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The downsides of conventional cancer monotherapies are profound and enormously consequential, as drug-resistant cancer cells and cancer stem cells (CSC) are typically not eliminated. Here, a targeted theranostic nano vehicle (TTNV) is designed using manganese-doped mesoporous silica nanoparticle with an ideal surface area and pore volume for co-loading an optimized ratio of antineoplastic doxorubicin and a drug efflux inhibitor tariquidar. This strategically framed TTNV is chemically conjugated with folic acid and hyaluronic acid as a dual-targeting entity to promote folate receptor (FR) mediated cancer cells and CD44 mediated CSC uptake, respectively. Interestingly, surface-enhanced Raman spectroscopy is exploited to evaluate the molecular changes associated with therapeutic progression. Tumor microenvironment selective biodegradation and immunostimulatory potential of the MSN-Mn core are safeguarded with a chitosan coating which modulates the premature cargo release and accords biocompatibility. The superior antitumor response in FR-positive syngeneic and CSC-rich human xenograft murine models is associated with a tumor-targeted biodistribution, favorable pharmacokinetics, and an appealing bioelimination pattern of the TTNV with no palpable signs of toxicity. This dual drug-loaded nano vehicle offers a feasible approach for efficient cancer therapy by on demand cargo release in order to execute complete wipe-out of tumor reinitiating cancer stem cells.
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Nanopartículas , Neoplasias , Animais , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Resistência a Medicamentos , Humanos , Camundongos , Neoplasias/tratamento farmacológico , Células-Tronco Neoplásicas , Medicina de Precisão , Dióxido de Silício/uso terapêutico , Distribuição Tecidual , Microambiente TumoralRESUMO
Generating stable and customizable topography on hydrogel surfaces with contact guidance potential is critical as it can direct/influence cell growth. This necessitates the development of new techniques for surface patterning of the hydrogels. We report on the design of a square grid template for surface patterning hydrogels. The template was 3-D printed and has the diameter of a well in a 24-well plate. Hyaluronic acid methacrylate (HA) hydrogel precursor solutions were cast on the 3D printed template's surface, which generated 3D square shape topographies on the HA hydrogel surface upon demolding. The 3D Laser Microscopy has shown the formation of a periodic array of 3D topographies on hydrogel surfaces. 3D Laser and Electron Microscopy Imaging have revealed that this new method has increased the surface area and exposed the underlying pore structure of the HA hydrogels. To demonstrate the method's versatility, we have successfully applied this technique to generate 3D topography on two more acrylate hydrogel formulations, gelatin Methacrylate and polyethylene glycol dimethacrylate. Human neonatal dermal fibroblast cells were used as a model cell line to evaluate the cell guidance potential of patterned HA hydrogel. Confocal fluorescence microscopy imaging has revealed that the 3D surface topographies on HA hydrogels can guide and align the actin filaments of the fibroblasts presumably due to the contact guidance mechanism. The newly developed methodology of 3D topography generation in acrylate hydrogels may influence the cell responses on hydrogel surfaces which can impact biomedical applications such as tissue engineering, wound healing, and disease modeling.
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Fibroblastos , Ácido Hialurônico , Hidrogéis , Impressão Tridimensional , Propriedades de Superfície , Hidrogéis/química , Hidrogéis/farmacologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Ácido Hialurônico/química , Metacrilatos/química , Acrilatos/química , Células Cultivadas , Polietilenoglicóis/químicaRESUMO
Materiobiology is an emerging field focused on the physiochemical properties of biomaterials concerning biological outcomes which includes but is not limited to the biological responses and bioactivity of surface-modified biomaterials. Herein, we report a novel in vitro characterization platform for characterizing nanoparticle surface-modified 3D printed PLA scaffolds. We have introduced innovative design parameters that were practical for ubiquitous in vitro assays like those utilizing 96 and 24-well plates. Subsequently, gold and silica nanoparticles were deposited using two low-temperature plasma-assisted processes namely plasma electroless reduction (PER) and dusty plasma on 3D scaffolds. Materiobiological testing began with nanoparticle surface modification optimization on 96 well plate design 3D scaffolds. We have employed 3D laser confocal imaging and scanning electron microscopy to study the deposition of nanoparticles. It was found that the formation and distribution of the nanoparticles were time-dependent. In vitro assays were performed utilizing an osteosarcoma (MG-63) cell as a model. These cells were grown on both 96 and 24 well plate design 3D scaffolds. Subsequently, we performed different in vitro assays such as cell viability, and fluorescence staining of cytoskeletal actin and DNA incorporation. The actin cytoskeleton staining showed more homogeneity in the cell monolayer growing on the gold nanoparticle-modified 3D scaffolds than the control 3D PLA scaffold. Furthermore, the mineralization and protein adsorption experiments conducted on 96 well plate design scaffolds have shown enhanced mineralization and bovine serum albumin adsorption for the gold nanoparticle-modified scaffolds compared to the control scaffolds. Taken together, this study reports the efficacy of this new in vitro platform in conducting more reliable and efficient materiobiology studies. It is also worth mentioning that this platform has significant futuristic potential for developing as a high throughput screening platform. Such platforms could have a significant impact on the systematic study of biocompatibility and bioactive mechanisms of nanoparticle-modified 3D-printed scaffolds for tissue engineering. It would also provide unique ways to investigate mechanisms of biological responses and subsequent bioactive mechanisms for implantable biomaterials. Moreover, this platform can derive more consistent and reliable in vitro results which can improve the success rate of further in vivo experiments.
