NERDG 2026
Poster 37 Abstract
Biosurfactant Stabilized Oral Nanosuspension of Vortioxetine hydrobromide for Treatment of Glioblastoma
Nidhi Gevariya, Himaxi Patel, Ketan Patel
College of Pharmacy and Health Sciences, St. John’s University, NY, USA
Presenting Author: Nidhi Gevariya
Corresponding Author: Ketan Patel, [email protected]
Purpose
Vortioxetine hydrobromide (VTX.HBr), an antidepressant drug, has recently gained attention as a potential therapeutic candidate for glioblastoma. However, its poor aqueous solubility limits its oral bioavailability for cancer treatment. Nanocrystal-based drug delivery systems, particularly nanosuspensions, offer an effective approach to enhance the solubility and dissolution of poorly water-soluble drugs. Sophorolipids (SLs), naturally derived amphiphilic glycolipid biosurfactants, and hydroxypropyl methylcellulose E5(HPMC E5), provide eco-friendly and efficient stabilization of nanosuspension. Therefore, this study aimed to design, optimize, and characterize biosurfactant-stabilized VTX.HBr nanosuspension using wet media milling to improve oral delivery.
Methods
A stable VTX.HBr nanosuspension was prepared using dual centrifugation nano-milling, wherein VTX.HBr powder was dispersed in Milli-Q water containing combinations of surfactants and stabilizers. The particle size, polydispersity index (PDI), and zeta potential were measured using Malvern zeta-sizer. Further optimized batch was freeze-dried using trehalose as cryoprotectant to improve further stability of formulation. Solid-state characterization was conducted using differential scanning calorimetry (DSC) to analyze its thermal behavior and crystallinity. In vitro dissolution assay was performed to assess drug release. Additionally, in vitro cytotoxicity of VTX.HBr and its nanosuspension was evaluated on U-87 MG, U-87 MG TR and T-98 G glioblastoma cell lines using the MTT assay. Ongoing studies include oral bioavailability prediction using Gastroplus.
Results
Formulations containing single stabilizer exhibited rapid phase separation, whereas the combination of sophorolipids and HPMC E5 resulted in physically stable nanosuspension. The VTX.HBr nanosuspension demonstrated mean particle size of 309 ± 0.131 nm and zeta potential of −20 mV, indicating adequate colloidal stability. Following freeze-drying nanosuspension retained nanoscale size upon reconstitution. Crystallinity was confirmed by differential scanning calorimetry. In vitro drug release studies demonstrated significantly higher dissolution compared to the pure drug in supersaturated state. The IC50 values of VTX.HBr in U-87 MG, U-87 MG/TR and T-98 G were found to be 13 µM-18 µM at 48 h.
Conclusion
A biosurfactant-stabilized VTX.HBr nanosuspension was successfully developed using wet media milling, demonstrating rational formulation strategy for improving the solubility of poorly water-soluble small molecules in glioblastoma therapy.
Keywords
Vortioxetine hydrobromide, Biosurfactants, Nanosuspension, Glioblastoma, Oral Delivery
Poster 37 Abstract
Biosurfactant Stabilized Oral Nanosuspension of Vortioxetine hydrobromide for Treatment of Glioblastoma
Nidhi Gevariya, Himaxi Patel, Ketan Patel
College of Pharmacy and Health Sciences, St. John’s University, NY, USA
Presenting Author: Nidhi Gevariya
Corresponding Author: Ketan Patel, [email protected]
Purpose
Vortioxetine hydrobromide (VTX.HBr), an antidepressant drug, has recently gained attention as a potential therapeutic candidate for glioblastoma. However, its poor aqueous solubility limits its oral bioavailability for cancer treatment. Nanocrystal-based drug delivery systems, particularly nanosuspensions, offer an effective approach to enhance the solubility and dissolution of poorly water-soluble drugs. Sophorolipids (SLs), naturally derived amphiphilic glycolipid biosurfactants, and hydroxypropyl methylcellulose E5(HPMC E5), provide eco-friendly and efficient stabilization of nanosuspension. Therefore, this study aimed to design, optimize, and characterize biosurfactant-stabilized VTX.HBr nanosuspension using wet media milling to improve oral delivery.
Methods
A stable VTX.HBr nanosuspension was prepared using dual centrifugation nano-milling, wherein VTX.HBr powder was dispersed in Milli-Q water containing combinations of surfactants and stabilizers. The particle size, polydispersity index (PDI), and zeta potential were measured using Malvern zeta-sizer. Further optimized batch was freeze-dried using trehalose as cryoprotectant to improve further stability of formulation. Solid-state characterization was conducted using differential scanning calorimetry (DSC) to analyze its thermal behavior and crystallinity. In vitro dissolution assay was performed to assess drug release. Additionally, in vitro cytotoxicity of VTX.HBr and its nanosuspension was evaluated on U-87 MG, U-87 MG TR and T-98 G glioblastoma cell lines using the MTT assay. Ongoing studies include oral bioavailability prediction using Gastroplus.
Results
Formulations containing single stabilizer exhibited rapid phase separation, whereas the combination of sophorolipids and HPMC E5 resulted in physically stable nanosuspension. The VTX.HBr nanosuspension demonstrated mean particle size of 309 ± 0.131 nm and zeta potential of −20 mV, indicating adequate colloidal stability. Following freeze-drying nanosuspension retained nanoscale size upon reconstitution. Crystallinity was confirmed by differential scanning calorimetry. In vitro drug release studies demonstrated significantly higher dissolution compared to the pure drug in supersaturated state. The IC50 values of VTX.HBr in U-87 MG, U-87 MG/TR and T-98 G were found to be 13 µM-18 µM at 48 h.
Conclusion
A biosurfactant-stabilized VTX.HBr nanosuspension was successfully developed using wet media milling, demonstrating rational formulation strategy for improving the solubility of poorly water-soluble small molecules in glioblastoma therapy.
Keywords
Vortioxetine hydrobromide, Biosurfactants, Nanosuspension, Glioblastoma, Oral Delivery
