Potential of Cubic Mesophases for Medical Applications
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Date
2023
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Doctoral Thesis
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yes
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Abstract
Drug delivery developments plays an important role in advancing medicine, driving innovation, and improving the patient’s quality of life. Among the various drug delivery systems, the cubic mesophase is a very promising platform. Cubic mesophase is a lipid system with unique structures, characterized by their well-ordered three-dimensional units. This system is capable of encapsulating, protecting, and controlling the release of drugs in a targeted manner, thereby optimizing therapeutic results. Furthermore, their potential to improve the solubility, stability, and bioavailability of drugs leads to more efficient treatments. This thesis investigates the versatile application of cubic mesophase in medical field. It aims to demonstrate their potential to innovate the drug delivery scenario and overcome the limitations of conventional treatments, particularly in the context of topical inflammatory diseases and cancer. We increase the complexity of the systems, explore different applications routes, and employ concepts from materials science to improve the efficiency of drugs by designing better delivery systems at the molecular level.
Chapter 1 introduces the importance of investigating drug delivery systems, the potential of the cubic phase, the pathology of inflammation and cancer, and the strategies addressed in this thesis to enhance existing treatments.
Exploring electrostatic attraction as a targeting for drug delivery: In chapter 2, curcumin is encapsulated in cubosomes prepared with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), a cationic lipid. This lipid confers a positive charge to the nanoparticles, increasing their mucoadhesive potential. These cubosomes can interact with the vaginal mucosa by electrostatic force, have antiangiogenic activity, improve the toxicity of curcumin to cervical cancer cells and improve the vaginal bioavailability of curcumin, enhancing topical cervical cancer treatment.
Enhancing the bioadhesion by amyloid fibrils: In chapter 3, we explore the potential of βlactoglobulin amyloid fibrils in increasing the bio-adhesiveness of cubic mesophase. The incorporation of this polymer increases the bio-adhesiveness of the cubic mesophase and enhances the topical anti-inflammatory activity of resveratrol in a croton oil-induced edema ear model.
Targeting treatment by modifying nanoparticles surfaces with antibodies: Finally, in chapter 4 we functionalize panobinostat-loaded cubosomes with trastuzumab, which is an antibody. The system, in addition to improving treatment efficiency, targets HER2-positive breast cancer cells, being able to reduce the side effects of treatment.
These studies highlight that cubic mesophase are an innovative technological platform, capable of improving the efficiency of current treatments and reducing their side effects, thus bringing a better quality of life to patients.
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Examiner : Mezzenga, Raffaele
Examiner : Murgia, Sergio
Examiner : Sagalowicz, Laurent
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ETH Zurich
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03857 - Mezzenga, Raffaele / Mezzenga, Raffaele