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Ouro , Impressão Tridimensional , Humanos , Ouro/química , Dióxido de Silício/química , Propriedades de Superfície , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Alicerces Teciduais/química , Linhagem Celular Tumoral , Tamanho da Partícula , Nanopartículas Metálicas/química , Nanopartículas/química , Teste de MateriaisRESUMO
BACKGROUND: Capsular contracture is a critical complication of silicone implantation caused by fibrotic tissue formation from excessive foreign body responses. Various approaches have been applied, but targeting the mechanisms of capsule formation has not been completely solved. Myofibroblast differentiation through the transforming growth factor beta (TGF-ß)/p-SMADs signaling is one of the key factors for capsular contracture development. In addition, biofilm formation on implants may result chronic inflammation promoting capsular fibrosis formation with subsequent contraction. To date, there have been no approaches targeting multi-facted mechanisms of capsular contracture development. METHODS: In this study, we developed a multi-targeting nitric oxide (NO) releasing bionanomatrix coating to reduce capsular contracture formation by targeting myofibroblast differentiation, inflammatory responses, and infections. First, we characterized the bionanomatrix coating on silicon implants by conducting rheology test, scanning electron microcsopy analysis, nanoindentation analysis, and NO release kinetics evaluation. In addition, differentiated monocyte adhesion and S. epidermidis biofilm formation on bionanomatrix coated silicone implants were evaluated in vitro. Bionanomatrix coated silicone and uncoated silicone groups were subcutaneously implanted into a mouse model for evaluation of capsular contracture development for a month. Fibrosis formation, capsule thickness, TGF-ß/SMAD 2/3 signaling cascade, NO production, and inflammatory cytokine production were evaluated using histology, immunofluorescent imaging analysis, and gene and protein expression assays. RESULTS: The bionanomatrix coating maintained a uniform and smooth surface on the silicone even after mechanical stress conditions. In addition, the bionanomatrix coating showed sustained NO release for at least one month and reduction of differentiated monocyte adhesion and S. epidermidis biofilm formation on the silicone implants in vitro. In in vivo implantation studies, the bionanomatrix coated groups demonstrated significant reduction of capsule thickness surrounding the implants. This result was due to a decrease of myofibroblast differentiation and fibrous extracellular matrix production through inhibition of the TGF-ß/p-SMADs signaling. Also, the bionanomatrix coated groups reduced gene expression of M1 macrophage markers and promoted M2 macrophage markers which indicated the bionanomatrix could reduce inflammation but promote healing process. CONCLUSIONS: In conclusion, the bionanomatrix coating significantly reduced capsular contracture formation and promoted healing process on silicone implants by reducing myfibroblast differentiation, fibrotic tissue formation, and inflammation. A multi-targeting nitric oxide releasing bionanomatrix coating for silicone implant can reduce capsular contracture and improve healing process. The bionanomatrix coating reduces capsule thickness, α-smooth muscle actin and collagen synthesis, and myofibroblast differentiation through inhibition of TGF-ß/SMADs signaling cascades in the subcutaneous mouse models for a month.
