Preparation Of Palmitoyl Pentapeptide-4 Flexible Liposome And Its Application In Skin Anti-wrinkle

The destruction and loss of collagen and elastin in the dermis is the main cause of skin wrinkles.Palmitoyl pentapeptide-4(Pal-KTTKS)is a small-molecule active peptide with good anti-wrinkle effect,which can stimulate fibroblasts to secrete collagen.However,due to its large molecular weight and negative charge at physiological p H,it has poor transdermal performance.Simultaneously,the barrier effect of the skin stratum corneum and the clearance of aminopeptidase and subdermal microvascular system in the skin make it difficult to function.In this thesis,with the goal of enhancing the transdermal absorption of Pal-KTTKS,firstly,a solid-phase method was used to synthesize Pal-KTTKS freeze-dried powder.After screening,the thin-film dispersion and high-pressure homogenization technology were used to prepare Pal-KTTKS flexible liposomes(hereinafter referred to as Pal-KTTKS FLs),and the optimal preparation process formula and the physical and chemical properties of the liposomes were investigated.Efficacy evaluation experiments such as in vitro release,enzymatic hydrolysis and transdermal absorption were carried out.Finally,Pal-KTTKS FLs was prepared into an anti-wrinkle serum and an anti-wrinkle smear test was carried out.The result shows:(1)The yield of Pal-KTTKS freeze-dried powder is 42.3%.The qualitative comparison by HPLC shows that the synthesized product is consistent with the commercial Pal-KTTKS standard product,and can be added into cosmetics as an anti-wrinkle raw material.(2)The optimal process conditions for high-pressure homogenization have been screened and established as the pressure of 1000 bar and the number of cycles of 3 times.Taking the encapsulation rate as the response value,through single factor experiment and response surface analysis,the best formula is obtained as the drug concentration=500?g.m L^-1,the mass ratio of soybean lecithin to cholesterol=20:1,and the mass ratio of soybean lecithin to sodium cholate=20:1.The liposome encapsulation rate(94.99%)prepared under the predicted optimal formulation process conditions is close to the predicted value(95.75%),indicating the success of the prediction model.The obtained liposome has a particle size of 50.50 nm and a Zeta potential of 47.56 m V.Stability tests show that Pal-KTTKS FLs has a leakage rate of less than20%after storage at 25?,-4?and-18?for 60 days,and the particle size tends to decrease slightly.The extrusion test shows that the deformation degree of Pal-KTTKS FLs is 0.86.(3)Efficacy evaluation results show that Pal-KTTKS FLs has an obvious slow-release effect,and the release kinetics is in accord with the Korsmeyer-Peppas equation.Enzymatic hydrolysis experiments show that Pal-KTTKS can protect drugs from quick decomposition by the enzyme solution after being encapsulated in flexible liposomes.Franz diffusion cell experiments show that the cumulative permeability of flexible liposomes reach 91.98%after48 hours,and the cumulative retention per unit area is as high as 11.42?g.cm^-2.Pal-KTTKS FLs is prepared as an anti-wrinkle essence.After 42 days of application on human body,the anti-wrinkle essence can significantly improve the elasticity of the skin.