Synthesis of poly (lactic-co-glycolic acid) microspheres loaded with (−)- epigallocatechin-3-gallate- β- cyclodextrin inclusion complex using double solvent emulsification

Abstract

High hydrophilicity of EGCG and its rapid partitioning to aqueous phase leads to low drug loading (−)-epigallocatechin-3-gallate (EGCG) into poly (lactic-co-glycolic acid) (PLGA) microparticles. The study aims was to improve drug loading efficiency of EGCG in PLGA through complexation of EGCG with beta-cyclodextrin (βCD) using w1/o/w2 double emulsion method which characterized in term of yield, drug loading efficiency, morphology, particle size and in vitro release profile. The materials used in this study were poly (lactic-co-glycolic acid) (PLGA, lactide/glycolide 75/25, hydroxy enol end, I.V. 0.85 dl/g0, (−)-epigallocatechin-3-gallate (EGCG, purity 85%) were extracted from green tea leaves, polyvinyl alcohol (PVA, MW 130, 000 Da) and beta-cyclodextrin (βCD) and dichloromethane (DCM, HPLC grade). Synthesis of PLGA microspheres was carried out to load EGCG-βCD using water-oil-water (double) emulsion with solvent extraction technique. EGCG-βCD solution was dissolved gradually to PLGA solution and vortexed for 2 minutes to achieve first degree emulsion. One (1.0) mg of drug loaded microspheres were dissolved using 1.0 mL of DMSO and concentration of EGCG was measured using UV-Vis spectrometer at 274nm. Each EGCG complexed with βCD loaded with PLGA (EGCG-βCD-PLGA) and ECCG-βCD complex were mixed with KBr salt (1:100) and press into pellets for analysis with FTIR spectrometer. The samples were subjected under scanning electron microscopy (SEM). In vitro release profile was fitted into five kinetic mathematical models: zero order kinetics, first order kinetics, Hixson Crowell kinetics, Higuchi kinetics and Korsmeyer Peppas. The results showed the drug loading efficiencies of 1 mg, 5 mg, 10 mg, 15 mg of EGCG/ βCD in PLGA were 1.26030%,1.3180%, 1.3218% and 1.3443% respectively. SEM images showed its integrated spherical shape with no drug crystal and pores on its surface. The particle size ranges between 0.11 to 15.50μm. The in vitro release behaviour of 1 mg, 5 mg, 10mg, 15 mg of EGCG/ βCD in PLGA at end of 96 hours were 85.54%, 80.98%, 77.00%, 72.35% with all formulation followed diffusion based release. βCD hosting EGCG prevented from rapidly partitioning to the aqueous phase during emulsion, thereby improved its drug loading efficiency. In the presence of βCD, EGCG was released slowly and continuously with no obvious initial burst release, allowing longer circulation time.