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The design of metal nanoparticle-modified polymer surfaces in a green and scalable way is both desirable and highly challenging. Herein, a new green low-temperature plasma-based in situ surface reduction strategy termed plasma electroless reduction (PER) is reported for achieving in situ metallic nanostructuring on polymer surfaces. Proof of concept for this new method was first demonstrated on hydrophilic cellulose papers. Cellulose papers were dip-coated with different metal ion (Ag+ and Au3+) solutions and then subjected to hydrogen plasma treatment for this PER process. Transmission electron microscopy (TEM) analysis has revealed that this PER process caused anisotropic growth of either gold or silver nanoparticles, resulting in the time-dependent formation of both distinct spherical nanoparticles (â¼20 nm) and anisotropic 2D nanosheets. Furthermore, we have demonstrated the adaptability of this process by applying it to hydrophobic fibrous and 3D printed polymeric materials such as surgical face masks and 3D printed polylactic acid scaffolds. The PER process on these hydrophobic polymer surfaces was accomplished via a sequential combination of air plasma and hydrogen plasma treatment. The metallic nanostructuring caused by the PER process on these hydrophobic surfaces was systematically studied using different surface imaging techniques including 3D confocal laser surface scanning microscopy and scanning electron microscopy. We have also systematically optimized the PER process on the surface of 3D scaffolds via varying the concentration of the silver ion precursor and by different postprocessing methods such as sonication and medium soaking. These optimization processes were found to be very important in generating uniform metallic nanoparticle-modified 3D printed scaffolds while simultaneously improving cytocompatibility. Through joint disk diffusion and inhibitory concentration testing, the antibacterial efficacy of silver coatings on face masks and 3D scaffolds was established. Altogether, these results clearly suggest the excellent futuristic potential of this new PER method for designing metallic nanostructured interfaces for different biomedical applications.
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Boron nitride (BN) is primarily a synthetically produced advanced ceramic material. It is isoelectronic to carbon and, like carbon, can exist as several polymorphic modifications. Microwave plasma chemical vapor deposition (MPCVD) of metastable wurtzite boron nitride is reported for the first time and found to be facilitated by the application of direct current (DC) bias to the substrate. The applied negative DC bias was found to yield a higher content of sp3 bonded BN in both cubic and metastable wurtzite structural forms. This is confirmed by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Nano-indentation measurements reveal an average coating hardness of 25 GPa with some measurements as high as 31 GPa, consistent with a substantial fraction of sp3 bonding mixed with the hexagonal sp2 bonded BN phase.
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Superhard boron-rich boron carbide coatings were deposited on silicon substrates by microwave plasma chemical vapor deposition (MPCVD) under controlled conditions, which led to either a disordered or crystalline structure, as measured by X-ray diffraction. The control of either disordered or crystalline structures was achieved solely by the choice of the sample being placed either directly on top of the sample holder or within an inset of the sample holder, respectively. The carbon content in the B-C bonded disordered and crystalline coatings was 6.1 at.% and 4.5 at.%, respectively, as measured by X-ray photoelectron spectroscopy. X-ray diffraction analysis of the crystalline coating provided a good match with a B50C2-type structure in which two carbon atoms replaced boron in the α-tetragonal B52 structure, or in which the carbon atoms occupied different interstitial sites. Density functional theory predictions were used to evaluate the dynamical stability of the potential B50C2 structural forms and were consistent with the measurements. The measured nanoindentation hardness of the coatings was as high as 64 GPa, well above the 40 GPa threshold for superhardness.
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Hemorrhagic blood loss from traumatic injury is the leading cause of death in severe accidents and combat injuries. Treating and stopping blood loss in a timely and effective manner is essential for the survival of the patient. Currently, QuikClot and dry fibrin sealant dressing are well-known approaches for hemostatic treatment. However, these dressings have limitations in slowing blood loss such as being brittle, low blood absorption, and a poor sealant of the injury site. Temperature-sensitive gels may have potential as a platform for delivery of coagulation factors to improve hemostasis and wound sealing in the treatment of traumatic injuries. Here, we developed a temperature-sensitive triblock copolymer (poly ethylene oxide (PEO)-poly propylene oxide (PPO)-poly ethylene oxide (PEO)) containing fibrinogen to promote blood coagulation through gel formation at body temperature. This temperature sensitive solution-to-gel (sol-gel) transition does not require cross-linking agents or UV photoinitiation. We determined that 22 wt % (weight percent) copolymers with and without fibrinogen was the maximum concentration for sol-gel transition at body temperature. Rheology results further confirmed this sol-gel transition of 22 wt % copolymers at body temperature. We showed that fibrinogen itself promoted blood coagulation. Additionally, 22 wt % copolymer with fibrinogen successfully demonstrated stable blood coagulation within the gel compared to 22 wt % copolymer without fibrinogen. Twenty-two weight percent copolymers with and without fibrinogen also exhibited excellent biocompatibility based on cell viability, proliferation, and morphology analysis. In addition, treatment of 22 wt % copolymers did not stimulate pro-inflammatory TNF-α production from differentiated human monocytes. Our results suggest that 22 wt % of a temperature-sensitive copolymer gel containing fibrinogen has great potential as a hemostatic agent stimulating coagulation and providing immediate wound coverage for protection through a sol-gel transition at body temperature.
