TY - JOUR
T1 - Novel polyvinyl-alcohol microsphere for everolimus delivery for subependymal giant cell astrocytoma
AU - Louis, Lynn
AU - Chee, Bor Shin
AU - Louis, Noreen
AU - De Lima, Gabriel Goetten
AU - McAfee, Marion
AU - Murphy, Alan
AU - Nugent, Michael J.D.
N1 - Publisher Copyright:
© 2023 The Author(s)
PY - 2023/3
Y1 - 2023/3
N2 - 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 end-goal to achieve higher bioavailability and sustained delivery. PVA-EVR microspheres were physically cross-linked using the freeze-thaw technique, and solvent-cast PVA-EVR 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.
AB - 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 end-goal to achieve higher bioavailability and sustained delivery. PVA-EVR microspheres were physically cross-linked using the freeze-thaw technique, and solvent-cast PVA-EVR 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.
KW - Drug delivery system
KW - Drug-release kinetics
KW - Everolimus
KW - Freeze-Thawing
KW - Polyvinyl alcohol
KW - Subependymal giant cell astrocytoma
UR - http://www.scopus.com/inward/record.url?scp=85147585667&partnerID=8YFLogxK
U2 - 10.1016/j.jddst.2023.104204
DO - 10.1016/j.jddst.2023.104204
M3 - Article
AN - SCOPUS:85147585667
SN - 1773-2247
VL - 81
JO - Journal of Drug Delivery Science and Technology
JF - Journal of Drug Delivery Science and Technology
M1 - 104204
ER -