Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica

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Design and synthesis of skeletal analogues of gambierol: Attenuation of amyloid-β and tau pathology with voltagegated potassium channel and N-methyl-D-aspartate receptor implications.
(American Chemical Society, 2012-04-04) Alonso, Eva; Fuwa, Haruhiko; Vale González, María del Carmen; Suga, Yuto; Goto, Tomomi; Konno, Yu; Sasaki, Makoto; LaFerla, Frank M.; Rodríguez Vieytes, Mercedes; Giménez-Llort, Lydia; Botana López, Luis Miguel; Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica; Universidade de Santiago de Compostela. Departamento de Fisioloxía
Gambierol is a potent neurotoxin that belongs to the family of marine polycyclic ether natural products and primarily targets voltage-gated potassium channels (Kv channels) in excitable membranes. Previous work in the chemistry of marine polycyclic ethers has suggested the critical importance of the full length of polycyclic ether skeleton for potent biological activity. Although we have previously investigated structure–activity relationships (SARs) of the peripheral functionalities of gambierol, it remained unclear whether the whole polycyclic ether skeleton is needed for its cellular activity. In this work, we designed and synthesized two truncated skeletal analogues of gambierol comprising the EFGH- and BCDEFGH-rings of the parent compound, both of which surprisingly showed similar potency to gambierol on voltage-gated potassium channels (Kv) inhibition. Moreover, we examined the effect of these compounds in an in vitro model of Alzheimer’s disease (AD) obtained from triple transgenic (3xTg-AD) mice, which expresses amyloid beta (Aβ) accumulation and tau hyperphosphorylation. In vitro preincubation of the cells with the compounds resulted in significant inhibition of K+ currents, a reduction in the extra- and intracellular levels of Aβ, and a decrease in the levels of hyperphosphorylated tau. In addition, pretreatment with these compounds reduced the steady-state level of the N-methyl-d-aspartate (NMDA) receptor subunit 2A without affecting the 2B subunit. The involvement of glutamate receptors was further suggested by the blockage of the effect of gambierol on tau hyperphosphorylation by glutamate receptor antagonists. The present study constitutes the first discovery of skeletally simplified, designed polycyclic ethers with potent cellular activity and demonstrates the utility of gambierol and its synthetic analogues as chemical probes for understanding the function of Kv channels as well as the molecular mechanism of Aβ metabolism modulated by NMDA receptors.
Effect of Gambierol and Its Tetracyclic and Heptacyclic Analogues in Cultured Cerebellar Neurons: A Structure−Activity Relationships Study
(American Chemical Society, 2012-08-15) Pérez, Sheila; Vale González, María del Carmen; Alonso, Eva; Fuwa, Haruhiko; Sasaki, Makoto; Konno, Yu; Goto, Tomomi; Suga, Yuto; Rodríguez Vieytes, Mercedes; Botana López, Luis Miguel; Universidade de Santiago de Compostela. Departamento de Farmacoloxía; Universidade de Santiago de Compostela. Departamento de Fisioloxía
The polycyclic ether class of marine natural products has attracted the attention of researchers due to their complex and large chemical structures and diverse biological activities. Gambierol is a marine polycyclic ether toxin, first isolated along with ciguatoxin congeners from the dinoflagellate Gambierdiscus toxicus. The parent compound gambierol and the analogues evaluated in this work share the main crucial elements for biological activity, previously described to be the C28═C29 double bond within the H ring and the unsaturated side chain [Fuwa, H., Kainuma, N., Tachibana, K., Tsukano, C., Satake, M., and Sasaki, M. (2004) Diverted total synthesis and biological evaluation of gambierol analogues: Elucidation of crucial structural elements for potent toxicity. Chem. Eur. J.10, 4894−4909]. With the aim to gain a deeper understanding of the cellular mechanisms involved in the biological activity of these compounds, we compared its activity in primary cultured neurons. The three compounds inhibited voltage-gated potassium channels (Kv) in a concentration-dependent manner and with similar potency, caused a small inhibition of voltage-gated sodium channels (Nav), and evoked cytosolic calcium oscillations. Moreover, the three compounds elicited a “loss of function” effect on Kv channels at concentrations of 0.1 nM. Additionally, both the tetracyclic and the heptacyclic derivatives of gambierol elicited synchronous calcium oscillations similar to those previously described for gambierol in cultured cerebellar neurons. Neither gambierol nor its tetracyclic derivative elicited cell toxicity, while the heptacyclic analogue caused a time-dependent decrease in cell viability. Neither the tetracyclic nor the heptacyclic analogues of gambierol exhibited lethality in mice after ip injection of 50 or 80 μg/kg of each compound. Altogether, the results presented in this work support an identical mechanism of action for gambierol and its tetracyclic and heptacyclic analogues and indicate a “loss of function” effect on potassium channels even after administration of the three compounds at subnanomolar concentrations. In addition, because gambierol is known to stabilize the closed state of Kv3 channels, the results presented in this paper may have implications for understanding of channel functions and for future development of therapies against ciguatera poisoning and potassium channel-related diseases.