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We report a novel and facile organosilane plasma polymerization method designed to improve the surface characteristics of poly(tetrafluoroethylene) (PTFE). We hypothesized that the polymerized silane coating would provide an adhesive surface for endothelial cell proliferation due to a large number of surface hydroxyl groups, while the large polymer networks on the surface of PTFE would hinder platelet attachment. The plasma polymerized PTFE surfaces were then systematically characterized via different analytical techniques such as FTIR, XPS, XRD, Contact angle, and SEM. The key finding of the characterization is the time-dependent deposition of an organosilane layer on the surface of PTFE. This layer was found to provide favorable surface properties to PTFE such as a very high surface oxygen content, high hydrophilicity and improved surface mechanics. Additionally, in vitro cellular studies were conducted to determine the bio-interface properties of the plasma-treated and untreated PTFE. The important results of these experiments were rapid endothelial cell growth and decreased platelet attachment on the plasma-treated PTFE compared to untreated PTFE. Thus, this new surface modification technique could potentially address the current challenges associated with PTFE for blood contact applications, specifically poor endothelial cell growth and risk of thrombosis.
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Materiais Biocompatíveis/farmacologia , Compostos de Organossilício/farmacologia , Politetrafluoretileno/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Plaquetas/efeitos dos fármacos , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Humanos , Estrutura Molecular , Compostos de Organossilício/síntese química , Compostos de Organossilício/química , Tamanho da Partícula , Adesividade Plaquetária/efeitos dos fármacos , Polimerização , Propriedades de SuperfícieRESUMO
Superhydrophobic surfaces have gained increased attention due to the high water-repellency and self-cleaning capabilities of these surfaces. In the present study, we explored a novel hybrid method of fabricating superhydrophobic poly(tetrafluoroethylene) (PTFE) surfaces by combining the physical etching capability of oxygen plasma with the plasma-induced polymerization of a organic monomer methyl methacrylate (MMA). This novel hybrid combination of oxygen-MMA plasma has resulted in the generation of superhydrophobic PTFE surfaces with contact angle of 154°. We hypothesized that the generation of superhydrophobicity may be attributed to the generation of fluorinated poly(methyl methacrylate) (PMMA) moieties formed by the combined effects of physical etching causing de-fluorination of PTFE and the subsequent plasma polymerization of MMA. The plasma treated PTFE surfaces were then systematically characterized via XPS, FTIR, XRD, DSC and SEM analyses. The results have clearly shown a synergistic effect of the oxygen/MMA combination in comparison with either the oxygen plasma alone or MMA vapors alone. Furthermore, the reported new hybrid combination of Oxygen-MMA plasma has been demonstrated to achieve superhydrophobicity at lower power and short time scales than previously reported methods in the literature. Hence the reported novel hybrid strategy of fabricating superhydrophobic PTFE surfaces could have futuristic potential towards biointerface applications.
