Preparation Of Imperatorin Ultradeformable Liposome Gel And Study Of Transdermal Mechanism

Imperatorin?IMP?has a wide range of physiological activities and high medicinal value.However,because of its low absorption rate in the gastrointestinal tract,wide metabolic pathway,low bioavailability after oral administration,and great limitations in clinical application,it was considered to be prepared as a transdermal drug delivery preparation to improve the bioavailability of the drug.The aim of this study is to develop a new transdermal drug delivery nanoparticle liposome gel.On the basis of this project,the ultradeformable liposome of imperatorin is gelatinized to improve the penetration of drug into the skin and prolong the action time of the drug in the epidermis.Simultaneously,imperatorin ultradeformable liposome gel was evaluated.1.This chapter discussed the structure of human skin,expounded the research progress of gels and explained the application of gels in transdermal drug delivery systems.The development of new gels has promoted the development of transdermal drug delivery.Preparation of imperatorin into a ultradeformable liposome gel can both promote the penetration of imperatorin in the skin,increase the viscosity of ultradeformable liposomes,and prolong the action time.2.In this chapter,a method for the determination of imperatorin is established.A thin film dispersion method is used to prepare imperatorin ultradeformable liposomes.A condensation method is used to prepare imperatorin ultradeformable liposome gel.Taking the cumulative permeation amount in units of 12 hours as an indicator,the gel prescription was optimized by using single-factor investigation and orthogonal experiment.The final prescription was determined to be 1%carbomer 940,15%glycerol,and 10%propylene glycol.3.Prepare the gel formulation determined in Chapter 2 and investigate the properties of imperatorin ultradeformable liposomes and gel.The morphology of liposomes was all spherical under electron microscope.The encapsulation rate of ultradeformable liposomes measured by dialysis was58.39±3.64%,the particle size was 85.37±1.62 nm,and the zeta potential was-22.91±0.73 mV.After gelation,the particle size of the ultradeformable liposome was 93.13±1.68 nm,and the zeta potential was-24.96±1.99 mV.The p H of the ultradeformable liposome gel was determined to be 7.32±0.03.The texture results showed that the ultradeformable liposome gel and blank gel have low bioadhesion force,but the former has greater adhesion work and viscosity,with lower gel strength and hardness.By examining the stability of the gel,it was found that imperatorin ultradeformable liposome gel has good stability at low and normal temperatures,and poor stability at high temperatures.The Franz diffusion cell method was used to investigate the cumulative permeation of the gel.The unit cumulative permeation of imperatorin ultradeformable liposome gel was 11.543±0.241?g·cm^-22 at 12h.The release curve conformed to the first-order and Higuchi release equation.4.In this chapter,HE staining,differential scanning calorimetry?DSC?,attenuated total reflection Fourier infrared spectroscopy?ATR-FTIR?and confocal fluorescence microscopy?CLSM?were used to investigate the permeation mechanism and transport properties of imperatorin ultradeformable liposome and gel in the skin.The results showed that the microstructure of the stratum corneum changed,the lipid structure and keratin structure in the stratum corneum changed,and the hydration was strengthened to promote drug transport.The fluorescence intensity of the skin after liposome and gel treatment was stronger than that of the aqueous solution,and the fluorescence intensity of the skin after ultradeformable liposome gel treatment is stronger,indicating that it can penetrate deeper into the skin.5.Further evaluate the safety of imperatorin ultradeformable liposome gel.To investigate the toxicity of imperatorin ultradeformable liposome gel solution on HaCaT cells and its effect on cell membrane permeability,it was found that the concentration in the range of 100?g·mL^-1 had no significant effect on the cells.The skin irritation of imperatorin ultradeformable liposome gel was investigated.The result showed that it had no significant irritation after single or repeated contact with the skin.