Differential Effects of Crambescins and Crambescidin 816 in Voltage-Gated Sodium, Potassium and Calcium Channels in Neurons
(American Chemical Society, 2012-12-27) Martín, Víctor; Vale González, María del Carmen; Bondu, Stéphanie; Thomas, Olivier P.; Rodríguez Vieytes, Mercedes; Botana López, Luis Miguel; Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica; Universidade de Santiago de Compostela. Departamento de Fisioloxía
Crambescins and crambescidins are two families of guanidine alkaloids from the marine sponge Crambe crambe. Although very little information about their biological effect has been reported, it is known that crambescidin 816 (Cramb816) blocks calcium channels in a neuroblastoma X glioma cell line. Taking this into account, and the fact that ion channels are frequent targets for natural toxins, we examined the effect of Cramb816 and three compounds from the crambescin family, norcrambescin A2 (NcrambA2), crambescin A2 (CrambA2), and crambescin C1 (CrambC1), in the main voltage-dependent ion channels in neurons: sodium, potassium, and calcium channels. Electrophysiological recordings of voltage gated sodium, potassium, and calcium currents, in the presence of these guanidine alkaloids, were performed in cortical neurons from embryonic mice. Different effects were discovered: crambescins inhibited K(+) currents with the following potency: NcrambA2 > CrambC1 > CrambA2, while Cramb816 lacked an effect. Only CrambC1 and Cramb816 partially blocked Na(+) total current. However, Cramb816 partially blocked Ca(2+) , while NcrambA2 did not. Since the blocking effect of Cramb816 on calcium currents has not been previously reported in detail, we further pharmacologically isolated the two main fractions of HVA Ca(2+) channels in neurons and investigated the Cramb816 effect on them. Here, we revealed that Cav1 or L-type calcium channels are the main target for Cramb816. These two families of guanidine alkaloids clearly showed a structure-activity relationship with the crambescins acting on voltage-gated potassium channels, while Cramb816 blocks the voltage-gated calcium channel Cav1 with higher potency than nifedipine. The novel evidence that Cramb816 partially blocked CaV and NaV channels in neurons suggests that this compound might be involved in decreasing the neurotransmitter release and synaptic transmission in the central nervous system. The findings presented here provide the first detailed approach on the different effects of crambescin and crambescidin compounds in voltage-gated sodium, potassium, and calcium channels in neurons and thus provide a basis for future studies.
Differential effects of ciguatoxin and maitotoxin in primary cultures of cortical neurons
(American Chemical Society, 2014-07-07) Martín, Víctor; Vale González, María del Carmen; Antelo, Álvaro; Hirama, Masahiro; Yamashita, Shuji; Rodríguez Vieytes, Mercedes; Botana López, Luis Miguel; Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica; Universidade de Santiago de Compostela. Departamento de Fisioloxía
Ciguatoxins (CTXs) and maitotoxins (MTXs) are polyether ladder shaped toxins derived from the dinoflagellate Gambierdiscus toxicus. Despite the fact that MTXs are 3 times larger than CTXs, part of the structure of MTXs resembles that of CTXs. To date, the synthetic ciguatoxin, CTX 3C has been reported to activate voltage-gated sodium channels, whereas the main effect of MTX is inducing calcium influx into the cell leading to cell death. However, there is a lack of information regarding the effects of these toxins in a common cellular model. Here, in order to have an overview of the main effects of these toxins in mice cortical neurons, we examined the effects of MTX and the synthetic ciguatoxin CTX 3C on the main voltage dependent ion channels in neurons, sodium, potassium, and calcium channels as well as on membrane potential, cytosolic calcium concentration ([Ca(2+)]c), intracellular pH (pHi), and neuronal viability. Regarding voltage-gated ion channels, neither CTX 3C nor MTX affected voltage-gated calcium or potassium channels, but while CTX 3C had a large effect on voltage-gated sodium channels (VGSC) by shifting the activation and inactivation curves to more hyperpolarized potentials and decreasing peak sodium channel amplitude, MTX, at 5 nM, had no effect on VGSC activation and inactivation but decreased peak sodium current amplitude. Other major differences between both toxins were the massive calcium influx and intracellular acidification produced by MTX but not by CTX 3C. Indeed, the novel finding that MTX produces acidosis supports a pathway recently described in which MTX produces calcium influx via the sodium-hydrogen exchanger (NHX). For the first time, we found that VGSC blockers partially blocked the MTX-induced calcium influx, intracellular acidification, and protected against the short-term MTX-induced cytotoxicity. The results presented here provide the first report that shows the comparative effects of two prototypical ciguatera toxins, CTX 3C and MTX, in a neuronal model. We hypothesize that the analogies and differences in the bioactivity of these two toxins, produced by the same microorganism, may be strongly linked to their chemical structure.
