Research On The Construction And Transdermal Delivery Of Borneol-modified Nanoalcohol

Transdermal drug delivery is a non-invasive system with some advantages which don't exist in other systems,such as the ability to avoid the first effect and interrupt at any time,etc.But the existence of the stratum corneum and close connection are the biggest obstacle for transdermal drug delivery system.Ethosome(ES),a new type of lipid carrier,is a kind of lipsome with high concentration of alcohols(ethanol,propylene glycol of isopropyl alcohol of their mixture).Borneol,a kind of small molecular,is already verified to be able to promote drug absorption through biological barriers.In this study,we prepare borneol physically-modified colchicine ethosome(COL-bpES),and prepare borneol chemically-modified colchicine ethosome(COL-bcES)by connecting borneol(BO)and dioleoyl phosphoethanloamine(DOPE)with succinic anhydride,and compare the effect of physically-modified and chemically-modified from in vitro transdermal permeation,pharmacokinetics and pharmacodynamics,and evaluate penetration promoting effect after modifying,colchicine(COL)was used as model drug.The preparation of COL-ES:use particle size as index,the optimum preparation process is ultrasonic injection-probe ultrasonic method,the average particle size of prepared COL-ES by this process was 70.232.34 nm,the average Zeta potential was 2.02±0.16 mV.The structure is multilaminar vesicles and colsed sphere by transmission electron microscope and scanning electron microscope.Preparation of borneol modified colchicine ethosome:COL-bpES was prepared by simply mixture,BO-DOPE was synthesized by amidation reaction and esterification,the structure was confirmed by MS,1H-NMR and 13C-NMR.Prepare COL-bcES with BO-DOPE.In vitro transdermal permeation:transdermal permeation of ethosome was evaluated using double-chamber diffusion cells.After 48 hours,the permeation rate of COL-bcES,COL-bpES and COL-ES were 5.47,5.13 and 5.08 times higher than colchicine ethanol solution,respectively.The accumulative permeability per unit area of COL-bcES,COL-bpES and COL-ES were 110.28±5.31,103.52±4.80 and 82.34±5.82?g·cm-2,respectively.In vivo evaluation:the evaluation of pharmacokinetics showed that the Tmax of COL-bcES,COL-bpES and COL-ES were 3.00±0.00,2.60±0.55 and 3.00±0.00 h,respectively;the AUCo0-? of COL-bcES,COL-bpES and COL-ES were 161.69±38.29,147.91±27.26 and 130.70±16.62 ng/mL,respectively.Establish the acute gout rat model was established and the perimeter and the inflammation factor after 72 hours treatment were compared.The results showed that,compared to colchicine ethanol solution,COL-bcES could significantly enhance the anti-inflammatory efficiency of colchicine.Conclusion:this study showed that the borneol modified ethosome had good transdermal permeation and treatment effect,which provide a nice transdermal drug delivery system.