Synthesis and In Vitro Release of Adriamycin from Star-Shaped Poly(Lactide-co-Glycolide) Nano- and Microparticles

Abstract

The star-shaped poly(lactide-co-glycolide (PLGA)-beta-cyclodextrin (PLGA-beta-CD) copolymer was synthesized by reacting L-lactide, glycolide, and beta-cyclodextrin in the presence of stannous octoate as a catalyst. The structure of PLGA-beta-CD copolymer was confirmed with (1)H-NMR, (13)C-NMR, and FT-IR spectra. Adriamycin (ADR), which is an antitumor antibiotic, was encapsulated within micro- and nanoparticles made of PLGA-beta-CD with a modified double emulsion method. Relatively low amount of beta-CD and catalyst were used in order to obtain high molecular weight polymers. Differential scanning calorimetry (DSC) was used to determine the thermal properties of star-shaped copolymers. The reduction of interactions between the star-shaped polyester molecules is due to their branched structure lowered T(g) and T(m) compared to linear PLGA copolymers. Effects of the experimental parameters, such as copolymer composition, ADR concentration, copolymer concentration, and poly(vinyl alcohol) concentration, on particular size and encapsulation efficiency were investigated. An increase in the internal aqueous phase volume led to a decrease in particles average size. A decrease in the polymer concentration resulted in increasing the particle average size from 135.5 to 325.6 nm. The high entrapment efficiency (EE) (about 65%) was obtained for 220 microm particles. All of the release profiles indicated a close relationship between each formulation variable and the amount of ADR released.