Determination of toxicity equivalent factors for paralytic shellfish toxins by electrophysiological measurements in cultured neurons
(American Chemical Society, 2011-07-18) Pérez, Sheila; Vale González, María del Carmen; Botana López, Ana María; Alonso, Eva; Rodríguez Vieytes, Mercedes; Botana López, Luis Miguel; Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica; Universidade de Santiago de Compostela. Departamento de Química Analítica, Nutrición e Bromatoloxía; Universidade de Santiago de Compostela. Departamento de Fisioloxía
The establishment of toxicity equivalent factors to develop alternative methods to animal bioassays for marine-toxin detection is an urgent need in the field of phycotoxin research. Paralytic shellfish poisoning (PSP) is one of the most severe forms of food poisoning. The toxins responsible for this type of poisoning are highly toxic natural compounds produced by dinoflagellates, which bind to voltage-gated Na+ channels causing the blockade of action potential propagation. In spite of the fact that several standards of PSP toxins are currently commercially available, there is scarcity of data on the biological activity of these toxins, a fact that limits the calculation of their toxicity equivalent factors. We have evaluated the potency of the commercial PSP toxin standards for their ability to inhibit voltage-dependent sodium currents in cultured neuronal cells by electrophysiological measurements. The in vitro potencies of the PSP toxin standards as indicated by their IC50 values were in the order Neosaxitoxin (NeoSTX) > decarbamoylsaxitoxin (dcSTX) > saxitoxin (STX) > gonyautoxin 1,4 (GTX1,4) > decarbamoylneosaxitoxin (dcNeoSTX) > gonyautoxin 2,3 (GTX2,3) > decarbamoylgonyautoxin 2,3 (dcGTX2,3) > gonyautoxin 5 (GTX5) > N-sulfocarbamoyl-gonyautoxin-2 and -3 (C1,2). The data obtained in this in vitro analysis correlated well with their previously reported toxicity values.
Oxygen-generating and antibacterial xanthan gum/PLA aerogels loaded with dexamethasone for potential wound healing
(Elsevier, 2025-04-19) Hozjan, Nika Atelšek; Horvat, Gabrijela; Finšgar, MMatjaž; Iglesias-Mejuto, Ana; Ardao Palacios, Inés; García González, Carlos A.; Knez, Zeljko A.; Novak, Zoran; Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica; Universidade de Santiago de Compostela. Instituto de Materiais (iMATUS)
Chronic wounds do not heal within a reasonable time frame due to hypoxia and bacterial inflammation, creating an urgent need for advanced biomaterials to address these challenges. In this study, oxygen-generating, antibacterial xanthan gum-polylactic acid (XA/PLA) aerogels loaded with dexamethasone were developed for the first time for potential wound healing applications. The aerogels contained sodium percarbonate and calcium peroxide as oxygen-releasing agents, providing sustained oxygen release for up to 48 h. The aerogels had a highly porous structure with a high specific surface area (up to 396 ± 8 m2/g) and revealed high liquid absorption capacity in simulated body fluid, absorbing up to 67 times their original weight and remaining stable for 72 h. The in vitro release tests showed controlled profiles of dexamethasone over 24 h. The antibacterial tests demonstrated strong antibacterial activity against Escherichia coli (an up to 15.92 mm inhibition zone diameter) and Staphylococcus aureus (up to a 31.07 mm inhibition zone diameter). The in vitro biocompatibility assays revealed good cytocompatibility with mouse fibroblast cells (NIH/3T3), with a cell viability of >90%. Hemocompatibility tests showed no hemolytic activity with human blood (lysis rate <2%). Overall, these results emphasise the versatility of the XA/PLA aerogels and their potential for the treatment of chronic wounds.
