Search Results (48)

Background: The quest for well-defined immunoadjuvants remains one of the highest priorities for the successful development of effective vaccines. Combination adjuvants, which are designed to integrate both the ability to activate a variety of immune mechanisms and synergistically improve the delivery of vaccine components, are well-positioned to address the unmet needs. The development of a preventive vaccine against hepatitis C virus (HCV)—a major public health concern—is a particular instance in which the choice of the immunoadjuvant is of utmost importance. Methods: We assembled a lipid A Toll-like receptor 4 (TLR4) agonist BECC438 and TLR7/8 agonist resiquimod (R848) on a polyphosphazene macromolecule (PCPP) to create a nanoscale immunoadjuvant-vaccine delivery system: PCPP-R+BECC438. This aqueous-based system was formulated with the HCV sE2 antigen, and the resulting vaccine candidate was evaluated in vivo for the ability to induce immune responses. Results: Co-assembly of adjuvants resulted in a visually clear aqueous system of nanoscale dimensions, monomodal size distribution, and entropy-driven interactions between components. Intramuscular immunization of mice with HCV sE2 antigen formulated in a polyphosphazene-based nano-system induced ten-fold higher IgG and IgG2a titers than the antigen adjuvanted with BECC438 alone. PCPP-R+BECC438 formulated HCV sE2 also produced statistically significant improvements in IgG2a/IgG1 ratio and more robust HCVpp neutralization ID₅₀ titers than control formulations. Conclusions: Polyphosphazene-assembled adjuvant nano-system promotes in vivo immune responses of enhanced quantity and quality of antibodies with increased potency of HCV neutralization. Full article

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

In recent years, polyphosphazene (POP) membranes have been gaining more and more attention owing to their excellent pervaporation desulfurization performance. To develop new POP membranes, three kinds of POPs with different side groups, Poly[bis(trifluoroethoxy)phosphazene] (PTFEP), Poly[bis(trifluorobutoxy)phosphazene] (PTFBP), and Poly[bis(octafluoropentyloxy)phosphazene] (POFPP), were synthesized. The NMR spectroscopy demonstrated that POPs with a designed structure were successfully prepared. Subsequently, the composite membranes based on these POPs were fabricated by solution casting. The influence of side groups on the desulfurization performance of membranes was systematically evaluated via a pervaporation test. Among these membranes, the PTFBP membrane exhibited the highest separation efficiency, significantly outperforming other membrane types with a permeation flux of 0.284 kg·m⁻²·h⁻¹ at 200 ppm and 85 °C, along with a sulfur enrichment factor of 26.48. In addition, the effects of temperature and feed concentration on separation performance were investigated in detail. Full article

Hepatitis C virus (HCV) is a major public health concern, and the development of an effective HCV vaccine plays an important role in the effort to prevent new infections. Supramolecular co-assembly and co-presentation of the HCV envelope E1E2 heterodimer complex and core protein presents an attractive vaccine design strategy for achieving effective humoral and cellular immunity. With this objective, the two antigens were non-covalently assembled with an immunostimulant (TLR 7/8 agonist) into virus-mimicking polymer nanocomplexes (VMPNs) using a biodegradable synthetic polyphosphazene delivery vehicle. The resulting assemblies were characterized using dynamic light scattering and asymmetric flow field-flow fractionation methods and directly visualized in their vitrified state by cryogenic electron microscopy. The in vivo superiority of VMPNs over the individual components and an Alum-formulated vaccine manifests in higher neutralizing antibody titers, the promotion of a balanced IgG response, and the induction of a cellular immunity—CD4+ T cell responses to core proteins. The aqueous-based spontaneous co-assembly of antigens and immunopotentiating molecules enabled by a synthetic biodegradable carrier offers a simple and effective pathway to the development of polymer-based supramolecular nanovaccine systems. Full article

