The range of systems and approaches that can be used to deliver therapeutics has advanced in the past few decades and it is growing at an incredible rate. By modifying the properties of materials like polymers and creating nanostructures, nanotechnology can provide superior medication delivery systems for more effective disease management and treatment. The use of nanostructures as drug delivery systems has several benefits over more traditional delivery methods. The materials employed in the fabrication of nanostructures determine the type of nanostructures obtained and these nanostructures, in turn, determine the different properties obtained. Organic nanoparticles have showed the greatest potential in clinical translating among the many nanomaterials created for medication delivery. Organic building blocks exhibit various unique properties when they self-assemble into nanostructures. Organic nanomaterials frequently self-assemble through a variety of noncovalent interactions, such as hydrogen bonds, van der Waals forces, electrostatic interactions, hydrophobic interactions, which make them more sensitive to environmental factors like pH variation, light exposure, temperature changes, or pressure. A lot of self-assembled organic nanostructures have great biodegradability, little cytotoxicity, and strong biocompatibility, and are of the right size for endocytosis. Additionally, they can be easily and inexpensively created using noncovalent synthesis. In this study mucin, the main constituent protein of mucus, was used as organic building block to synthesize the so-called “mucosomes”. Mucosomes are multifunctional nanoparticles produced and loaded with the desire drug within the same synthetic procedure. Drug encapsulation efficiency was assessed by means of UV-Visible spectrophotometer, fluorimeter, and HPLC-MS, depending on the properties of the drug. Intrinsic glycosylation, one of the main strengths of mucin-based nanoparticles, has played a key role in the choice of the therapeutic molecules to be trapped. Glycans present on the surface of nanocarriers have high affinity towards certain adhesion proteins overexpressed in many human tumours on tumour cells and in tumour vasculature. Furthermore, many bacterial toxins exhibit cell, tissue, and species tropism based on the presentation of host cell glycans as cellular receptors, demonstrating the essential function of glycointeractions in disease. The mucosomes were then first loaded with a photosensitiser. After testing the latter's ability to produce reactive oxygen species (ROS), they were tested on MCF-7 cells to study their cytotoxicity and photoactivity. The in vitro photodynamic activity studies were conducted by the Department of Life Sciences and Systems Biology at the University of Turin. The second drug chosen to be encapsulated is the most potent fluoroquinolone that has been shown to be effective against a variety of bacteria. Also with regard to the potential of glycans on the surface of mucosomes to act as receptors for pathogens, a fluorophore with no therapeutic activity was also encapsulated to assess the interaction between mucosomes and bacteria by confocal microscopy. Antimicrobial activity studies were then conducted by the University of Pavia.
Biopolimeri di mucina come sistemi di drug delivery per applicazioni farmaceutiche
FRASCA, ENRICA
2021/2022
Abstract
The range of systems and approaches that can be used to deliver therapeutics has advanced in the past few decades and it is growing at an incredible rate. By modifying the properties of materials like polymers and creating nanostructures, nanotechnology can provide superior medication delivery systems for more effective disease management and treatment. The use of nanostructures as drug delivery systems has several benefits over more traditional delivery methods. The materials employed in the fabrication of nanostructures determine the type of nanostructures obtained and these nanostructures, in turn, determine the different properties obtained. Organic nanoparticles have showed the greatest potential in clinical translating among the many nanomaterials created for medication delivery. Organic building blocks exhibit various unique properties when they self-assemble into nanostructures. Organic nanomaterials frequently self-assemble through a variety of noncovalent interactions, such as hydrogen bonds, van der Waals forces, electrostatic interactions, hydrophobic interactions, which make them more sensitive to environmental factors like pH variation, light exposure, temperature changes, or pressure. A lot of self-assembled organic nanostructures have great biodegradability, little cytotoxicity, and strong biocompatibility, and are of the right size for endocytosis. Additionally, they can be easily and inexpensively created using noncovalent synthesis. In this study mucin, the main constituent protein of mucus, was used as organic building block to synthesize the so-called “mucosomes”. Mucosomes are multifunctional nanoparticles produced and loaded with the desire drug within the same synthetic procedure. Drug encapsulation efficiency was assessed by means of UV-Visible spectrophotometer, fluorimeter, and HPLC-MS, depending on the properties of the drug. Intrinsic glycosylation, one of the main strengths of mucin-based nanoparticles, has played a key role in the choice of the therapeutic molecules to be trapped. Glycans present on the surface of nanocarriers have high affinity towards certain adhesion proteins overexpressed in many human tumours on tumour cells and in tumour vasculature. Furthermore, many bacterial toxins exhibit cell, tissue, and species tropism based on the presentation of host cell glycans as cellular receptors, demonstrating the essential function of glycointeractions in disease. The mucosomes were then first loaded with a photosensitiser. After testing the latter's ability to produce reactive oxygen species (ROS), they were tested on MCF-7 cells to study their cytotoxicity and photoactivity. The in vitro photodynamic activity studies were conducted by the Department of Life Sciences and Systems Biology at the University of Turin. The second drug chosen to be encapsulated is the most potent fluoroquinolone that has been shown to be effective against a variety of bacteria. Also with regard to the potential of glycans on the surface of mucosomes to act as receptors for pathogens, a fluorophore with no therapeutic activity was also encapsulated to assess the interaction between mucosomes and bacteria by confocal microscopy. Antimicrobial activity studies were then conducted by the University of Pavia.File | Dimensione | Formato | |
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https://hdl.handle.net/20.500.14240/147410