| Ivermectin has been widely used as antiparasitic agent.However,toxicity to animals frequently occurred due to the unreasonable application of ivermectin.Compared with oral and parenteral administartion,transdermal drug delivery can effectively reduce drug side effects,stress response,labor input and avoid first-pass effect,etc.Solid lipid nanopartilces(SLN)could be utilized as a good carrier of transdermal drug delivery to effectively promote skin permeation and enhance the therapeutic effect.In the current study,ivermection-loaded solid lipid nanoparticles(IVM-SLNs)were prepared by hot homogenization followed by ultrasonic process.Their physichemical properties,stability,encapsulation efficiency,in vitro release and in vitro transdermal effect were then investigated.Firstly,the palmitic acid,polyving akohol(PVA)and polyglyceryl-10 laurate(P10)were screened as solid lipid and compound emulsifier,respectively.Subsequently,ivermectin was dissolved in oil phage and then mixed with aqueous phase with 1%PVA,followed by a series of treatment including hot homogenation,sonication and cold solidification.In the end,11.99%nd,icat IVM-SLNs were prepared.Photon correlation spectroscopy(PCS)transmission electron microscopy(TEM)was used to determine the morphology zeta potential,polydisersion index,and size distribution of optimized formuation.Differential scanning calorimetry(DSC)and Fourier transform infrared spectroscopy(FT-IR)were used to evaluate their molecular internal structures.In addition,the effect of pH,storage,centrifugae and dilution on the the physical stability of the as-prepared IVM-SLNs was investigated.In order to strengthen their storage stability,the lyophilized powder of IVM-SLNs was prepared using the freeze-drying technology.The detailed characterization by transmission electron microscopy(TEM)analysis in the present study revealed that the as-synthesized IVM-SLNs had approximately spherical shape and were quite uniform.The corresponding size distribution is represented by histogram from the IVM-SLNs,with(270.34 ± 0.35)nm mean diameter ranging from 150 to 400 nm.The hydrodynamic diameter of the IVM-SLNs in colloidal solution was(312.8±2.40)nm with a polydispersity index(PDI)of(0.082±0.005).Zeta potential of the IVM-SLNs was(-30.5 ± 1.51)mV,which predicts a long-term stability.DSC curves confirmed that ivermectin in the carrier existed in an amorphous form.The changed characteristic frequency in FT-IR revealed that interaction via intermolecular hydrogen bonding between drug and the components of SLN.IVM-SLNs kept their stability at 4 ℃up to 31d.The entrapment efficiency(EE)and loading capacity(LD)of IVM-SLNs were detected by high performance liquid chromatography(HPLC).The free drug was separated by ultrafiltration process,and the total drug of the optimized formulations was obtained by demulsification method.The data showed that the EE and LD of the IVM-SLNs formulation was 98.48%± 0.052%and 11.99%LNs formulation vasrap.The peaks of ivermectin,excipients and solvent were well separated under optimal chromatographic conditions.The HPLC method are simple,accurate and sensitive(0.05～100 μg/mL),and applicable for determining EE and LD of the IVM-SLNs.In vitro drug release behavior of IVM-SLNs was investigated by dynamic dialysis.The results showed that sustainable release(56.95 ± 0.38%)compared with active pharmaceutical ingredients(API,89.51 ± 1.27%)in 48 h.Their transdermal effect was evaluated using modified Franz diffusion cells.The cumulative amount of IVM-SLNs and commercial cream were 46.67 ± 1.57 μg/cm2,27.62 ± 2.27 μg/cm2,respectively,suggesting that SLNs showed higher transdermal effect than the commercial cream at 24 h after administration(P<0.05,n=3).In conclusion,the as-prepared IVM-SLNs were a novel promising formulation of ivermection transdermal delivery. |
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