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Broad Application of Conotoxins As Molecular Probes, Therapeutic Leads and Drug Delivery Vectors In Excitable and Non-Excitable Systems
Title
Broad Application of Conotoxins As Molecular Probes, Therapeutic Leads and Drug Delivery Vectors In Excitable and Non-Excitable Systems.
Creator
Padilla, Alberto, Hartmann, James X., Mari, Frank, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
Conotoxins are peptides expressed by the exogenome of more than 800 species of marine mollusks belonging to the genus Conus (cone snails.) Owing to their high specificity and affinity for ion channels, transporter molecules, and cell receptors of the central and peripheral nervous systems, conotoxins have been investigated for nearly four decades. These efforts on conotoxin research made possible the FDA approved use of Ziconitide/Prialt, a conotoxin derived from the venom of Conus magus,...
Show moreConotoxins are peptides expressed by the exogenome of more than 800 species of marine mollusks belonging to the genus Conus (cone snails.) Owing to their high specificity and affinity for ion channels, transporter molecules, and cell receptors of the central and peripheral nervous systems, conotoxins have been investigated for nearly four decades. These efforts on conotoxin research made possible the FDA approved use of Ziconitide/Prialt, a conotoxin derived from the venom of Conus magus, which effectively treats patients suffering from severe chronic pain without consequent narcotic effects. Additionally, six other conotoxins have reached clinical trials and many novel ones are being discovered every day. Investigations reported in this dissertation broadens the applicability of conotoxins to non-excitable systems. Here, conotoxins from the dissected venom of the vermivorous cone snail Conus nux were isolated and purified by size exclusion and reverse phase HPLC and characterized by MALDI-TOF and MS/MS spectrometry. The purified conopeptide fractions revealed: 1) antagonist activity of conotoxin NuxVID on two human voltage-gated sodium channels, displaying capabilities as a practical molecular probe and a potential therapeutic lead. 2) Ability for two novel conotoxins to traverse artificial biological membranes, suggesting their potential as drug delivery systems. 3) In vitro capacity of several novel conopeptides to interfere with the adhesion of PfEMP1 domains, expressed in P. falciparum infected erythrocytes, to vascular endothelial and placenta receptors. Lastly, this work reveals binding of the synthetic form of α-conotoxin ImI, from the vermivorous cone snail Conus imperialis, to the α7 nAChR of macrophage-like-cells derived from the pre-monocytic leukemic cell line THP-1 in support of the involvement of this receptor in the cholinergic anti-inflammatory pathway.
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Date Issued
2019
PURL
http://purl.flvc.org/fau/fd/FA00013250
Subject Headings
Conotoxins, Drug Delivery Systems, Molecular Probes
Format
Document (PDF)
DEVELOPMENT OF AN ELASTIC POLYMER-BASED DRUG DELIVERY SYSTEM FOR TISSUE REGENERATION
Title
DEVELOPMENT OF AN ELASTIC POLYMER-BASED DRUG DELIVERY SYSTEM FOR TISSUE REGENERATION.
Creator
Firoozi, Negar, Kang, Yunqing, Florida Atlantic University, College of Engineering and Computer Science, Department of Ocean and Mechanical Engineering
Abstract/Description
In spite of the vast research on polymer-based tissue regeneration, extensive studies to develop an elastic and cell-promoting polymer biomaterial are still ongoing. However, using a renewable resource and a simple, environment-friendly synthesis route to synthesize an elastic polymer has not been successfully achieved yet. The objective of this work was to develop an elastic polymer for tissue engineering and drug delivery applications by using non-toxic, inexpensive and renewable monomers....