Disulfiram-loaded electrospun fibers with antimicrobial and antitumoral properties for glioblastoma treatment
(Elsevier, 2025-03-12) González Prada, Iago; Barcelos Ribeiro, Arthur; Dion, Marine; Magariños Ferro, Beatriz; Lapoujade, Clémentine; Rousseau, Audrey; Concheiro Nine, Ángel Joaquín; Garcion, Emmanuel; Álvarez Lorenzo, Carmen; Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica; Universidade de Santiago de Compostela. Departamento de Microbioloxía e Parasitoloxía; Universidade de Santiago de Compostela. Instituto de Materiais (iMATUS)
Glioblastoma (GB) is a malignant brain tumor with low survival rates and a high recurrence ratio due to limited therapeutic arsenal. The repurposed drug disulfiram (DSF), approved for alcoholism treatment, shows promising anticancer and antimicrobial activity, but its poor biopharmaceutical profile hinders its clinical use. This work aimed to develop DSF-loaded silk fibroin (SF) electrospun fibers for controlled release in the postsurgical resection cavity. Incorporating hydroxypropyl-β-cyclodextrin (HPβCD), which formed inclusion complexes with DSF, enhanced drug release rate and antimicrobial activity (>3 logCFUs reduction) against Staphylococcus aureus and Pseudomonas aeruginosa. Addition of CuCl2 enabled in situ formation of Cu(DDC)2 complexes, further boosting antimicrobial and in vitro antitumoral effects of the nanofibers (≤ 500 nm) while maintaining adequate mechanical properties. Selective toxicity of DSF and DSF-loaded fibers against glioblastoma cells, while sparing against astrocytes, highlights the potential of the nanofibers for targeted brain cancer therapy. Increased potency of DSF at low concentrations when combined with SF fibers, HPβCD and copper was remarkable. Thus, DSF delivery and bioavailability can be significantly optimized through electrospun nanofibers, which may also allow for more precise dosing. Combination with radiotherapy was also explored to assess the translational potential of DSF as part of a combination therapy regimen for glioblastoma. In vivo studies in a rat model simulating GB surgery confirmed the safety of selected formulations in healthy brain tissue. However, findings suggest that DSF-loaded fibers alone may be insufficient for complete tumor eradication, indicating the need for combination with existing therapies to target residual tumor cells effectively.
Hyaluronic acid-g-poly(lactic acid) and poly(vinyl alcohol) inks for 3D printed berberine loaded foldable dressings
(Elsevier, 2025-12) Virzì, Nicola Filippo; Álvarez Lorenzo, Carmen; Concheiro Nine, Ángel Joaquín; Casagranda, Veronica; Pittalà, Valeria; Díaz Rodríguez, Patricia; Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica
Antimicrobial resistance (AMR) has increased the urgency for novel wound care strategies. Semi Solid Extrusion (SSE)-3D printing technology holds significant promise in this area, allowing for the creation of personalized and customizable wound dressings. This study focused on developing a foldable and flexible dressing capable of incorporating and releasing non-antibiotic antimicrobial compounds, such as berberine (Ber). To this end, a hyaluronic acid (HA)-g-poly(lactic acid) (PLA)-based polymer (DAC®) was combined with poly(vinyl alcohol) (PVA) to enhance the mechanical properties and foldability of 3D-printed dressings. On the other hand, propylene glycol (PG) was incorporated to facilitate the integration of non-water soluble natural antimicrobial compounds like berberine (Ber). The rheological profile of DAC/PVA/PG blends was optimized for 3D printing, resulting in printing-compatible inks. After freeze-drying, a sterilization/crosslinking process through autoclave allowed to reduce dressings swelling (∼98 % less in simulated wound fluid and ∼ 99 % less in water), suitable to preserve their foldability without losing structural shape, while improving mechanical properties (from 1.74 MPa to 2.85 MPa tensile strength). The antimicrobial efficacy of Ber-loaded dressings against Staphylococcus aureus was demonstrated by microcalorimetry, although the incorporation of Ber did not significantly enhance antibiofilm activity when compared to blank dressings. In vitro cytotoxicity tests confirmed that over 70 % of human dermal fibroblasts remained viable after 24 h of exposure to the Ber-loaded dressings. This work suggests the chosen polymer combination is promising to produce flexible and foldable dressings that can be adapted to anatomically complex wounds. The loading of natural antimicrobial agents, such as Ber, holds potential for addressing infected wounds as an alternative to traditional treatments in the face of AMR.
