RESUMEN
Chemodynamic therapy (CDT) and photothermal therapy (PTT) have both demonstrated considerable efficacy in the tumor treatment individually, owing to their non-invasive nature and excellent selectivity. However, due to the propensity of tumors for metastasis and recurrence, a singular therapeutic approach falls short of achieving optimal treatment outcomes. Polydopamine (PDA) has excellent photothermal conversion ability and polyoxometalates (POMs) possess diverse enzymatic activities. Here, we synthesized PDA@POM nanospheres comprising polydopamine-coated Tungsten-based polyoxometalate (W-POM). These nanospheres leverage dual enzymatic activities that synergistically enhance both chemodynamic and photothermal therapies for tumor treatment. The PDA-mediated PTT effect enables precise tumor cell destruction, while the W-POM nanozymes catalyzes the generation of highly toxic reactive oxygen species (ROS) from hydrogen peroxide within tumor cells through a Fenton-like reaction, which mitigates tumor hypoxia and induces tumor cell death. This synergistic photothermal catalytic therapy shows enhanced efficacy in tumor suppression, providing a promising new approach for tumor treatment.
Asunto(s)
Antineoplásicos , Indoles , Nanocompuestos , Polímeros , Indoles/química , Indoles/farmacología , Nanocompuestos/química , Polímeros/química , Polímeros/farmacología , Animales , Humanos , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Especies Reactivas de Oxígeno/metabolismo , Terapia Fototérmica , Supervivencia Celular/efectos de los fármacos , Fototerapia , Ensayos de Selección de Medicamentos Antitumorales , Compuestos de Tungsteno/química , Compuestos de Tungsteno/farmacología , Línea Celular Tumoral , Tamaño de la Partícula , Propiedades de Superficie , Proliferación Celular/efectos de los fármacos , Polielectrolitos , AnionesRESUMEN
HYPOTHESIS: Lipid nanoparticle self-assembly is a complex process that relies on ion pairing between nucleic acids and hydrophobic cationic lipid counterions for encapsulation. The chemical factors influencing this process, such as formulation composition, have been the focus of recent research. However, the physical factors, particularly the mixing protocol, which directly modulates these chemical factors, have yet to be mechanistically examined using a reproducible mixing platform comparable to the industry standard. We here utilize Flash NanoPrecipitation (FNP), a scalable rapid mixing platform, to isolate and systematically investigate how mixing factors influence this complexation step, first by using a model polyelectrolyte-surfactant system and then generalizing to a typical RNA lipid nanoparticle formulation. EXPERIMENTS: Aqueous polystyrene sulfonate (PSS) and cetrimonium bromide (CTAB) solutions are rapidly homogenized using reproducible FNP mixing and controlled flow rates at different stoichiometric ratios and total solids concentrations to form polyelectrolyte-surfactant complexes (PESCs). Then, key mixing factors such as total flow rate, inlet stream relative volumetric flow rate, and magnitude of flow fluctuation are studied using both this PESC system and an RNA lipid nanoparticle formulation. FINDINGS: Fluctuations in flow as low as ± 5 % of the total flow rate are found to severely compromise PESC formation. This result is replicated in the RNA lipid nanoparticle system, which exhibited significant differences in size (132.7 nm vs. 75.6 nm) and RNA encapsulation efficiency (34.0 % vs. 82.8 %) under fluctuating vs. steady flow. We explain these results in light of the chemical variables isolated and studied; slow or nonuniform mixing generates localized concentration gradients that disrupt the balance between the hydrophobic and electrostatic forces that drive complex formation. These experiments contribute to our understanding of the complexation stage of lipid nanoparticle formation and provide practical insights into the importance of developing controlled mixing protocols in industry.
