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Search Results (434)

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Keywords = polyelectrolyte complexation

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18 pages, 6433 KB  
Article
Enhanced Fire Retardancy of Epoxy Resins upon Addition of Boron Nitride Nanoparticles Using Boron Polyol Complex
by Lalson D. Mathews, Srikanth Mateti, Jyotishkumar Parameswaranpillai, Nishar Hameed and Nisa V. Salim
Materials 2025, 18(17), 4101; https://doi.org/10.3390/ma18174101 - 1 Sep 2025
Abstract
Fire retardancy and thermal management improvements in epoxy resins can critically impact their use in electronics for IoT and 5G devices. This study proposes a facile method to improve the fire retardancy and thermal properties of epoxy resins (EPs) by incorporating boron nitride [...] Read more.
Fire retardancy and thermal management improvements in epoxy resins can critically impact their use in electronics for IoT and 5G devices. This study proposes a facile method to improve the fire retardancy and thermal properties of epoxy resins (EPs) by incorporating boron nitride nanoparticles (BNNPs) with boron polyol complex (BPC) to form an ionanofluid and explores the synergistic effect of polyelectrolytes with BN. The modified multifunctional additive BPC–BNNPs were then used for the functional modification of epoxy resin. Our detailed tests and analyses on these materials confirm that by adding 0.2 wt% of BNNPs in the EP–BPC–BN complex achieved a V-0 rating in the UL-94 vertical burning test. The resultant composite demonstrated that the modification of BN with the polyol complex imparted a low smoke and char formation in the modified epoxy composites. The current study shows that EP–BPC–BN complex has great potential as a thermal interface material for the thermal management of electronics or similar applications. The presented EP–BPC–BN composite can also be utilised as a fire-retardant coating, adhesive, and binding agent in the aerospace, transportation, and building industries. Full article
(This article belongs to the Special Issue Novel Materials for Additive Manufacturing)
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24 pages, 7133 KB  
Article
Critical Adsorption of Polyelectrolytes onto Patchy Particles with a Low-Dielectric Interior
by Dante A. Anhesini, Daniel L. Z. Caetano, Icaro P. Caruso, Andrey G. Cherstvy and Sidney J. de Carvalho
Polymers 2025, 17(16), 2205; https://doi.org/10.3390/polym17162205 - 12 Aug 2025
Cited by 1 | Viewed by 452
Abstract
A polyelectrolyte (PE) chain in the vicinity of an oppositely charged surface can exhibit a discontinuous transition from the adsorbed to the desorbed state once the electrostatic attractive interactions are not strong enough to overcome the entropic losses caused by the PE-surface adsorption. [...] Read more.
A polyelectrolyte (PE) chain in the vicinity of an oppositely charged surface can exhibit a discontinuous transition from the adsorbed to the desorbed state once the electrostatic attractive interactions are not strong enough to overcome the entropic losses caused by the PE-surface adsorption. In the context of PE–protein interactions, the heterogeneity of the charge distribution and the effects of a low dielectric permittivity underneath the surface are crucial. Studies of the combined effects of these two properties are very sparse, especially in the spherical geometry; we thus fill this gap here. We study the adsorption of PE chains onto spherical particles with heterogeneously charged surfaces, with the main focus on the critical-adsorption conditions and the effects of a low-dielectric core. Metropolis Monte Carlo simulations are employed, with the PE exploring the phase-space around the binding particle in the canonical ensemble. Two adsorption–desorption transitions are observed when the particle possesses a net charge of the same sign as that of the PE, resulting in nonmonotonic behavior of the critical charge density required for the PE–particle electrostatically driven adsorption. An increased affinity between the PEs and low-dielectric particles with variable heterogeneous charge distributions is observed, in contrast to the behavior detected for homogeneous low-dielectric particles. This higher affinity occurs when the Debye screening length in the solution becomes comparable to the dimensions of a patch of the opposite sign to the PE. A number of real-life applications of the considered PE–particle system is presented in the discussion, in particular regarding the properties of the complex formation between various PEs and globular proteins featuring a dipolar-type distribution of electric charges on their surfaces, such as insulin and bovine serum albumin. Full article
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32 pages, 2710 KB  
Review
Polyphosphazene-Based Nanotherapeutics
by Sara Gutierrez-Gutierrez, Rocio Mellid-Carballal, Noemi Csaba and Marcos Garcia-Fuentes
J. Funct. Biomater. 2025, 16(8), 285; https://doi.org/10.3390/jfb16080285 - 2 Aug 2025
Viewed by 891
Abstract
Poly(organo)phosphazenes (PPZs) are increasingly recognized as versatile biomaterials for drug delivery applications in nanomedicine. Their unique hybrid structure—featuring an inorganic backbone and highly tunable organic side chains—confers exceptional biocompatibility and adaptability. Through precise synthetic methodologies, PPZs can be engineered to exhibit a wide [...] Read more.
