Abstract:

Chickpea (Cicer arietinum L.) flour is a promising raw material for the development of biodegradable packaging due to its protein and polyphenol content. In this study, thermocompressed chickpea flour sheets were reinforced with cellulose nanocrystals (CNC) to improve their barrier, mechanical, thermal, and structural properties. Preliminary trials identified 22% moisture as the most suitable condition for consistent sheet formation. CNC was incorporated at 0, 2.5, 5.0, and 7.5% (w/w), and the resulting sheets were evaluated for phenolic content, antioxidant activity, water vapor permeability (WVP), optical properties, thermal behavior, morphology, and structural characteristics. Thermocompression reduced the measurable phenolic fractions, although antioxidant activity was not significantly affected. CNC markedly reduced WVP, from 5.16x10^-10 (control) to 5.93x10^-12 g∙m^-1∙s^-1∙Pa^-1 at 7.5% CNC. Tensile strength and Young's modulus increased with CNC loading, while elongation at break was highest at intermediate concentrations. SEM, DSC, XRD, and FTIR analyses indicated matrix reorganization and modified thermo-structural behavior. Overall, CNC improved the barrier and mechanical performance of thermocompressed chickpea flour sheets, supporting their potential for biodegradable packaging applications.

Abstract: The poor performance of neat polylactic acid (PLA) and gelatin has driven the development of co- electrospun composites in biomaterials to achieve enhanced functional properties. In this study gelatin extracted from Crocker fish scale was co-electrospin with PLA. The composite fibres were fabricated at 2-17 wt.% gelatin. The electrospun fibres were evaluated via scanning electron microscope (SEM), Fourier transform spectroscopy (FTIR), differential scanning microscopy (DSC), thermogravimetric analysis (TGA), and Tensile test. FTIR analysis of PLA/gelatin fibres showed a peak growth at 1525cm-1 and a shift in the amide III band from 1239 cm-1 to 1192cm-1, indicating hydrogen bonding and chemical interaction between PLA and gelatin. The thermogram of the PLA/gelatin scaffold revealed an enhanced thermal stability with peak thermal stability (324oC) attained at 14 wt.% Gelatin. The DSC further confirms the interaction of PLA (Tg 75 OC) and gelatin (49 OC), forming a single glass transition temperature (Tg) at 70 OC. There was a slight increase in Tg of the composite fibres as the wight fraction of the gelatin increased. The SEM showed a good morphology resembling the native extracellular matrix (ECM) of the body. The ultimate tensile strength and percentage elongation of the fibres declined with increasing gelatin content. The introduction of this gelatin into PLA resulted in improved physiochemical properties of PLA/gelatin fibres due to chemical interaction. Thus, this composite fibre could serve as a potential wound dressing material.

Abstract: Sulfated chitosan (ChS) is a chemically modified polysaccharide derived from chitin that mimics heparan sulfate (HS) structures and has emerged as a promising antimicrobial biomaterial. Piscirickettsia salmonis (P. salmonis), the etiological agent of Salmonid Rickettsial Septicemia (SRS), represents the main driver of antibiotic use in Chilean aquaculture. In this study, the in vitro antibacterial activity of ChS against P. salmonis was evaluated. Elemental characterization by SEM-EDS confirmed successful sulfation of the polymer, with a degree of sulfation ranging from 0.92 to 0.95. Antibacterial assays revealed a minimum inhibitory concentration (MIC) of 1500 µg/mL and a minimum bactericidal concentration (MBC ≥1500 µg/mL). LIVE/DEAD™ fluorescence imaging showed the formation of bacterial aggregates with increasing size, frequency, and red fluorescence compared to controls over the exposure to ChS, indicating progressive membrane damage. This was supported by a reduction (p < 0.05) in the Green/Red fluorescence ratio of 37–46% between 5h and 96h of exposure, corresponding to alteration of cell membrane. Scanning electron microscopy revealed pronounced morphological alterations by ChS, including surface disruption and loss of cellular integrity. This was more severe compared to native chitosan. Also, ChS reduced (p < 0.05) biofilm formation (>50% at day 6 and 34.8% at day 8). These results demonstrated that ChS disrupts cell membrane and reduces biofilm formation in P. salmonis, which in consequence affects viability. This is currently the first report of the antibacterial effect of ChS as a HS analogue on P. salmonis.

