Lyotrpic Liquid Crystals As A Drug Delivery System For Transdermal Application Of Cinnamaldehyde

Objective: To prepare cinnamaldehyde-loaded cubic liquid crystal and hexagonal liquid crystal,and characterize them by polarized light microscopy(PLM),small angle X-ray scattering(SAXS)and rheological study.The transdermal permeation properties of two kinds of liquid crystals were investigated in vitro and in vivo.The pharmacodynamics behavior of cinnamaldehyde-loaded hexagonal liquid crystal was investigated in AA rats.Methods: The phytantriol-cinnamaldehyde(CA)-water ternary phase diagram was drawn and the optimal prescription was screened by appearance and polarizing microscope.Polarizing microscope,small angle X-ray scatterometer and rheometer were utilized during characterization of the prepared liquid crystals.The transdermal permeation behavior of CA-loaded cubic liquid crystal and hexagonal liquid crystal was investigated by Franz diffusion cell method.The pharmacokinetic behavior of CA-loaded liquid crystals in rats was studied.Anti-inflammatory effects of CA-loaded liquid crystal were studied in adjuvant arthritis rats while commercially available Voltaren used as positive drug,IL-1? and TNF-? as pharmacodynamic indicators.The transdermal mechanism of lyotropic liquid crystals in rat skin was investigated via DSC and ATR-FTIR.Results: The optimal prescription of cubic and hexagonal liquid crystal consisted of PT/CA/water(77:3:20,w/w/w)and PT/TAG/CA/water(73.15:3.85:3:20,w/w/w/w)respectively.Both cubic and hexagonal liquid crystals could maintain their phase structure at room and surface temperature.The cumulative permeation quantity and permeation rates of cubic crystals were 1.26 and 1.31 times higher than those of the gel.The cumulative permeation quantity and permeation rates of the hexagonal liquid crystal were 1.80 and 1.83 respectively.The results of in vivo transdermal penetration experiment showed that the AUC(0-?)of the hexagonal and the cubic liquid crystal were 1.62 and 1.53 times higher than those of the gel group,respectively,and the residence time(MRT)of the both phases in rats was prolonged significantly.Pharmacodynamics studies have shown that high dose group of CA significantly inhibited the paw swelling of AA rats,the synovial hyperplasia and inflammatory cell infiltration were improved,the serum IL-1? and TNF-? levels were downregulated.There was no significant difference between CA-loaded hexagonal liquid crystal and the Voltaren.Compared to the blank group,endothermic peak temperature of stratum corneum treated by cubic and hexagonal liquid crystal decreased in DSC scanning,the peak area decreased and the peak intensity was weakened.In the infrared spectrogram,methylene symmetrical stretching vibration peak and asymmetric stretching vibration peak of the SC showed blue-shift,the amide I peak and amide II peak showed red-shift.Conclusion: The prepared CA-loaded cubic liquid crystal and hexagonal liquid crystal enhanced the transdermal absorption of drugs and released slowly after percutaneous administration,thus improve herapeutic effect.