| OBJECTIVE: Dipalmitoyl hydroxyproline(DPHP),as an effective anti wrinkle and anti-aging additive,is widely used in the cosmetics industry.It has the triple effects of scavenging free radicals for anti-aging,moisturizing and wrinkle removing.However,DPHP is insoluble in water and has large molecular weight.It is difficult to penetrate the stratum corneum during local skin administration,and the drug utilization rate is low,which affects its use in cosmetics.Therefore,it is considered to prepare dipalmitoyl hydroxyproline nanostructured lipid carrier(DPHP-NLC)to increase drug solubility and promote drug percutaneous absorption.However,nanostructured lipid carriers are highly mobile and difficult to adhere to the skin surface and are prone to aggregation and leakage.Therefore,dipalmitoyl hydroxyproline nanostructured lipid carrier gel(DPHP-NLC-gel)was prepared on the basis of DPHP-NLC,which increased drug stability,prolonged drug action time and improved drug utilization.METHODS: HPLC method was used to establish the content determination method of DPHP-NLC and the encapsulation efficiency determination method of DPHP-NLC.DPHP-NLC was prepared by high pressure homogenization method.The effects of preparation process and prescription on particle size,PDI,Zeta potential and encapsulation efficiency of DPHP-NLC were investigated by single factor experiment.Box-Behnken design response surface method was used to optimize the prescription,and the optimal prescription was obtained and characterized.DPHP-NLC-gel was prepared and its stability was investigated by influencing factors test and accelerated test.With rat back skin as the model skin,the in vitro transdermal properties of DPHP-NLC and DPHP-NLC-gel were investigated by Franz diffusion cell method.The drug retention in the skin was determined.The transdermal mechanisms of DPHP-NLC and DPHP-NLC-gel were studied by histopathological staining,DSC and FTIR.HSF cells were used as model cells to investigate the cytotoxicity of DPHP-NLC-gel.The aging cell model induced by D-galactose was established to investigate the anti-aging effect of DPHP-NLC-gel with cell viability,intracellular SOD,MDA and type I collagen content as evaluation indexes.RESULTS: The established DPHP content determination method had good specificity,good standard curve fitting,and repeatability,stability,sample recovery and durability met the requirements.Ultrafiltration centrifugation was used to determine the encapsulation efficiency of DPHP-NLC.The DPHP-NLC prepared by the optimal prescription process was milky white translucent liquid,and the particles were round or oval and evenly distributed under TEM.The particle size,PDI,Zeta potential and encapsulation efficiency were 112.0±1.8 nm,0.258±0.005,-46.45±0.26 m V and 97.66±0.56 %,respectively.DPHP-NLC-gel prepared with SEPMAX ZEN as gel matrix is a thick liquid with milky white color,moderate viscosity,fine and uniform,and no particle micelles.DPHP-NLC-gel was stable under strong light and low temperature,and was not resistant to high temperature.Compared with DPHP suspension gel,DPHP-NLC and DPHP-NLC-gelgel increased the cumulative permeation amount per unit area and skin retention amount per 24 h,and the drug release process conformed to Higuchi equation.DPHP-NLC and DPHP-NLC-gel mainly reduced the barrier function of the stratum corneum by changing the structure of keratin and increasing the fluidity between the lipids in the stratum corneum,thereby promoting drug penetration.Skin appendages such as sweat glands and hair follicles also provided a way for drug penetration.DPHP-NLC-gel had no effect on cell viability at 240 μg/m L.Compared with the model,DPHP-NLC-gel could enhance cell viability,SOD activity,MDA and type I collagen content.CONCLUSION: DPHP-NLC prepared by high pressure homogenization has uniform particle size and high encapsulation efficiency.DPHP-NLC-gel has moderate viscosity and exquisite uniformity,which improves the skin penetration and retention of DPHP and better exerts the anti-aging effect. |
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