Abstract: Conventional oxidative hair dyes rely on aromatic amines, raising concerns about human health and environmental safety. This study reports a natural hair-coloring system using size-controlled ink particles (SIPs, ~170 nm in diameter) from cuttlefish ink and chitosan. Because both SIPs and hair surfaces carry negative charges near neutral pH, pristine SIPs exhibited poor deposition onto hair. Polyelectrolyte complexation with chitosan reversed the SIP surface charge under acidic conditions (maximum ζ ≈ +41 mV at pH 2.4), enabling electrostatic deposition onto hair fibers. Dynamic light scattering (DLS) revealed pH-responsive aggregation at pH 1.6–1.8 and redispersion at pH 2.8–4.3, while ultraviolet–visible (UV–Vis) spectra confirmed that the broadband absorption of melanin was preserved, consistent with predominantly noncovalent interactions. Scanning electron microscopy (SEM) showed a particle-based composite coating on hair fibers. An optimal SIP:chitosan weight ratio of 10:1 at pH ~4.7 yielded the darkest and most uniform coloration (L* = 32.89, ΔE*_ab = 55.89) without metallic mordants, achieving darker coloration than representative plant-based natural colorants reported in the literature. These results demonstrate a marine-biomass-derived approach to natural black hair coloration with strong darkening performance.

Abstract: Photodynamic therapy (PDT) is a clinically established, minimally invasive modality that relies on the interaction between a photosensitizer (PS), light, and molecular oxygen to generate cytotoxic reactive oxygen species (ROS). Despite decades of development, the clinical performance of many photosensitizers remains limited—not primarily due to insufficient photodynamic activity, but rather to unfavorable physicochemical and biopharmaceutical properties that impair in vivo efficacy. Natural products represent a structurally diverse and biologically relevant source of photosensitizers with intrinsic photochemical potential. However, their translation into clinically viable PDT agents has remained disproportionately limited. This discrepancy highlights a critical and often underappreciated bottleneck: pharmaceutical incompatibility. In this mini-review, we provide a pharmaceutics-centered perspective on natural product-based photosensitizers, shifting the focus from molecule discovery toward translational feasibility. We critically examine the key barriers that restrict clinical progression—including poor aqueous solubility, aggregation-induced quenching, instability, and suboptimal biodistribution—and assess the formulation strategies that enable their resolution. Particular emphasis is placed on nanotechnology-enabled delivery systems, targeted carriers, and hybrid platforms that enhance solubility, stability, and tissue selectivity. Representative compounds are discussed within a translational context, highlighting the contrast between advanced candidates such as hypericin and chlorophyll-derived chlorins and more limited systems such as curcumin. Collectively, this work demonstrates that the success of natural photosensitizers in PDT is determined less by intrinsic photodynamic efficiency and more by their compatibility with pharmaceutical engineering strategies. This perspective provides a concise framework to guide the rational development of clinically relevant natural photosensitizer systems.

Abstract: The rapid emergence of antibiotic-resistant bacteria represents one of the most critical challenges in modern healthcare and has stimulated intense research into alternative antimicrobial strategies. Antibacterial hydrogels have emerged as versatile biomaterials due to their high water content, tunable physicochemical properties, and ability to function as multifunctional platforms for drug delivery and tissue regeneration. This review analyzes recent advances in antibacterial hydrogel systems through a conceptual framework based on three complementary pillars: biological antibacterial agents, inorganic functional components, and structural material engineering. Biological strategies, particularly bacteriophage-based approaches, provide highly specific antibacterial activity capable of targeting multidrug-resistant pathogens and disrupting bacterial biofilms. Inorganic components such as hydroxyapatite nanoparticles contribute additional functionalities including drug adsorption, modulation of the ionic microenvironment, and osteoconductive behavior relevant for bone-related infections. Structural design strategies based on electrospinning enable the fabrication of fibrous architectures that enhance mechanical stability, regulate therapeutic release, and mimic extracellular matrix organization. The integration of these three pillars within multifunctional hydrogel platforms offers promising opportunities for developing advanced antibacterial biomaterials capable of addressing infection control while supporting tissue regeneration.

