Publications

Abstract Soft nanomaterials can form stimuli-responsive self-assembled structures with significant potential for pharmaceutical and biomedical applications. Polymer/surfactant (P/S) solutions and hydrogels, in particular, have drawn great interest for the development of effective delivery systems, yet molecular insight into these systems and their mechanisms of action is still needed. Here, we examine the colloidal properties of mixtures comprising the amino acid-derived surfactant 14Lys10 and the amphiphilic triblock copolymers Pluronic F127 and P84, which have distinct hydrophobic/hydrophilic balances. We hypothesized that the two F127/14Lys10 and P84/ 14Lys10 systems would show strong, complex associative behavior and this was indeed observed. Combined data from light and electron microscopy, differential scanning microcalorimetry, rheology and surface tension provide a comprehensive picture. At room temperature, the bio-inspired surfactant forms a gel network of entangled nano and micro-tubes that transitions into vesicles at 33 degrees C. The polymers form micelles upon heating. When mixed, the polymer significantly decreases the strength of the tube network and lowers the tube-to-vesicle transition temperature, with the effect strongly dependent on polymer concentration and hydrophobic/hydrophilic balance. Upon tube disassembly, evidence indicates the formation of mixed vesicles coexisting with mixed micelles. Molecular-level insights into the interactions and self-assembly phenomena are provided. This study opens avenues for rationally designing hybrid soft materials as advanced functional biomaterials in nano-medicine and pharmaceutics.

Abstract Polymeric hydrogels are traditionally employed as drug reservoirs in topical delivery, but they can also function as scaffolds for drug-loaded nanocarriers, enabling hybrid systems with enhanced performance. In this work, we report a thermo-adaptive hybrid hydrogel-composed of a block copolymer scaffold and a network of surfactant-based nano- and microtubes-which exhibits a mechanism herein termed inversely coupled thermogelation (ICT). The scaffold consists of Pluronic F127, a biocompatible triblock copolymer that transitions from micellar solution to a cubic liquid crystalline gel upon heating. The tubular network arises from the self-assembly of biomimetic lysine-derived surfactants. Crucially, when the block copolymer/surfactant hybrid is heated from 20 degrees C to 35 degrees C (approx. skin temperature), the surfactant tubes disassemble into micelles or vesicles, while the block copolymer forms the cubic phase. Accordingly, a tube-dominated gel evolves into a block copolymer-dominated gel through a gel-solution-gel sequence uniquely driven by the opposing thermal responses of the two constituents. This results in a hybrid system that is not only spreadable, self-healing, and mechanically robust, but also well-suited for sustained topical delivery. Imaging, calorimetry, and rheology provide detailed insights into the structure, phase transitions, and flow behavior of the hybrid system and its individual components. As a proof-of-concept, the gel enables slow, sustained release of a fluorescent model probe (carboxyfluorescein), exhibits excellent cytocompatibility, and promotes high cell internalization. Overall, this ICT-based strategy establishes a versatile and sustainable platform with strong potential for long-term topical drug delivery.

Abstract Hydroponics is an advanced agricultural technique that involves growing plants without soil. Instead, plants are cultivated in a nutrient-rich water solution that provides all the essential minerals they need to thrive, allowing plants to grow either with their roots directly in the solution or supported by inert substrates like pine bark, coconut husk fiber, and rice husk. The solid waste generated from hydroponic cultivation is valuable due to its low cost, abundance, biodegradability, and renewability. These residues are rich in lignocellulosic materials, which can be extracted and refined to produce cellulose and nanocellulose (NC). In this work, cellulose and nanocellulose were extracted from residues of coconut husk fiber and a mixture of pine bark and coconut husk fiber, used in tomato and strawberry hydroponics, respectively. The residues were ground, washed, and chemically treated to obtain cellulose and NC. The chemical process involved several stages: (i) acid treatment, alkaline treatment, and bleaching to isolate cellulose, and (ii) acid hydrolysis followed by ultrasonication to obtain NC. Both materials underwent characterization using various techniques such as TGA, DSC, XRD and FTIR-ATR, which confirmed very low levels of lignin and hemicellulose. Morphological characterization through SEM revealed the presence of micro- and nano-crystals in the cellulose and NC samples, respectively, highlighting the effectiveness of the extraction method. The high purity and quality of the extracted materials make them competitive with commercially available products, suitable for applications in healthcare, food packaging, and automotive industries, while supporting recycling and reuse principles.