Show moreIn spite of the vast research on polymer-based tissue regeneration, extensive studies to develop an elastic and cell-promoting polymer biomaterial are still ongoing. However, using a renewable resource and a simple, environment-friendly synthesis route to synthesize an elastic polymer has not been successfully achieved yet. The objective of this work was to develop an elastic polymer for tissue engineering and drug delivery applications by using non-toxic, inexpensive and renewable monomers. A new nature-derived renewable material, xylitol, was used to synthesize an elastic polymer with the presence of a crosslinking agent, dodecanedioic acid. Here a simple melt condensation polymerization method was used to synthesize the poly(xylitoldodecanedioic acid)(PXDDA). The physicochemical and biological properties of the new PXDDA polymer were characterized. Fourier transform infrared (FTIR) confirmed the formation of ester bonding in the polymer structure, and thermal analysis demonstrated that the polymer was completely amorphous. The polymer shows high elasticity. Increasing the molar ratio of dodecanedioic acid resulted in higher hydrophobicity and lower glass transition temperature. Further, the polymer degradation and in vitro dye release studies revealed that the degradation and dye release from the polymer became slower when the amount of dodecanedioic acid in the composite increased.
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Date Issued
2019
PURL
http://purl.flvc.org/fau/fd/FA00013306
Subject Headings
Drug Delivery Systems, Polymers, Tissue Engineering, Xylitol
Format
Document (PDF)
Development of MnO2 Hollow Nanoparticles for Drug Delivery
Title
Development of MnO2 Hollow Nanoparticles for Drug Delivery.
Creator
Greene, Allison, Kang, Yunqing, Florida Atlantic University, Department of Ocean and Mechanical Engineering, College of Engineering and Computer Science
Abstract/Description
This thesis reports the development of a novel drug delivery system consisting of hollow nanoparticles, formed from manganese dioxide (δ-MnO2) sheets, that are coated with polydopamine and folic acid to selectively target cancer cells. The biodegradability and colloidal stability of the uncoated hollow nanoparticles were investigated in comparison to solid MnO2 nanoparticles and graphene oxide sheets. The MnO2 hollow nanoparticles degraded at a faster rate and seem to have a higher surface...
Show moreThis thesis reports the development of a novel drug delivery system consisting of hollow nanoparticles, formed from manganese dioxide (δ-MnO2) sheets, that are coated with polydopamine and folic acid to selectively target cancer cells. The biodegradability and colloidal stability of the uncoated hollow nanoparticles were investigated in comparison to solid MnO2 nanoparticles and graphene oxide sheets. The MnO2 hollow nanoparticles degraded at a faster rate and seem to have a higher surface area and better colloidal dispersion than solid MnO2 nanoparticles. Xanthan gum was proven to improve colloidal dispersion of these hollow nanoparticles and were used for further cell studies. In this study, cancer and healthy cells were treated with coated hollow nanoparticles, and results indicate that this novel hollow nanoparticle may preferentially target and kill cancer cells. Particle aggregation has shown to be toxic to cells. Further studies with this novel drug delivery system may lead to a groundbreaking solution to targeted cancer therapy.
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Date Issued
2020
PURL
http://purl.flvc.org/fau/fd/FA00013513
Subject Headings
Drug Delivery Systems, Nanoparticles, Manganese dioxide, Xanthan gum, Cancer cells
Format
Document (PDF)
Overcoming Multidrug Resistance in Prostate Cancer Cells Using Nanoparticle Delivery of a Two-Drug Combination
Title
Overcoming Multidrug Resistance in Prostate Cancer Cells Using Nanoparticle Delivery of a Two-Drug Combination.
Creator
Toluleke, O. Famuyiwa, Kumi-Diaka, James, Florida Atlantic University, Department of Biological Sciences, Charles E. Schmidt College of Science
Abstract/Description
Prostate cancer (PCa) is the second most diagnosed cancer in men. The resistance of prostate cancer to chemotherapy has been linked to the ATP Binding Cassette (ABC)-Mediated Multidrug Resistance (MDR). This study investigated the combination of 3-Bromopyruvate (3-BPA) and the anti-inflammatory molecule SC-514 in reducing MDR in prostate cancer. The compounds were incorporated into a PLGA nanoparticles to increase delivery to target cells. To investigate the effectiveness of SC-514 and/3-BPA,...
