Formulation And Ameliorative Effect On Psoriasis Of Nanostructured Lipid Carriers-based Gel Of Tanshinone ?A

Tanshinone ?A?Tan ?A?is the main chemical composition of Salvia miltiorrhiza Bunge,and belongs to Phenanthrenequinone.In recent years,it has been widely used to treat and prevent Psoriasis,atopic dermatitis and other related diseases of inflammation^[1].But Tan ?A has strong fat solubility,almost insoluble in water,can easily resolve when exposed to heat and light,and is poor in transdermal absorption,thus Tan ?A's efficacy is limited^[2-3].Nanostructure lipid carriers?NLCs?are a new type of nano-drug delivery system^[4],show a higher loading capability and solubility for compounds,increase drugs'tability and bioavailability.This article studies the Tan ?A-NLC and Tan ?A-NLC-gel's preparation technology,and their evaluations in vitro.The Tan ?A-NLC was prepared by using High pressure homogenization and it's prescription was optimized by Box-Behnken design and response surface methodology.The optimum preparation of Tan ?A-NLC are as follows:under the condition of dark,5.86%GMS with heated up to 70?with 2.94%Miglyol^?812.Then 0.10%Tan ?A was dissolved in the lipid melt.The lipid phase was subsequently dispersed in water with 1.00%F68 of same temperature by high-speed stirrer at 2000r·min^-11 for 20 minutes.The obtained pre-emulsion was passed through a high speed probe ultrasound at 13300 r·min^-11 for 5 cycles and one cycle equal to one minute.And then passed through a high-pressure homogenizer applying 6 cycles at 12000 psi.The obtained dispersion cooled by room temperature water was filtered through a millipore filter?0.45?m?.The average particle size,PDI,zeta potential,EE and DL of Tan ?A-NLC prepared by optimal formulation was:?182±14?nm,?0.1906±0.0245?,?-27.8±5.4?mV,?86.44±9.26?%,and?0.98±0.18?%.The images of DSC and XRD showed that Tan ?A exists in NLC in the amorphous state.Photostability and quality in vitro of Tan ?A-NLC was studied.Tan ?A's degradation velocity was significantly reduced,and it only degrated for about 7.04%after exposuring to light;The results demonstrated that Tan ?A-NLC showed a fast initial phase of drug release at first,and then followed by a sustained release of52.28%until 72 h;Compared with Tan ?A solution,Tan ?A-NLC had a lower cumulative penetration through the skin after applying drug for 24 h,but it's retention in the epidermis was 3.06 fold higher;In a certain range,Tan ?A-NLC controled the proliferation of HaCaT cells in the manner of dose-dependent.Tan ?A-NLC had stronger functions on the HaCaT cells when compared with Tan ?A solution group.The Tan ?A-NLC-gel was prepared by direct swelling method.The formulations of Tan ?A-NLC-gel was optimized by central composite design and response surface methodology on the basis of single factor investigation.The optimum preparation of Tan ?A-NLC-gel are as follows:0.68 g carbopol 940 was swelled for about 24 h with an appropriate amount of distilled water,and then 50 mL Tan ?A-NLC,1.17 g azone,8.95 g propylene glycol were added into.The 20%triethanolamine was added until the pH was 5.5⁶.5.In the end,distilled water was added to adjust to 100 g.The skin retention within 24 h was?17.12±2.38??g·cm^-2,particle size was?198±15?nm,PDI was 0.218±0.022 and zeta potential was?-43.5±4.6?mV.The pH and viscosity index of Tan ?A-NLC-gel was found to be 6.07±0.11 and?45.2±3.8?Pa.s,which met the standards of extermal preparations.Stability studies showed that Tan ?A-NLC-gel exhibited good stability when storaged at room temperature for 90 days.The in vivo anti-psoriasis efficacy of Tan ?A-NLC-gel was proved out to be significant and had no irritation to intact skin.