The efficient hydrogenation of N-heterocycles with H₂ under mild conditions remains a significant challenge. In this work, polyphosphazene (PZs) microspheres, novel organic–inorganic hybrid materials possessing unique –P=N– structural units and a diverse range of side groups, were used to serve as support for the design of a stable and efficient Pd nanocatalyst (Pd/PZs). The PZs microspheres were prepared by self-assembly induced by precipitation polymerization, and Pd nanoparticles were grown and loaded on the support by a chemical reduction process. Several characterization techniques, including XRD, FTIR, SEM, TEM, XPS, BET and TGA, were used to study the structural features of the nanocomposites. The results revealed that Pd nanoparticles were uniformly distributed on the PZs microspheres, with primary sizes ranging from 4 to 9 nm based on the abundance of functional P/N/O groups in PZs. Remarkably high catalytic activity and stability were observed for the hydrogenation of quinoline compounds using the Pd/PZs nanocatalyst under mild conditions. Rates of 98.9% quinoline conversion and 98.5% 1,2,3,4-tetrahydroquinoline selectivity could be achieved at a low H₂ pressure (1.5 bar) and temperature (40 °C). A possible reaction mechanism for quinoline hydrogenation over Pd/PZs was proposed. This work presents an innovative approach utilizing a Pd-based nanocatalyst for highly efficient multifunctional hydrogenation. Full article

“Hot spot” ¹⁹F magnetic resonance imaging (MRI) has garnered significant attention recently for its ability to image various disease markers quantitatively. Unlike conventional gadolinium-based MRI contrast agents, which rely on proton signal modulation, ¹⁹F-MRI’s direct detection has a unique advantage in vivo, as the human body exhibits a negligible background ¹⁹F-signal. However, existing perfluorocarbon (PFC) or PFC-based contrast materials suffer from several limitations, including low longitudinal relaxation rates and relatively low imaging efficiency. Hence, we designed a macromolecular contrast agent featuring a high number of magnetically equivalent ¹⁹F-nuclei in a single macromolecule, adequate fluorine nucleus mobility, and excellent water solubility. This design utilizes superfluorinated polyphosphazene (PPz) polymers as the ¹⁹F-source; these are modified with sodium mercaptoethanesulfonate (MESNa) to achieve water solubility exceeding 360 mg/mL, which is a similar solubility to that of sodium chloride. We observed substantial signal enhancement in MRI with these novel macromolecular carriers compared to non-enhanced surroundings and aqueous trifluoroacetic acid (TFA) used as a positive control. In conclusion, these novel water-soluble macromolecular carriers represent a promising platform for future MRI contrast agents. Full article

Lithium-ion polymer batteries, also known as lithium-polymer, abbreviated Li-po, are one of the main research topics nowadays in the field of energy storage. This review focuses on the use of the phosphorus containing compounds in Li-po batteries, such as polyphosphonates and polyphosphazenes. Li-po batteries are mini-devices, capable of providing power for any portable gadget. From a constructive point of view, Li-po batteries contain an anode (carbon), a cathode (metal oxide), and a polymer electrolyte, which could be liquid electrolytes or solid electrolytes. In general, a divider is used to keep the anode and cathode from touching each other directly. Since liquid electrolytes have a generally high ionic conductivity, they are frequently employed in Li-ion batteries. In the last decade, the research in this field has also focused on solving safety issues, such as the leakage of electrolytes and risk of ignition due to volatile and flammable organic solvents. The research topics in the field of Li-po remain focused on solving safety problems and improving performance. Full article

Degradable layer-by-layer (LbL) polymeric coatings have distinct advantages over traditional biomedical coatings due to their precision of assembly, versatile inclusion of bioactive molecules, and conformality to the complex architectures of implantable devices. However, controlling the degradation rate while achieving biocompatibility has remained a challenge. This work employs polyphosphazenes as promising candidates for film assembly due to their inherent biocompatibility, tunability of chemical composition, and the buffering capability of degradation products. The degradation of pyrrolidone-functionalized polyphosphazenes was monitored in solution, complexes and LbL coatings (with tannic acid), providing the first to our knowledge comparison of solution-state degradation to solid-state LbL degradation. In all cases, the rate of degradation accelerated in acidic conditions. Importantly, the tunability of the degradation rate of polyphosphazene-based LbL films was achieved by varying film assembly conditions. Specifically, by slightly increasing the ionization of tannic acid (near neutral pH), we introduce electrostatic “defects” to the hydrogen-bonded pairs that accelerate film degradation. Finally, we show that replacing the pyrrolidone side group with a carboxylic acid moiety greatly reduces the degradation rate of the LbL coatings. In practical applications, these coatings have the versatility to serve as biocompatible platforms for various biomedical applications and controlled release systems. Full article