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Cetrimonio , Nanopartículas , Poliestirenos , ARN , Tensoactivos , Tensoactivos/química , Nanopartículas/química , ARN/química , Poliestirenos/química , Cetrimonio/química , Polielectrolitos/química , Tamaño de la Partícula , Compuestos de Cetrimonio/química , Propiedades de Superficie , Lípidos/química , Interacciones Hidrofóbicas e Hidrofílicas , LiposomasRESUMEN
Nano- and micro-sized vesicular and colloidal structures mediate cell-cell communication. They are important players in the physiology of plants, animals, and humans, and are a subject of increasing interest. We investigated the effect of three surfactants, N-cetylpyridinium chloride (CPC), sodium dodecyl sulfate (SDS), and Triton X-100 (TX100), and two anionic polyelectrolytes, sodium polystyrene sulfonate (NaPSS) and sodium polymethacrylate (NaPMA), on nanoliposomes. In addition, the effect of SDS and TX100 on selected biological membranes (erythrocytes and microalgae) was investigated. The liposomes were produced by extrusion and evaluated by microcalorimetry and light scattering, based on the total intensity of the scattered light (Itot), hydrodynamic radius (Rh), radius of gyration (Rg), shape parameter p (=Rh/Rg,0), and polydispersity index. The EPs shed from erythrocytes and microalgae Dunaliella tertiolecta and Phaeodactylum tricornutum were visualized by scanning electron microscopy (SEM) and analyzed by flow cytometry (FCM). The Rh and Itot values in POPC liposome suspensions with added CPC, SDS, and TX100 were roughly constant up to the respective critical micelle concentrations (CMCs) of the surfactants. At higher compound concentrations, Itot dropped towards zero, whereas Rh increased to values higher than in pure POPC suspensions (Rh ≈ 60-70 nm), indicating the disintegration of liposomes and formation of larger particles, i.e., various POPC-S aggregates. Nanoliposomes were stable upon the addition of NaPSS and NaPMA, as indicated by the constant Rh and Itot values. The interaction of CPC, SDS, or TX100 with liposomes was exothermic, while there were no measurable heat effects with NaPSS or NaPMA. The SDS and TX100 increased the number density of EPs several-fold in erythrocyte suspensions and up to 30-fold in the conditioned media of Dunaliella tertiolecta at the expense of the number density of cells, which decreased to less than 5% in erythrocytes and several-fold in Dunaliella tertiolecta. The SDS and TX100 did not affect the number density of the microalgae Phaeodactylum tricornutum, while the number density of EPs was lower in the conditioned media than in the control, but increased several-fold in a concentration-dependent manner. Our results indicate that amphiphilic molecules need to be organized in nanosized particles to match the local curvature of the membrane for facilitated uptake. To pursue this hypothesis, other surfactants and biological membranes should be studied in the future for more general conclusions.
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Eritrocitos , Liposomas , Polielectrolitos , Tensoactivos , Tensoactivos/química , Tensoactivos/farmacología , Polielectrolitos/química , Eritrocitos/efectos de los fármacos , Liposomas/química , Membrana Celular/efectos de los fármacos , Membrana Celular/química , Microalgas/química , Humanos , Membranas ArtificialesRESUMEN
More than half of the global population is unable to consume dairy products due to lactose intolerance (hypolactasia). Current enzyme replacement therapy methods are insufficiently effective as a therapeutic approach to treating lactose intolerance. The encapsulation of ß-galactosidase in polyelectrolyte microcapsules by using the layer-by-layer method could be a possible solution to this problem. In this study, adsorption and co-precipitation methods were employed for encapsulating ß-galactosidase in polyelectrolyte microcapsules composed of (polyallylamine /polystyrene sulphonate)3. As a result, the co-precipitation method was chosen for ß-galactosidase encapsulation. The adsorption method permits to encapsulate six times less enzyme compared with the co-precipitation method; the ß-galactosidase encapsulated via the co-precipitation method released no more than 20% of the initially encapsulated enzyme in pH 2 or 1 M NaCl solutions. In contrast, when using the sorption method, about 100% of the initially encapsulated enzyme was released from the microcapsules under the conditions described above. The co-precipitation method effectively prevents the complete loss of enzyme activity after 2 h of incubation in a solution with pH 2 while also alleviating the adverse effects of ionic strength. Consequently, the encapsulated form of ß-galactosidase shows promise as a potential therapeutic agent for enzyme replacement therapy in the treatment of hypolactasia.