Show moreProstate cancer (PCa) is the second most diagnosed cancer in men. The resistance of prostate cancer to chemotherapy has been linked to the ATP Binding Cassette (ABC)-Mediated Multidrug Resistance (MDR). This study investigated the combination of 3-Bromopyruvate (3-BPA) and the anti-inflammatory molecule SC-514 in reducing MDR in prostate cancer. The compounds were incorporated into a PLGA nanoparticles to increase delivery to target cells. To investigate the effectiveness of SC-514 and/3-BPA, cytoxicity assays including trypan blue dye exclusion, MTT tetrazolium reduction, NBT, LDH release poly caspase detection, cell titer glow assay, and ELISA were utilized. Both immunofluorescence and multidrug resistance efflux assays were utilized to estimate the number of drug resistant cells. SC-514 was encapsulated in PLGA nanoparticles via single-emulsion method. SC-514 nanoparticles were analyzed utilizing Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). Liquid chromatography–mass spectrometry (LC–MS) was used to measure the amount of SC- 514 released from the nanoparticle. Alternative SC-514 drug release quantification methods such as colony forming assay, wound healing assay, and transwell and migration assay were explored.
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Date Issued
2021
PURL
http://purl.flvc.org/fau/fd/FA00013677
Subject Headings
Prostate--Cancer, Nanoparticles, Drug Delivery Systems, Multidrug resistance
Format
Document (PDF)
Cell-surface glycan-lectin interactions for biomedical applications
Title
Cell-surface glycan-lectin interactions for biomedical applications.
Creator
Rodriguez Benavente, Maria Carolina, Lepore, Salvatore D., Cudic, Predrag, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description
Carbohydrate recognition is one of the most sophisticated recognition processes in biological systems, mediating many important aspects of cell-cell recognition, such as inflammation, cell differentiation, and metastasis. Consequently, lectin-glycan interactions have been intensively studied in order to mimic their actions for potential bioanalytical and biomedical applications. Galectins, a class of ß-galactoside-specific animal lectins, have been strongly implicated in inflammation and...
Show moreCarbohydrate recognition is one of the most sophisticated recognition processes in biological systems, mediating many important aspects of cell-cell recognition, such as inflammation, cell differentiation, and metastasis. Consequently, lectin-glycan interactions have been intensively studied in order to mimic their actions for potential bioanalytical and biomedical applications. Galectins, a class of ß-galactoside-specific animal lectins, have been strongly implicated in inflammation and cancer. Galectin-3 is involved in carbohydrate-mediated metastatic cell heterotypic and homotypic adhesion via interaction with Thomsen-Friedenreich (TF) antigen on cancer-associated MUC1. However, the precise mechanism by which galectin-3 recognizes TF antigen is poorly understood. Our thermodynamic studies have shown that the presentation of the carbohydrate ligand by MUC1-based peptide scaffolds can have a major impact on recognition, and may facilitate the design of more potent and specific galectin-3 inhibitors that can be used as novel chemical tools in dissecting the precise role of galectin-3 in cancer and inflammatory diseases. Another lectin, odorranalectin (OL), has been recently identified from Odorrana grahami skin secretions as the smallest cyclic peptide lectin, has a particular selectivity for L-fucose and very low toxicity and immunogenicity, rendering OL an excellent candidate for drug delivery to targeted sites, such as: (1) tumor-associated fucosylated antigens implicated in the pathogenesis of several cancers, for overcoming the nonspecificity of most anticancer agents; (2) the olfactory epithelium of nasal mucosa for enhanced delivery of peptide-based drugs to the brain.
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Date Issued
2015
PURL
http://purl.flvc.org/fau/fd/FA00004405
Subject Headings
Biopharmaceutics, Carbohydrates -- Therapeutic use, Cell differentiation, Drug delivery systems, Glycoproteins, Glycoslation, Mice as laboratory animals, Peptides -- Derivatives, Pharmaceutical biotechnology
Format
Document (PDF)