Poly(organo)phosphazenes (PPZs) are increasingly recognized as versatile biomaterials for drug delivery applications in nanomedicine. Their unique hybrid structure—featuring an inorganic backbone and highly tunable organic side chains—confers exceptional biocompatibility and adaptability. Through precise synthetic methodologies, PPZs can be engineered to exhibit a wide spectrum of functional properties, including the formation of multifunctional nanostructures tailored for specific therapeutic needs. These attributes enable PPZs to address several critical challenges associated with conventional drug delivery systems, such as poor pharmacokinetics and pharmacodynamics. By modulating solubility profiles, enhancing drug stability, enabling targeted delivery, and supporting controlled release, PPZs offer a robust platform for improving therapeutic efficacy and patient outcomes. This review explores the fundamental chemistry, biopharmaceutical characteristics, and biomedical applications of PPZs, particularly emphasizing their role in zero-dimensional nanotherapeutic systems, including various nanoparticle formulations. PPZ-based nanotherapeutics are further examined based on their drug-loading mechanisms, which include electrostatic complexation in polyelectrolytic systems, self-assembly in amphiphilic constructs, and covalent conjugation with active pharmaceutical agents. Together, these strategies underscore the potential of PPZs as a next-generation material for advanced drug delivery platforms. Full article
(This article belongs to the Special Issue Nanomaterials for Drug Targeting and Drug Delivery (2nd Edition))
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25 pages, 2451 KB  
Article
Complexation and Thermal Stabilization of Protein–Polyelectrolyte Systems via Experiments and Molecular Simulations: The Poly(acrylic acid)/Lysozyme Case
by Sokratis N. Tegopoulos, Sisem Ektirici, Vagelis Harmandaris, Apostolos Kyritsis, Anastassia N. Rissanou and Aristeidis Papagiannopoulos
Polymers 2025, 17(15), 2125; https://doi.org/10.3390/polym17152125 - 1 Aug 2025
Viewed by 621
Abstract
Protein–polyelectrolyte nanostructures assembled via electrostatic interactions offer versatile applications in biomedicine, tissue engineering, and food science. However, several open questions remain regarding their intermolecular interactions and the influence of external conditions—such as temperature and pH—on their assembly, stability, and responsiveness. This study explores [...] Read more.
Protein–polyelectrolyte nanostructures assembled via electrostatic interactions offer versatile applications in biomedicine, tissue engineering, and food science. However, several open questions remain regarding their intermolecular interactions and the influence of external conditions—such as temperature and pH—on their assembly, stability, and responsiveness. This study explores the formation and stability of networks between poly(acrylic acid) (PAA) and lysozyme (LYZ) at the nanoscale upon thermal treatment, using a combination of experimental and simulation measures. Experimental techniques of static and dynamic light scattering (SLS and DLS), Fourier transform infrared spectroscopy (FTIR), and circular dichroism (CD) are combined with all-atom molecular dynamics simulations. Model systems consisting of multiple PAA and LYZ molecules explore collective assembly and complexation in aqueous solution. Experimental results indicate that electrostatic complexation occurs between PAA and LYZ at pH values below LYZ’s isoelectric point. This leads to the formation of nanoparticles (NPs) with radii ranging from 100 to 200 nm, most pronounced at a PAA/LYZ mass ratio of 0.1. These complexes disassemble at pH 12, where both LYZ and PAA are negatively charged. However, when complexes are thermally treated (TT), they remain stable, which is consistent with earlier findings. Atomistic simulations demonstrate that thermal treatment induces partially reversible structural changes, revealing key microscopic features involved in the stabilization of the formed network. Although electrostatic interactions dominate under all pH and temperature conditions, thermally induced conformational changes reorganize the binding pattern, resulting in an increased number of contacts between LYZ and PAA upon thermal treatment. The altered hydration associated with conformational rearrangements emerges as a key contributor to the stability of the thermally treated complexes, particularly under conditions of strong electrostatic repulsion at pH 12. Moreover, enhanced polymer chain associations within the network are observed, which play a crucial role in complex stabilization. These insights contribute to the rational design of protein–polyelectrolyte materials, revealing the origins of association under thermally induced structural rearrangements. Full article
(This article belongs to the Section Polymer Physics and Theory)
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43 pages, 19225 KB  
Review
Recent Progress in Flexible Wearable Sensors Utilizing Conductive Hydrogels for Sports Applications: Characteristics, Mechanisms, and Modification Strategies
by Jie Wu, Jingya Hong, Xing Gao, Yutong Wang, Wenyan Wang, Hongchao Zhang, Jaeyoung Park, Weiquan Shi and Wei Guo
Gels 2025, 11(8), 589; https://doi.org/10.3390/gels11080589 - 30 Jul 2025
Viewed by 798
Abstract
Conductive hydrogels demonstrate substantial potential for flexible wearable sensors in motion monitoring, owing to their unique physicochemical properties; however, current implementations still confront persistent challenges in long-term stability, sensitivity, response speed, and detection limits under complex dynamic conditions, which material innovations are urgently [...] Read more.
