Preparation Of Sustained-release Microspheres Loaded With All-trans Retinoic Acid And Their Evaluation In Vitro And In Vivo

To prepare the poly(d,l-lact ic-co-glycolic acid)(PLGA)sustained-release microspheres loaded with all-trans retinoic acid(ATRA),and detect microspheres shape,size,the drug loading,encapsulation efficiency,the release of drugs in vitro and the determination of blood Concentration in vivo.Biodegradable materials PLGA as the carrier,PLGA sustained-release microspheres loaded with ATRA was prepared with Emulsion-solvent evaporation method,high-performance liquid chromatography detected encapsulation efficiency and drug loading.Electron microscope scan morphology of the microspheres.The testing methods that determined drug concentrations in vitro and in vivo have been investigated.The results showed that, microspheres of ATRA were spherical appearance,size in the range of 90-150 nm; The HPLC conditions and the standard curve were determined by exploring the proportion of components of flow phase and the detection wavelength.Linear relations is very good in the range of 0.103～103μg/ml.The regression equation:y=0.1372x+1.0514,r²ï¼ž0.9999(n=11).The average recovery was 101.7%,RSD=1.01%(n=5);In vitro,release of 67 d of the microspheres in three media(pH7.4 phosphate buffer saline,pH7.4 phosphate buffer saline and Tween 80, pH7.0 PBS plus Tween 80)was detected.The cumulative emissions in three media were 2.79%and 32.51%,21.77%;The method of the internal standard was used to determine the Content of ATRA in blood samples.The internal standard was nimodipine.The regression equation is:As/Ai=0.0013C+0.9056(n=8),r²= 0.9999,As was the peak area of retinoic acid,Ai was the peak area of nimodipine. Three relative recoveries of high,medium and low doses were 95.4%and 97.9%, 98.5%,the lowest detection limit was 50 ng/ml^-1.The sustained-release effects of ATRA sustained-release microspheres was very notable in vitro and release a long time,the release was more stable,there is no sudden release.The method that determine the ATRA content in vivo needs further study..