| Objective:Daidzein was a natural Isoflavone of Pueraria Lobata Ohwi and has been widely applied to the treatment of hypertension and Cardio-Cerebral-Vascular diseases.However,with the nature of low water solubility,the therapeutic efficacy and clinical applies of daidzein has been limited.Previously,daidzein was almost used in the oral administration system,yet the percutaneous drug absorption has been studied to develop new formulation with advantages of preventing gastrointestinal irritation and metabolism.The goal of this study was to design and develop a novel core-shell nano-carrier by combing the properties of polymer and lipid nanoparticles to improve the transdermal drug delivery for DZ.Another part of article was aimed to develop a new type of skin disinfectant and evaluate the sterilization effect.Methods:Core-shell-type polymer-lipid nanoparticles for loading daidzein and Azon were successfully obtained by two-step preparation method.The final preparation technology was optimized by single factor experiment.The average size（diameter,nm）,polydispersity index,and surface charge（zeta potential,m V）of D-P-Azon-LN core-shell nanoparticles were measured by Zeta sizer（Malvern,UK）.Ultracentrifugation and HPLC was applied to detectthe quantity of daidzein in optimal core-shell nanoparticles according to drug loading（DL）and entrapment efficiency（EE）.Transmission electron microscopy（Tokyo,Japan）was applied to capture the morphology of D-P-Azon-LNs.The test was completed by D8 Advance Powder X-ray Diffractometer（Bruker AXS GMBH,Karlsruhe,Germany）to identify the crystalline structure of D-P-Azon-LNs.To evaluate the stability of D-P-Azon-LNs,samples were stored at a low temperature of 4℃in refrigeration and room temperature 25℃±2℃for one month,respectively.Diffusion dialysis method was performed to investigate the drug release profile in vitro.In vitroskin penetration、in vivoskin retention experiments were carried out to estimate the transdermal effect of D-P-Azon-LNs.Confocal Laser Scanning Microscopy（CLSM）was employed to observe the enhancing skin permeation of D-P-Azon-LNs.Furthermore,skin irritation of D-P-Azon-LNs was investigated.The double chain quaternary ammonium salt skin disinfectant was developed in the lab and optimized.Major content was determined and germicidal test was conducted.Results:The mean particle diameter,encapsulation efficiencyand drug-loading rate of D-P-Azon-LNcore-shell nanoparticles were77.59±2.26nm,79.91±1.46%and 1.50±0.02%,respectively.Round shape and entrapped structure of daidzein in D-P-Azon-LNs were observed by transmission electron microscopy and Powder X-ray Diffractometer.The in vitro release curves of D-P-Azon-LNs fitted the Korsmeyer-Peppas equation and showed a constant and stable release.In vitro skin penetrationexperiment,the cumulative amount of daidzein from D-P-Azon-LN reached 14.91μg.cm-2at 72h,which was 1.44 times higher than D-P-LN and 6.01 times higher than DZ solution.It was further confirmed by CLSM（visual and qualitative）that the skin permeability of D-P-Azon-LNs was stronger than that of D-P-LNs.In vivo skin retention study,the core-shell lipid-polymer nanoparticles with Azon had the maximum retention in the skin after 12 h or 24h treatments as expected.Furthermore,there was no significant irritation observed in skin irritation experiment.Treatment efficiency of compound disinfectant of quaternary ammonium salt was more than 5 and met the requirements.Conclusion:Core-shell-typepolymer-lipidnanoparticles（D-P-Azon-LNs）could be a potentially safe and promising nanocarrier for daidzein to enhance skin permeation in the transdermal delivery system.The compound disinfectant of quaternary ammonium salt has good germicidal efficacy and good stability. |
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