Conductive hydrogels demonstrate substantial potential for flexible wearable sensors in motion monitoring, owing to their unique physicochemical properties; however, current implementations still confront persistent challenges in long-term stability, sensitivity, response speed, and detection limits under complex dynamic conditions, which material innovations are urgently required to resolve. Consequently, this paper comprehensively reviews the recent advancements in conductive hydrogel-based flexible wearable sensors for sports applications. The paper examines the conductivity, self-adhesion, self-repair, and biocompatibility of conductive hydrogels, along with detailed analyses of their working principles in resistance, capacitance, piezoelectric, and battery-based sensing mechanisms. Additionally, the paper summarizes innovative strategies to enhance sensor performance through polymer blending, polyelectrolyte doping, inorganic salt doping, and nanomaterial integration. Furthermore, the paper highlights the latest applications of conductive hydrogel flexible wearable sensors in human motion monitoring, electrophysiological signal detection, and electrochemical biosignal monitoring. Finally, the paper provides an in-depth discussion of the advantages and limitations of existing technologies, offering valuable insights and new perspectives for future research directions. Full article
(This article belongs to the Special Issue Gels for Removal and Adsorption (3rd Edition))
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14 pages, 3526 KB  
Article
Three-Dimensional Printing and Supercritical Technologies for the Fabrication of Intricately Structured Aerogels Derived from the Alginate–Chitosan Polyelectrolyte Complex
by Natalia Menshutina, Andrey Abramov, Eldar Golubev and Pavel Tsygankov
Gels 2025, 11(7), 477; https://doi.org/10.3390/gels11070477 - 20 Jun 2025
Viewed by 415
Abstract
Patient-specific scaffolds for tissue and organ regeneration are still limited by the difficulty of simultaneously shaping complex geometries, preserving hierarchical porosity, and guaranteeing sterility. Additive technologies represent a promising approach for addressing problems in tissue engineering, with the potential to develop personalized matrices [...] Read more.
Patient-specific scaffolds for tissue and organ regeneration are still limited by the difficulty of simultaneously shaping complex geometries, preserving hierarchical porosity, and guaranteeing sterility. Additive technologies represent a promising approach for addressing problems in tissue engineering, with the potential to develop personalized matrices for the growth of tissue and organ cells. The utilization of supercritical technologies, encompassing the processes of drying and sterilization within a supercritical fluid environment, has demonstrated significant opportunities for obtaining highly effective matrices for cell growth based on biocompatible materials. We present a comprehensive methodology for fabricating intricately structured, sterile aerogels based on alginate–chitosan polyelectrolyte complexes. The target three-dimensional macrostructure is achieved through (i) direct ink writing or (ii) heterophase printing, enabling the deposition of inks with diverse rheological profiles (viscosities ranging from 0.8 to 2500 Pa·s). A coupled supercritical carbon dioxide drying–sterilization regimen at 120 bar and 40 °C is employed to preserve the highly porous architecture of the printed constructs. The resulting aerogels exhibit 96 ± 2% porosity, a BET surface area of 108–238 m2 g−1, and complete sterility. The proposed integration of 3D printing and supercritical processing yields sterile, intricately structured aerogels with substantial potential for the fabrication of patient-specific scaffolds for tissue and organ regeneration. Full article
(This article belongs to the Special Issue Polymer Aerogels and Aerogel Composites)
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32 pages, 5511 KB  
Article
Development of Carbohydrate Polyelectrolyte Nanoparticles for Use in Drug Delivery Systems that Cross the Blood–Brain Barrier to Treat Brain Tumors
by Vladimir E. Silant’ev, Mikhail E. Shmelev, Andrei S. Belousov, Fedor O. Trukhin, Nadezhda E. Struppul, Aleksandra A. Patlay, Anna K. Kravchenko, Sergey P. Shchava and Vadim V. Kumeiko
Polymers 2025, 17(12), 1690; https://doi.org/10.3390/polym17121690 - 18 Jun 2025
Cited by 1 | Viewed by 608
Abstract
The low effectiveness of various brain cancer treatment methods is due to a number of significant challenges. Most of them are unable to penetrate the blood–brain barrier (BBB) when drugs are administered systemically through the bloodstream. Nanoscale particles play a special role among [...] Read more.