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Metilmetacrilato/química , Polímeros/química , Polimetil Metacrilato/química , Politetrafluoretileno/química , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Varredura , Polimerização , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Difração de Raios XRESUMO
Creatinine measurement in blood and urine is an important diagnostic test for assessing kidney health. In this study, a molecularly imprinted polymer was obtained by incorporating fluorescent nanodiamond into a creatinine-imprinted polyacrylamide hydrogel. The quenching of peak nanodiamond fluorescence was significantly higher in the creatinine-imprinted polymer compared to the non-imprinted polymer, indicative of higher creatinine affinity in the imprinted polymer. Fourier transform infrared spectroscopy and microscopic imaging was used to investigate the nature of chemical bonding and distribution of nanodiamonds inside the hydrogel network. Nanodiamonds bind strongly to the hydrogel network, but as aggregates with average particle diameter of 3.4 ± 1.8 µm and 3.1 ± 1.9 µm for the non-imprinted and molecularly imprinted polymer, respectively. Nanodiamond fluorescence from nitrogen-vacancy color centers (NV- and NV0) was also used to detect creatinine based on nanodiamond-creatinine surface charge interaction. Results show a 15% decrease of NV-/NV0 emission ratio for the creatinine-imprinted polymer compared to the non-imprinted polymer, and are explained in terms of changes in the near-surface band structure of diamond with addition of creatinine. With further improvement of sensor design to better disperse nanodiamond within the hydrogel, fluorescent sensing from nitrogen-vacancy centers is expected to yield higher sensitivity with a longer range (Coulombic) interaction to imprinted sites than that for a sensor based on acceptor/donor resonance energy transfer.
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Herein we have reported a new magneto-fluorescent nanogel built on photoluminescent comacromer [PEG-maleic acid-glycine], N,N-dimethyl aminoethylmethacrylate and citrate-capped superparamagnetic iron oxide nanoparticles (SPION). The nanogel was found to have core-shell morphology (SPION core and PEG shell) with particle size around 80 nm. The cytocompatibility of the synthesized nanogel was studied using MTT, live/dead assays, and flow cytometry. The cellular uptake of the nanogel on cervical cancer cell line Hela evaluated through Prussian blue staining and fluorescence microscopy has revealed good cancer cell imaging capability. Magnetic hyperthermia experiments have shown that the synthesized nanogel caused the lysis of cancer cells. The fluorescence bioimaging capability of the nanogel in the murine model has shown good near IR imaging capability. Overall, the reported results suggest that the magneto-fluorescent nanogel shows promising future potential for cancer theranostic applications.
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Excellent multiplexing capability, molecular specificity, high sensitivity and the potential of resolving complex molecular level biological compositions augmented the diagnostic modality of surface-enhanced Raman scattering (SERS) in biology and medicine. While maintaining all the merits of classical Raman spectroscopy, SERS provides a more sensitive and selective detection and quantification platform. Non-invasive, chemically specific and spatially resolved analysis facilitates the exploration of SERS-based nano probes in diagnostic and theranostic applications with improved clinical outcomes compared to the currently available so called state-of-art technologies. Adequate knowledge on the mechanism and properties of SERS based nano probes are inevitable in utilizing the full potential of this modality for biomedical applications. The safety and efficiency of metal nanoparticles and Raman reporters have to be critically evaluated for the successful translation of SERS in to clinics. In this context, the present review attempts to give a comprehensive overview about the selected medical, biomedical and allied applications of SERS while highlighting recent and relevant outcomes ranging from simple detection platforms to complicated clinical applications.
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Ouro/química , Nanopartículas Metálicas/química , Análise Espectral Raman/métodos , Nanopartículas Metálicas/ultraestrutura , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Propriedades de SuperfícieRESUMO
Targeted nanocarriers can significantly increase the efficiency of therapeutic formulations by ensuring the site specific delivery of the cargo. Here in, we report a novel actively targeted fluorescent nanogel, PMB-OctN, based on photoluminescent comacromer [PEG-maleic acid-4 aminobenzoic acid], diethylene glycoldimethacrylate and octreotide. The nanogel has spherical morphology with average particle size around 40nm. The PMB-OctN can load 78% of anticancer drug and release for 5days and beyond in a sustained way. The studies on drug delivery of doxorubicin from PMB-OctN carried out with cervical cancer cells. Hela revealed appreciable therapeutic capability. The studies on cellular uptake of the nanogel revealed increased cellular uptake when compared to the nontargeted nanogel. The study on fluorescence bioimaging of the PMB-OctN in mice has demonstrated near-IR imaging capability. Then biodistribution studies of the PMB-OctN in mice have also revealed longer in vivo circulation lifetime. Taken together, these results suggest that the synthesized actively targeted nanogel, PMB-OctN stands as a promising candidate for theranostic applications. As octreotide based therapeutic formulation are already used in clinics, this newly reported strategy of near-IR fluorescence labeling of octreotide has important clinical relevance.