Abstract Thermotropic ionic liquid crystals (TILCs) are ion-containing fluids forming upon heating between the crystalline and liquid phases of ionic amphiphiles. Bis(quaternary ammonium) gemini surfactants with general formula n-s-n—where n and s are the main tail and the spacer lengths, respectively—are able to form TILCs, but systematic studies on the effect of the spacer length are still lacking. Here, we investigated the possibility of tuning TILC formation by varying s for 14-s-14 gemini surfactants using an unusually wide range of spacers, from 2 up to 20 methylene groups (s = 2, 6, 8, 12, 14, 18 and 20). The thermal stability of these compounds was assessed by thermogravimetric analysis (TGA) and the thermodynamic parameters of the phase transitions (temperature, enthalpy and entropy changes) by differential scanning calorimetry (DSC), while TILCs were assigned by polarized light microscopy (PLM). X-ray diffraction (XRD) of the powder compounds was also carried out to provide insight into the solid phase packing. Notably, the isotropization temperature to the ionic liquid phase shows an inverted V trend with increasing s in the s = 2–12 range, and then increases linearly in the range s = 12–20. Smectic A liquid crystals form for all compounds, with 14-2-14, 14-12-14 and 14-14-14 displaying lower temperatures (approx. range 100–120 °C) than the rest. Overall, the results show that incrementally varying the spacer length affects the phase behavior, thermal stability, thermodynamic parameters of the thermotropic phase transitions, and solid-phase smectic d-spacings in a marked and complex manner, with several non-monotonic trends observed. Moreover, the spacer length can be selected to tune the formation of ionic liquid crystals, pointing to a fine balance between the main chain and spacer lengths. © 2025 Elsevier B.V., All rights reserved.

Abstract Catanionic mixtures, composed of cationic and anionic surfactants, spontaneously form robust self-assembled aggregates whose morphology, size, and surface charge can be tailored by adjusting the surfactant mixing ratio. This straightforward and scalable approach, based on easily obtainable components, offers a versatile and simple platform with high potential for drug delivery. However, developing viable nanocarriers also requires a favorable cytotoxicity profile, high drug loading, and strong bioactivity-features that catanionic vesicles often lack. Here, we present a systematic study of pH-sensitive catanionic vesicles composed of mixtures of the biocompatible, FDA-approved anionic surfactant sodium lauroyl sarcosinate (SLSar) and various cationic double-tailed surfactants (didodecyldimethylammonium bromide and bis-quat 12-s-12 gemini surfactants). The different vesicle systems form spontaneously at low critical aggregation concentrations (approximate to 3-30 mu mol kg-1), and exhibit a broad range of size distributions, high surface charge (positive and negative), and long-term colloidal stability. Cytotoxicity screening in healthy L929 fibroblasts enabled the selection of highly biocompatible compositions, with gemini/SLSar systems showing superior doxorubicin (DOX) encapsulation efficiency. These vesicles exhibit enhanced DOX release at acidic pH (approximate to 6.0), mimicking tumor microenvironments, and demonstrate rapid and efficient uptake in lung carcinoma cells within 30 min, increasing over 3 h. Remarkably, DOX-loaded vesicles achieve potent cytotoxicity at only 5 nM DOX-well below the IC50 of free drug-highlighting enhanced therapeutic efficacy and potential for reduced systemic toxicity. Overall, SLSar-based catanionic vesicles constitute a simple, stable, and tunable nanocarrier platform with significant potential for pH-responsive, low-dose cancer chemotherapy.

Abstract The efficient delivery of nucleic acids (NAs) remains a major challenge in gene therapy due to their poor stability and limited cellular uptake. Even though non-viral vectors have been pivotal to overcoming some of these challenges, significant barriers, such as intracellular digestion of NAs and limited endosomal escape, still remain. Here, we developed novel stimuli-responsive lipoplexes integrating a 2-hydroxychalcone-based cationic amphiphile (CnNCh, with 4 or 6 carbons in their alkyl chains, n = 4 or 6) and monoolein (MO). This combination leverages the photoisomerization and pH-sensitivity of chalcone derivatives, along with the fusogenic capabilities of MO, to achieve enhanced transfection efficiency via light irradiation. To reach this goal, we first assessed the cytotoxicity of the cationic amphiphiles in healthy and tumor cells. We then prepared mixtures with varying CnNCh/MO molar ratios, yielding net cationic vesicles with long-term colloidal stability. Subsequently, NAs were efficiently compacted into lipoplexes at N/P ratios (positively charged nitrogen/negatively charged phosphate) higher than 1, attaining near-complete compaction. Light and pH stimuli induce the formation of the expected products, but without compromising lipoplex stability or activating premature NA release. Vesicles with different CnNCh/MO molar ratios do not induce the loss of viability of normal fibroblasts for concentrations up to 50 mu M. Crucially, siRNA-lipoplex mixtures having C4NCh/MO molar ratios of 1/1 and 2/1 (N/P = 6) achieve significant GFP knockdown after irradiation, indicative of successful siRNA delivery and biological effects. Using biomimicking endosomal membranes, we show that photoactivation enhances membrane fusion, suggesting a mechanism entailing light-mediated endosomal escape. Our study provides proof-of-concept for a light-switch mechanism offering precise spatiotemporal control over gene silencing, a highly desirable feature in therapeutic applications.