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Cápsulas , Poliaminas , Poliestirenos , beta-Galactosidasa , beta-Galactosidasa/química , beta-Galactosidasa/metabolismo , Poliaminas/química , Poliestirenos/química , Polielectrolitos/química , Concentración de Iones de Hidrógeno , Adsorción , Concentración OsmolarRESUMEN
PURPOSE: The study explored the enhanced skin moisturizing capabilities and moisture retention effects achieved by forming a polyion complex using sulfated glycosaminoglycan (GAG), specifically chondroitin sulfate (CS), and amino acids (AA) such as glutamine (Q) and arginine (R). The overall hydration effect of this CS-AA complex was examined. METHODS: After analyzing the CS-AA polyion complex structure using spectroscopic methods, the ex vivo moisture retention ability was assessed under dry conditions using porcine skin samples. Additionally, the efficacy of the CS-AA polyion complex in reducing transepidermal water loss (TEWL) and improving skin hydration was evaluated on human subjects using a digital evaporimeter and a corneometer, respectively. RESULTS: Validating a systematic reduction in particle size, the following order was observed: CS > CS/AA simple mixture > CS-AA complex based on dynamic light scattering (DLS) and transmission electron microscopy (TEM) analysis. Furthermore, observations revealed that the CS-AA complex exhibits negligible surface charge. Additionally, Fourier-transform infrared spectroscopy (FT-IR) analysis demonstrated a distinct peak shift in the complex, confirming the successful formation of the CS-AA complex. Subsequently, the water-holding effect through porcine skin was assessed, revealing a notable improvement in moisture retention (weight loss) for the CS-Q complex: 40.6% (1 h), 20.5% (2 h), and 18.7% (4 h) compared to glycerin. Similarly, the CS-R complex demonstrated enhancements of 50.2% (1 h), 37.5% (2 h), and 33% (4 h) compared to glycerin. Furthermore, TEWL improvement efficacy on human skin demonstrated approximately 25% improvement for both the CS-Q complex and CS-R complex, surpassing the modest 12.5% and 18% improvements witnessed with water and glycerin applications, respectively. Finally, employing a corneometer, hydration changes in the skin were monitored over 4 weeks. Although CS alone exhibited nominal alterations, the CS-Q complex and CS-R complex showed a significant increase in moisture levels after 4 weeks of application. CONCLUSION: In this study, polyion complexes were successfully formed between CS, a sulfated GAG, and AA. Comparisons with glycerin, a well-known moisturizing agent, confirmed that the CS-AA complex exhibits superior moisturizing effects in various aspects. These findings suggest that the CS-AA complex is a more effective ingredient than CS or AA alone in terms of efficacy.
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Sulfatos de Condroitina , Cosméticos , Pérdida Insensible de Agua , Humanos , Animales , Porcinos , Pérdida Insensible de Agua/efectos de los fármacos , Cosméticos/farmacología , Cosméticos/química , Sulfatos de Condroitina/química , Sulfatos de Condroitina/farmacología , Femenino , Piel/química , Piel/efectos de los fármacos , Piel/metabolismo , Adulto , Aminoácidos/química , Aminoácidos/farmacología , Emolientes/farmacología , Emolientes/administración & dosificación , Emolientes/química , Polímeros/farmacología , Polímeros/química , Glutamina/farmacología , PolielectrolitosRESUMEN
Anterior uveitis is one of the most prevalent forms of ocular inflammation caused by infections, trauma, and other idiopathic conditions if not treated properly, it can cause complete blindness. Therefore, this study aimed to formulate and evaluate dexamethasone sodium phosphate (DSP) loaded polyelectrolyte complex (PEC) nanoparticles (NPs) for the treatment of anterior uveitis. DSP-loaded PEC-NPs were formed through complex coacervation by mixing low molecular weight chitosan and the anionic polymer carboxy methyl cellulose (CMC). The formulations were optimized using Box-Behnken design and evaluated the effect of independent variables: Chitosan concentration, CMC concentration, and pH of chitosan solution on the dependent variables: particle size (PS), Polydispersity Index (PDI), pH of the formulation, and % entrapment efficacy (%EE). The PS, PDI, zeta potential, and pH of the optimized formulation were found 451 ± 82.0995 nm, 0.3807 ± 0.1862, +20.33 ± 1.04 mV and 6.8367 ± 0.0737 respectively. The %EE and drug loading of formulation were 61.66 ± 4.2914% and 21.442 ± 1.814% respectively.In vitrodrug release studies of optimized formulation showed the prolonged release up to 12 h whereas, the marketed formulation showed the burst release 85.625 ± 4.3062% in 1 h and 98.1462 ± 3.0921% at 6 h, respectively. Fourier transform infrared studies suggested the effective incorporation of the drug into the PEC-NPs formulation whereas differential scanning calorimetry and x-ray diffraction studies showed the amorphized nature of the drug in the formulation. Transmission electron microscopy study showed self-assembled, nearly spherical, core-shell nanostructures. The corneal permeation study showed higher permeation of the drug from PEC-NPs compared to the marketed formulation. Hen's Eggs test-Chorioallantoic Membrane test of the optimized formulation revealed non-irritant and safe for ocular administration. Therefore, DSP-loaded PEC-NPs are an effective substitute for conventional eye drops due to their ability to increase bioavailability through longer precorneal retention duration and sustained drug release.
