Comparison Of Three Novel Transdermal Vesicles

AIMThe aim of this study was to compare the skin permeation of ethosomes, binary ethosomes and transfersomes of Terbinafine Hydrochloride (TH) or Diclofenac Sodium (DS) under non-occlusive conditions.METHODS(1) Insusing method was used to prepare ethosomes and binary ethosomes, transfersomes were prepared by Rotary evaporation-sonication method. These lipid vesicles were prepared and characterized for shape, size, zeta-potential and entrapment efficiency.(2) The single factor experiments was used to optimize formula of DS lipid vesicles.(3) Franz diffusion cells and confocal laser scanning microscopy (CLSM) were used for the percutaneous absorption studies of TH lipid vesicles.(4) The franz diffusion cells and in vivo comparison of various lipid vesicles in mice was evaluated in ethosomes, binary ethosomes and transfersomes of DS.(5) The skin histological examination was used to show the microscopic appearance of mouse skin treated with ethosomes, binary ethosomes [Ethanol-Propylene Glycol (PG)=7:3, v/v] and transfersomes.(6) The stability of TH/DS ethosomes, binary ethosomes and transfersomes was determined by storing these vesicles at4℃or room temperature, the EE of vesicles were measured at various times (0,1,2,3and4months).RESULTS(1) The prepared vesicles were spheroid or spheroid-like vesicular structure. The average size of ethosomes, binary ethosomes (Ethanol-PG=7:3, v/v) and transfersomes with TH were105.0,104.3and157.6nm, respectively, the Zeta potential of these vesicles were-7.12,-7.76and-31.3mv, the EE of these vesicles was more than99.0%. The average size of ethosomes, binary ethosomes (Ethanol-PG=7:3, v/v) and transfersomes with DS were221.3,198.1and343.1nm, respectively, the Zeta potential of these vesicles were-15.0,-12.1and-42.3mv, the EE of optimize formula of DS vesicles were59.63±2.40%,56.25±1.80%and54.51±2.79%, respectively. (2) The quantity of drug in the skin from TH ethosomes, binary ethosomes (Ethanol-PG=7:3,v/v), and transfersomes was1.26(p>0.05),1.51(p＜0.05),1.56(p<0.01) times higher than that of TH from traditional liposomes (control), respectively. The skin deposition of the applied dose (DD%) of TH from ethosomes, binary ethosomes, and transfersomes was3.34(p<0.05),9.88(p<0.01),2.52(p>0.05) times higher than that of TH from control, respectively.(3) The quantity of drug in the skin (Qs) from DS ethosomes, binary ethosomes (Ethanol-PG=7:3, v/v) and transfersomes was2.01(p<0.05),2.33(p<0.01),3.78(p<0.01) times higher than that of DS from traditional liposomes (control), respectively. The skin deposition of applied dose (DD%) of TH from ethosomes, binary ethosomes (Ethanol-PG=7:3,v/v) and transfersomes was2.30(p<0.01),3.70(p<0.01),1.78(p<0.05) times higher than that of DS from control, respectively.(4) In binary ethosomes, the proper combination of ethanol and propylene glycol make the drug permeate into the skin more easily.(5) The results of CLSM experiments showed that the fluorescence intensities of ethosomes, binary ethosomes (Ethanol-PG=7:3, v/v) and transfersomes were82.03,190.59, and165.02AU, respectively. And penetration depth and fluorescence intensity of Rhodamine B from binary ethosomes was much greater than that from ethosomes and transfersomes.(6) The AUC0-10h of ethosomes and binary ethosomes were improved1.37-fold (p<0.05) and2.10-fold (p<0.01) compared with transfersomes. Cmax of these lipid vesicles were16.46±5.92,18.53±3.55and10.79±2.60μg/mL, respectively, binary ethosomes also increased Cmax(p<0.01) compared with transfersomes. The Tmax of binary ethosomes was less than those of ethosomes and transfersomes, although the differences were not statistically significant.(7) From the microscopic appearance of mouse skin treated with vesicles, ethosomes make SC loose locally, SC of transfersomes was largely intact, but binary ethosomes made SC largely lost.(8) The EE of the TH/DS three lipid vesicle system showed no significant changes within4months at4℃or room temperature.CONCLUSION(1) Three lipid vesicles of TH/DS were spheroid or spheroid-like vesicular structure, EE of TH three lipid vesicles was no significant difference, EE of DS three lipid vesicles was no significant difference..(2) Three lipid vesicles of TH/DS all could improve the transdermal delivery of TH/DS, the ability of penetration through skin of binary ethosomes (Ethanol-PG=7:3, v/v) was the strongest; the ability of accumulation in the skin of transfersomes was the strongest.(3) The three lipid vesicle systems prepared were all stable.