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Polietilenoglicóis , Polietilenoimina , Animais , Camundongos , Nanogéis , Octreotida , Nanomedicina Teranóstica , Distribuição TecidualRESUMO
We report a new prodrug micelle-based approach in which a model hydrophobic non-steroidal anti-inflammatory drug (NSAID), ibuprofen (Ibu), is tethered to amphiphilic methoxy polyethylene glycol-polypropylene fumarate (mPEG-PPF) diblock copolymer via hydrolytic anhydride linkages for potential controlled release applications of NSAIDs. Synthesized mPEG-PPF-Ibu polymer drug conjugates (PDCs) demonstrated high drug conjugation efficiency (â¼90%) and self-assembled to form micellar nanostructures in aqueous medium with critical micelle concentrations ranging between 16 and 30µg/mL. The entrapment efficiency of Ibu in prepared PDC micelles was as high as 18% (w/w). Crosslinking of prodrug micelles with N,N'-dimethylaminoethyl methacrylate conferred pH-responsive characteristics. pH-responsive PDC micelles averaged 100nm in size at pH 7.4 and exhibited concomitant changes in size upon incubation in physiologically relevant mildly acidic conditions. Ibu release was observed to increase with increasing acidic conditions and could be controlled by varying the amount of crosslinker used. Furthermore, the prepared mPEG-PPF-based micelles demonstrated excellent cytocompatibility and cellular internalization in vitro. More importantly, PDC micelles exerted anti-inflammatory effects by significantly decreasing monosodium urate crystal-induced prostaglandin E2 levels in rabbit synoviocyte cultures in vitro. Cumulatively, our results indicate that this new prodrug micelle approach is promising for NSAID-based therapies in the treatment of arthritis and cancer.
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Liberação Controlada de Fármacos , Ibuprofeno/administração & dosagem , Ibuprofeno/química , Micelas , Pró-Fármacos/administração & dosagem , Anidridos/química , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos , Fumaratos/química , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Interações Hidrofóbicas e Hidrofílicas , Ibuprofeno/farmacologia , Nanopartículas/química , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polipropilenos/síntese química , Polipropilenos/farmacologia , Pró-Fármacos/síntese química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Coelhos , Solubilidade , Propriedades de SuperfícieRESUMO
We have engineered hybrid polymer products based on a hybrid inorganic-organic comacromer consisting of hydroxyapatite (HA), carboxyl terminated polypropylene fumarate (CTPPF), PEG300 and ascorbic acid (AA) as a bone graft material. The integration and the spatial distribution of HA in the polymer backbone were facilitated by silanisation and 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) coupling technique. These comacromers and crosslinked polymer products were characterized by Fourier transform infrared spectroscopy (FTIR), Nuclear magnetic resonance (NMR), Scanning electron microscopy (SEM) and Raman mapping techniques. SEM and EDAX analysis substantiate high invitro bioactivity of the polymer products. SEM studies depict a distinct macroporous structure with pore size of 50 to 300µm. These crosslinked hybrid products demonstrated no significant difference in compressive moduli after 4weeks immersion in SBF. In particular, the compressive moduli were found to be comparable with that of trabecular bone. We suggest that the formation of an apatite layer on the surface of the composites deter initial degradation leading to better mechanical stability. As expected, the polymer products displayed negligible degradation in SBF during the first 4weeks which increased to a maximum of 25% by the end of the 8weeks time period. In addition these crosslinked products which are hydrophilic exhibit favorable albumin adsorption, cell viability, HOS cell adhesion and exemplary compatibility. Cumulatively, the results deduced in the present study suggest that these hybrid products have potential as a bone graft material.
