Has PEG-PLGA advantages for the delivery of hydrophobic drugs? Risperidone as an example

Abstract

To overcome the disadvantages seen with current long-acting injectable formulations for risperidone (i.e., nonlinear release with initial lag time), an alternative delivery system was developed. The use of biodegradable PEG-PLGA polymers enabled us to formulate microparticles with a linear release over one month with no observable lag time.Diblock copolymers with PEG contents of 5 and 10% were transformed into risperidone-loaded highly porous microparticles with median particle sizes of 20–30 μm and narrow size distributions as confirmed by laser diffraction, electron and confocal microscopy. In parallel to characterizing the in vitro drug release behavior of the formulations, we studied their degradation/erosion profile by a couple of complementary techniques in detail. Compared to drug-free microparticles, the presence of risperidone led to a significantly faster polymer degradation accompanied by a more rapid mass loss and release of lactic acid. Proton nuclear magnetic resonance spectroscopy revealed a constant PEG content for the PEG-PLGA containing 5% of PEG over the course of incubation, while a decrease was observed for the diblock copolymer having an initial PEG content of 10%.In conclusion, PEG-PLGA polymers are also useful materials for the prolonged drug delivery of small lipophilic molecules, in addition to their application for the sustained release of sensitive drugs like peptides and proteins. Compared to “standard” polyesters such as PLGA, diblock copolymers avoid initial lag times and nonlinear “unpredictable” drug release profiles.