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Carboximetilcelulosa de Sodio , Quitosano , Dexametasona , Nanopartículas , Tamaño de la Partícula , Polielectrolitos , Uveítis Anterior , Dexametasona/química , Dexametasona/administración & dosificación , Dexametasona/análogos & derivados , Quitosano/química , Carboximetilcelulosa de Sodio/química , Nanopartículas/química , Animales , Uveítis Anterior/tratamiento farmacológico , Polielectrolitos/química , Conejos , Concentración de Iones de Hidrógeno , Portadores de Fármacos/química , Liberación de Fármacos , Difracción de Rayos X , Espectroscopía Infrarroja por Transformada de Fourier , Antiinflamatorios/química , Antiinflamatorios/farmacologíaRESUMEN
In this study, we synthesized polyelectrolyte complexed nanoparticles using an ion exchange reaction between poly(hexamethylene guanidine hydrochloride) and sodium caffeate. The morphology of the obtained antiparticle was observed by scanning electron microscopy, and FT-IR and XPS were employed for the structural characterization. The antimicrobial properties of E. coli and S. aureus were characterized through minimum inhibitory concentration (MIC), growth curve analysis, plate colony counting method, and crystal violet method. Notably, the sample showed a 100% bactericidal rate against E. coli at 0.095 µg/mL and against S. aureus at 0.375 µg/mL within 1 h, demonstrating excellent antimicrobial performance against E. coli and S. aureus. The CA-PHMG-containing acrylic resin coatings exhibited exceptional antimicrobial and antiadhesive properties when examined under an inverted fluorescence microscope, particularly at a 4% weight concentration of the antibacterial agent. This study holds vast potential for development in the field of antimicrobial coatings.
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Antibacterianos , Escherichia coli , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Nanopartículas , Tamaño de la Partícula , Staphylococcus aureus , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Nanopartículas/química , Ácidos Cafeicos/química , Ácidos Cafeicos/farmacología , Polielectrolitos/química , Polielectrolitos/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis químicaRESUMEN
Triple-negative breast cancer (TNBC) has poor prognosis. Carboplatin (Crb) is a widely used chemotherapeutic agent, in TNBC but with serious systemic toxicity and poor tumor targeting. Bioinspired drug-loaded platelets (Plt) and Plt-coated nanocarriers evade macrophage phagocytosis by membrane proteins like CD47. The goal of this study was preparation of a novel alginate-poly (ß-amino ester) (PßAE) nanoparticles (NPs) for targeted delivery of Crb to TNBC cells by developing and comparison of two bioinspired carriers of Plt membrane (PltM) coated Crb-loaded alginate-poly (ß-amino ester) nanoparticles (PltM@Crb-PßAE-ALG NPs) and Plt loaded Crb (Plt@Crb). The NPs were prepared by ionic gelation and subsequently were coated by platelet membrane using ultra-sonication method. The loading efficiency, release profile, and in vitro cytotoxicity of both formulations were evaluated on HUVEC and 4 T1 cells. Additionally, the in vivo tumor targeting, therapeutic efficacy, and organ toxicity of the two formulations were assessed in a murine tumor model. Results showed both Plt@Crb and (PltM@Crb-PßAE-ALG NPs) exhibited high drug loading efficiency, sustained release, enhanced cytotoxicity against 4 T1 cells, and decreased cytotoxicity in normal cells (HUVEC) in vitro. In vivo studies revealed that although both formulations considerably improved tumor inhibition compared to free Crb, but the PltM@Crb-PßAE-ALG NPs demonstrated superior cytotoxicity and therapeutic efficacy, thanks to improved Crb's internalization efficiency, enhanced stability, and controlled release properties.
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Alginatos , Antineoplásicos , Plaquetas , Carboplatino , Liberación de Fármacos , Células Endoteliales de la Vena Umbilical Humana , Nanopartículas , Polímeros , Animales , Alginatos/química , Alginatos/administración & dosificación , Femenino , Humanos , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Carboplatino/administración & dosificación , Carboplatino/química , Nanopartículas/química , Nanopartículas/administración & dosificación , Línea Celular Tumoral , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/farmacocinética , Polímeros/química , Portadores de Fármacos/química , Ratones , Polielectrolitos/química , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Ratones Endogámicos BALB C , Supervivencia Celular/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patologíaRESUMEN
In this investigation, the photophysical properties and interaction mechanisms of Janus green blue (JGB) dye with polyanions were systematically studied using spectroscopic techniques. The absorption spectral analysis revealed that JGB binds cooperatively to sodium alginate, leading to dye stacking along the polymer chain. The interaction of JGB dye with DNA was characterized by the emergence of a metachromatic peak at 564 nm, indicating the formation of dye aggregates. The analysis of absorption data reveals that JGB dye interacts with DNA at multiple binding sites, including at least one high-affinity site. The AutoDock Vina based blind docking approach was used to analyze the most probable binding location of JGB dye in DNA. By making use of the DNA-induced metachromasia, a colorimetric approach was developed for the visualization of loop-mediated isothermal amplification (LAMP) and polymerase chain reaction (PCR). The LAMP-colorimetric assay, targeting the Streptococcus pneumoniae gene, demonstrated a noticeable colour change with a detection limit of 1 pg µL-1. The practical applicability was validated by detecting S. pneumoniae in artificial urine. In addition to LAMP, we tested the JGB dye based colorimetric assay for applicability in PCR reactions. The colorimetric PCR assay using the metal-responsive transcription factor (MTF-1) gene achieved a detection limit as low as 0.1 pg µL-1. The study highlights the potential of DNA binding metachromic dye to significantly enhance colorimetric assays, offering a robust and sensitive tool for molecular diagnostics.
