59 research outputs found
Development of Advanced Drug Delivery Systems for Respiratory Diseases
No full textUniversity of Technology Sydney. Graduate School of Health.This thesis addresses the significant health burden posed by Chronic Respiratory Disorders (CRDs), including chronic obstructive pulmonary disease (COPD), asthma, and lung cancer. These diseases share common pathophysiological mechanisms including inflammation, oxidative stress, airway remodelling, and are major contributors to global mortality, collectively causing about 5 million annual deaths. Current treatments have limited efficacy and severe adverse effects. Promising therapies include phytoceuticals such as berberine and Agarwood, and modern nucleic acid-based therapies. However, their clinical application is limited by challenges like poor solubility and unfavourable pharmacokinetics. In this thesis, advanced drug delivery systems (ADDS) are tested in vitro to overcome these limitations. The thesis presents three main chapters:
1. Encapsulation of a NFkB-inhibiting decoy oligodeoxynucleotide in nanoparticles for lung cancer, showing significant inhibition of proliferation, migration, and colony formation.
2. Formulation of an Agarwood oil nanoemulsion, demonstrating potent anti-inflammatory and antioxidant activity in a COPD model.
3. Encapsulation of berberine in liquid crystalline nanoparticles, mitigating TGF-β-induced airway remodelling in bronchial cells.
Overall, the findings of the present thesis underscore the enormous potential of ADDS to improve drug efficacy, offering a promising avenue for effective treatment and management of respiratory diseases
Extracellular Vesicles in Chemoresistance
No full textAbstract Chemotherapy represents the current mainstay therapeutic approach for most types of cancer. Despite the development of targeted chemotherapeutic strategies, the efficacy of anti-cancer drugs is severely limited by the development of drug resistance. Multidrug resistance (MDR) consists of the simultaneous resistance to various unrelated cytotoxic drugs and is one of the main causes of anticancer treatment failure. One of the principal mechanisms by which cancer cells become MDR involves the overexpression of ATP Binding Cassette (ABC) transporters, such as P-glycoprotein (P-gp), mediating the active efflux of cytotoxic molecules from the cytoplasm. Extracellular vesicles (EVs) are submicron lipid-enclosed vesicles that are released by all cells and which play a fundamental role in intercellular communication in physiological and pathological contexts. EVs have fundamental function at each step of cancer development and progression. They mediate the transmission of MDR through the transfer of vesicle cargo including functional ABC transporters as well as nucleic acids, proteins and lipids. Furthermore, EVs mediate MDR by sequestering anticancer drugs and stimulate cancer cell migration and invasion. EVs also mediate the communication with the tumour microenvironment and the immune system, resulting in increased angiogenesis, metastasis and immune evasion. All these actions contribute directly and indirectly to the development of chemoresistance and treatment failure. In this chapter, we describe the many roles EVs play in the acquisition and spread of chemoresistance in cancer. We also discuss possible uses of EVs as pharmacological targets to overcome EV-mediated drug resistance and the potential that the analysis of tumourderived EVs offers as chemoresistance biomarkers
Extracellular Vesicles in Chemoresistance.
No full textChemotherapy represents the current mainstay therapeutic approach for most types of cancer. Despite the development of targeted chemotherapeutic strategies, the efficacy of anti-cancer drugs is severely limited by the development of drug resistance. Multidrug resistance (MDR) consists of the simultaneous resistance to various unrelated cytotoxic drugs and is one of the main causes of anticancer treatment failure. One of the principal mechanisms by which cancer cells become MDR involves the overexpression of ATP Binding Cassette (ABC) transporters, such as P-glycoprotein (P-gp), mediating the active efflux of cytotoxic molecules from the cytoplasm. Extracellular vesicles (EVs) are submicron lipid-enclosed vesicles that are released by all cells and which play a fundamental role in intercellular communication in physiological and pathological contexts. EVs have fundamental function at each step of cancer development and progression. They mediate the transmission of MDR through the transfer of vesicle cargo including functional ABC transporters as well as nucleic acids, proteins and lipids. Furthermore, EVs mediate MDR by sequestering anticancer drugs and stimulate cancer cell migration and invasion. EVs also mediate the communication with the tumour microenvironment and the immune system, resulting in increased angiogenesis, metastasis and immune evasion. All these actions contribute directly and indirectly to the development of chemoresistance and treatment failure. In this chapter, we describe the many roles EVs play in the acquisition and spread of chemoresistance in cancer. We also discuss possible uses of EVs as pharmacological targets to overcome EV-mediated drug resistance and the potential that the analysis of tumour-derived EVs offers as chemoresistance biomarkers
Splitting of the ruby fluorescence under stress
No full textA splitting of the R1 ruby fluorescence is observed when a pressure P is applied on the crystal along special directions. It is linear as a function of P2, in agreement with the theory. It comes from the lifting of the degeneracy of Cr3+ ions located in two different sublattices.Un dédoublement de la fluorescence R1 du rubis est observé quand une pression P est appliquée sur le cristal suivant des directions bien particulières. Il est linéaire en fonction de P2 en accord avec la théorie. Il provient de la levée de dégénérescence des ions Cr3+ situés dans deux sousréseaux différents
Liquid Biopsies in Cancer Diagnosis, Monitoring, and Prognosis
