Biological Amphiphilic Molecules Construct Lyotropic Liquid Crystals And Have Drug-carrying Properties

At present,most of the surfactants in the market are derived from chemical methods in petroleum.These synthetic surfactants are toxic and difficult to decompose by microbes.Biological amphiphiles are obtained from natural raw materials,containing natural polar head groups and natural hydrophobic tails.These amphiphiles are generally characterized by low toxicity,biocompatibility and environmental friendliness,making them safe for use in food,cosmetics and pharmaceuticals.Lyotropic liquid crystal system?LCs?as a drug carrier has good solubilization effect on active molecules.The LCs constructed by biological amphiphiles make them more suitable for drug delivery.Plant polyphenols are generally less stable and poor water-soluble.and thus their application is limited.Therefore,in this paper,we used biological amphiphilic molecules to construct lyotropic liquid crystal and solubilizing drugs,and studied the sustained-release and controlled-release properties of the carrier,and discussed the kinetics of drug release in vitro.The relationship between LCs structure and drug release was analyzed by means of rheology and small angle X-ray scattering?SAXS?.The main works of this thesis are as follows:I.The literature on biological amphiphiles was reviewed before the experiment,and the classification of biological amphiphilic molecules and the properties of different types of amphiphilic molecules were comprehensively understood.Lecithin from natural phospholipid was selected as biological amphiphilic molecule in the research.The application of lyotropic liquid crystal in the field of drug delivery and its beneficial results were further reviewed.We found that LCs as a drug carrier can not only reduce the dosage of drugs and adverse reactions caused by drugs,but also improve the pharmacokinetics and tolerance of drugs,and achieve controlled and sustained release of drugs.The introduction of specific component to liquid crystal nanoparticles could make the carrier target and improve the therapeutic effect of drugs.Based on the work of our laboratory,lecithin was selected as surfactant,oil phase and auxiliary agent with good solubility of DMY were selected to construct LCs.The properties and drug release properties of the carrier were further studied.II.In this paper,the ternary phase diagram of lecithin/PEG 400/H₂O system is constructed at 37 ^?.PEG 400 has good solubility to the target model drug.DMY is solubilized at the representative samples in the liquid crystal region.A sample was prepared by introducing oleic acid into the oil phase.The phase state of the liquid crystal sample is H_II phase,which determined by polarizing microscope and SAXS.The changes of rheological properties,microstructure and drug release behavior caused by the change of components in the samples were studied.DMY solubilized in the lipid water interface layer,which can be inferred from the increase of the interface area of each surfactant molecule,a_s,in the SAXS parameter of H_II samples and the infrared spectrum.The rheological spectra showed that the H_II mesophase has high elastic Maxwell properties and shear dilution characteristics.With the ratio of lecithin to PEG 400 increasing,the increase of modulus and the decrease of a_s indicated that the internal structure of samples tend to be stable.Oleic acid improves the viscoelasticity of samples and the release stability of DMY under acidic conditions.The results of in vitro release showed that the release of DMY was controlled by concentration diffusion.III.The pseudo-ternary phase diagram of the system of lecithin/oleic acid/PEG400/H₂O was constructed at 37 ^?.The water-soluble drug tea polyphenols was encapsulated in the liquid crystal formed by the above system.Five H_II liquid crystal samples were prepared by immobilization of surfactant and water content respectively.In order to compare the properties and properties of different phase carriers,a sample was selected in the non-hexagonal phase region.With the increase of oil phase content,the lipid-water interfacial layers of the H_II phase become dense,and the interfacial area of each surfactant molecule decreases as a result.The IR spectra show that the formation of intermolecular hydrogen bonds and the high oil content are favorable to the formation of hydrogen bonds,which makes the structure of the samples more stable.In vitro release experiments showed that the liquid crystal carrier had an ideal sustained release effect on tea polyphenols,and the kinetic model showed that the drug was controlled by concentration diffusion.IV.In the phase diagram of lecithin/castor oil/1,2-propanediol/H₂O system,the H_II sample points were selected and an appropriate amount of stabilizer Tween 80 was introduced.After encapsulating curcumin,the bulk LCs were dispersed into liquid crystal nanoparticles by ultrasonic cell crushing instrument.The particle size and polydispersity index of liquid crystal nanoparticles were measured by DLS.The in vitro release properties of curcumin in liquid crystal nanoparticles at different temperatures and the antioxidant activity of drug loaded liquid crystal nanoparticles were determined.It is found that the size of the liquid crystal nanoparticles is about90-160 nm and the particle size distribution is uniform.At 37 ^? and 45 ^?,the release of curcumin showed a biphasic pattern,including sudden release in the early stage and sustained release in the middle late stages.At 25 ^?,the sudden release was weakened,and the time to reach the release platform was prolonged.The combination antioxidant effect between curcumin and nano-carrier is shown,the IC₅₀ value of free radical scavenging was significantly lower than that of curcumin ethanol solution.The kinetics of in vitro release showed that curcumin was controlled by concentration diffusion in the early stage of release,and the release process was not a single diffusion mechanism in the later release process.