The Construction And Performance Of Dihydromyricetin Lyotropic Liquid Crystal System

Dihydromyricetin(DMY)was a natural polyphenol flavonoid which was abundantly present in the grapevine tea.In recent years,pharmacological experiments have proved that dihydromyricetin has various effects such as antibacterial,antioxidation,anti-tumor,hypoglycemic,hypolipidemic and hangover.However,due to its poor stability,low water solubility and low absorption,which limited its clinical application.Compared with other preparation technologies,lyotropic liquid crystals with high viscoelasticity and structural controllability as drug carriers have good solubilization effect on active molecules,strong stability of encapsulated DMY and remarkable sustained drug release effect.Therefore,the food grade and medically acceptable surfactants,as well as oil phases with high solubility for DMY,have been selected to construct lyotropic liquid crystal systems.The sustained release properties of the carrier against the drug were studied.Rheology,small angle X-ray scattering(SAXS)and other means were used to characterize and analyze the relationship between drug release behavior and carrier structure properties.The main work was as follows:I.First,the literature on hydrophobic polyphenols was reviewed in the early stage of the experimental work.The physicochemical properties and pharmacological effects of DMY and other polyphenols were comprehensively understood.The preparation of micelles,liposomes,emulsions,cyclodextrins and so on,which can improve the stability and bioavailability of polyphenols,are also discussed.The recent research progress of lyotropic liquid crystals as carriers of polyphenols in improving their stability and sustained release effect was further reviewed.Compared with other preparations,lyotropic liquid crystals have higher viscoelasticity and structure controllability.After drug encapsulation,the stability of the drug can be improved,and the dosage and adverse reactions of the drug can be reduced.Therefore,food-grade double-tailed amphoteric surfactant lecithin(SL)and medically acceptable non-ionic surfactants Brij97,Brij98 were selected.A lyotropic liquid crystal system was constructed by using PEG400 and Geraniol as additives with high solubility todihydromyricetin.The structure and properties of liquid crystal were studied,and the release behavior of DMY in vitro was also discussed.II.In the second chapter,the lyotropic liquid crystals formed in lecithin/oil(Isoamyl acetate+PEG400)/H2 O system were prepared as a drug carrier system to encapsulate polyphenols.The components and introduction of drug have influences in the structure and rheological properties of lyotropic liquid crystals.The structure undergoes a phase transition from lamellar phase(L?)to L?+HII(reverse hexagonal phase)mixed phases and micelle by increasing its oil/H2 O mass ratio from 5/35 to 20/20 and 35/5,consistent with the transition from solid-like properties to viscous fluid properties.For the L?+HII phase,the encapsulation of DMY induced the structural transition to the HII phase,confirmed by SAXS.This may be due to the penetration of DMY into the interface layer of surfactants.The in vitro release kinetic resulted that the release of drug in L? was associated with diffusional mass transport and matrix swelling.While the release in HII was predominantly controlled by concentration diffusion.These lead to the difference in release behaviors.These relationships among structure,rheology and release kinetics were useful to further design the drug sustained carrier system formed by lyotropic liquid crystals.III.In the third chapter,the reverse hexagonal liquid crystal(HII)and viscous micelles based on SL/geraniol/water system were prepared and used to encapsulate DMY.The rheological properties of liquid crystals with different oil/water mass ratios and different SL/geraniol mass ratios,as well as the microstructure of liquid crystals,were investigated.The experimental results show that when the content of the fixed surfactant was 70 wt %.With the mass ratio of geraniol/water was increased from 5/25 to 10/20.The viscoelastic modulus value of the sample increased and the internal friction of the system decreased.It was indicated that the stability of the carrier was increased.And within the frequency sweep range,G' > G ",exhibited elastic properties.When the mass ratio of geraniol/water increased to 15/15,G" > G',the viscous properties predominate.And the steady-state rheological properties of the sample showed that the sample appeared the Newtonian platform at low shear rates,indicating the formation of a viscous micelle solution.When the water content was fixed,theviscoelastic modulus value of the sample increased as the lecithin/geraniol mass ratio was increased from 75/15 to 5/10.The structure changed from the micelle to the reverse hexagonal phase structure confirmed by SAXS.In vitro release experiments revealed that the drug exhibited different release behavior in the liquid crystal phase and in the micelle solution.The release kinetics indicated that drug release is primarily controlled by concentration diffusion.IV.In the fourth chapter.Based on our laboratory,the samples in the Brij97/bmimBF4/H2 O system were selected to construct lamellar and hexagonal phase.The effect of the concentration of DMY in the carrier on the structural properties of the liquid crystal was also investigated.Based on Brij98/[bmim]BF4/H2 O system,the cubic phase liquid crystals were constructed.The structural properties of cubic phase liquid crystals with different concentrations of DMY were studied.The results showed that the phase transition from lamellar phase to Fd3 m cubic phase was induced by the increased concentration of DMY.This may be due to the solubilization of DMY to the surfactant interfacial layer.However,the changes in DMY concentration does not have a significant effect on the hexagonal phase and cubic phase liquid crystal structure.In addition,we have also found that the relaxation spectrum of liquid crystal samples can be used as a criterion for judging the structure of different liquid crystal mesophases.In vitro release showed that the liquid crystal carrier exhibited sustained release behavior for the drug.At a drug content of less than 1wt%,an increase in drug concentration accelerated the release rate.When the drug content was higher than 1wt%,the increase in concentration had no regular effect on the release rate.The release kinetics indicated that the release of the drug was more consistent with the first-order release kinetics,mainly controlled by concentration diffusion.