No full textLiquid biopsies, comprising the noninvasive analysis of circulating tumorderived material (the 'tumor circulome'), represent an innovative tool in precision oncology to overcome current limitations associated with tissue biopsies. Within the tumor circulome, circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) are the only components the clinical application of which is approved by the US Food and Drug Administration (FDA). Extracellular vesicles (EVs), circulating tumor RNA (ctRNA), and tumor-educated platelets (TEPs) are relatively new tumor circulome constituents with promising potential at each stage of cancer management. Here, we discuss the clinical applications of each element of the tumor circulome and the prevailing factors that currently limit their implementation in clinical practice. We also detail the most recent technological developments in the field, which demonstrate potential in improving the clinical value of liquid biopsies
Circulating tumor DNA – Current state of play and future perspectives
No full textCancer management paradigms are shifting towards a personalized approach thanks to the advent of the -omics technologies. Liquid biopsies, consisting in the sampling of blood and other bodily fluids, are emerging as a valid alternative to circulating tumor biomarkers and tumor tissue biopsies for cancer diagnosis, routine monitoring and prognostication. The content of a liquid biopsy is referred to as the “tumor circulome”. Among its components, circulating tumor DNA (ctDNA), including both cell-free and exosome-associated DNA, is the most widely characterized element. ctDNA analysis has a tremendous capability in the diagnostic arena. Its potential has been demonstrated at each level of disease staging and management and supported by a recent FDA approval for companion diagnostic, and the investments being made by pharmaceutical companies in this sector are numerous. The approaches available for ctDNA analysis allow both quantitative and qualitative studies and range from PCR and dPCR-mediated single/multiple gene mutational assessment to whole genome next generation sequencing and methylation mapping. Although the principal object of a liquid biopsy is blood, other body fluids such as urine and saliva show potential as complementary DNA sources for tumor analysis. In this review we provide a synopsis on the state of play of current ctDNA application. We discuss the clinical significance of ctDNA analysis and review the state of the art of technologies being currently developed to this aim. We also discuss the current issues limiting ctDNA application and highlight the promising approaches being developed to overcome these
Technological Advances and Innovations in the Treatment of Chronic Respiratory Disorders
No full textTechnological Advances and Innovations in the Treatment of Chronic Respiratory Disorders focuses on 3D printing, bioprinting, microfluidics, organ-on-a-chip systems, and molecular modeling. The book, written by a team of leading experts in the field, is an essential resource for anyone interested in the future of CRD treatment. Chapters discuss the emerging therapeutic approaches for CRDs, including biologicals and phytoceuticals. Core chapters of the book then cover the application of 3D printing, bioprinting, microfluidics, organ-on-a-chip systems, and molecular modeling to different CRDs. The book concludes with a discussion of the current clinical trials and future prospects for the management of CRDs. This is a valuable resource for researchers, clinicians, and other healthcare professionals who are interested in the latest technological advances in the field of CRDs. It will also be of interest to students and scientists working in the fields of pharmaceutical sciences, microfluidics, bioinformatics, drug design, drug delivery, and 3D printing.</p
Technological Advances and Innovations in the Treatment of Chronic Respiratory Disorders
No full textTechnological Advances and Innovations in the Treatment of Chronic Respiratory Disorders focuses on 3D printing, bioprinting, microfluidics, organ-on-a-chip systems, and molecular modeling. The book, written by a team of leading experts in the field, is an essential resource for anyone interested in the future of CRD treatment. Chapters discuss the emerging therapeutic approaches for CRDs, including biologicals and phytoceuticals. Core chapters of the book then cover the application of 3D printing, bioprinting, microfluidics, organ-on-a-chip systems, and molecular modeling to different CRDs. The book concludes with a discussion of the current clinical trials and future prospects for the management of CRDs. This is a valuable resource for researchers, clinicians, and other healthcare professionals who are interested in the latest technological advances in the field of CRDs. It will also be of interest to students and scientists working in the fields of pharmaceutical sciences, microfluidics, bioinformatics, drug design, drug delivery, and 3D printing.</p
Technological Advances and Innovations in the Treatment of Chronic Respiratory Disorders
No full textTechnological Advances and Innovations in the Treatment of Chronic Respiratory Disorders focuses on 3D printing, bioprinting, microfluidics, organ-on-a-chip systems, and molecular modeling. The book, written by a team of leading experts in the field, is an essential resource for anyone interested in the future of CRD treatment. Chapters discuss the emerging therapeutic approaches for CRDs, including biologicals and phytoceuticals. Core chapters of the book then cover the application of 3D printing, bioprinting, microfluidics, organ-on-a-chip systems, and molecular modeling to different CRDs. The book concludes with a discussion of the current clinical trials and future prospects for the management of CRDs. This is a valuable resource for researchers, clinicians, and other healthcare professionals who are interested in the latest technological advances in the field of CRDs. It will also be of interest to students and scientists working in the fields of pharmaceutical sciences, microfluidics, bioinformatics, drug design, drug delivery, and 3D printing.</p
- …