Abstract Nanocomposites have garnered attention for their potential as catalysts in electrochemical reactions vital for technologies like fuel cells, water splitting, and metal-air batteries. This work focuses on developing threedimensional (3D) nanocomposites through aqueous phase exfoliation, non-covalent functionalization of building blocks with surfactants and polymers, and electrostatic interactions in solution leading to the nanocomposites assembly and organization. By combining molybdenum disulfide (MoS2) layers with graphene nanoplatelets (GnPs) to form a binary 2D composite (MoS2/GnP), and subsequently incorporating multiwalled carbon nanotubes (MWNTs) to create ternary 3D composites, we explore their potential as catalysts for the oxygen reduction reaction (ORR) critical in fuel cells. Characterization techniques such as X-ray photoelectron spectroscopy, scanning electron microscopy, and X-ray diffraction elucidate material composition and structure. Our electrochemical studies reveal insights into the kinetics of the reactions and structure-activity relationships. Both the (MoS2/GnP)-to-MWNT mass ratio and nitrogen-doping of GnPs (N-GnPs) play a key role on the electrocatalytic ORR performance. Notably, the (MoS2/N-GnP)/MWNT material, with a 3:1 mass ratio, exhibits the most effective ORR activity. All catalysts demonstrate good long-term stability and methanol crossover tolerance. This facile fabrication method and observed trends offer avenues for optimizing composite electrocatalysts further.

Abstract Malaria is one of the big three global infectious diseases, having caused above two hundred million cases and over half a million deaths in 2020. The continuous demand for new treatment options prioritizes the cost-effective development of new chemical entities with multi-stage antiplasmodial activity, for higher efficacy and lower propensity to elicit drug-resistant parasite strains. Following up on our long-term research towards the rescue of classical antimalarial aminoquinolines like chloroquine and primaquine, we have developed new organic salts by acid-base pairing of those drugs with natural bile acids. These antimalarial drug-derived bile salts were screened in vitro against the hepatic, blood and gametocyte stages of Plasmodium parasites, unveiling chloroquine bile salts as unprecedented triple-stage antiplasmodial hits. These findings pave a new pathway for drug rescuing, even beyond anti-malarial and other anti-infective drugs. Malaria is one of the big three global infectious diseases, with the heaviest toll on human lives in low-to-middle income countries. Cost-effective antimalarial drugs with multi-stage action remain an unmet and urgent need in global healthcare.

Abstract Introduction: Intravaginal drug delivery has emerged as a promising avenue for treating a spectrum of systemic and local female genital tract (FGT) conditions, using biomaterials as carriers or scaffolds for targeted and efficient administration. Much effort has been made to understand the natural barriers of this route and improve the delivery system to achieve an efficient therapeutic response. Areas covered: In this review, we conducted a comprehensive literature search using multiple databases (PubMed Scopus Web of Science Google Scholar), to discuss the potential of intravaginal therapeutic delivery, as well as the obstacles unique to this route. The in vitro cell models of the FGT and how they can be applied to probing intravaginal drug delivery are then analyzed. We further explore the limitations of the existing models and the possibilities to make them more promising for delivery studies or biomaterial validation. Complementary information is provided by in vitro acellular techniques that may shed light on mucus-drug interaction. Expert opinion: Advances in 3D models and cell cultures have enhanced our understanding of the FGT, but they still fail to replicate all variables. Future research should aim to use complementary methods, ensure stability, and develop consistent protocols to improve therapy evaluation and create better predictive in vitro models for women's health. [GRAPHICS]

Abstract Cationic gemini surfactants have emerged as potential gene delivery agents as they can co-assemble with DNA due to a strong electrostatic association. Commonly, DNA complexation is enhanced by the inclusion of a helper lipid (HL), which also plays a key role in transfection efficiency. The formation of lipoplexes, used as non-viral vectors for transfection, through electrostatic and hydrophobic interactions is affected by various physicochemical parameters, such as cationic surfactant:HL molar ratio, (+/-) charge ratio, and the morphological structure of the lipoplexes. Herein, we investigated the DNA complexation ability of mixtures of serine-based gemini surfactants, (nSer)2N5, and monoolein (MO) as a helper lipid. The micelle-forming serine surfactants contain long lipophilic chains (12 to 18 C atoms) and a five CH2 spacer, both linked to the nitrogen atoms of the serine residues by amine linkages. The (nSer)2N5:MO aggregates are non-cytotoxic up to 35-90 mu M, depending on surfactant and surfactant/MO mixing ratio, and in general, higher MO content and longer surfactant chain length tend to promote higher cell viability. All systems efficaciously complex DNA, but the (18Ser)2N5:MO one clearly stands as the best-performing one. Incorporating MO into the serine surfactant system affects the morphology and size distribution of the formed mixed aggregates. In the low concentration regime, gemini-MO systems aggregate in the form of vesicles, while at high concentrations the formation of a lamellar liquid crystalline phase is observed. This suggests that lipoplexes might share a similar bilayer-based structure.