NERDG 2026
Poster 15 Abstract
Vortioxetine-Loaded Liposomes: A Repurposed Approach for Glioblastoma therapies
Reshma Sarkar, Naveen Rajana, Suman Choudhary, Vivek Gupta
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA
Presenting and Corresponding Author: Reshma Sarkar, [email protected]
Abstract
Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor, with a median survival of under 24 months despite surgery, radiotherapy, and Temozolomide (TMZ). The chemotherapeutic efficacy of TMZ in GBM is reduced by at least 50% in patients who do not respond to TMZ, due to the overexpression of O6-methylguanine methyltransferase (MGMT) and/or the lack of a DNA repair pathway in GBM cells. A recent high-throughput screening identified Vortioxetine (Vort), a blood-brain barrier (BBB)- penetrating multimodal antidepressant, as a potential GBM candidate for repurposing. This study aims to formulate and evaluate vortioxetine loaded liposomes to enhance drug delivery, improve therapeutic efficacy, and offer a promising alternative to existing GBM chemotherapies. Vort liposomes were prepared via the thin-film hydration method using DPPC and Cholesterol (Molar ratio 7:3) with 10mM total lipid content. Formulations were characterized for entrapment, drug loading, particle size, PDI, and zeta potential. Morphological studies were carried out using TEM. In-vitro 2D and 3D cell culture studies were performed to show anticancer efficacy. Stability testing was conducted at different storage conditions. Vort was efficiently loaded in liposomes with a higher drug loading of 4.6±0.2%. DSC and XRD confirmed Vort entrapment within the liposomal core. Vort exhibited time-dependent and dose-dependent toxicity on U87 and LN229 glioblastoma cell lines with IC50 values of 12.5 µM and 6 µM, respectively. Enhanced cellular uptake was exhibited by Coumarin-6-loaded liposomes as compared to Coumarin-6. With multiple-dose treatments, Vort liposomes demonstrated effective penetration and efficacy, reducing tumor volume at an IC50 concentration. Clonogenic assay demonstrated superior inhibitory effect of Vort liposomes over plain Vort. High microglial cell viability and induction of apoptosis through mitochondrial disruption emphasize both safety and therapeutic potential. Vort liposomes were stable at 4°C for up to 4 weeks. This study demonstrates that a stable liposomal formulation can be prepared using the thin film method. In-vitro studies indicate the efficacy of Vort liposomes in monolayer and spheroid cancer models.
Keywords
Liposome, Glioblastoma, drug repurposing
Poster 15 Abstract
Vortioxetine-Loaded Liposomes: A Repurposed Approach for Glioblastoma therapies
Reshma Sarkar, Naveen Rajana, Suman Choudhary, Vivek Gupta
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, NY 11439, USA
Presenting and Corresponding Author: Reshma Sarkar, [email protected]
Abstract
Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor, with a median survival of under 24 months despite surgery, radiotherapy, and Temozolomide (TMZ). The chemotherapeutic efficacy of TMZ in GBM is reduced by at least 50% in patients who do not respond to TMZ, due to the overexpression of O6-methylguanine methyltransferase (MGMT) and/or the lack of a DNA repair pathway in GBM cells. A recent high-throughput screening identified Vortioxetine (Vort), a blood-brain barrier (BBB)- penetrating multimodal antidepressant, as a potential GBM candidate for repurposing. This study aims to formulate and evaluate vortioxetine loaded liposomes to enhance drug delivery, improve therapeutic efficacy, and offer a promising alternative to existing GBM chemotherapies. Vort liposomes were prepared via the thin-film hydration method using DPPC and Cholesterol (Molar ratio 7:3) with 10mM total lipid content. Formulations were characterized for entrapment, drug loading, particle size, PDI, and zeta potential. Morphological studies were carried out using TEM. In-vitro 2D and 3D cell culture studies were performed to show anticancer efficacy. Stability testing was conducted at different storage conditions. Vort was efficiently loaded in liposomes with a higher drug loading of 4.6±0.2%. DSC and XRD confirmed Vort entrapment within the liposomal core. Vort exhibited time-dependent and dose-dependent toxicity on U87 and LN229 glioblastoma cell lines with IC50 values of 12.5 µM and 6 µM, respectively. Enhanced cellular uptake was exhibited by Coumarin-6-loaded liposomes as compared to Coumarin-6. With multiple-dose treatments, Vort liposomes demonstrated effective penetration and efficacy, reducing tumor volume at an IC50 concentration. Clonogenic assay demonstrated superior inhibitory effect of Vort liposomes over plain Vort. High microglial cell viability and induction of apoptosis through mitochondrial disruption emphasize both safety and therapeutic potential. Vort liposomes were stable at 4°C for up to 4 weeks. This study demonstrates that a stable liposomal formulation can be prepared using the thin film method. In-vitro studies indicate the efficacy of Vort liposomes in monolayer and spheroid cancer models.
Keywords
Liposome, Glioblastoma, drug repurposing