Multi-Responsive Nanogels Based on Sulfoxide Polymethacrylates for Biomedical Applications
(Wiley, 2025-02-10) Stauber, Hannah Elodie; López Iglesias, Clara; Kanwal, Sidra; Quaas, Elisa; Klinger, Daniel; Universidade de Santiago de Compostela. Instituto de Materiais (iMATUS); Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica
Nanogels for biomedical applications require polymeric building blocks that show high hydrophilicity and (thermo-)responsive properties without immune response risks. Polysulfoxides offer these advantages but have not yet been translated to 3-dimensional colloidal materials. To examine their potential as alternatives to established systems, we developed a synthetic platform with synthetic control and chemical versatility. For this, we utilize the thermo-responsive properties of a polymethacrylate with propyl sulfoxide side groups, that is, poly(2-(n-propyl-sulfoxide)ethyl methacrylate) (P(nPr-SEMA)). Its phase transition near body temperature enables nanogel preparation via conventional precipitation polymerization in an all-aqueous system. To fully assess this approach's potential, we first demonstrate control over colloidal properties like size, size distribution, and crosslinking density. We examine the influence of these parameters on the temperature-dependent swelling profiles and develop a standard synthetic protocol. Second, we examine synthetic versatility to introduce additional stimuli-responsiveness. For this, we introduce methacrylic acid (MAA) as pH-responsive co-monomer and examine resulting double-sensitive swelling. Third, we add network degradability through reduction-cleavable crosslinker bis(2-methacryloyloxyethyl) disulfide (DSDMA). Fourth, we demonstrate that multi-responsive nanogels exhibit low cytotoxicity and high colloidal stability in biologically relevant media. Overall, this systematic study establishes P(nPr-SEMA)-based nanogels as versatile alternatives to established temperature-responsive nanogels for biomedical applications, for example, drug delivery.
Structural Screening of Short Peptide Amphiphiles with Autocatalytic Self-Replication
(Wiley, 2025-01-09) Turcan, Ion; Insua López, Ignacio; Universidade de Santiago de Compostela. Centro de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS)
There is great interest in developing small synthetic molecules that imitate some of the functions and behaviour of living beings. Here, we describe the structural screening of peptide amphiphiles with autocatalytic self-replication, which mimics the perpetuation mechanisms of living matter. Our design uses two reactive precursors to generate self-assembling peptide amphiphiles, which form micelles that catalyse their own synthesis. A collection of precursors with varying sizes was screened combinatorially, revealing a minimal tripeptide amphiphile required to trigger autocatalytic self-replication. These results contribute to the structural simplification of synthetic supramolecular monomers with life-like behaviour.
Biomimetic core-shell breast cancer models using alginate, gelatin, and collagen I: simulating the tumor matrix for drug evaluation
(Elsevier, 2026-01) Gato Díaz, Uxía; Castro Alves, Lisandra de; Concheiro Nine, Ángel Joaquín; Piñeiro Redondo, Yolanda; Álvarez Lorenzo, Carmen; Blanco Fernández, Bárbara; Rivas Rey, José; Universidade de Santiago de Compostela. Instituto de Materiais (iMATUS); Universidade de Santiago de Compostela. Departamento de Física Aplicada; Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica
Breast cancer remains among the most prevalent cancers in women worldwide. During tumor development, the extracellular matrix is altered to support tumor progression and therapy resistance. Therefore, there is a need to develop breast cancer models that replicate the complex tumor extracellular matrix to accurately mimic the mechanisms by which it influences drug resistance and cancer cell malignancy. In this study, we fabricated an innovative breast cancer 3D in vitro model consisting of core-shell hydrogel beads from alginate, gelatin, and collagen I by extrusion through a coaxial needle. Breast cancer cells proliferated in the core of all prototypes designed, forming spheroids and cell aggregates with a high resistance to doxorubicin. The addition of Collagen I to the developed model enabled the upregulation of malignancy markers (Col1A1, Ki67, FOXC2, SNAI1, NFKB1, WWTR1), invasion markers (WASL, ACTA1, MYO1E, TPM4, PODXL, ITGA2, ITGA5, MENA, EGFR, CDC42), and drug resistance markers (ABCG2, CYP1A1, BAX, HSP90AA1) occurring in vivo. The developed 3D in vitro model can clarify the contribution of the extracellular matrix to the tumor outcome and drug efficacy by replicating some key characteristics of breast tumors, establishing a novel tool for chemotherapeutic agents and drug screening.
