Self-assembly Of Lamellar Structures Of Conjugated Linoleic Acid To Fabricate Drug Delivery Systems

Lamellar structure of fatty acids is composed of fatty acid bilayer,including planar bilayer,vesicles,disk micelles,and lamellar liquid crystal?LLC?and so on.Because of the structure of planar bilayer and LLC is similar to that of the cell membranes,it has good membrane permeability.Lamellar structure of fatty acid also has good liquidity and excellent slow release and osmosis.It has potential application in areas such as drug delivery systems?DDS?.LLC has good membrane permeability,drug slow release and biological adhesion.It has been used in percutaneous drug delivery systems and mucosal drug delivery systems.At present,the raw materials of LLC are mostly non-toxic and low-stimulation non-ionic surfactants.There are few studies on using fatty acids as raw materials and using them in DDS.However,fatty acids,as a cheap and biological small molecule materials,have good environmental compatibility and biocompatibility,and have the potential to be used as DDS.Therefore,the first concern of this paper is whether LLC can be prepared from fatty acid and used as DDS.At present,the construction of the planar bilayer of fatty acids is mainly in the solution environment.Once the structure is removed from the solution,it no longer exists,which brings great inconvenience to the characterization and application of fatty acid bilayer.However,the study of self-assembly induced by solid surface provides a new idea for the fabrication of planar bilayer.Therefore,the second question concerned in this paper is whether the induced self-assembly method can be used to prepare planar bilayer of fatty acids which is beneficial to both characterization and application.Based on the above questions,conjugated linoleic acid?CLA?was selected as the template fatty acid.On the one hand,the self-assembly and self-crosslinking activity of CLA can enhance the colloid stability and characterization convenience of the self-assembly structures,which is conducive to the solution of the problem in this paper.On the other hand,as a nutritional and health functional product,CLA has physiological functions such as anti-cancer,anti-atherosclerosis and enhancing immunity,which makes it possible for the application of CLA self-assembly structure used as DDS.To sum up,the main research contents and results of this paper are as follows:1.Self-assembled SCL/H₂O binary system LLC and its DDS characteristicsThe LLC phase in SCL/H₂O binary system was preliminarily determined by polarizing microscope and visual inspection.Three experimental sites with different SCL contents in the LLC phase area were selected as the research objects,the polarization texture of the three experimental points is oil-striated texture.The steady-state and dynamic rheological parameters were obtained by the rotational rheometer.The results indicated that FALLC has good shear resistance,viscoelasticity,good temperature resistance and has the potential to be used as DDS.FALLC loaded with hydrophilic drug 5-FU or hydrophobic drug curcumin was prepared by simple mixing,and the releasing curves were measured by dialysis experiments.The results show that FALLC has good sustained release for both hydrophilic and hydrophobic drugs.2.Self-assembled CLA/SCL/H₂O ternary system LLC and its DDS characteristicsThe LLC phase in the CLA/SCL/H₂O ternary phase diagram was determined by means of polarizing microscopy and visual inspection.The polarized texture,phase parameters and rheological parameters of the LLC were obtained by polarizing microscope,small-angle X-ray scattering system and rotational rheometer,and the experimental results confirm that the LLC are suitable for DDS.With different composition of FALLC as hydrophilic/hydrophobic drug DDS,and the same composition of FALLC as the DDS of different kinds of charged drugs and both hydrophilic and hydrophobic drugs,the effects of FALLC composition,drug hydrophilicity/hydrophobicity and the charge of drugs on in vitro drug release performance of LLC were investigated.It is showed that the FALLC has different characteristics of release ability on three different charged type or different hydrophilic/hydrophobic drugs.3.Induced self-assembly of SCL bilayer@chitosan composite film and its DDS characteristicsSCL bilayer was prepared on the surface of chitosan film by soaking chitosan film in SCL solution.Four kinds of SCL@CS composite films were obtained by controlling the number of surfaces of the chitosan film which was immersed in SCL solution and the self-crosslinking process,respectively:mono-side SCL bilayer modified chitosan composite film?SCL@MCS?,mono-side self-crosslinking SCL bilayer modified chitosan composite film?SSCL@MCS?,double-side SCL bilayer modified chitosan composite film?SCL@DCS?,double-side self-crosslinking SCL bilayer modified chitosan composite film?SSCL@DCS?.It was determined that SCL was modified on the surface of chitosan film with the structure of bilayer Using FT-IR and TGA.The surface morphology of the composite film was obtained by AFM.Then,the properties of the four kinds of composite films were studied.It was found that the presence of SCL bilayer did not significantly affect the light transmittance,water vapor transmittance,oxygen permeability and swelling rate of chitosan film,but can improve the poor hydrophilicity of chitosan membrane and can improve the permeability of polar drugs.It was also found that the SCL@CS composite film could be stable in neutral solution.In conclusion,the SCL@CS composite film has potential application in DDS.