The low effectiveness of various brain cancer treatment methods is due to a number of significant challenges. Most of them are unable to penetrate the blood–brain barrier (BBB) when drugs are administered systemically through the bloodstream. Nanoscale particles play a special role among materials capable of binding drug molecules and successfully crossing the BBB. Biopolymeric nanoparticles (NPs) demonstrate excellent biocompatibility and have the remarkable ability to modify the environment surrounding tumor cells, thereby potentially improving cellular uptake of delivery agents. In our research, nanoscale polyelectrolyte complexes (PECs) ranging in size from 56 to 209 nm were synthesized by ionic interaction of the oppositely charged polysaccharides pectin and chitosan. The structural characteristics of these complexes were carefully characterized by infrared (FTIR) and Raman spectroscopy. The immobilization efficiency of antitumor drugs was comprehensively evaluated using UV spectrophotometry. The cytotoxicity of the NPs was evaluated in the U87-MG cell line. The preliminary data indicate a significant decrease in the metabolic activity of these tumor cells. Important details on the interaction of the NPs with an endothelial layer structurally similar to the BBB were obtained by simulating the BBB using a model based on human blood vessels. Our studies allowed us to establish a significant correlation between the kinetic parameters of drug immobilization and the ratio of biopolymer concentrations in the initial compositions, which provides valuable information for future optimization of drug delivery system design. Full article
(This article belongs to the Special Issue Advanced Polymeric Biomaterials for Drug Delivery Applications)
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15 pages, 1269 KB  
Article
Linear DNA–Chitosan Nanoparticles: Formulation Challenges and Transfection Efficiency in Lung Cell Line
by Chiara Migone, Angela Fabiano, Ylenia Zambito, Rebecca Piccarducci, Laura Marchetti, Chiara Giacomelli, Claudia Martini and Anna Maria Piras
Appl. Biosci. 2025, 4(2), 29; https://doi.org/10.3390/applbiosci4020029 - 6 Jun 2025
Viewed by 730
Abstract
Linear DNA constructs are used in gene delivery and therapy application due to their capacity of integration into the mammalian genome, offering stable transgene expression. Compared to circular plasmids, linear DNA also has the advantage that its dimension and steric hindrance are directly [...] Read more.
Linear DNA constructs are used in gene delivery and therapy application due to their capacity of integration into the mammalian genome, offering stable transgene expression. Compared to circular plasmids, linear DNA also has the advantage that its dimension and steric hindrance are directly correlated to the length of the nucleotide chain. These considerations make linear DNA an effective choice for gene delivery pilot studies, where formulations and transfection efficiency calculations are studied considering the nucleic acid dimensions. Meanwhile, the development of DNA–chitosan nanoparticles (NPs) has gained significant interest for their potential in nucleic acid delivery, especially as non-viral gene delivery systems and for embedding linear DNA fragments, as well as gene delivery to the lung. This study explored an easy polyelectrolyte complexing preparation of linear DNA-loaded chitosan nanoparticles. Among the different formulations of nanoparticles prepared, the optimal one exhibited a size of approximately 290 nm, an encapsulation efficiency of 86% and a zeta potential of 25 mV. Additionally, this study examined how the concentration of DNA in solution influenced nanoparticle formation, encapsulation efficiency and particle size. In particular, transient transfection of the chitosan–linear DNA fragment complex, encoding for green fluorescent protein (GFP), was conducted in human pulmonary distal lung cells (NCI-H441 cells), demonstrating successful cellular internalization and protein expression. These studies highlight the potential of DNA–chitosan NPs in nucleic acid delivery, particularly for pulmonary applications. Future works will focus on formulating the achieved carrier into an inhalable dosage form to improve its translational application. Full article
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29 pages, 6689 KB  
Article
A Novel Approach for the Activity Assessment of L-Asparaginase Formulations When Dealing with Complex Biological Samples
by Igor D. Zlotnikov and Elena V. Kudryashova
Int. J. Mol. Sci. 2025, 26(11), 5227; https://doi.org/10.3390/ijms26115227 - 29 May 2025
Cited by 1 | Viewed by 847
Abstract
Majority of commercial L-asparaginase (L-ASNase) activity assays are based on coupled enzymatic reaction, which converts aspartate into pyruvate, subsequently reacting with the probe to form a stable chromophore, which can be detected spectrophotometrically. However, in complex biological samples this method can be inaccurate [...] Read more.