Degradable polymers (both biomacromolecules and several synthetic polymers) for biomedical applications have been promising very much in the recent past due to their low cost, biocompatibility, flexibility, and minimal side effects. Here, we present an overview with updated information on natural and synthetic degradable polymers where a brief account on different polysaccharides, proteins, and synthetic polymers viz. polyesters/polyamino acids/polyanhydrides/polyphosphazenes/polyurethanes relevant to biomedical applications has been provided. The various approaches for the transformation of these polymers by physical/chemical means viz. cross-linking, as polyblends, nanocomposites/hybrid composites, interpenetrating complexes, interpolymer/polyion complexes, functionalization, polymer conjugates, and block and graft copolymers, are described. The degradation mechanism, drug loading profiles, and toxicological aspects of polymeric nanoparticles formed are also defined. Biomedical applications of these degradable polymer-based biomaterials in and as wound dressing/healing, biosensors, drug delivery systems, tissue engineering, and regenerative medicine, etc., are highlighted. In addition, the use of such nano systems to solve current drug delivery problems is briefly reviewed. Full article

This study investigates the mechanical properties, degradation behavior, and biocompatibility of poly[(α-amino acid ester) phosphazene] electrospun fibers based on the ethyl ester of L-methionine (PαAPz-M), a material with potential applications in tissue engineering. We utilized atomic force microscopy (AFM) to evaluate the fiber mechanical characteristics and calculate its Young’s modulus, revealing it to closely mimic the stiffness of a natural extracellular matrix (ECM). We also studied the degradation behavior of PαAPz-M scaffolds over 21 days, showing that they maintain the highly porous structure required for tissue engineering. Further evaluation of mesenchymal multipotent 10T1/2 cell and mesenchymal stem cell (MSC) behavior on the scaffolds demonstrated significant cell viability, proliferation, and successful MSC differentiation into smooth muscle cells. Expression of collagen and elastin by MSCs on the fiber mats highlighted potential ECM formation during scaffold degradation, confirming PαAPz-M as a promising material for vascular tissue engineering. Full article

The structural versatility of polydichlorophosphazene derived from the inestimable possibilities to functionalize the two halogens, attached to each phosphazene main chain unit, attracted increasing attention in the last decade. This uncountable chemical derivatization is doubled by the amphiphilic roleplay demonstrated by polyphosphazenes containing twofold side-chained hydrophilic and hydrophobic moieties. Thus, it is able to encapsulate specific bioactive molecules for various targeted nanomedicine applications. A new amphiphilic graft, polyphosphazenes (PPP/PEG–NH/Hys/MAB), was synthesized via the thermal ring-opening polymerization of hexachlorocyclotriphosphazene, followed by a subsequent two-step substitution reaction of chlorine atoms with hydrophilic methoxypolyethylene glycol amine/histamine dihydrochloride adduct (PEG–NH₂)/(Hys) and hydrophobic methyl-p-aminobenzoate (MAB), respectively. Fourier transform infrared spectroscopy (FTIR) and ¹H and ³¹P-nuclear magnetic resonance spectroscopy (NMR) have been used to validate the expected architectural assembly of the copolymer. Docetaxel loaded micelles based on synthesized PPP/PEG–NH/Hys/MAB were designed by dialysis method. The micelles size was evaluated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The drug release profiles from the PPP/PEG–NH/Hys/MAB micelles were established. In vitro cytotoxicity tests of PPP/PEG–NH/Hys/MAB micelles loaded with Docetaxel revealed that designed polymeric micelles exhibited an increased cytotoxic effect on MCF-7 cells. Full article

The inclusion of fluorine motifs in drugs and drug delivery systems is an established tool for modulating their biological potency. Fluorination can improve drug specificity or boost the vehicle’s ability to cross cellular membranes. However, the approach has yet to be applied to vaccine adjuvants. Herein, the synthesis of fluorinated bioisostere of a clinical stage immunoadjuvant—poly[di(carboxylatophenoxy)phosphazene], PCPP—is reported. The structure of water-soluble fluoropolymer—PCPP-F, which contains two fluorine atoms per repeat unit—was confirmed using ¹H, ³¹P and ¹⁹F NMR, and its molecular mass and molecular dimensions were determined using size-exclusion chromatography and dynamic light scattering. Insertion of fluorine atoms in the polymer side group resulted in an improved solubility in acidic solutions and faster hydrolytic degradation rate, while the ability to self-assemble with an antigenic protein, lysozyme—an important feature of polyphosphazene vaccine adjuvants—was preserved. In vivo assessment of PCPP-F demonstrated its greater ability to induce antibody responses to Hepatitis C virus antigen when compared to its non-fluorinated counterpart. Taken together, the superior immunoadjuvant activity of PCPP-F, along with its improved formulation characteristics, demonstrate advantages of the fluorination approach for the development of this family of macromolecular vaccine adjuvants. Full article