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Colorimetría , Colorantes , Técnicas de Amplificación de Ácido Nucleico , Polímeros , Colorimetría/métodos , Colorantes/química , Polímeros/química , Polielectrolitos/química , Reacción en Cadena de la Polimerasa/métodos , Streptococcus pneumoniae , ADN/química , Técnicas de Diagnóstico MolecularRESUMEN
Specific lipid isomers are functionally critical, but their structural rigidity and usually minute geometry differences make separating them harder than other biomolecules. Such separations by ion mobility spectrometry (IMS) were recently enabled by new high-definition methods using dynamic electric fields, but major resolution gains are needed. Another problem of identifying many isomers with no unique fragments in ergodic collision-induced dissociation (CID) was partly addressed by the direct ozone-induced dissociation (OzID) that localizes the double bonds, but a low reaction efficiency has limited the sensitivity, dynamic range, throughput, and compatibility with other tools. Typically lipids are analyzed by MS as singly charged protonated, deprotonated, or ammoniated ions. Here, we explore the differential IMS (FAIMS) separations with OzID for exemplary lipids cationized by polyvalent metals. These multiply charged adducts have much greater FAIMS compensation voltages (UC) than the 1+ ions, with up to 10-fold resolution gain enabling baseline isomer separations even at a moderate resolving power of the SelexION stage. Concomitantly OzID speeds up by many orders of magnitude, producing a high yield of diagnostic fragments already in 1 ms. These capabilities can be ported to the superior high-definition FAIMS and high-pressure OzID systems to take lipidomic analyses to the next level.
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Espectrometría de Movilidad Iónica , Ozono , Ozono/química , Espectrometría de Movilidad Iónica/métodos , Lípidos/química , Isomerismo , Cationes/química , Metales/química , Polielectrolitos/químicaRESUMEN
The impact of electrical stimulation has been widely investigated on the wound healing process; however, its practicality is still challenging. This study explores the effect of electrical stimulation on fibroblasts in a culture medium containing different electrically-charged polysaccharide derivatives including alginate, hyaluronate, and chitosan derivatives. For this aim, an electrical stimulation, provided by a zigzag triboelectric nanogenerator (TENG), was exerted on fibroblasts in the presence of polysaccharides' solutions. The analyses showed a significant increase in cell proliferation and an improvement in wound closure (160 % and 90 %, respectively) for the hyaluronate-containing medium by a potential of 3 V after 48 h. In the next step, a photo-crosslinkable hydrogel was prepared based on hyaluronic acid methacrylate (HAMA). Then, the cells were cultured on HAMA hydrogel and treated by an electrical stimulation. Surprisingly, the results showed a remarkable increase in cell growth (280 %) and migration (82 %) after 24 h. Attributed to the electroosmosis phenomenon and an amplified transfer of soluble growth factors, a dramatic promotion was underscored in cell activities. These findings highlight the role of electroosmosis in wound healing, where TENG-based electrical stimulation is combined with bioactive polysaccharide-based hydrogels to promote wound healing.
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Alginatos , Proliferación Celular , Fibroblastos , Ácido Hialurónico , Hidrogeles , Cicatrización de Heridas , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Alginatos/química , Proliferación Celular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/citología , Hidrogeles/química , Hidrogeles/farmacología , Cicatrización de Heridas/efectos de los fármacos , Estimulación Eléctrica , Polielectrolitos/química , Animales , Ratones , Quitosano/química , Movimiento Celular/efectos de los fármacos , Humanos , Células 3T3 NIHRESUMEN
Chronic wounds represent a significant global health concern, statistically impacting 1-2% of the population in developed countries throughout their lifetimes. These wounds cause considerable discomfort for patients and necessitate substantial expenditures of time and resources for treatment. Among the emerging therapeutic approaches, medicated dressings incorporating bioactive molecules, including natural compounds, are particularly promising. Hence, the objective of this study was to develop novel antimicrobial dressings for wound treatment. Specifically, polycaprolactone membranes were manufactured using the electrospinning technique and subsequently coated with natural polyelectrolytes (chitosan as a polycation and a mixture of manuka honey with essential oils nanoemulsions as a polyanion) employing the Layer-by-Layer assembly technique. Physico-chemical and morphological characterization was conducted through QCM-D, FTIR-ATR, XPS, and SEM analyses. The results from SEM and QCM-D demonstrated successful layer deposition and coating formation. Furthermore, FTIR-ATR and XPS analyses distinguished among different coating compositions. The coated membranes were tested in the presence of fibroblast cells, demonstrating biocompatibility and expression of genes coding for VEGF, COL1, and TGF-ß1, which are associated with the healing process (assessed through RT-qPCR analysis). Finally, the membranes exhibited excellent antibacterial activity against both Staphylococcus aureus and Pseudomonas aeruginosa, with higher bacterial strain inhibition observed when cinnamon essential oil nanoemulsion was incorporated. Taken together, these results demonstrate the potential application of nanocoated membranes for biomedical applications, such as wound healing.
