Novel polyvinyl-alcohol microsphere for everolimus delivery for subependymal cell astrocytoma

Abstract

Everolimus (EVR) has demonstrated efficacy in treating subependymal giant cell astrocytoma (SEGA) and other tuberous sclerosis (TSC) manifestations. Oral use of EVR is associated with low bioavailability and systemic toxicities culminating in treatment cessation in an appreciable patient population. To circumvent undesired effects, we developed a microsphere embedded formulation of EVR using polyvinyl alcohol (PVA) with an endgoal to achieve higher bioavailability and sustained delivery. PVA-EVR microspheres were physically cross-linked using the freeze-thaw technique, and solvent-cast PVAEVR films were developed as a control, without freezing and thawing cycles to ascertain the techniques significance. In vitro analyses and characterisation was performed to determine drug release and drug-polymer compatibility whereas In silico studies was done to analyse the non-crosslinked polymer and to evaluate qualitatively the interaction between EVR and PVA. The PVA-EVR microspheres were found to have high encapsulation efficiency, resulting in sustained release of EVR when compared to solvent cast films. The molecular docking studies showed excellent compatibility of the drug-polymer combination, further confirmed by the characterisation studies performed using DSC, FTIR, SEM and XRD. The developed PVA-EVR microspheres in this study can serve as a highly effective drug-delivery system with better bioavailability in treating SEGA tumours.