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Materiais Biocompatíveis/química , Adesão Celular , Durapatita , Microscopia Eletrônica de Varredura , Polímeros , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
We present the development of theranostic nanoplatforms (NPs) based on a europium (Eu3+) doped calcium deficient hydroxyapatite (CDHA) core functionalized with cyclodextrin (ß-CD) and cucurbitural (CB[7]). The composition, crystalline structure, aspect ratio, surface area, morphology, and luminescence property of the NPs were investigated by means of X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray analysis (EDAX), the Brunauer-Emmett-Teller (BET) method, transmission electron microscopy (TEM), and fluorescence spectroscopy. The perceivable effects of Eu3+ doping appear in the minor peak shift to larger angles attributed to lower crystallite size and smaller aspect ratios coupled with greater structural strain in the rod shaped theranostic NPs and a shift in their zeta potential toward less negative values. Cell parameter calculations suggest that the doping of Eu3+ would cause the a-axis parameter to decrease slightly as the ionic radius of Eu3+ is smaller than that of Ca2+. Moreover drug release profiles employing 5-fluorouracil (5FU) suggest that these luminescent NPs depict controlled and sustained release profiles. Further the emissive intensities of the NPs in the carrier systems increase with cumulative released amounts of 5FU, suggesting that release of the drug can be monitored by changes in luminescent intensity. In addition, native NPs manifest commendable cytocompatibility as demonstrated by MTT and live/dead protocols, whereas the 5FU loaded NPs demonstrated over 80% HeLa cell death, signifying their therapeutic potential. We envision that these NPs can serve as effective and practical multifunctional probes for theranostic applications.
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A brighter, non toxic and biocompatible optical imaging agent is one of the major quests of biomedical research. Here in, we report a photoluminescent comacromer [PEG-poly(propylene fumarate)-citric acid-glycine] and novel stimulus (pH) responsive nanogel endowed with excitation wavelength dependent fluorescence (EDF) for combined drug delivery and bioimaging applications. The comacromer when excited at different wavelengths in visible region from 400nm to 640nm exhibits fluorescent emissions from 510nm to 718nm in aqueous condition. It has high Stokes shift (120nm), fluorescent lifetime (7 nanoseconds) and quantum yield (50%). The nanogel, C-PLM-NG, prepared with this photoluminescent comacromer and N,N-dimethyl amino ethylmethacrylate (DMEMA) has spherical morphology with particle size around 100nm and 180nm at pH 7.4 (physiological) and 5.5 (intracellular acidic condition of cancer cells) respectively. The studies on fluorescence characteristics of C-PLM NG in aqueous condition reveal large red-shift with emissions from 523nm to 700nm for excitations from 460nm to 600nm ascertaining the EDF characteristics. Imaging the near IR emission with excitation at 535nm was accomplished using cut-off filters. The nanogel undergoes pH responsive swelling and releases around 50% doxorubicin (DOX) at pH 5.5 in comparison with 15% observed at pH 7.4. The studies on in vitro cytotoxicity with MTT assay and hemolysis revealed that the present nanogel is non-toxic. The DOX-loaded C-PLM-NG encapsulated in Hela cells induces lysis of cancer cells. The inherent EDF characteristics associated with C-PLM NG enable cellular imaging of Hela cells. The studies on biodistribution and clearance mechanism of C-PLM-NG from the body of mice reveal bioimaging capability and safety of the present nanogel. This is the first report on a polymeric nanogel with innate near IR emissions for bioimaging applications.
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Doxorrubicina/farmacologia , Fluorescência , Hemólise/efeitos dos fármacos , Raios Infravermelhos , Polietilenoglicóis/química , Polietilenoimina/química , Polímeros/química , Imagem Corporal Total , Animais , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Processamento de Imagem Assistida por Computador/métodos , Camundongos , Nanogéis , Distribuição TecidualRESUMO
We report a novel multi-modal biodegradable photoluminescent comacromer [poly(propylene fumarate)-PEG-glycine] (PLM) having excitation-dependent fluorescence (EDF) for biomedical applications. The photoluminescence of the synthesized PLM in aqueous and solid state condition, fluorescence life time and photo stability were evaluated. Hydrogels and nanogels were prepared from the PLM by cross linking with acrylic acid. Nanogels exhibited spherical morphology with a particle size of 100 nm as evaluated by transmission electron microscopy (TEM). In vitro cytotoxic and hemolytic studies revealed cytocompatibility. Furthermore, cellular imaging of nanogels on L929 fibroblast and Hela cell lines revealed EDF characteristics. We hypothesize that the EDF characteristics of the synthesized PLM may be attributed to the presence of n-π* interactions of the hydroxyl oxygen atoms of PEG with carbonyl groups of the ester linkages. Taken together, our results indicate that the synthesized PEG-based comacromer can serve as biocompatible fluorophores for various biomedical applications. More importantly, the facile way of synthesizing fluorescent polymers based on PEG with EDF characteristics demonstrated in this work can pave the way for developing more novel biocompatible fluorophores with wide range of biomedical applications.