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Miel , Aceites Volátiles , Poliésteres , Cicatrización de Heridas , Aceites Volátiles/farmacología , Aceites Volátiles/química , Cicatrización de Heridas/efectos de los fármacos , Poliésteres/química , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Membranas Artificiales , Leptospermum/química , Vendajes , Staphylococcus aureus/efectos de los fármacos , Quitosano/química , Quitosano/farmacología , Fibroblastos/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Polielectrolitos/químicaRESUMEN
Miktoarm star polymers exhibit a captivating range of physicochemical properties, setting them apart from their linear counterparts. This study devised a synthetic pathway to synthesize cationic miktoarm stars utilizing polypept(o)ides (PeptoMiktoStars), comprising 3 or 6 polysarcosine (pSar) arms (AB3×100, AB6×50, overall 300) for shielding and a cross-linkable poly(S-ethylsulfonyl-l-homocysteine) (pHcy(SO2Et)20) block and a poly(l-lysine) ((pLys)20) block for nucleic acid complexation. Precise control over the DPn and narrow molecular weight distributions (D̵ ≈ 1.2) were achieved for both structures. Both PeptoMiktoStars efficiently complexed mRNA and pDNA into polyion complex micelles (PICMs). AB6-PICMs provided modest (mRNA) to high (pDNA) stability against glutathione and heparin sulfate (HS), while even cross-linked AB3-PICMs were susceptible to HS. All PICMs delivered pDNA and mRNA into D1 cells (over 80%) and Jurkat T cells (over 50%) in vitro. Despite payload- and cell-dependency, AB3 showed overall higher transfection efficiency, while AB6 demonstrated better shielding and enhanced stability.
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Micelas , Humanos , Polímeros/química , ARN Mensajero/genética , ADN/química , Polilisina/química , Polielectrolitos/química , Péptidos , Sarcosina/análogos & derivadosRESUMEN
Utilizing enzyme cascades as a promising approach for targeted cancer therapies holds significant potential, yet its clinical effectiveness is substantially hindered by functional losses during delivery. Complex coacervation emerges as an intriguing strategy for designing functional nanoreactors. In this study, a noteworthy achievement is presented in the development of lactobionic acid-modified tumor microenvironment (TME)-responsive polyelectrolyte complex vesicles (HGS-PCVs) based on bioinspired homopolypeptoids, which serve as a facile, intelligent, and highly efficient nanoreactor tunable for glucose oxidase, hemoglobin, and sorafenib (SRF) to hepatic cancer cells. The TME-responsive permeability of HGS-PCVs enables the selective entry of glucose into their interior, triggering an enzymatic cascade reaction within the tumor. This intricate process generates toxic hydroxyl radicals while concurrently lowering the pH. Consequently, this pH shift enhances the SRF release, effectively promoting ferroptosis and apoptosis in the target cancer cells. Further, the administration of the HGS-PCVs not only initiates immunogenic cell death but also plays a crucial role in inducing the maturation of dendritic cells within lymph nodes. It stimulates an adaptive T-cell response, a crucial mechanism that contributes to impeding the growth of distant tumors in vivo, demonstrating the promising potential of PCVs for cancer immunotherapy.
