Estudis en la síntesi d'alcaloides indòlics : transfromacions sobre la desetildasicarpidona

Tesi de Llicenciatura per a la obtenció del Grau de Farmàcia. Facultat de Farmàcia. Universitat de Barcelona. Director: Josep Bonjoch i Sesé. 1986

Gemini imidazolium gels enhance the photodynamic performance of porphyrins

Photodynamic therapy (PDT) successful clinical use has led to an emerging interest in the development of improved delivery systems for photosensitizers. Amongst different formulations, gels have the advantage of being easier to apply, providing greater adhesion to the affected region and allowing light penetration. Importantly, we have previously reported that by incorporating porphyrin into a bisimidazolium gelator matrix there is an increased reactive oxygen species (ROS) generation compared to the photosensitizer in solution [1]. Motivated by this, we report further assessment on the photosensitizing capabilities of porphyrins in a gel structure. In this work, we evaluated effect of varying the chemical structures of porphyrins on their photosensitizing capabilities whilst embedded within a supramolecular hydrogel based on gemini imidazolium amphiphiles. The investigated porphyrins presented enhanced singlet oxygen (1O2) within the hydrogel matrix compared to solution and showed negligent release in relevant biological media. Rheological measurements revealed that porphyrin hydrogels presented desirable viscoelastic properties as a functional delivery system for PDT

Electrochemical analysis of gold nanoparticles multifunctionalised withCytochrome c and a zinc Porphyrin

Cytochrome c (Cyt c), known for its functional redox capabilities, plays a pivotal role in biologicalprocesses such as the electron transport chain and apoptosis. However, understanding how differentconjugation strategies impact its structural and redox characteristics is limited. To fill this gap, weinvestigated the effects of conjugating Cyt c and a zinc(II) porphyrin (Zn Porph) to gold nanoparticles(AuNPs). We used circular dichroism (CD) spectroscopy to detect structural conformational changesin Cyt c upon conjugation and time-of-flight secondary ion mass spectrometry (TOF-SIMS) toidentify protein orientation. Cyt c was predicted to have different orientations depending on the sizeof AuNPs and methods used to conjugate the protein, it was hypothesised that the orientation of Cythttps://doi.org/10.26434/chemrxiv-2023-rsrwv ORCID: https://orcid.org/0000-0002-4872-8928 Content not peer-reviewed by ChemRxiv. License: CC BY 4.02c may influence the redox properties of the protein. The electrochemical properties of Cyt c wereassessed using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). We used DPVbasedto determine the heterogeneous rate constant (k0). The results show a lower k0 for conjugatedCyt c than free Cyt c, likely due to structural changes in the protein. The spatial orientation of Cyt chad minimal influence on k0, while ligand density and AuNP size had an effect. The k0 value of ZnPorph did not decrease on conjugation. Despite these changes, Cyt c and Zn Porph maintained theirelectrochemical capabilities after conjugation.</p

Permeation Protection by Waterproofing Mucosal Membranes

The permeability of the oral or nasal mucosa is higher than that of the skin. Mucosa permeabilitydepends mainly on the thickness and keratinization degree of the tissues. Their permeabilitybarrier is conditioned by the presence of certain lipids. This work has the main aim of reinforcing thebarrier effect of oral mucosa with a series of formulations to reduce permeation. Transmembranewater loss of different formulations was evaluated, and three of them were selected to be tested onthe sublingual mucosa permeation of drugs. Caffeine, ibuprofen, dexamethasone, and ivermectinwere applied on porcine skin, mucosa, and modified mucosa in order to compare the effectiveness ofthe formulations. A similar permeation profile was obtained in the different membranes: caffeine> ibuprofen~dexamethasone > ivermectin. The most efficient formulation was a liposomal formulationcomposed of lipids that are present in the skin stratum corneum. Impermeability providedby this formulation was notable mainly for the low-molecular-weight compounds, decreasing theirpermeability coefficient by between 40 and 80%. The reinforcement of the barrier function of mucosaprovides a reduction or prevention of the permeation of different actives, which could be extrapolatedto toxic compounds such as viruses, contaminants, toxins, etc.</p

Cationic supramolecular hydrogels for overcoming the skin barrier in drug delivery

A cationic bis‐imidazolium‐based amphiphile was used to form thermoreversible nanostructured supramolecular hydrogels incorporating neutral and cationic drugs for the topical treatment of rosacea. The concentration of the gelator and the type and concentration of the drug incorporated were found to be factors that strongly influenced the gelling temperature, gel‐formation period, and overall stability and morphology. The incorporation of brimonidine tartrate resulted in the formation of the most homogeneous material of the three drugs explored, whereas the incorporation of betamethasone resulted in a gel with a completely different morphology comprising linked particles. NMR spectroscopy studies proved that these gels kept the drug not only at the interstitial space but also within the fibers. Due to the design of the gelator, drug release was up to 10 times faster and retention of the drug within the skin was up to 20 times more effective than that observed for commercial products. Experiments in vivo demonstrated the rapid efficacy of these gels in reducing erythema, especially in the case of the gel with brimonidine. The lack of coulombic attraction between the gelator-host and the guest-drug seemed particularly important in highly effective release, and the intermolecular interactions operating between them were found to lie at the root of the excellent properties of the materials for topical delivery and treatment of rosacea

