Clinical Trail And In Vivo Three Dimensional Investigation Of Dermal Penetration For Podophyllotoxin-Loaded Solid Lipid Nanoparticles

Objectives1,To improve the therapeutic efficacy and to reduce the side effect by preparing stearic acid solid lipid nanoparticles containing podophyllotoxin.2,To determine the efficacy and safety of podophyllotoxin-loaded solid lipid nanoparticles gel(PPT-SLN)applied topically for 8weeks after laser therapy in the treatment of condyloma acuminatum(CA).A prospective study of 82 patients with CA was conducted3,Observing the process of SLN containing podophyllotoxin penetrating into the skin. to reveal the characteristic of SLN for dermal penetration.Methods1,SLN containing PPT was prepared using the method of modified emulsion evaporation at a high temperature and solidification at a low temperatrue,whose morphology was examined by transmission microscope.Particle-diameter-analysator and high performance of liquid chromatography were employed to determine the particle size, potential and trapment efficiency of PPT in the nanoparticles respectively.2,First,all the patients were treated by CO2 laser therapy to clean the warts.The treatment group received PPT-SLN gel,and the control group received 5%imiquimod cream,3 times a week for 8weeks.All patients were followed up for three months to determine the recurrence rates and the adverse effect.3,Skin of forearm was applied with PPT-SLN,Suspension of PPT-Lipid,PPT Tincture and Suspension of PPT-SLN;Dermal computed tomography was used to scanning the distribution of these preparations and the process of their dermal penetration the real time.Results1,PPT-SLN appeared as round shape or ellipse.The mean diameter of particles, potential and the entrapment efficiency of PPT in the nanoparticles were 67.3±24.7nm,25.2±4.1 mV and 83.4%respectively.2,The recurrence rates in the treatment group was 9.5%;respectively,in the control group was 10.0%%;there was no difference of recurrence rates between the two groups (P＞0.05).There was no systemic but topical adverse effect in the study group.The local adverse effect was35.7%in the treatment group and 57.5%in the control group (P＜0.05).3,Solid lipid nanoparticles containing podophyllotoxin can penetrate into the skin in 15minutes and disappear in 2 hours.4,podophyllotoxin-loaded solid lipid nanoparticles in gel stay in grooves of skin for more than 6 hours.Conclusions1,podophyllotoxin-loaded SLN have high entrapment efficiency and an even distribution ??in size,indicating that it is a hopeful epidermis targeted preparation.2,Treatment with PPT-SLN gel after laser therapy appears to be a safety and efficacy therapeutic approach in reducing the recurrence of CA.3,Solid lipid nanoparticles containing podophyllotoxin can penetrate into the skin immediately.4,Podophyllotoxin-loaded solid lipid nanoparticles gel appears to be fine delayed releasing preparation.5,Grooves of skin are important structure for dermal penetration of nanoparticles.