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Glucosa Oxidasa , Sorafenib , Microambiente Tumoral , Humanos , Glucosa Oxidasa/metabolismo , Glucosa Oxidasa/química , Animales , Microambiente Tumoral/efectos de los fármacos , Sorafenib/química , Sorafenib/farmacología , Ratones , Línea Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Disacáridos/química , Hemoglobinas/química , Hemoglobinas/metabolismo , Polielectrolitos/química , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Concentración de Iones de Hidrógeno , Terapia Combinada , Nanopartículas/químicaRESUMEN
The growth plate is a cartilage structure at the end of long bones which mediates growth in children. When fractured, the formation of bony repair tissue known as a "bony bar" can occur and cause limb deformities. There are currently no effective clinical solutions for the prevention of the bony bar formation or regeneration of healthy growth plate cartilage after a fracture. This study employs previously developed alginate/chitosan polyelectrolyte complex (PEC) hydrogels as a sustained release vehicle for the delivery of short-interfering RNA (siRNA). Specifically, the siRNA targets the p38-MAPK pathway in mesenchymal stem cells (MSCs) to prevent their osteogenic differentiation. In vitro experimental findings show sustained release of siRNA from the hydrogels for 6 months. Flow cytometry and confocal imaging indicate that the hydrogels release siRNA to effectively knockdown GFP expression over a sustained period. MAPK-14 targeting siRNA was used to knockdown the expression of MAPK-14 and correspondingly decrease the expression of other osteogenic genes in MSCs in vitro over the span of 21 days. These hydrogels were used in a rat model of growth plate injury to determine whether siMAPK-14 released from the gels could inhibit bony bar formation. No significant reduction of bony bar formation was seen in vivo at the one concentration of siRNA examined. This PEC hydrogel represents a significant advancement for siRNA sustained delivery, and presents an interesting potential therapeutic delivery system for growth plate injuries and other regenerative medicine applications.
Asunto(s)
Preparaciones de Acción Retardada , Hidrogeles , Células Madre Mesenquimatosas , Osteogénesis , Polielectrolitos , ARN Interferente Pequeño , Ratas Sprague-Dawley , Hidrogeles/química , Hidrogeles/farmacología , Animales , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Osteogénesis/efectos de los fármacos , ARN Interferente Pequeño/farmacología , Preparaciones de Acción Retardada/farmacología , Polielectrolitos/química , Ratas , Placa de Crecimiento/efectos de los fármacos , Quitosano/química , Alginatos/química , Masculino , Diferenciación Celular/efectos de los fármacosRESUMEN
This study reports the successful synthesis of flame-retardant and smoke-suppressing epoxy resin (EP) via bio-based polyelectrolyte flame retardants. Herein, a novel polyelectrolyte flame retardant was prepared from chitosan (CS) and hexa-(4-carboxyl-phenoxy)-cyclotriphosphazene (HCPCP) by acid-base neutralization reaction, which the HCPCP was synthesized with hexachlorocyclotriphosphazene (HCCP) and methyl p-hydroxybenzoate (MP) by nucleophilic substitution reaction. The combined effect of the addition on the flame retardant, smoke suppression and mechanical properties of EP samples were systematically investigated. The presence of this bio-based polyelectrolyte provided excellent smoke suppression and flame-retardant properties of the prepared EP. Among them, the peak heat release rate (PHRR), peak smoke production rate (PSPR) and total smoke production (TSP) of EP/9wt%3CS-HCPCP composite (the ratio of CS to HCPCP was 3: 7, and the dosage was 9 wt%) were reduced by 45.42 %, 41.66 % and 22.56 %, respectively. In addition, the EP/CS-HCPCP composites showed a 207.80 % enhancement in char residue compared to pure EP. These results suggest a green and cost-effective strategy for the production of flame-retardant, drip-proof and smoke-suppressed EP composites.
Asunto(s)
Quitosano , Resinas Epoxi , Retardadores de Llama , Humo , Quitosano/química , Resinas Epoxi/química , Polielectrolitos/químicaRESUMEN
Microencapsulation has the potential to address the stability issues associated with vitamin A. This study examined the effectiveness of emulsifying a saponin-chitosan polyelectrolyte complex to encapsulate vitamin A. Utilizing response surface methodology (RSM), the effects of the chitosan, saponin, and vitamin A contents on various response variables were measured to optimize the formulation. The optimized emulsion was characterized through fluorescence microscopy, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), storage stability, and release profile. Fluorescence microscopy showed that vitamin A was evenly distributed throughout the optimized emulsion. The polyelectrolyte complex and vitamin A were shown to interact hydrophobically and electrostatically by FTIR analysis. The DSC results verified the effective encapsulation and showed that vitamin A heat stability had been enhanced. Study on storage stability demonstrated that during a 2-month storage period, the encapsulated vitamin A remained stable. Moreover, vitamin A was significantly released from the encapsulated form at pH 1.2, based on release assays. In conclusion, saponin-chitosan polyelectrolyte coating proved to be a potentially useful new material for the stability and applications of vitamin A in a range of formulations.
