| In recent years,transfersomes,as a kind of efficient transdermal drug delivery carriers,attracted much attention.However,the application of transfersomes is greatly limited because of the serious stability of them.This problem was solved by using the technology of composite phospholipid,which provides an efficient and stable carrier for transdermal drug delivery system.The composite phospholipid was determined in this paper.The composite phospholipid liposomes were prepared by thin film ultrasonic method by choosing composite phospholipid with high phase transition temperature(Tm>40?)from DPPC,HSPC,DSPC and low phase transition temperature(Tm<30?)from SPC,DLPC,DMPC,which has a combination of 5 proportion,respectively 9:1,3:1,1:1,1:3,1:9(mass ratio).The Differential Scanning Calorimetry was used to determine the phase transition temperature of liposomes to screen composite phospholipid with high transformation strength,small transformation range and good linear fitting relationship;To verify the phase transition temperature of liposomes with the release test of calcein.The results show that the ratio of DPPC/DMPC is best fitted to the phase transition temperature and the correlation coefficient is 0.9991,and DPPC/DMPC liposomes has the strongest phase transition strength and the smallest phase transition range;The calcein release experiment shows that the phase transition temperature of liposomes was different from that of HSDSC,but the phase transition temperature is less than 2?.The type and dosage of the edge active agent were selected by the stability and deformation of transfersomes.The composite phospholipid transfersomes with defined composite phospholipid,which's phase transition temperature is set to 32?,adding different edge active agent(sodium cholate,sodium deoxycholate,span80 or tween80)accounting for 15%of the proportion of the total phospholipid,were prepared to select the type and dosage of the edge active agent by stability and temperature-sensitive deformation of composite phospholipid transfersomes.The results show that the DPPC/DMPC(mass ratio 2:3,phase transition temperature is 32?)composite phospholipid transfersomes with span80 as the edge active agent,the dosage was 15%,have the highest temperature-sensitive deformation and the best stability.The liposomes and transfersomes containing brucine were prepared by ammonium sulfate gradient method and characterized for parameters such as the particle size,encapsulation efficiency and deformation properties and stability.The transdermal properties in vitro of different prescriptions of liposome and transfersomes were compared by using Franz-diffustion cells with the skin of rats.The analgesic effects of liposomes and transfersomes were investigated using a mouse model of acetic acid writhing.The particle size of liposomes and transfersomes containing brucine ranged from 100nm to 150nm.Compared with the SPC transfersomes,the encapsulation efficiency and storage stability of DPPC/DMPC transfersomes were significantly improved.The deformation index of DPPC/DMPC transfersomes containing brucine was 2.09 times and 1.76 times as much as SPC liposomes and SPC transfersomes respectively.The transdermal flux of DPPC/DMPC transfersomes was 3.43 times and 1.41 times as much as SPC liposomes and SPC transfersomes.The transdermal flux of the physical mixture of brucine and blank DPPC/DMPC transfersomes was 2.20 times as much as brucine solution.In conclusion,compared with liposomes,the permeation behavior of transfersomes was significantly improved.Complex phospholipid technology can improve the membrane phase behavior of transfersomes,for return,further improve deformation and transdermal flux of transfersomes.Blank transfersomes have promoting effect on transdermal absorption of brucine.Compared with brucine solution and liposomes,the in vivo analgesic effect of compound phospholipid transfersomes was significantly improved.The transdermal mechanism of composite phospholipid transfersomes was studied in this paper.In vitro permeation behavior of different time points were compared by preparing the liposomes and transfersomes containing brucine and strychnine at the same time.The integrity and the penetration depth of the carrier were investigated in the transdermal process by combining Confocal laser scanning microscope.The effects of carriers on the permeability of skin and the structure of stratum corneum were investigated by Fourier transform infrared spectroscopy and Differential scanning calorimetry.The results of permeation in vitro show that the transfersomes were not consistent with that of the encapsulated drug.There was drug release process during the permeation.CLSM shows that the composite phospholipid transfersomes significantly increased the permeation behavior.And the fluorescence intensity was more obvious and the penetration depth was deeper than other groups.The FTIR data shows that the peak height and peak area of the skin stratum corneum's characteristic absorption peak were decreased after treated by liposomes and transfersomes.The DSC data shows a significant increase in liquidity of the stratum corneum after treated by liposomes and transfersomes.The barrier function of skin decreased.Especially the transfersomes group,intensity of phase transition of stratum corneum decreased significantly and permeation behavior improved significantly.basically no phase change composite phospholipid transfersomes group.There was no obvious phase transition in the stratum corneum of the skin after treated by composite phospholipid transfersomes.Blank transfersomes have promoting effect on transdermal absorption of brucine.The type and concentration of transfersomes and LogP of different drugs and other factors were further investigated in this paper because of this effect.Results shows that the type and concentration of transfersomes effect promoting permeation of blank transfersomes.And the promoting effect of the blank transfersomes is not the same for the drugs with different physical and chemical properties. |
PDF Full Text Request