Chitosan/lyotropic Liquid Crystal Construction And Drug Loading Research

Lyotropic liquid crystals have been widely used in pharmaceutical filed due to its special structures and properties.It had attracted much interest in recent years.In this thesis,natural polymer chitosan and biocompatible surfactants?lecithin,alkyl glycoside?were selected to construct lyotropic liquid crystal for encapsulating polyphenols.X-ray scattering technology?SAXS?and rheology were used to study the microstructure and properties of lyotropic liquid crystals.In vitro release method was used to research the release behaviors of polyphenols from lyotropic liquid crystals.This thesis may provide a certain theoretical guidance for the drug-loading carriers and contain the following four parts:?.Firstly,the literature on chitosan-based aggregates used as drug carriers reviewed before the experiment.Secondly,the structures and drug delivery properties of surfactant aggregates?lyotropic liquid crystals,microemulsions,micelles,liposomes?containing chitosan were further discussed.Finally,the research status of lyotropic liquid crystals as carriers was reviewed.Lyotropic liquid crystals had good ability to encapsulate hydrophilic and hydrophobic drug,they can also achieve the sustained release of drugs.Therefore,chitosan/lytropic liquid crystals were constructed as drug carrier based on the previous work of our lab.The microstructure,rheological properties and release behavior of lyotropic liquid crystals were studied.?.In this work,lyotropic liquid crystal phases were observed in quaternary systems of Tween 80/Soybean lecithin?SL?/Ethyl Oleate?EtOL?/Water?H₂O?with different Tween 80/SL molar ratios of 4/1,1/1 and 1/4 systems at 25 ^oC.The microstructure,rheological properties and release behavior of lyotropic liquid crystals with different composition at fixed Tween 80/SL molar ratios and different Tween 80/SL molar ratios were investigated.At 4/1 system,a microstructural transition from lamellar to hexagonal phase was found with the mass ratio of surfactants/water decreasing from70/20 to 55/35.Meanwhile,the rheological behavior transition from elastic gel-like to viscoelastic liquid-like property was investigated.The reductions of cumulative release percentage and rate were consistent to the transitions of microstructure and rheological properties.In contrast,a microstructural transition from hexagonal to lamellar phase was found with Tween 80/SL molar ratio decreasing from 4/1 to 1/4.In vitro drug release study indicated that the cumulative release percentage and rate decreased distinctly,which was possible due to the enhancement of interaction between lecithin and curcumin molecules.Moreover,the phasetransition from hexagonal phase to micellar was observed for A₄Cur at 35.2 ^oC.In vitro release results of A₄Cur showed that the cumulative release percentage of curcumin increased with temperature,implying that the release behaviors were simultaneously dominated by structure and temperature.?.Firstly,the phase behaviors of the Tween 80-SL/chitosan?wt/wt,97/3,93/7and 9/1?/EtOL/H₂O systems where the molar ratio of Tween 80/SL was held at 4/1were studied at 25 ^oC.Then,the effects of chitosan,compositions and temperature on the microstructure and rheological properties of apigenin-loaded liquid crystals were investigated.Finally,the in vitro release behaviors of apigenin from liquid crystal under different conditions were studied.The results showed that the viscosity and dynamic modulus liquid crystal increased with the introduction of chitosan and the water/surfactant ratio decreasing,which may be related to the entlementment of chitosan.The chithosan enhanced stability of liquid crystals and prolonged the release time of the drug.Upon the increasing temperature,the structural strength of liquid crystal weakened.The cumulative release of apigenin increased with temperature.Notably,the viscosity and the dynamic modulus of the liquid crystal containing chitosan were higher than that of liquid crystal without chitosan at the same temperature,suggested that chitosan maintained the higher molecular organization of liquid crystals by decreasing the fluctuations of membrane curvature.In addition,the cumulative release of apigenin from liquid crystals with chitosan increased by reducing medium pH value,which may be due to the amino group protonation of chithsoan.The in vitro release behaviors of apigenin were consistent with the first-order kinetic model,which indicated that the release process of apigenin was controlled by concentration diffusion.?.The lamellar liquid crystals were constructed in APG_1.46/WCS?w_t=0,0.063?/EtOL/H₂O systems at 37 ^oC.The microstructures,rheological properties and interaction between molecules of the lamellar liquid crystals with different chitosan contents and compositions were studied by SAXS,rheoloy and FI-IR measurements,respecsitively.Then,the in vitro release behaviors of curcumin from lamellar liquid crystals under different factors?chitosan content,compositions,temperatures and pH?were studied by in vitro dialysis method.The viscosity and dynamic modulus of lamellar liquid crystals were increased by adding chitosan.The release time of curcumin from lamellar liquid crystals was prolonged with this change.Those results reflected that the stability of liquid crystals was enhanced by adding chitosan.The dynamic modulus of the lamellar liquid crystal decreased with the increase of water content and oil/surfactants mass ratio.The result reflected the stability of liquid crystals was weakened.It was consistant with the result that the cumulative release of curcumin increased by increasing oil/surfactant mass ratio.In addition,the cumulative release of curcumin increased with temperature.It was worth noting that the cumulative release of curcumin from lamellar liquid crystals with chitosan increased by reducing medium pH value,which may be due to the amino group protonation of chitosan.