Study On Transdermal Properties Of Lyotropic Liquid Crystal Based Phytantriol

Objective:Lyotropic liquid crystal has excellent properties of loading and releasing drug used as a novel drug carrier in transdermal drug delivery systems.The transdermal property of lyotropic liquid crystals with different internal structures is different.The study of the in vitro and in vivo transdermal properties of V₂ phase and H₂ phase loaded with SH or CAP aimed to explain the transdermal properties of lyotropic liquid crystals with different internal structures.Methods:Using phytantriol as matrix material and n-decane as additive to construct drug-loaded lyotropic liquid crystals,and the optimal prescription was screened by the study of stability and in vitro release.The structure was characterized by polarized light microscope and small angle X-ray scatterometer,and the rheological properties were investigated by rheometer.The transdermal behavior of drug-loaded liquid crystal was investigated by Franz diffusion cell method in vitro.The dynamic changes of the concentration of drug in the skin and blood of rats were monitored by microdialysis in vivo.The transdermal mechanism of lyotropic liquid crystals was investigated via DSC,ATR-FTIR and TPM.Results:The prescription for drug-loaded cubic liquid crystal is PT/water=70:30（w/w）,and the drug-loaded hexagonal liquid crystal is PT/n-decane/water=63:7:30（w/w/w）,the drug-loading of SH and CAP were respectively 14 mg/g and 0.75 mg/g.The in vitro transdermal experiments showed that the infiltration rate and cumulative permeation amount of SH-loaded liquid crystals were superior to those of gel.The cumulative permeation amount of the CAP-loaded gel group was1.37 times and 1.17times that of the V₂ phase group and the H₂ phase group,respectively.The results of pharmacokinetic parameters in skin of the hydrophilic drug SH showed that the AUC_（0-∞）and C_max of the liquid crystal group were larger than those of the gel group（P<0.05）,and the AUC_（0-∞）of the V₂ phase group was 1.08 times that of H₂ phase group.The results of pharmacokinetic parameters in skin of the lipophilic drug CAP showed that the AUC_（0-∞）of the gel group was larger than that of the liquid crystal group（P<0.05）,and the AUC_（0-∞）of the V₂ phase group was 1.72 times of the H₂phase group.The blood pharmacokinetic parameters indicated that the AUC_（0-∞）of the liquid crystal group was larger than that of the gel group.There was no difference in penetration of drugs into the blood between V₂ phase and H₂ phase（P>0.05）.The results of DSC scanning showed that compared to the blank group,endothermic peak temperature and peak area of rat skin treated by liquid crystal decreased.The ATR-FTIR spectrum showed that the peak of the amide peak I and II were red-shifted.The TPM experiment showed that the liquid crystal penetrated the skin by accumulating the drug in the microcracks of the skin tissue and then spreading laterally in the tissue,while the gel penetrated the skin mainly through the intercellular lipid.Conclusion:The phytantriol-based lyotropic liquid crystals have different percutaneous penetration effects on drugs of different polarities.Compared with gel,the lyotropic liquid crystal increased the retention of the hydrophilic drug SH in the skin,but reduced the retention of the lipophilic drug CAP in the skin.And V₂ phase are more suitable for dermal delivery systems administration compared with H₂phase.The lyotropic liquid crystal could promote the percutaneous penetration of SH and CAP into the blood,and the promoting effect on CAP is more remarkable,and there is no significant difference between the V₂ phase and H₂ phase.