrier mass fraction,and RFN mass on RFN-NPs preparation were investigated through single-factor experiments.Combined with response surface methodology,the preparation process of the novel RFN-NPs was optimized.Subsequently,lyophilization technology was applied to convert the nanoparticles into a nano lyophilized powder(here-inafter referred to as the lyophilized powder)and the safety of lyophilized powder was characterized and evaluated.Morphological and structural characterization was performed using transmission elec-tron microscopy(TEM),Fourier transform infrared spectroscopy(FTIR),and X-ray diffraction(XRD).Stability was characterized through in vitro release tests and stability studies.Safety evalua-tion was conducted both in vitro and in vivo,including biochemical parameter analysis,histopathologi-cal examination,and hemolysis assays.[Result]The optimized preparation process is as follows:organic solvent volume ratio of 1∶2,polyvinyl alcohol mass fraction of 1%,oil-to-water phase volume ratio of 2∶3,carrier mass fraction of 3%,RFN mass of 20 mg,and ultrasonication time of 5 min,and RFN-NPs had a particle size of 256.6 nm,a polydispersity index of 0.082,an encapsulation effi-ciency of 96.48%,and a drug loading capacity of 17.07%.After lyophilization,the reconstituted lyophilized powder exhibited high dispersion and a distinct Tyndall effect.The prepared lyophilized powder appeared fluffy with a granular texture.Transmission electron microscopy(TEM)revealed that the particles of the lyophilized powder displayed a relatively regular spherical structure with smooth edges and no significant agglomeration.Fourier transform infrared spectroscopy(FTIR)and X-ray dif-fraction(XRD)confirmed that RFN was successfully encapsulated into the carrier and integrated with the carrier material.in vitro,the lyophilized powder released the drug slowly under different pH condi-tions.The fastest release rate was observed in a medium with a pH of 6.8,where the cumulative release reached 44.17%at 72 hours.After storage at 4 or 25℃for 30 days,the reconstituted lyophi-lized powder showed no significant changes in particle size or PDI,indicating good stability.The lyophilized powder was administered intraperitoneally to mice at doses of 20,40,and 80 mg·kg-1 once daily for 7 consecutive days.Necropsy results showed that the morphological structures and histopatho-logical sections of organs such as the heart,liver,spleen,lungs,and kidneys in all dose groups showed no significant differences compared with the negative control group.Biochemical indicators fur-ther confirmed no significant alterations in liver or kidney function.Additionally,the lyophilized powder did not induce hemolysis of red blood cells.[Conclusion]The novel RFN-NPs lyophilized powder was successfully prepared.This lyophilized powder exhibits uniform particle size,high stabi-lity,no hemolytic effect on red blood cells,and excellent safety.