| Aims、This present study selected sophoridine/matrine as a model drug to optimize its binary ethosomes encapsulation efficiency and stability. The sophoridine/matrine binary ethosomes gel was further prepared in order to realize transdermal drug delivery; and the effect of sophoridine/ matrine binary ethosomes gel of sophoridine/matrine on eczema was evaluated.(1) Using phospholipid as the carrier material, sophoridine/matrine binary ethosomes was prepared by the passive loading method(Ⅰ Method), active loading method (Ⅱ method) and passive plus active drug loading method (Ⅲ method). and the shape. size, zeta-potential and encapsulation efficiency of prepared binary ethosomes were evaluated further.(2) Franz diffusion cells and confocal laser scanning microscopy (CLSM) were used for the percutaneous absorption study of sophoridine/matrine binary ethosomes.(3) The stability of sophoridine/matrine binary ethosomes was determined by conserving these vesicles at 4℃and room temperature, respectively. The encapsulation efficiency and stability of the prepared vesicles were measured at various time points (0.1,2,3 and 4 months).(4) The sophoridine/inatrine binary ethosomes gel was prepared using Carbomer as the matrix, the stability of the binary ethosomes gel was determined by conserving them at 4℃and room temperature, respectively. The content of sophoridine or matrine were measured at various time points (0,1,2,3, and 6 months)(5) The effect of sophoridine/inatrine binary ethoosomes gel on chronic dermatitis-eczema was investigated using 2,4-dinitrochlorobenzene induced eczema model in mice, the degree of ear swelling, differential value of ears, pathological alteration, and inflammatory cells infiltration in the dermis were evaluated.(6) To observe whether the prepared matrine binary ethoosomes gel has skin irritation; rabbits were used here to evaluate skin effect of binary ethoosomes gel. To investigate the toxicology of sophoridine binary ethoosomes gel, rats were used as the experimental animals to give the preliminary data.Results(1) When the drug/lipid ratio was 1:1, the sophoridine binary ethosomes prepared by the Ⅰ method showed the highest encapsulation efficiency (EE), the EE is 70.56%. The matrine binary ethosomes prepared by Ⅲ method showed the highest EE, the EE is 61.12%. While using the Ⅱ methods, the encapsulation efficiency of two alkaloids increased with the decrease of drug/lipid ratio; whereas using Ⅰ or Ⅲ method, the EE of two alkaloids decreased with the decrease of drug/lipid ratio.(2) When the drug/lipid ratio was 1:1, sophoridine binary ethosomes prepared by the Ⅰ method showed a normal distribution of particle size, the average particle diameter is 537.10 ± 1.50 nm, the PDI is 0.22±0.09, and the zeta potential is-41.8±2.7 mV. When the drug/lipid ratio was 1:1, matrine binary ethosomes prepared by the Ⅲ method showed a normal distribution of particle size, the average particle diameter is 484.65±1.77 nm; the PDI is 0.13±0.04, and Zeta potentials is 120.3±2.8 mV.(3) The EE of the Sophoridine/matrine binary ethosomes showed no significant changes at 4℃ or room temperature during 4 months" observation.(4) Under the condition of pH value of 6 to 7, heat or cold test as well as centrifugal test, there was no emerge stratification of Sophoridine/matrine binary ethosomes gel. When placed at 4℃and room temperature for 6 months, its characters and content did not show significant changes. The cumulative amount of Sophoridine binary ethosomes gel in transdermal is 5.4 fold of sophoridine gel within 24 h, and the cumulative amount of matrine binary ethosomes gel in transdermal is 5.1 fold of matrine gel within 24 h.(5) There is significant difference in the therapeutic effect betweem Sophoridine/matrine binary ethosomes gel-treated mice and the chronic dermatitis-eczema mice (p<0.05). The content of TNF-α of mouse ear tissue were also reduced after Sophoridine/matrine binary ethosomes gel administration.(6) In skin irritation test, rabbit in sophoridine/matrine ethosomes gel-treated group and the control group both did not show any skin redness and spots phenomenon. In the acute toxicity test, no significant pathological alteration was found in skin, kidney, and liver tissue in ophoridine/matrine ethosomes gel-treated group.Conclusions(1) Preparation of sophoridine/matrine binary ethosomes, methods and drug to lipid ratio has significant impact on its encapsulation efficiency. The passive loading method is suitable for preparation of sophoridine binary ethosomes, while the passive plus active drug loading method II is suitable for preparation of matrine binary ethosomes.(2) The prepared sophoridine/matrine binary ethosomes gel both showed good stability and therapeutic effect in chronic dermatitis-eczema rat model. Concerning the therapeutic effect, the sophoridine binary ethosomes gel is superior to that of the matrine binary ethosomes gel.(3) In skin irritation test and acute toxicity test, the sophoridine binary ethosomes gel-treated animal did not show any skin irritation test and acute toxicity. |
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