Abstract: The self-assembly of peptide-based building blocks into ordered structures is widely exploited for the development of novel biomaterials, including hydrogels. In this review, we analyze the effect of chirality on the ability of peptides to form hydrogels. We describe systems composed of peptides of opposite chirality i.e. peptides composed of all L- or D-amino acids and peptides composed of amino acids with alternate chirality, i.e. one L- and D-amino acid or one block containing all L-amino acid followed by one block composed of all D-amino acids. Finally, we illustrate systems composed of mixtures of L- and D-peptides. The structural features of these compounds are discussed. We further compare the mechanical properties of hydrogels formed by homochiral and heterochiral peptides. Finally, we discuss the potential biological applications of these systems, focusing on the differences between hydrogels formed from peptides of opposite chirality or mixed chirality.

Abstract: Bacterial infections can delay the wound healing and represent serious medical problems both in the hospital and community setting. In this work a gelatin hydrogel modified with photo-cross-linkable methacrylamide groups at 10% concentration (GelMA10%), enriched with titanium dioxide nanoparticles (TiO2NPs) and loaded with Neomycin Sulphate was developed with the aim to realize a tissue for wound care with improved mechanical and antimicrobial properties. TiO2 nanocomposite GelMA films with two TiO2NP concentrations were characterized to assess physicochemical, structural and mechanical properties by Scanning Electron Microscopy equipped with energy-dispersive X-ray spectrometer (SEM/EDX), micro-Computed Tomography (micro-CT) and X-ray Photoelectron Spectroscopy (XPS). Nanocomposite GelMA films showed more compact structure, reduced pore sizes and higher compressive modulus at the increasing NP concentration. They were able to absorb and retain water for prolonged time, however no significant differences in the swelling degree at the increasing of NP concentration were observed. In vitro drug release and antibacterial activity against Staphylococcus aureus of nanocomposite GelMA film enriched with 1 mg/ml of TiO2NPs, identified as good candidate for wound healing, were investigated. Both GelMA and TiO2 nanocomposite GelMA films loaded with drug exhibited a strong antibacterial action, whereas GelMA containing only TiO2NPs did not show any antimicrobial properties.

Abstract: Background/Objectives:A. aegypti larval control is essential for reducing arbovirus transmission; however, increasing insecticide resistance and environmental concerns demand sustainable alternatives. This study reports the development of a solvent-free, thermoresponsive Pluronic F127/Carbopol 974P nanogel (NGLp) encapsulating Lippia pedunculosa Hayek essential oil (OELp) to enhance larvicidal performance through improved dispersion and controlled release (Figure ). Methods: OELp was obtained by hydrodistillation and chemically characterized by GC–MS and NMR. Nanogels were prepared using a low-energy cold method (F127 20% w/w; Carbopol 0.2% w/w), selecting the most stable formulation (1% w/w OELp). The system was characterized by FTIR, dynamic light scattering (DLS), zeta potential, and scanning electron microscopy (SEM). Larvicidal activity was evaluated against third-instar A. aegypti larvae (20–60 μg mL−1; 24, 48, and 72 h), and LC50/LC90 values were estimated by logistic fitting. Results: OELp contained 28 identified constituents (96.65%), predominantly rotundifolone (62.68%) and limonene (20.74%), with NMR confirming rotundifolone as the major compound. The optimized nanogel exhibited nanometric size (239.9 nm; PdI 0.474) and a negative zeta potential (−22.3±3.90 mV), indicating electrosterically stabilized dispersion. FTIR confirmed physical incorporation of OELp. The nanogel demonstrated dose- and time-dependent larvicidal activity, achieving 100% mortality at ≥50 μg mL−1 (48–72 h). Mortality at intermediate concentrations increased over time (e.g., 53% at 30 μg mL−1 at 72 h), indicating sustained release. LC50/LC90 values decreased from 38.6/46.0 μg mL−1 (24 h) to 31.6/40.9 μg mL−1 (48 h), with further improvement at 72 h. Conclusions: NGLp enhances larvicidal performance through improved dispersion and sustained release of OELp, supporting its potential as a sustainable and eco-compatible nanoplatform for mosquito control.