Innovative Processing and Sterilization Techniques to Unlock the Potential of Silk Sericin for Biomedical Applications
(MDPI, 2025-02-01) Veiga, Anabela; Ramírez-Jiménez, Rosa Ana; Santos Rosales, Víctor; García González, Carlos A.; Aguilar, Maria Rosa; Rojo, Luis; Oliveira, Ana L.; Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica
Silk sericin (SS), a by-product of the textile industry, has gained significant attention for its biomedical potential due to its biocompatibility and regenerative potential. However, the literature lacks information on SS processing methods and the resulting physicochemical properties. This study represents the first step in protocol optimization and standardization. In the present work, different processing techniques were studied and compared on SS extracted from boiling water: evaporation, rotary evaporation, lyophilization, and dialysis, which presented a recovery yield of approximately 27–32%. The goal was to find the most promising process to concentrate extracted SS solutions, and to ensure that the SS structure was highly preserved. As a result, a new cryo-lyophilization methodology was proposed. The proposed method allows for the preservation of the amorphous structure, which offers significant advantages including complete dissolution in water and PBS, an increase in storage stability, and the possibility of scaling-up, making it highly suitable for industrial and biomedical applications. The second part of the work focused on addressing another challenge in SS processing: efficient and non-destructive sterilization. Supercritical CO2 (scCO2) has been gaining momentum in the last years for sterilizing sensitive biopolymers and biological materials due to its non-toxicity and mild processing conditions. Thus, scCO2 technology was validated as a mild technique for the terminal sterilization of SS. In this way, it was possible to engineer a sequential cryo-lyophilization/scCO2 sterilization process which was able to preserve the original properties of this natural silk protein. Overall, we have valorized SS into a sterile, off-the-shelf, bioactive, and water-soluble material, with the potential to be used in the biomedical, pharmaceutical, or cosmetic industries.
Nanoassemblies for oral protein delivery — The case of monoclonals for inflammatory bowel disease
(Elsevier, 2026-01-10) López Estévez, Ana María; González Portela, María; Piñeiro Alonso, Laura; Gómez Lado, Noemí; Fraga Codesido, Jessica; García Otero, Xurxo; Aguiar Fernández, Pablo; Alonso Fernández, María José; Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS); Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina
Biological drugs such as monoclonal antibodies (mAbs) or peptides are the preferred therapeutic approach for the treatment of chronic diseases such as inflammatory bowel disease (IBD) or diabetes. Unfortunately, the necessity of their parenteral administration and poor access to their targets have limited their full exploitation. Nanotechnology has been explored for the oral administration of biologicals, however, the nanocarriers reported so far have shown limited translational value. The objective of this work has been to design a new nanocarrier for the oral administration of therapeutic proteins with a translational potential. We chose as cargos, insulin and two clinically relevant mAbs, Bevacizumab (BVZ, anti-VEGF-A mAb) and Adalimumab (anti-Tumor Necrosis Factor (TNF) mAb). These macromolecules were assembled with amphiphilic biodegradable polymers, either positively charged (based on octaarginine-lauric r8C12) or negatively charged (polyglutamic acid derivatized with myristic acid, PGAC14) with the intention to assess their potential to facilitate the targeted delivery of the selected proteins. After a screening of a library of compositions, nanoformulations named as nanoassemblies (NAs) exhibiting singular features were selected, namely (i) a ultra-small and unimodal size of 50 nm and negative to neutral surface charge, (ii) a high drug loading capacity (>10 %, w/w), (iii) the ability to protect the cargo in simulated GI fluids, and (iv) the capacity to interact with the intestinal epithelium. In vivo PET/MRI biodistribution profile indicates that NAs consisting of BVZ-r8C12 are significantly retained in the colon as compared to free BVZ. The biodistribution analysis in a rat colitis model revealed that the inflamed conditions enhanced significantly the retention pattern of the NAs. On the other hand, a specific prototype containing anti-TNF (PEGylated NAs of anti-TNF mAb and PGAC14) were able to reduce the production of pro-inflammatory cytokines and decrease the colonic inflammation. Briefly, we present a new oral protein delivery platform and show the potential of specific prototypes for treating local inflammation in intestinal tissues. We also realize that to assess their potential further we need to fully understand their mechanism of action.
Engineering of green sterilization technology to obtain biocompatible aerogels: Supercritical CO2 versus ethylene oxide and gamma radiation
(Elsevier, 2026-01-02) Carracedo Pérez, María; Boccia, Antonella Caterina; Ardao Palacios, Inés; Passos, Cláudia Pereira; Santos Rosales, Víctor; Santos Torres, Beatriz; Bernardo, Fábio Gabriel Pereira; Blanco Vales, María; Magariños Ferro, Beatriz; García González, Carlos A.; Universidade de Santiago de Compostela. Departamento de Microbioloxía e Parasitoloxía; Universidade de Santiago de Compostela. Instituto de Materiais (iMATUS); Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS); Universidade de Santiago de Compostela. Instituto de Investigación do Medio Acuático para Unha Saúde Global (iARCUS)
The growing relevance of aerogels in biomedicine demands the choice of compatible sterilization techniques with these materials. Conventional methods, such as ethylene oxide (EO) and gamma radiation (γ-rays) sterilization, have significant drawbacks while facing important environmental restrictions. In this study, supercritical CO2 (scCO2) sterilization is tested for polysaccharide (starch and alginate) aerogels as an eco-friendly alternative to conventional procedures. Three post-processing treatments under different CO2 exposure regimes (static, dynamic and combined) and in the presence of H2O2 as additive were developed and assessed to reach sterility assurance levels (SAL) below 10−6. After sterilization, a vacuum treatment was implemented to ensure a low residual presence of H2O2 in the aerogels so that the material biocompatibility was not compromised according to in vitro cell tests with fibroblasts. The residual adsorbed H2O2 was quantified for the first time in aerogels by nuclear magnetic resonance spectroscopy. The effects of the supercritical sterilization treatments on the textural and chemical properties of the aerogels were evaluated and compared to those treated with EO and γ-rays. Results highlight the unique efficiency of scCO2 sterilization as a post-processing method that preserves the aerogel structure while offering an eco-sustainable potential for producing sterile and biocompatible materials.