Electrochemical preparation and characterization of magnetic core–shell nanowires for biomedical applications

Magnetic CoNi@Au coreshell nanorods have been electrochemically synthesized, characterized and functionalized to test their inherent cytotoxicity in order to assess their potential use for biomedical applications. The initially electrodeposited CoNi nanorods have been covered with a gold layer bymeans of galvanic displacement to minimize the nanowires toxicity and their aggregation, and favour the functionalization. The presence of a gold layer on the nanorod surface slightlymodifies themagnetic behaviour of the asdeposited nanorods, maintaining their softmagnetic behaviour and high magnetization of saturation. The complete covering of the nanorodswith the gold shell favours a good functionalization with a layer of (11Mercaptoundecyl) hexa(ethylene glycol)molecules, in order to create a hydrophilic coating to avoid the aggregation of nanorods, keeping themin suspension and give them stability in biological media. The presence of the organic layer incorporated was detected by means of electrochemical probe experiments. A cytotoxicity test of functionalized coreshell nanorods, carried out with adherent HeLa cells, showed that cell viability was higher than 80% for amounts of nanorods up to 10 μgmL−1. These results make functionalized nanorods promising vehicles for targeted drug delivery inmedicine, which gives a complementary property to the magnetic nanoparticles. © 2015 Elsevier B.V. All rights reserved

Integrating magnetic capabilities to intracellular chips for cell trapping

Current microtechnologies have shown plenty of room inside a living cell for silicon chips. Microchips as barcodes, biochemical sensors, mechanical sensors and even electrical devices have been internalized into living cells without interfering their cell viability. However, these technologies lack from the ability to trap and preconcentrate cells in a specific region, which are prerequisites for cell separation, purification and posterior studies with enhanced sensitivity. Magnetic manipulation of microobjects, which allows a non-contacting method, has become an attractive and promising technique at small scales. Here, we show intracellular Ni-based chips with magnetic capabilities to allow cell enrichment. As a proof of concept of the potential to integrate multiple functionalities on a single device of this technique, we combine coding and magnetic manipulation capabilities in a single device. Devices were found to be internalized by HeLa cells without interfering in their viability. We demonstrated the tagging of a subpopulation of cells and their subsequent magnetic trapping with internalized barcodes subjected to a force up to 2.57 pN (for magnet-cells distance of 4.9 mm). The work opens the venue for future intracellular chips that integrate multiple functionalities with the magnetic manipulation of cells

Wireless Electrical-Molecular Quantum Signalling for Cancer Cell Induced Death

Quantum biological electron tunnelling (QBET) underpins cellular behaviour. Control ofelectrical-molecular communication could revolutionise the development of disruptivetechnologies for understanding and modulating molecular signalling. Current communicationtechnology is not appropriate for interfacing with cells at a spatial/temporal level equivalent tothe native biological signalling. We merge bipolar nano-electrochemical tools with cancercells. Gold-bipolar nanoelectrodes functionalised with electron acceptor-donor-species, weredeveloped as electric field bio-actuators we term bio-nanoantennae. Remote electrical inputregulated electron transport between the acceptor-donor species at the bio-nanoantennae in aselective manner. The wireless modulation of electron transport results in QBET triggeringapoptosis in patient-derived cancer cells representing electrical-molecular communication.Transcriptomics data highlight the electric field targets the cancer cells in a unique manner.The stated insight and invention open a plethora of applications in healthcare. This may leadto new quantum-based medical diagnostics and treatments, as well as understanding of thebiological physics.</p

Wireless electrical–molecular quantum signalling for cancer cell apoptosis

Quantum biological tunnelling for electron transfer is involved incontrolling essential functions for life such as cellular respiration andhomoeostasis. Understanding and controlling the quantum effects inbiology has the potential to modulate biological functions. Here we mergewireless nano-electrochemical tools with cancer cells for control overelectron transfer to trigger cancer cell death. Gold bipolar nanoelectrodesfunctionalized with redox-active cytochrome c and a redox mediatorzinc porphyrin are developed as electric-field-stimulating bio-actuators,termed bio-nanoantennae. We show that a remote electrical input regulateselectron transport between these redox molecules, which results inquantum biological tunnelling for electron transfer to trigger apoptosisin patient-derived cancer cells in a selective manner. Transcriptomicsdata show that the electric-field-induced bio-nanoantenna targets thecancer cells in a unique manner, representing electrically induced controlof molecular signalling. The work shows the potential of quantum-basedmedical diagnostics and treatments.</p