Abstract: Consumer demand for sustainable solutions to protect against hair damage is growing, yet quantitative studies linking molecular interactions to mechanical strengthening and structural changes remain limited. Here, we investigated the effectiveness of biotechnologically obtained Saccharomyces Lysate as an active ingredient for hair care. Molecular modeling was used to explore the interactions between peptides in the lysate with keratin and suggested a network of intermolecular interactions at multiple sites of the proteins. Based on these observations, the strength and structural integrity of hair fibers treated with Saccharomyces Lysate were assessed using tensile measurements. We observed an improvement in the strength of hair tresses, with an increased Young’s Modulus compared to hair tresses treated only with water along with a significantly increased break stress. To visualize the hair fibers and their surface roughness after treatment with the lysate, we employed micro-computed tomography (µ-CT) offering high-resolution visualization of hair fibers. We introduce this method to qualitatively highlight the surface appearance following the application of a cosmetic product and complemented it with combing-force measurements. Our results demonstrate the potential of this complex mixture of small peptides to strengthen hair integrity and we propose a hypothesis for its mode of action on the molecular level.

Abstract: Sustainable nanotechnologies derived from renewable resources are increasingly positioned at the interface of green chemistry, advanced drug delivery, and translational pharma- ceutics. Over the past decade, lignocellulosic nanomaterials, chitin/chitosan platforms, polysaccharide-based nanogels and hydrogels, lignin- and polyphenol-derived nanos- tructures, and bio-based lipid nanocarriers have been engineered through progressively eco-efficient routes, including solvent-minimized self-assembly, nanoprecipitation, spray drying, hot-melt extrusion, and microfluidic-assisted fabrication. This work provides a structured evidence map of nano-enabled drug delivery and therapeutic platforms derived from renewable biological resources. Specifically, we aim to (i) identify and classify nano- platform classes and renewable feedstocks, (ii) summarize reported pharmaceutical critical quality attributes (CQAs), performance and safety endpoints, and (iii) appraise how ‘re- newability’ and ‘green’ claims are evidenced (feedstock origin vs process sustainability) and how frequently translational readiness factors (scalability, quality control, regulatory align- ment) are addressed. We critically compare renewable and conventional nanomaterial plat- forms across key translational dimensions, including carbon footprint, batch consistency, biodegradability, functional tunability, safety/persistence, and scale-up maturity. Finally, we delineate a practical translational pathway—from biomass sourcing and fractionation to nanoformulation, characterization/stability, and GMP scale-up—highlighting cross-cutting enablers such as life-cycle assessment, EHS/toxicology risk assessment, Quality-by-Design, and regulatory alignment. Collectively, the evidence supports renewable nanomaterials as viable, scalable candidates for next-generation therapeutics, provided that variability control, standardized characterization, and safety-by-design principles are embedded early in development.

Abstract: Modern agriculture faces major challenges driven by rapid population growth, climate change, and environmental concerns. Advanced polymeric architectures for controlled-release fertilizers (CRFs) are essential to mitigate these issues. Urea is one of the most widely used nitrogen fertilizers for field crops; however, its agronomic efficiency is limited by volatilization and leaching losses. In this study, we report a sustainable strategy to encapsulate urea using a matrix derived from industrial sulfur waste and vegetable oil, promoting both improved agronomic efficiency and the valorization of industrial residues and renewable resources. Through inverse vulcanization, we synthesized Bp-SF, a sponge-like polymeric material. Two bio-composites loaded with urea, Bp-SF25U and Bp-SF32U, were also prepared. FT-IR analysis confirmed urea encapsulation and the formation of polymeric structures from sunflower oil. SEM imaging revealed a porous morphology, while contact angle measurements confirmed the hydrophobic nature of the polymer matrix. Release kinetics studies demonstrated slow nitrogen release for more than 77 days, governed by diffusion. Pot experiments with maize showed that Bp-SF32U improved plant growth compared with conventional urea. These sulfur cross-linked biopolymers represent a promising approach to enhance urea efficiency while supporting greener fertilization strategies aligned with circular economy principles.