Carbon capture has been an important topic of the twenty-first century because of the elevating carbon dioxide (CO₂) levels in the atmosphere. CO₂ in the atmosphere is above 420 parts per million (ppm) as of 2022, 70 ppm higher than 50 years ago. Carbon capture research and development has mostly been centered around higher concentration flue gas streams. For example, flue gas streams from steel and cement industries have been largely ignored due to lower associated CO₂ concentrations and higher capture and processing costs. Capture technologies such as solvent-based, adsorption-based, cryogenic distillation, and pressure-swing adsorption are under research, but many suffer from higher costs and life cycle impacts. Membrane-based capture processes are considered cost-effective and environmentally friendly alternatives. Over the past three decades, our research group at Idaho National Laboratory has led the development of several polyphosphazene polymer chemistries and has demonstrated their selectivity for CO₂ over nitrogen (N₂). Poly[bis((2-methoxyethoxy)ethoxy)phosphazene] (MEEP) has shown the highest selectivity. A comprehensive life cycle assessment (LCA) was performed to determine the life cycle feasibility of the MEEP polymer material compared to other CO₂-selective membranes and separation processes. The MEEP-based membrane processes emit at least 42% less equivalent CO₂ than Pebax-based membrane processes. Similarly, MEEP-based membrane processes produce 34–72% less CO₂ than conventional separation processes. In all studied categories, MEEP-based membranes report lower emissions than Pebax-based membranes and conventional separation processes. Full article

The flame-retardant polyamide 66 composites (FR-PA66) were prepared by in situ loading of amino-functionalized polyphosphazene microspheres (HCNP), which were synthesized in the laboratory and confirmed by a Fourier transform infrared spectrometer (FTIR), scanning electron microscope (SEM), and transmission electron microscope (TEM). The thermal stabilities and flame retardancy of FR-PA66 were measured using thermogravimetric analysis (TGA), a thermogravimetric infrared instrument (TG-IR), the limiting oxygen index (LOI), the horizontal and vertical combustion method (UL-94), and a cone calorimeter. The results illustrate that the volatile matter of FR-PA66 mainly contains carbon dioxide, methane₄, and water vapor under heating, accompanied by the char residue raising to 14.1 wt% at 600 °C and the value of the LOI and UL-94 rating reaching 30% and V-0, respectively. Moreover, the addition of HCNP decreases the peak of the heat release rate (pHRR), total heat release (THR), mass loss (ML), and total smoke release (TSR) of FR-PA66 to 373.7 kW/m², 106.7 MJ/m², 92.5 wt%, and 944.8 m²/m², respectively, verifying a significant improvement in the flame retardancy of PA66. Full article

Ebolavirus (EBOV) infection in humans is a severe and often fatal disease, which demands effective interventional strategies for its prevention and treatment. The available vaccines, which are authorized under exceptional circumstances, use viral vector platforms and have serious disadvantages, such as difficulties in adapting to new virus variants, reliance on cold chain supply networks, and administration by hypodermic injection. Microneedle (MN) patches, which are made of an array of micron-scale, solid needles that painlessly penetrate into the upper layers of the skin and dissolve to deliver vaccines intradermally, simplify vaccination and can thereby increase vaccine access, especially in resource-constrained or emergency settings. The present study describes a novel MN technology, which combines EBOV glycoprotein (GP) antigen with a polyphosphazene-based immunoadjuvant and vaccine delivery system (poly[di(carboxylatophenoxy)phosphazene], PCPP). The protein-stabilizing effect of PCPP in the microfabrication process enabled preparation of a dissolvable EBOV GP MN patch vaccine with superior antigenicity compared to a non-polyphosphazene polymer-based analog. Intradermal immunization of mice with polyphosphazene-based MN patches induced strong, long-lasting antibody responses against EBOV GP, which was comparable to intramuscular injection. Moreover, mice vaccinated with the MN patches were completely protected against a lethal challenge using mouse-adapted EBOV and had no histologic lesions associated with ebolavirus disease. Full article