Preparation Of Naringenin Loaded Solid Lipid Nanoparticles And Its Preliminary Evaluation To Improve Lung Absorption

ObjectiveNaringenin(NRG),a flavonoid compound,had been reported to exhibit extensive pharmacological effects,but its water solubility and oral bioavailability are only approximately(46±6)?g/m L and 5.8%,respectively.The purpose of the present study is to design and develop naringenin-loaded solid lipid nanoparticles(NRG-SLNs)to provide prolonged and sustained drug release,with improved stability,involving nontoxic nanocarriers,and increase the bioavailability by means of pulmonary administration.MethodsInitially,a group contribution method(GCM)was used to screen the best solid lipid matrix for SLNs preparation.NRG-SLNs were prepared by an emulsification and low-temperature solidification method and optimized using an orthogonal experiment approach.The morphology was examined by transmission electron microscopy(TEM)and the particle size and zeta potential were determined by photon correlation spectroscopy.The total drug content(TDC)of NRG-SLNs was measured by ultraviolet spectrophotometric method(UV)and the encapsulation efficiency(EE)was determined by Sephadex gel-50 chromatography and UV.The in vitro NRG release studies were carried out using a dialysis bag.The best cryoprotectant to prepare NRG-SLN lyophilized powder for future structural characterization was selected using Differential scanning calorimetry(DSC),Powder X-ray Diffraction(PXRD),and Fourier Transformed Infra-Red Spectroscopy(FT-IR).The short-term stability,MTT assay,cellular uptake and pharmacokinetics in rats were studied after pulmonary administration of NRG-SLN lyophilized powder.ResultsGlycerin monostearate(GMS)was selected to prepare SLNs and the optimal formulation of NRG-SLNs was spherical in shape,with a particle size of(98±0.61)nm,a PDI of(0.258±0.058),a zeta potential of(-31.4±0.98)mV,a TDC of(9.76±0.26)mg,an EE of(79.1±0.56)%,and a cumulative drug release of 80% in 48h with a sustained profile.In addition,5% mannitol(w/v)was screened as a cryoprotectant.FTIR,DSC and powder XRD studies confirmed that the drug was encapsulated into SLNs in an amorphous form.The lyophilized powder was stable at both refrigeration(4 ?)and ambient temperature(25 ?)for three months and the MTT assay demonstrated that the SLNs were nontoxic.The cellular uptake of FITC-labeled SLNs in A549 cells was highly time-dependent over a period of 3 h while the pharmacokinetic study in SD rats showed that the relative bioavailability of NRG-SLNs was 2.53-fold greater than that of NRG suspension after pulmonary administration.ConclusionsThe paper successfully developed naringenin solid lipid nanoparticles formulations.In vitro drug release experiments showed that the preparation has obvious sustained-release effect.To enhance the solubility and stability of defect and improve the in vivo bioavailability of naringenin,which provide a suitable new dosage forms for pulmonary drug delivery system.Therefore,The study shows that SLNs offer a promising pulmonary delivery system to increase the bioavailability of the poorly water-soluble drug,NRG.