Poly (Glycerol Adipate): From a Functionalized Nanocarrier to a Polymeric-Prodrug Matrix to Create Amorphous Solid Dispersions

Abstract

Amorphous solid dispersions are a promising strategy to overcome poor solubility and stability limitations, reducing the crystallinity of the drug through incorporation within a polymer matrix. However, to achieve an effective amorphous solid dispersion, the polymer and drug must be compatible, otherwise the drug can undergo recrystallization. In this work, we investigated the potential of the enzymatically synthesized poly(glycerol-adipate), as a pharmaceutical tool for producing a nanoamorphous formulation. A polymeric prodrug of poly(glycerol-adipate) was synthesized by coupling mefenamic acid as drug. The amorphicity of the polymeric prodrug was assessed combining differential scanning calorimetry and polarized optical microscopy. The prodrug was then formulated into nanoparticles and studied for stability and drug release in the presence of lipase. To realize the goal of combination drug therapies for overcoming drug resistance and improving treatment outcomes, the prodrug was screened as a solubility enhancer for a series of fenamic drugs and compared with commercially available polymers commonly used in solid dispersions. Screening was carried out by developing a high-throughput miniaturized screening assay using a 2D printer to dispense the polymer and drug combinations. Finally, the collected data showed that drug conjugation could improve drug-polymer compatibility, in addition to facilitating the release of drugs by 2 different mechanisms.