Majority of commercial L-asparaginase (L-ASNase) activity assays are based on coupled enzymatic reaction, which converts aspartate into pyruvate, subsequently reacting with the probe to form a stable chromophore, which can be detected spectrophotometrically. However, in complex biological samples this method can be inaccurate due to poor optical transparency or presence of compounds interfering with the coupled enzyme reaction–for this kind of cases alternative methods have been suggested. Here we suggest a strategy to rationally pick a method of choice in a variety of situations, taking into consideration the upsides and downsides of each method. A high-throughput fluorometric assay employing the substrate Asp-AMC was rigorously validated for L-ASPNase activity screening. Aassay performance is evaluated in complex biological matrices, including bovine serum, whole and diluted human blood, and finally the mouse blood and liver homogenates samples obtained from pharmacokinetic studies. This comprehensive validation process ensures the reliability and applicability of the assay for assessing L-asparaginase activity in diverse and physiologically relevant environments. Potential interfering factors and matrix effects were addressed, and assay conditions were optimized for each matrix. The optimized assay was employed to screen various L-asparaginase types (intracellular L-ASNases type I RrA, periplasmic L-ASNases type II EcA and EwA) and ASPNase formulations (conjugates with polyamines or polyelectrolyte complexes), comparing their kinetic parameters and stability. Fourier-transform infrared (FTIR) spectroscopy was further employed to investigate the fine features of molecular mechanisms of L-asparaginase catalysis. FTIR spectra of Asn during hydrolysis were analyzed in buffer solutions and in complex biological matrices, such as blood sample or liver homogenates which is crucial in the context of pharmacokinetic research. This combined fluorometric and FTIR approach provides a powerful platform for optimizing L-ASNase formulations and therapeutic strategies for ALL. Based on the results obtained we have developed a strategy to choose an approach for L-Asparaginase activity assessment for a variety of difficult situations when dealing with complex biological samples. Full article
(This article belongs to the Special Issue New Agents and Novel Drugs Use for the Oncological Diseases Treatment)
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28 pages, 9876 KB  
Article
Nanofiltration Membranes from Poly(sodium-p-styrenesulfonate)/Polyethylenimine Polyelectrolyte Complex Modified with Carbon Nanoparticles for Enhanced Water Treatment
by Mariia Dmitrenko, Olga Mikhailovskaya, Roman Dubovenko, Anton Mazur, Anna Kuzminova, Igor Prikhodko, Konstantin Semenov, Rongxin Su and Anastasia Penkova
Polymers 2025, 17(10), 1306; https://doi.org/10.3390/polym17101306 - 10 May 2025
Viewed by 616
Abstract
Industrial wastewater poses a significant environmental challenge due to its harmful effects. The development of sustainable membrane processes for water treatment and the environmentally friendly production of polymer membranes is one of the major challenges of our time. An alternative approach is to [...] Read more.
Industrial wastewater poses a significant environmental challenge due to its harmful effects. The development of sustainable membrane processes for water treatment and the environmentally friendly production of polymer membranes is one of the major challenges of our time. An alternative approach is to prepare polyelectrolyte complex (PEC) membranes using the aqueous phase separation (APS) method without the use of toxic solvents. In this work, PEC nanofiltration membranes of poly(sodium-p-styrenesulfonate) (PSS)/polyethylenimine (PEI) modified with carbon nanoparticles (graphene oxide, polyhydroxylated fullerene (HF), multi-walled carbon nanotubes) were developed for enhanced water treatment from anionic food dyes and heavy metal ions. The effect of varying the PSS/PEI monomer ratio, carbon nanoparticles, the content of the optimal HF modifier, and the cross-linking agent on the membrane properties was studied in detail. The changes in the structure and physicochemical properties of the PEC-based membranes were investigated using spectroscopic, microscopic, thermogravimetric analysis methods, and contact angle measurements. The PSS and PEI interactions during PEC formation and the effect of PEI protonation on membrane properties were investigated using computational methods. The optimal cross-linked PEC/HF(1%) (1:1.75 PSS/PEI) membrane had more than 2 times higher permeability compared to the pristine PEC membrane, with dye and heavy metal ion rejection of 99.99 and >97%, respectively. Full article
(This article belongs to the Section Polymer Membranes and Films)
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23 pages, 10091 KB  
Article
Size and Shape of Primary (Bio)Polyelectrolyte Complexes Chitosan/Gelatin: Study Using Small-Angle X-Ray Scattering from Synchrotron Radiation
by Aleksandr Podshivalov, Mikhail Litvinov, Aleksandr Kashurin and Ksenia Danilova
Polymers 2025, 17(9), 1236; https://doi.org/10.3390/polym17091236 - 30 Apr 2025
Viewed by 490
Abstract
In this work, using small-angle X-ray scattering from synchrotron radiation, the macromolecular structure of chitosan and gelatin polyelectrolytes and their mixtures at various pH values and ratios was studied to determine the size and shape of primary supramolecular (bio)PEC. Analysis of the scattering [...] Read more.