Asunto(s)
Quitosano , Preparaciones de Acción Retardada , Estabilidad de Medicamentos , Polielectrolitos , Saponinas , Vitamina A , Quitosano/química , Saponinas/química , Vitamina A/química , Polielectrolitos/química , Rastreo Diferencial de Calorimetría , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Emulsiones/química , Concentración de Iones de Hidrógeno , Composición de Medicamentos/métodosRESUMEN
OBJECTIVE: Lindqvist-type polyoxometalates (POMs) exhibit potential antitumor activities. This study aimed to examine the effects of Lindqvist-type POMs against breast cancer and the underlying mechanism. METHODS: Using different cancer cell lines, the present study evaluated the antitumor activities of POM analogues that were modified at the body skeleton based on molybdenum-vanadium-centered negative oxygen ion polycondensations with different side strains. Cell colony formation assay, autophagy detection, mitochondrial observation, qRT-PCR, Western blotting, and animal model were used to evaluate the antitumor activities of POMs against breast cancer cells and the related mechanism. RESULTS: MO-4, a Lindqvist-type POM linking a proline at its side strain, was selected for subsequent experiments due to its low half maximal inhibitory concentration in the inhibition of proliferation of breast cancer cells. It was found that MO-4 induced the apoptosis of multiple types of breast cancer cells. Mechanistically, MO-4 activated intracellular mitophagy by elevating mitochondrial reactive oxygen species (ROS) levels and resulting in apoptosis. In vivo, breast tumor growth and distant metastasis were significantly reduced following MO-4 treatment. CONCLUSION: Collectively, the results of the present study demonstrated that the novel Lindqvist-type POM MO-4 may exhibit potential in the treatment of breast cancer.
Asunto(s)
Antineoplásicos , Apoptosis , Neoplasias de la Mama , Mitofagia , Especies Reactivas de Oxígeno , Compuestos de Tungsteno , Humanos , Mitofagia/efectos de los fármacos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/genética , Apoptosis/efectos de los fármacos , Compuestos de Tungsteno/farmacología , Animales , Ratones , Antineoplásicos/farmacología , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Proliferación Celular/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Molibdeno/farmacología , Polielectrolitos , AnionesRESUMEN
Due to dwindling petroleum resources and the need for environmental protection, the development of bio-based flame retardants has received much attention. In order to explore the feasibility of fully biomass polyelectrolyte complexes (PEC) for polyolefin flame retardant applications, chitosan (CS), sodium alginate (SA), and sodium phytate (SP) were used to prepare CS-based fully biomass PEC intercalated montmorillonite (MMT) hybrid biomaterials (SA-CS@MMT and SP-CS@MMT). The effects of two hybrid biomaterials on the fire safety and mechanical properties of intumescent flame-retardant polypropylene (PP) composites were compared. The SP-CS@MMT showed the best flame retardancy and toughening effect at the same addition amount. After adding 5 wt% SP-CS@MMT, the limiting oxygen index (LOI) value of PP5 reached 30.9 %, and the peak heat release rate (pHRR) decreased from 1348 kW/m2 to 163 kW/m2. In addition, the hydrogen bonding between polyelectrolyte complexes significantly improved the mechanical properties of PP composites. Compared with PP2, the tensile strength of PP5 increased by 59 %. This study provided an efficient and eco-friendly strategy for the large-scale production of renewable biomaterials with good thermal stability and expanded the application of macromolecular biomaterials in the field of fire safety.
Asunto(s)
Bentonita , Quitosano , Retardadores de Llama , Polielectrolitos , Polipropilenos , Quitosano/química , Bentonita/química , Polipropilenos/química , Polielectrolitos/química , Resistencia a la Tracción , Tecnología Química Verde/métodos , Materiales Biocompatibles/química , Fenómenos MecánicosRESUMEN
Local anesthesia is essential in dental practices, particularly for managing pain in tooth socket wounds, yet improving drug delivery systems remains a significant challenge. This study explored the physicochemical characteristics of lidocaine hydrochloride (LH) incorporated into a polyelectrolyte complex and poloxamer thermosensitivity hydrogel, assessing its local anesthetic efficacy in mouse models and its onset and duration of action as topical anesthetics in clinical trials. The thermoresponsive hydrogel exhibited a rapid phase transition within 1-3 minutes and demonstrated pseudo-plastic flow behavior. Its release kinetics followed Korsmeyer-Peppas, with 50% of biodegradation occurring over 48 h. In mouse models, certain thermogels showed superior anesthetic effects, with rapid onset and prolonged action, as evidenced by heat tolerance in tail-flick and hot plate models. In clinical trials, the LH-loaded thermoresponsive hydrogel provided rapid numbness onset, with anesthesia (Ton) beginning at an average of 46.5 ± 22.5 seconds and lasting effectively (Teff) for 202.5 ± 41.0 seconds, ranging from 120 to 240 seconds, indicating sustained release. These results highlight the promising properties of these formulations: rapid onset, prolonged duration, mucoadhesion, biodegradability, and high anesthesia effectiveness. This study demonstrates the potential for advancing local anesthesia across various medical fields, emphasizing the synergy between material science and clinical applications to improve patient care and safety.