Abstract: This study focused on the development and characterization of bioactive polymeric patches based on agar–chitosan and gellan–chitosan matrices, with and without naringin, aiming to identify formulations with optimal physicochemical and biological performance. FTIR spectroscopy, thermogravimetric (TGA), and differential scanning calorimetry (DSC) analyses confirmed effective crosslinking, stable incorporation of the bioactive compound, and high thermal stability of the patches. Antimicrobial testing against Staphylococcus aureus ATCC 33591 demonstrated that naringin-loaded agar–chitosan films, particularly those with lower chitosan and glutaraldehyde content, exhibited significant activity (MIC = 12.5 mg/mL; inhibition zone 27.67 ± 0.58 mm). Biocompatibility studies, including local skin irritation in rabbits and 28-day topical application in mice, showed no adverse effects. Anti-inflammatory evaluation using the λ-carrageenan-induced paw edema model indicated modest activity of naringin under acute conditions. Overall, agar–chitosan films offered tunable properties and reproducible bioactive incorporation, while gellan–chitosan films provided mechanically robust matrices suitable for further optimization. The results highlight the potential of agar–chitosan patches as biocompatible, structurally stable, and antimicrobial platforms for topical and transdermal delivery of bioactive flavonoids.

Abstract: Bleeding and bacterial infection remain major challenges in surgical procedures. Thus, hemostatic biomaterials capable of controlling bleeding rapidly while preventing microbial contamination are highly desirable. This study developed and evaluated photocrosslinkable composite hydrogels made of methacrylated chitosan (ChiMA) and methacrylated oxidized cellulose nanofibers (OCNFMA) for antibacterial hemostatic applications. Chitosan (Chi) was methacrylated using methacrylic anhydride, cellulose nanofibers were oxidized with sodium periodate, and 2-aminoethyl methacrylate (AEMA) was added to introduce photocrosslinkable groups. For the preparation of composite hydrogel networks, the precursor solutions were mixed and photocrosslinked under UV irradiation (365 nm) in the presence of lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP). A Fourier transform infrared spectrometer (FTIR), scanning electron microscope (SEM), and rheological analysis were utilized to characterize the materials. Hydrogels were evaluated for swelling behavior, degradation profile, and blood clotting ability. Furthermore, antibacterial activity against Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) was evaluated, and cytocompatibility was evaluated using NIH3T3 fibroblasts and MC3T3 preosteoblasts. Incorporating OCNFMA with low degrees of functionalization (L) or high degrees of functionalization (H) at different ratios into the ChiMA network significantly influenced the physicochemical and structural properties of the hydrogels. The composite hydrogels exhibited interconnected porous structures, improved mechanical stability, and tunable swelling and degradation behavior. Furthermore, some formulations demonstrated measurable antibacterial activity against both bacterial strains. Moreover, cytocompatibility studies revealed that the composite hydrogels supported higher cell viability than ChiMA alone. The developed ChiMA–OCNFMA composite hydrogels exhibit promising physicochemical, antibacterial, and biological properties. The findings suggest that the materials may be useful as multifunctional hydrogels for wound management, as well as candidates for broader biomedical applications.

Abstract:

Marine exopolysaccharides (EPS) are emerging as sustainable bioactive polymers for biomedical hydrogels. Here, we report hydrogels from sulfated EPS produced by Porphyridium cruentum and ionically crosslinked with Ca²⁺, Ce³⁺, or Cu²⁺ to generate tunable networks for wound-healing applications. Rheological analysis showed that viscoelastic behavior was primarily governed by cation nature and accessible binding-site density, with diminishing gains above 2.5 wt% EPS and limited benefit beyond 10 wt% crosslinker. Ce³⁺ produced the most solid-like gel, Ca²⁺ yielded more thixotropic networks, and Cu²⁺ promoted rapid, heterogeneous crosslinking consistent with fast surface complexation. These network signatures translated into distinct in vitro performances. Cation selection tuned antibacterial activity against Staphylococcus aureus and Escherichia coli, with Cu²⁺ achieving rapid bactericidal effects and Ce³⁺ enabling an 8-log reduction after 24 h. Antioxidant capacity was assay-dependent (ABTS vs DPPH), reflecting combined EPS radical-quenching and metal-associated redox contributions. Conditioned-media assays using human dermal fibroblasts and keratinocytes indicated the most favorable cytocompatibility balance for Ce³⁺-crosslinked gels, whereas Cu²⁺ gels were limited by cytotoxicity. Macrophage cytokine readouts (TNF-α, IL-6) further supported formulation-dependent immunobiological activity. This work establishes microalgal EPS as a versatile polymer platform and links ionic crosslinking chemistry to rheological control and multifunctional biomedical performance.