In this work, using small-angle X-ray scattering from synchrotron radiation, the macromolecular structure of chitosan and gelatin polyelectrolytes and their mixtures at various pH values and ratios was studied to determine the size and shape of primary supramolecular (bio)PEC. Analysis of the scattering profiles of the initial solutions of chitosan and gelatin with the building of the pair distance function showed the formation of single-modal distributions with a maximum molecular size of 46 and 32.2 nm, respectively. Ab initio reconstruction of the macromolecule’s shape showed the formation of objects shaped like an oblate spheroid. In mixtures of chitosan and gelatin at a pH below the isoelectric point, it was found that the scattering structures correspond to the initial biopolymers. However, it is observed that values of the aspect ratio at a ratio above 1:10 gradually increase, which indicates a slight elongation of the average particle and indirectly indicates the formation of dissipative structures of (bio)PEC. In mixtures at a pH above the isoelectric point, it was shown that at ratios above 1:5, the formation of primary supramolecular complexes is observed, which is accompanied by an increase in zero-scattering intensity by about three times, maximum molecular size by two to two-and-a-half times relative to the initial polymers, and the formation of elongated structures corresponding to the cylinder (swollen spiral). It may be a consequence of the increased efficiency of the polyelectrolyte associative interaction between chitosan and gelatin. Full article
(This article belongs to the Special Issue Advances in Polyelectrolytes and Polyelectrolyte Complexes)
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18 pages, 3344 KB  
Article
Chondroitin Sulfate/Cyanocobalamin–Chitosan Polyelectrolyte Complexes for Improved Oral Delivery of Colistin
by Natallia V. Dubashynskaya, Andrey Y. Borovskoy, Anton N. Bokatyi, Tatiana S. Sall, Tatiana S. Egorova, Elena V. Demyanova, Ekaterina A. Murashko and Yury A. Skorik
Polysaccharides 2025, 6(1), 21; https://doi.org/10.3390/polysaccharides6010021 - 7 Mar 2025
Cited by 1 | Viewed by 1383
Abstract
Introduction. The rise of multidrug resistance in Gram-negative ESKAPE pathogens is a critical challenge for modern healthcare. Colistin (CT), a peptide antibiotic, remains a last-resort treatment for infections caused by these superbugs due to its potent activity against Gram-negative bacteria and the rarity [...] Read more.
Introduction. The rise of multidrug resistance in Gram-negative ESKAPE pathogens is a critical challenge for modern healthcare. Colistin (CT), a peptide antibiotic, remains a last-resort treatment for infections caused by these superbugs due to its potent activity against Gram-negative bacteria and the rarity of resistance. However, its clinical use is severely limited by high nephro- and neurotoxicity, low oral bioavailability, and other adverse effects. A promising strategy to improve the biopharmaceutical properties and safety profile of antibiotics is the development of biopolymer-based delivery systems, also known as nanoantibiotics. Objective. The aim of this study was to develop polyelectrolyte complexes (PECs) for the oral delivery of CT to overcome its major limitations, such as poor bioavailability and toxicity. Methods. PECs were formulated using chondroitin sulfate (CHS) and a cyanocobalamin–chitosan conjugate (CSB12). Vitamin B12 was incorporated as a targeting ligand to enhance intestinal permeability through receptor-mediated transport. The resulting complexes (CHS-CT-CSB12) were characterized for particle size, ζ-potential, encapsulation efficiency, and drug release profile under simulated gastrointestinal conditions (pH 1.6, 6.5, and 7.4). The antimicrobial activity of the encapsulated CT was evaluated in vitro against Pseudomonas aeruginosa. Results. The CHS-CT-CSB12 PECs exhibited a hydrodynamic diameter of 446 nm and a ζ-potential of +28.2 mV. The encapsulation efficiency of CT reached 100% at a drug loading of 200 µg/mg. In vitro release studies showed that approximately 70% of the drug was released within 1 h at pH 1.6 (simulating gastric conditions), while a cumulative CT release of 80% over 6 h was observed at pH 6.5 and 7.4 (simulating intestinal conditions). This release profile suggests the potential use of enteric-coated capsules or specific administration guidelines, such as taking the drug on an empty stomach with plenty of water. The antimicrobial activity of encapsulated CT against P. aeruginosa was comparable to that of the