2020
Permanent URI for this communityhttps://hdl.handle.net/20.500.12503/29915
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Browsing 2020 by Author "Ahmed, Nadia"
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Item Evaluation of Lipoprotein Mimetic Anthracycline Formulation for the Treatment of Ewing Sarcoma(2020) Kvinta, Ryan; Dossou, Akpedie; Saranya Conjeevaram Nagarajan, Bhavani; Sabnis, Nirupama; Raut, Sangram; Lacko, Andras G.; Ahmed, NadiaPurpose: Anthracyclines are effective in treating many types of cancer, including pediatric cancers such as Ewing Sarcoma. Currently, their use is limited due to cardiotoxicity, but a novel drug delivery method using lipoprotein-based technologies could mitigate this via selective delivery of its payload to cancer cells using a receptor-mediated mechanism. Methods: A soluble formulation of HDL-mimetic peptide (Myr-5A)-Valrubicin was fabricated using Nanoassemblr. Payload efficiency was characterized using spectrophotometric measurements. Size and zeta potential were measured with Zetasizer. Homogeneity was measured using FPLC. Hemolysis assays were performed by incubating Rabbit Red Blood Cells with Myr-5A-Valrubicin at different time intervals and measuring the absorbance of the supernatant at 550nm after centrifugation for 5 minutes. Cytotoxicity assays were performed on Ewing sarcoma cell lines TC205, TC32, CHLA10 and rat cardiomyocytes H9C2 using Cell counting kit (CCK 8). Results: The Myr-5A-Valrubicin nanoparticle formulation was observed to be stable, non-leaky and homogeneous with payload efficiency of 65%, size 87.75 ± 28.4nm, zeta potential -2.89 ± 9.81mV. The percentage hemolysis for Myr-5A-Valrubicin formulation was 5 and 2 times less compared to the free valrubicin formulation at 3.25 and 32.5�g/mL Valrubicin concentration, respectively. The cytotoxicity assays revealed Myr-5A-Valrubicin is effective in protecting cardiomyocytes. Conclusion: These studies indicate the potential of this novel drug delivery platform as an alternative or adjuvant therapy for combating Ewing Sarcoma. More experiments with tumor bearing model are needed to evaluate the efficacy of this formulation before reaching clinic.Item Lipoprotein Based Targeted Therapy for Acute Myelogenous Leukemia(2020) Sabnis, Nirupama; Lacko, Andras G.; Saranya Conjeevaram Nagarajan, Bhavani; Dossou, Akpedie; Raut, Sangram; Ahmed, Nadia; Kvinta, RyanPurpose: The purpose of this project was to initiate studies to develop nano-formulations for anti-cancer agents to treat Acute Myeloid Leukemia (AML) via enhancing their targeting efficiency, cytotoxicity and reducing off-target toxicities. Methods: A computer optimized formulation of rHDL-Valrubicin was characterized for its physical and chemical properties. The diameter of the nanoparticles and the zeta potential were measured by Malvern Zetasizer. The anisotropy was measured by Cary eclipse spectrofluometer. The drug entrapment efficiency was measured by absorbance of valrubicin at 490nm. The cytotoxicity of the formulation was tested in 2 Leukemia cell lines, Kasumi-1 and AML-193, using cell counting kit 8, Dojindo Molecular Technologies. The cardioprotective effect of the formulation was investigated in Rat cardiomyocytes cells, (H9C2). Results: rHDL-Valrubicin formulations were successfully prepared with drug entrapment efficiency of 31.8%. The formulation was non leaky and homogeneous with average particle diameter of the 13.2 ± 2.2 nm and the average zeta potential was found to be -2.39 ± 9.81 mV. The rHDL-Valrubicin formulation exhibited 50 times more cardioprotective effect as compared to free valrubicin. In the Leukemia cell lines Kasumi-1 and AML-193, the inhibitory concentration required to kill 50% of cells (IC50) using the rHDL-Valrubicin formulation was observed to be 1.5 and 1.9 times more effective than the free valrubicin respectively. Conclusion: These proof of concept studies indicate the potential of rHDL as a drug delivery platform to mitigate the cardiotoxicity associated with anthracycline use in the treatment of AML.