Abstract:

This study evaluated the in vitro anti-inflammatory and antidiabetic activities of methanolic leaf extracts of Ximenia caffra (sour plum), a medicinal plant widely used in traditional healthcare systems across tropical Africa. Medicinal plants remain an important source of bioactive phytochemicals, and growing interest in phytopharmaceuticals has intensified the search for natural compounds with therapeutic potential. The present investigation aimed to scientifically validate the ethnomedicinal use of X. caffra leaves by assessing their enzyme inhibitory and anti-inflammatory properties. Fresh leaves of X. caffra were collected, authenticated, air-dried, pulverized, and extracted using methanol through maceration. Anti-inflammatory activity was determined using protein denaturation inhibition and membrane stabilization assays, while antidiabetic potential was evaluated through α-amylase and α-glucosidase enzyme inhibition assays. The extract exhibited concentration-dependent biological activities across all experimental models. Anti-inflammatory evaluation showed significant inhibition of protein denaturation and membrane stabilization, with IC₅₀ values of 129.83 µg/mL and 288.11 µg/mL, respectively. Similarly, the extract demonstrated appreciable antidiabetic activity, inhibiting α-amylase and α-glucosidase enzymes with IC₅₀ values of 227.01 µg/mL and 179.35 µg/mL, respectively, indicating stronger inhibition of α-glucosidase. These findings suggest that X. caffra leaves contain bioactive compounds capable of modulating inflammatory responses and carbohydrate-digesting enzymes, thereby supporting their traditional medicinal use. The study highlights the potential of X. caffra as a promising natural source for the development of plant-based anti-inflammatory and antidiabetic therapeutic agents.

Abstract: The growing worldwide need for sustainable, high-quality protein sources has intensified interest in single-cell protein (SCP) production, particularly mycoproteins derived from filamentous fungi. Concurrently, the agricultural sector generates vast quantities of starch-rich by-products, such as broken rice, cassava peels, potato waste and cereal processing residues, that remain largely underutilized despite their high carbohydrate content. This literature review examines the potential of starch-based agricultural by-products as low-cost, renewable feedstocks for mycoprotein production. Key topics include the chemical characteristics of starch residues, pretreatment and enzymatic hydrolysis strategies for efficient saccharification and the metabolic suitability of fungal strains such as Neurospora and Fusarium spp. for biomass and protein synthesis. In addition, the review evaluates optimization of fermentation processes, including maximizing biomass yield and improving overall feedstock valorization to enhance process efficiency. Furthermore, considerations related to process design, environmental benefits and techno-economic feasibility are evaluated in the context of converting starch residues into fungal protein. In summary, the evidence suggests that valorizing starch by-products for mycoprotein fermentation, used as a protein alternative and as an ingredient, represents a promising strategy to reduce waste, lower production costs and support global food sustainability.

Abstract: Intraperitoneal (I.P.) delivery of cell-based therapeutics represents a promising strategy for treating regional peritoneal diseases; however, rapid cellular clearance severely limits therapeutic durability. A critical unmet need is the development of implantable biomaterial platforms that can both mechanically integrate within the dynamic I.P. cavity and sustain viable cell persistence in vivo. Here, we establish a Continuous Liquid Interface Production (CLIP)-based 3D bioprinting strategy to engineer transplantable, cell-laden hydrogel scaffolds optimized for I.P. implantation. Through systematic bioresin design, we identify a GelMA-PEGDA formulation that achieves a balance between high-resolution printability, tissue-matched mechanical compliance (Young’s modulus 10-15 kPa), and controlled biodegradation (~75% mass loss over 14 days). The resulting constructs support sustained cell viability and proliferation for over 30 days in vitro. Importantly, in vivo I.P. implantation demonstrates a ~10-fold extension in cellular persistence compared to direct cell injection, prolonging the time to 50% signal decay from ~3 days to ~30 days, with detectable cell retention approaching two months in select animals. The platform further accommodates multiple clinically relevant cell types, including human mesenchymal stem cells and neural stem cells, highlighting its translational versatility. Collectively, this work defines key material and architectural parameters required for I.P. implantable cell therapeutics and establishes CLIP-based bioprinting as a scalable strategy for regional delivery of living therapeutics.