Surface-modified iron oxide nanoprobes in biomedical scaffolds
(Royal Society of Chemistry, 2025-11-17) González Gómez, Manuel Antonio; Arnosa Prieto, Ángela; García Acevedo, Pelayo; Díaz Rodríguez, Patricia; Castro Alves, Lisandra de; Piñeiro Redondo, Yolanda; Rivas Rey, José; Universidade de Santiago de Compostela. Instituto de Materiais (iMATUS); Universidade de Santiago de Compostela. Departamento de Física Aplicada
Magnetic (PU) scaffolds incorporating superparamagnetic iron oxide nanoparticles (SPIONs) offer a promising platform for localized cancer therapy. By enhancing the functional performance of these scaffolds through surface modification of iron oxide nanoprobes, their biomedical utility—particularly in targeted therapeutic applications—can be significantly improved. In this study, we report the synthesis and characterization of magnetite nanoparticles (Fe3O4 NPs) functionalized with biocompatible coatings—citrate, polyethylene glycol (PEG), oleic acid (OA), and aluminum hydroxide (Al(OH)3)—and their integration into porous PU scaffolds via a salt-leaching/phase-inversion method. Among all tested formulations, SPIONs@Al(OH) demonstrated superior colloidal stability, magnetic responsiveness, and cytocompatibility. When embedded in PU scaffolds, these magnetic nanocomposites exhibited optimal mesoporosity, homogeneous nanoparticle distribution, and efficient magnetic hyperthermia performance under clinically relevant alternating magnetic fields. This work highlights the synergistic potential of material design and surface engineering in developing next-generation implantable platforms for targeted oncological treatment.
Emergent properties of supramolecular peptide assemblies
(Royal Society of Chemistry, 2026) Vila García, Álvaro; González Domínguez, Sela; Insua López, Ignacio; Universidade de Santiago de Compostela. Centro de Investigación en Química Biolóxica e Materiais Moleculares (CiQUS)
The self-assembly of supramolecular monomers can change their chemical properties and produce emergent functions that are absent in their dispersed state. In this review article, we describe structural and functional material properties emerging from the self-assembly of peptides, which are based on interactions between neighbouring monomers and the supramolecular environments they create. The non-covalent cooperativity of peptides is here discussed in terms of emergent properties like catalysis, chiral amplification, hierarchical self-assembly and life-like function. These collective effects are rationalised by the monomer packing structure and reactive group proximity, providing a perspective of self-assembling peptide designs and supramolecular material applications, including our own contribution to this topic.
Engineering aerogel particles as next-generation drug delivery systems: a comprehensive review of recent advances
(Elsevier, 2026) Gomes, Susana M.; Illanes Bordomás, Carlos; García González, Carlos A.; Akgün, Işık Sen; Universidade de Santiago de Compostela. Instituto de Materiais (iMATUS); Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica
Aerogels, defined as low-density solid materials with high porosities, open pore structures, and high specific surface areas, have shown increasing interest among the scientific and industrial communities. The engineering of aerogels in the form of spherical particles has been well documented for several applications and recent studies have highlighted the promising potential of use them as drug delivery systems. Therefore, this review article consolidates the recent progress on aerogel particle technology by providing a comprehensive and focused synthesis of the state-of-the-art of aerogel particle design specifically intended to enhance biocompatibility, stability, and targeted drug delivery. The engineering technologies herein presented, based on droplets production and on the milling technology, are critically discussed, highlighting critical aspects used to control their features. Moreover, surface modification and coating techniques are critically examined as tools to enhance biocompatibility, colloidal stability, and targeted delivery. Then, key results in the diverse biomedical applications, namely for oral, skin and pulmonary drug delivery, were discussed. In oral delivery, their capacity to improve drug loading and enable sustained release is emphasized. In skin delivery, aerogels show potential to enhance dermal permeation and provide a sustained release. For pulmonary administration, their low density and aerodynamic properties make them ideal for deep lung deposition. By bridging particle engineering with therapeutic functionality, this review highlights the unique features and advantages of aerogel particles to become the next-generation aerogel-based therapeutic systems. Finally, the current challenges to be addressed and future trends are identified.