free drug, with a minimum inhibitory concentration of 1 µg/mL for both. The inclusion of vitamin B12 in the PECs significantly improved intestinal permeability, as evidenced by an apparent permeability coefficient (Papp) of 1.1 × 10−6 cm/s for CT. Discussion. The developed PECs offer several advantages over conventional CT formulations. The use of vitamin B12 as a targeting ligand enhances drug absorption across the intestinal barrier, potentially increasing oral bioavailability. In addition, the controlled release of CT in the intestinal environment reduces the risk of systemic toxicity, particularly nephro- and neurotoxicity. These findings highlight the potential of CHS-CT-CSB12 PECs as a nanotechnology-based platform for improving the delivery of CT and other challenging antibiotics. Conclusions. This study demonstrates the promising potential of CHS-CT-CSB12 PECs as an innovative oral delivery system for CT that addresses its major limitations and improves its therapeutic efficacy. Future work will focus on in vivo evaluation of the safety and efficacy of the system, as well as exploring its applicability for delivery of other antibiotics with similar challenges. Full article
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22 pages, 3631 KB  
Article
Improving Atorvastatin Release from Polyelectrolyte Complex-Based Hydrogels Using Freeze-Drying: Formulation and Pharmaceutical Assessment of a Novel Delivery System for Oral Candidiasis Treatment
by Joanna Potaś-Stobiecka, Radosław Aleksander Wach, Bożena Rokita, Weronika Kaja Simonik, Magdalena Wróblewska, Karolina Borkowska, Silje Mork, Nataša Škalko-Basnet and Katarzyna Winnicka
Int. J. Mol. Sci. 2025, 26(5), 2267; https://doi.org/10.3390/ijms26052267 - 4 Mar 2025
Viewed by 1057
Abstract
Atorvastatin calcium, an antifungal agent, has the potential to be repositioned/repurposed to combat the increasing antimicrobial resistance. However, one of the most crucial issues in developing atorvastatin calcium-loaded products with a topical antifungal effect is achieving the optimal release and dissolution rates of [...] Read more.
Atorvastatin calcium, an antifungal agent, has the potential to be repositioned/repurposed to combat the increasing antimicrobial resistance. However, one of the most crucial issues in developing atorvastatin calcium-loaded products with a topical antifungal effect is achieving the optimal release and dissolution rates of this statin to produce the desired therapeutic effect. In this paper, we report on the development and pharmaceutical assessment of hydrogels composed of low-molecular-weight chitosan, tragacanth, and xanthan gum/pectin/κ-carrageenan as potential drug carriers for atorvastatin calcium for buccal delivery. Multidirectional analysis of the carriers with regard to their drug-release profiles and mucoadhesive, antimicrobial, and cytotoxic properties was accompanied by an evaluation of the freeze-drying process used to improve the hydrogels’ applicability. Using differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy techniques, the role of lyophilization in enhancing atorvastatin calcium delivery from polyelectrolyte complex-based matrices via drug amorphization was demonstrated. The freeze-dried hydrogels had significantly improved release and dissolution rates for the amorphic statin. Therefore, there is great potential for the use of lyophilization in the design of polyelectrolyte complex-based semi-solids in usable dosage forms for numerous crystalline and poorly water-soluble active substances. Full article
(This article belongs to the Special Issue Applications of Biomaterials in Drug Development)
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24 pages, 5579 KB  
Article
Uptake and Inhibition of P-Glycoprotein-Mediated Efflux Evaluation of Encapsulated Methotrexate Chitosan and Hypromellose Phthalate Nanoparticles for Potential Glioblastoma Treatment
by Valéria de Moura Leite Naves, Rafaela Franco Dias Bruzadelli, Marisa Ionta, Maria Palmira Daflon Gremião, Liliane Neves Pedreiro, Gislaine Ribeiro Pereira and Flávia Chiva Carvalho
Pharmaceutics 2025, 17(2), 239; https://doi.org/10.3390/pharmaceutics17020239 - 12 Feb 2025
Cited by 2 | Viewed by 1052
Abstract
Background: Methotrexate (MTX), a folic acid antagonist used in chemotherapy, faces limitations due to cancer cell resistance, high toxicity, and low bioavailability. Objective: This study developed nanoparticles (NPs) of chitosan (QS) and hydroxypropylmethylcellulose phthalate (HPMCP) to encapsulate MTX for potential effect investigation on [...] Read more.
