Development And Evaluation Of Andrographolide-loaded Nanoemulsion Sustained-release Hydrogel

Andrographolide(AG)is the main extract of the Andrographis paniculata,which has a prominent anti-inflammatory effect.Related studies have demonstrated the potential application value of andrographolide in the periodontal therapy.However,andrographolide has some problems such as poor water solubility and low bioavailability,which greatly affect the effect of andrographolide in periodontal therapy and restrict the clinical application of andrographolide.Nanoemulsion(NE),as a new drug delivery system,which can improve the water-solubility and stability of drugs and prevent the oxidative decomposition of drugs.In this study,andrographolide was prepared into nanoemulsion to improve its bioavailability.To meeting the needs of the periodontal drug-delivery system,thermosensitive hydrogel was prepared to complete the liquid-to-gel transition at physiological temperature.The purpose of this project is to prepare andrographolide nanoemulsion gels and promote the clinical application of andrographolide.The physicochemical properties of andrographolide-loaded nanoemulsions and gels were studied.The main research contents and results are as follows:1.The high-performance liquid chromatography(HPLC)method of andrographolide content was established and investigated before the preparation of andrographolide nanosemulsion.The standard curve equation of andrographolide is y=35987.87846+18746.46989x,and the R~2-value is 0.999,which has a good linear relationship.The results showed that the method had high precision,reproducibility and stability.Based on the solubility and emulsification capacity of andrographolide,the oil phase,emulsifier,and cosurfactant were successfully screened.This study used IPM/ethanol(v/v,1:1)as oil phase,RH-40 as surfactant,and isopropanol as cosurfactant.The pseudo-ternary phase diagrams were drawn to screen the composition and proportion of nanoemulsions.The results showed that andrographolide:oil phase:surfactant:water=13.8mg:1.29g:2g:1g:4.5g.The nanoemulsion prepared with this prescription was transparent and clear,and the distribution was uniform.2.Based on the formula,andrographolide nanoemulsions was successfully prepared by low-energy emulsification,and the AG-NE has a translucent,blue appearance.The prepared andrographolide was identified by staining method and the physical and chemical properties(SEM,TEM nanoparticle size,Zeta potential,PDI,pH value,stability,entrapment efficiency)were determined.The results showed that the AG-NE were O/W type nanosemulsions.The SEM and TEM results showed that the nanoemulsions were spherical in appearance and evenly distributed,with a particle size of about 50 nm and no adhesion between each other.The nanoparticle size test results showed that the average particle size was 227.2±0.69 nm,PDI was0.138±0.03,the pH was 6.75.The results of stability experiments showed that andrographolide nanosemulsions could be maintained for one month at 4°C and25°C,the entrapment efficiency of AG-NE was 86.4%.3.In this experiment,Poloxamer P407 and Poloxamer P188(6:1)was chosen as the hydrogel matrix.Taking the gel phase transition temperature as index,the effects of different concentrations of Poloxamer on the phase change temperature of andrographolide nanoemulsion gels were measured.SEM morphology,stability,rheological properties of andrographolide nanoemulsion was measured.Studies have shown that the phase change temperature of the gel at a content of 13.5%is 36.3°C,SEM results showed a porous structure and the gel rheological results showed that the energy storage modulus(G’)≥loss modulus(G’’)at body temperature,which is characterized by the gel.