Nail tattooing: a novel and minimally invasive technique for enhancing drug penetration through the nail
(Springer, 2026-03-26) Seoane Viaño, Iria; Bendicho Lavilla, Carlos; Díaz Tomé, Victoria; Seoane Viaño, Iria; Monte Vidal, Vinicius de; Otero Espinar, Francisco Javier; Universidade de Santiago de Compostela. Instituto de Materiais (iMATUS)
Onychomycosis, a prevalent fungal infection, and psoriasis, a chronic immune disorder affecting the nail plate, present therapeutic challenges due to the limited efficacy of current treatments, often leading to prolonged therapy and a high relapse rate. The highly cross-linked keratin network of the nail plate acts as a barrier, impeding effective drug delivery. This pioneering study explores a novel approach using a tattoo device to enhance drug penetration through the nail. Ciclopirox olamine and clobetasol lacquers were selected as the model formulations. Drug permeation tests conducted on non-treated, filed (mechanically abraded), and tattooed nails demonstrated significantly higher drug permeation in tattooed nails, suggesting the potential of this delivery method. Nail tattooing offers a simple method to enhance topical therapy, allowing treatment initiation in the clinic and continuation at home.
Nanoemulsion-based colistin for pulmonary delivery: Enhanced antibacterial efficacy against Acinetobacter baumannii
(Springer, 2026-03-30) Martínez Guitián, Marta; Sanjurjo Bouza, Lucía; Vázquez Ucha, Juan Carlos; Muras Mora, Andrea; Beceiro Casas, Alejandro; Crecente Campo, José; Alonso Fernández, María José; Universidade de Santiago de Compostela. Centro de Investigación en Medicina Molecular e Enfermidades Crónicas (CiMUS)
Infections caused by Acinetobacter baumannii, which frequently result in pneumonia and/or bacteraemia, represent a significant clinical challenge. Colistin, an antimicrobial peptide used as a last-resort therapy due to its high toxicity, is employed to treat severe infections, i.e. those caused by A. baumannii. The aim of this study was to develop a colistin-loaded nanoformulation (COL-NE) capable of targeting infected cells in the lung, thereby enhancing antibacterial efficacy while reducing toxicity. After screening multiple formulations, an optimized colistin nanoemulsion (COL-NE) was developed, exhibiting a particle size of 180 nm and a 1–4-fold reduction in MIC against A. baumannii compared to free colistin. The nanoemulsion also displayed significant antibiofilm activity, enhanced cellular penetration, and a 27–45% reduction in in vitro toxicity relative to colistin. Notably, following intratracheal administration, COL-NE improved the elimination of intracellular bacteria in macrophages through passive targeting while maintaining activity against extracellular bacteria. In a murine pneumonia model, COL-NE reduced lung bacterial burden by 2 log₁₀ CFU/mL compared with untreated controls and by 1.25 log₁₀ CFU/mL relative to colistin-treated mice. These findings highlight the potential of colistin-loaded nanoemulsions as a promising therapeutic strategy against A. baumannii infections, enhancing antibacterial efficacy while mitigating colistin-associated toxicity.
Marine toxins and the cytoskeleton: okadaic acid and dinophysistoxins
(Wiley, 2008-09-25) Vale González, María del Carmen; Botana López, Luis Miguel; Universidade de Santiago de Compostela. Departamento de Farmacoloxía
Okadaic acid (OA) and its analogs, the dinophysistoxins, are potent inhibitors of protein phosphatases 1 and 2A. This action is well known to cause diarrhea and gastrointestinal symptons when the toxins reach the digestive tract by ingestion of mollusks. A less well-known effect of these group of toxins is their effect in the cytoskeleton. OA has been shown to stimulate cell motility, loss of stabilization of focal adhesions and a consequent loss of cytoskeletal organization due to an alteration in the tyrosine-phosphorylated state of the focal adhesion kinases and paxillin. OA causes cell rounding and loss of barrier properties through mechanisms that probably involve disruption of filamentous actin (F-actin) and/or hyperphosphorylation and activation of kinases that stimulate tight junction disassembly. Neither methyl okadaate (a weak phosphatase inhibitor) nor OA modify the total amount of F-actin, but both toxins cause similar changes in the F-actin cytoskeleton, with strong retraction and rounding, and in many cases cell detachment. OA and dinophysistoxin-1 (35S-methylokadaic acid) cause rapid changes in the structural organization of intermediate filaments, followed by a loss of microtubules, solubilization of intermediate filament proteins, and disruption of desmosomes. The detailed pathways that coordinate all these effects are not yet known.

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