Background: Methotrexate (MTX), a folic acid antagonist used in chemotherapy, faces limitations due to cancer cell resistance, high toxicity, and low bioavailability. Objective: This study developed nanoparticles (NPs) of chitosan (QS) and hydroxypropylmethylcellulose phthalate (HPMCP) to encapsulate MTX for potential effect investigation on glioblastoma cell targeting and P-gp efflux inhibition. Method: NPs were produced by the polyelectrolyte complexation method and were characterized by DLS, PDI, DSC, FTIR, PXRD, MEV, drug release profile, and an in vitro mucoadhesion test. Cell viability, flow cytometry, and LSCM using U251MG (glioblastoma) and CCD 1059Sk (fibroblasts) cells were used to evaluate glioblastoma and the P-gp efflux effect. Results: NPPM29 (QS3:1) showed 91.72% encapsulation efficiency, a mean diameter of 452.6 nm, and a zeta potential of +22.5 mV. DSC, FTIR, and PXRD confirmed the QS-HPMCP supramolecular interaction. Liquid falling mucoadhesion tests demonstrated strong retention of NPPM29 (84%) compared to free MTX (10.5%). In vitro release studies indicated controlled drug release at pH 7.4. Cytotoxicity assays in U251MG revealed enhanced efficacy of NPPM29 (IC50 = 68.79 µg/mL) compared to free MTX (IC50 = 80.54 µg/mL), with minimal impact on fibroblasts, confirming tumor specificity. Flow cytometry and LSCM confirmed improved cellular internalization and P-gp inhibition. Conclusions: These findings highlight the potential of MTX-QS-HPMCP-NPs for glioblastoma therapy. Full article
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25 pages, 5193 KB  
Article
Polyelectrolyte Complex Dry Powder Formulations of Tobramycin with Hyaluronic Acid and Sodium Hyaluronate for Inhalation Therapy in Cystic Fibrosis-Associated Infections
by Yanina de Lafuente, Eride Quarta, María S. Magi, Ana L. Apas, Joaquín Pagani, María C. Palena, Paulina L. Páez, Fabio Sonvico and Alvaro F. Jimenez-Kairuz
Antibiotics 2025, 14(2), 169; https://doi.org/10.3390/antibiotics14020169 - 8 Feb 2025
Cited by 1 | Viewed by 1213
Abstract
Background/Objectives: Pulmonary delivered tobramycin (TOB) is a standard treatment for Pseudomonas aeruginosa lung infections, that, along with Staphylococcus aureus, is one of the most common bacteria causing recurring infections in CF patients. However, the only available formulation on the market containing tobramycin, TOBI [...] Read more.
Background/Objectives: Pulmonary delivered tobramycin (TOB) is a standard treatment for Pseudomonas aeruginosa lung infections, that, along with Staphylococcus aureus, is one of the most common bacteria causing recurring infections in CF patients. However, the only available formulation on the market containing tobramycin, TOBI®, is sold at a price that makes the access to the treatment difficult. Therefore, this work focuses on the development and characterization of an ionic complex between a polyelectrolyte, hyaluronic acid (HA) and its salt, sodium hyaluronate (NaHA), and TOB to be formulated as an inhalable dry powder. Methods: The solid state complex obtained by spray drying technique was physicochemically characterized by infrared spectroscopy, thermal analysis and X-ray diffraction, confirming an ionic interaction for both complexes. Results: The powder density, geometric size, and morphology along with the aerodynamic performance showed suitable properties for the powder formulations to reach the deep lung. Moisture uptake was found to be low, with the complex HA-TOB remaining physicochemically unchanged, while the NaHA-TOB required significant protection against humidity. The biopharmaceutical in vitro experiments showed a rapid dissolution which can have a positively impact in reducing side effects, while the drug release study demonstrated a reversible polyelectrolyte–drug interaction. Microbiological experiments against P. aeruginosa and S. aureus showed improved bacterial growth inhibition and bactericidal efficacy, as well as better inhibition and eradication of biofilms when compared with to TOB. Conclusions: A simple polyelectrolyte-drug complex technique represents a promising strategy for the development of antimicrobial dry powder formulations for pulmonary delivery in the treatment of cystic fibrosis (CF) lung infections. Full article
(This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship)
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