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

Enhancing Singlet Oxygen Generation by Self-Assembly of a Porphyrin Entrapped in Supramolecular Fibers

Singlet oxygen (SO) is one of the reactive oxygen species that is effective in various uses, including performing chemical reactions, treating water impurities, and aiding in medicinal therapy. The generation of SO is often efficient in solution, although generation from the solid phase in nanomaterials is less reliable. Here, we report the preparation of hybrid supramolecular materials that incorporate a photosensitizer within their nanostructured fibers and demonstrate their high efficiency in promoting SO formation. The incorporation of tetrakis(4-carboxyphenyl)porphyrin within the nanofibers of a bis-imidazolium gelator was proved by various techniques, including super-resolution radial fluctuations (SRRF) microscopy, which shows the location of the chromophore precisely. SO is generated from the dispersed nanofibers far more efficiently than the dissolved porphyrin; a 14-fold higher rate is observed initially. These results point to an effective approach to the generation of SO for several applications, from optimizing synthetic protocols to photomedicine

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

A New Porphyrin for the Preparation of Functionalized Water-Soluble Gold Nanoparticles with Low Intrinsic Toxicity

A potential new photosensitizer based on a dissymmetric porphyrin derivative bearing a thiol group was synthesized. 5-[4-(11-Mercaptoundecyloxy)-phenyl-10,15,20-triphenylporphyrin (PR-SH) was used to functionalize gold nanoparticles in order to obtain a potential drug delivery system. Water-soluble multifunctional gold nanoparticles GNP-PR/PEG were prepared using the Brust-Schiffrin methodology, by immobilization of both a thiolated polyethylene glycol (PEG) and the porphyrin thiol compound (PR-SH). The nanoparticles were fully characterized by transmission electron microscopy and 1H nuclear magnetic resonance spectroscopy, UV/Vis absorption spectroscopy, and X-ray photoelectron spectroscopy. Furthermore, the ability of GNP-PR/PEGs to induce singlet oxygen production was analyzed to demonstrate the activity of the photosensitizer. Cytotoxicity experiments showed the nanoparticles are nontoxic. Finally, cellular uptake experiments demonstrated that the functionalized gold nanoparticles are internalized. Therefore, this colloid can be considered to be a novel nanosystem that could potentially be suitable as an intracellular drug delivery system of photosensitizers for photodynamic therapy. Keywords: drug delivery, gold nanoparticles, photodynamic therapy, photosensitizers, porphyrin

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

Effect of the viscosity ratio on the PLA/PA10.10 bioblends morphology and mechanical properties

PLA bio-blends with a predominantly biosourced PA10.10 in the composition range 10-50wt.% were prepared by melt blending in order to overcome the advanced brittleness of PLA. Due to the inherent immiscibility of the blends, 30 wt.% of PA was needed to achieve a brittle-to-ductile transition and a co-continuous morphology was predicted at 58 wt.% of PA. The initial enhancement of the PLA rheological behaviour through the environmentally friendly reactive extrusion process yielded a finer and more homogeneous microstructure and hence enhanced the mechanical properties of the bio-blends at much lower PA contents. The brittle-to-ductile transition could be achieved with only 10 wt.% and co-continuity was observed already at 44 wt.% of PA. Results indicate the significant potential of modifying PLA flow behaviour as a promising green manufacturing method toward expanding PLA-based bio-blends applications.Peer ReviewedPostprint (published version

PLA/PA bio-blends: induced morphology by extrusion

The effect of processing conditions on the final morphology of Poly(Lactic Acid) (PLA) with bio-based Polyamide 10.10 (PA) 70/30 blends is analyzed in this paper. Two types of PLA were used: Commercial (neat PLA) and a rheologically modified PLA (PLAREx), with higher melt elasticity produced by reactive extrusion. To evaluate the ability of in situ micro-fibrillation (µf) of PA phase during blend compounding by twin-screw extrusion, two processing parameters were varied: (i) Screw speed rotation (rpm); and (ii) take-up velocity, to induce a hot stretching with different Draw Ratios (DR). The potential ability of PA-µf in both bio-blends was evaluated by the viscosity (p) and elasticity (k’) ratios determined from the rheological tests of pristine polymers. When PLAREx was used, the requirements for PA-µf was fulfilled in the shear rate range observed at the extrusion die. Scanning electron microscopy (SEM) observations revealed that, unlike neat PLA, PLAREx promoted PA-µf without hot stretching and the aspect ratio increased as DR increased. For neat PLA-based blends, PA-µf was promoted during the hot stretching stage. DMTA analysis revealed that the use of PLAREx PLAREx resulted in a better mechanical performance in the rubbery region (T > Tg PLA-phase) due to the PA-µf morphology obtained.Peer ReviewedPostprint (published version

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

Microscale coiling in bis-imidazolium supramolecular hydrogel fibres induced by release of a cationic serine protease inhibitor

Gels formed by a gemini dicationic amphiphile incorporate a serine protease inhibitor, which could be used in a new approach to the treatment of Rosacea, within the fibres as well as in the space between them, affecting a number of gel properties but most importantly inducing remarkable fibre coiling at the microscopic level as a result of drug release from the gel. Drug release and skin permeation experiments show its potential for topical administration