Abstract: The transition toward sustainable pest management requires evaluation frameworks that extend beyond conventional efficacy-based pesticide assessment. This study proposes the Structural–Activity–Economic Sustainability (SAES) framework, a multidimensional composite model designed to evaluate natural bioactive compounds through integrated molecular, biological, and economic performance indicators. Ten representative phytochemical compounds were assessed using standardized molecular descriptors, bioactivity metrics, and economic sustainability parameters. A composite SAES Index was constructed using balanced domain weighting to quantify overall sustainability performance. The results revealed a tiered distribution of sustainability scores ranging from 0.730 to 0.498, demonstrating measurable differentiation among compounds. Pyrethrin (0.730) and Azadirachtin (0.716) formed a high-performance cluster, whereas mid-ranked compounds exhibited relatively compressed values, suggesting competitive equilibrium zones. Lower-ranked compounds showed sharper declines, indicating cross-domain imbalance. Sensitivity and robustness analyses confirmed ranking stability under weight perturbation and scenario variation, supporting the structural consistency of the SAES framework. These findings indicate that sustainability cannot be reduced solely to biological potency or structural magnitude, but instead emerges from multidimensional balance across molecular optimization, functional efficacy, and economic viability. By operationalizing sustainability into a quantifiable composite metric, the SAES model provides a decision-support framework for compound selection, regulatory evaluation, and sustainability-oriented agricultural investment strategies.

Abstract:

Background. Quaternary phosphonium salts (QPSs) are extensively researched since represent new promising weapons to counteract critical superbugs, regardless their robust pattern of resistance. Methods. Here, dynamic light scattering analysis was carried out on QPSs 1, 3 and 4 recently reported and already found active against cancer cells, and phosphine 2 unveiling particles of 700-800 nm for 2, 3 and 4 and positive Zeta-potential (ζ-p ) for all (+4.2-+38.1 mV). 1, 3 and 4 plus 2, were microbiologically evaluated, assessing minimum inhibitory concentration values (MICs) (1-4), time-killing curves (1), and anti-biofilm capacity (1). Results. MICs on a total of 23 Gram-positive and Gram-negative clinically isolated superbugs, evidenced that, poorly soluble 2, 3 and 4 exhibited not reproducible MICs, while 1 provided interesting MICs, which made it worthy of further investigations. In fact, 1 was active against clinically relevant multidrug-resistant (MDR) Gram-positive species and not active against MDR Gram-negative species including Pseudomonas aeruginosa. Specifically, MICs = 16-32 µg/mL and 16-64 µg/mL were determined against methicillin-resistant Staphylococcus aureus (MRSA) and S. epidermidis (MRSE) respectively. MICs = 32-64 µg/mL were observed against teicoplanin- and vancomycin-resistant (VRE) Enterococcus faecalis and E. faecium and no activity against P. aeruginosa (> 128 µg/mL). Notably, time-kill experiments established that 1 was bactericidal against MRSA, while strongly inhibited (up to 100%) the formation of biofilm produced by the strongest biofilm-producers S. epidermidis and S. aureus isolates of our collection, at MICs and 2.5 × MIC concentrations, depending on isolates considered. Interestingly, if used against Staphylococci, and mainly MRSA, 1 was softly haemolytic. It was no cytotoxic against not tumorigenic human keratinocytes (HaCaT) and murine embryonic fibroblasts (3T3) in all cases. Structure-activity relationships have been studied, leading to outcomes which could be of great help for designing optimized new QPSs. Conclusions. Findings of this study overturn previous antimicrobial reports on compound 1, suggesting it as a new excellent weapon to counteract bacterial resistance and biofilm production by MRSA and MRSE superbugs, as well as thinkable for future in vivo experiments and clinical development.