RESUMEN
Diabetes mellitus (DM)-associated impairments in wound healing include prolonged inflammation, the overexpression of matrix metalloproteases (MMPs), and low levels of growth factors at the wound site. To this end, a layer-by-layer scaffold (SL-B-L) made of cross-linked silk fibroin and hyaluronic acid is developed to deliver chlorhexidine, an antimicrobial agent and an MMP-9 inhibitor, along with the PDGF-BB protein. SL-B-L exhibited highly porous morphology. Diabetic rats treated with SL-B-L demonstrated an early wound closure, a fully reconstructed epithelial layer by 14 days, and reduced levels of IL-6, TNF-α, TGF-ß1, and MMP-9. Interestingly, SL-B-L treatment increased angiogenesis, the bioavailability of collagen, DNA content, and VEGF-A levels. Furthermore, enhanced keratinocyte-fibroblast interaction along with ordered collagen deposition was observed in SL-B-L-treated rats. Most interestingly, when compared with a clinically used scaffold SEESKIN+, SL-B-L outperformed in promoting wound healing in a diabetic rat model by regulating the inflammation while delivering growth factor and the MMP-9 inhibitor.
Asunto(s)
Citocinas , Diabetes Mellitus Experimental , Animales , Becaplermina , Clorhexidina , Diabetes Mellitus Experimental/tratamiento farmacológico , Hidrogeles , Péptidos y Proteínas de Señalización Intercelular , Metaloproteinasa 9 de la Matriz , Ratas , Piel , Factor A de Crecimiento Endotelial VascularRESUMEN
The present study demonstrates the epigenetic mechanisms underlying the effect of Bacoside rich extract of Bacopa monniera-a nootropic herb, on scopolamine treated amnesic mice conferred via chromatin modifying enzymes. The focus of the work was to elucidate the modulation of the chromatin modifying enzymes: DNMT1, DNMT3a, DNMT3b, HDAC2, HDAC5 and CPB in scopolamine induced amnesic mice after treatment with bacoside rich extract of Bacopa monniera (BA) and BA encapsulated in lactoferrin conjugated PEG-PLA-PCL-OH based polymersomes (BAN). We observed remarkable difference between the results obtained after the treatment with BA and BAN. Interestingly BAN was found to be more efficient in downregulating DNA methylation and histone chain deacetylation. Scopolamine treatment showed up-regulation of DNMT1 expression in qRT-PCR by 3.14-fold as compared to the control, which was considerably decreased by 1.5-fold after treatment with BA and remarkably decreased 0.11-fold by BAN treatment. Scopolamine treatment up-regulated the expression of DNMT3a by 1.6-fold while for DNMT3b by 3.13-fold. In DNMT3a and DNMT3b the fold change decreased to 0.64 and 0.76 after BA treatment, whereas the BAN treatment further down-regulated to 0.32- and 0.63-fold, respectively. Similarly scopolamine up-regulated HDAC2 and HDAC5 by 3.12 fold and 3.64-fold, respectively. BA treatment reversed the changes by reducing HDAC2 mRNA to 0.89-fold and HDAC5 mRNA 0.83-fold. BAN further reduced expression of HDAC2 further to 0.39-fold and HDAC5 to 0.31-fold. On the other hand scopolamine down-regulated CBP mRNA expression by 0.28-fold and increased by 1.09 after BA treatment. BAN significantly increased the CPB expression by 1.65-fold as compared to BA treatment. These findings were consolidated by DNMT and HDAC enzyme activity assay, methylation in the promoter region of the memory related genes: ARC and BDNF and Dot blot assay for DNA methylation. The percent activity increase of DNMT and HDAC after scopolamine administration was 375.74 and 240.90 respectively. After treatment with BA the downfall in percent activity was observed as 167.99 in DMNT and 130.57 in HDAC. BAN treatment further decreased the percent enzyme activity of DNMT and HDAC significantly by 30.0 and 61.81 respectively. The potency of BAN in reversing the epigenetic changes of scopolamine induced amnesic mouse brain, can be attributed to the brain specific delivery of BA through polymersomes which are able to cross the blood brain barrier (BBB) via receptor mediated endocytosis.
Asunto(s)
Amnesia/tratamiento farmacológico , Portadores de Fármacos/química , Epigénesis Genética/efectos de los fármacos , Saponinas/uso terapéutico , Amnesia/inducido químicamente , Animales , Bacopa/química , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Histona Desacetilasas/metabolismo , Lactoferrina/química , Masculino , Ratones , Poliésteres/química , Polietilenglicoles/química , EscopolaminaRESUMEN
Ultrafine gold particles (AuPs) can be emerged as a good candidate in the field of drug delivery as well as in imaging applications. However, little attention has been paid to detailed study of nanoparticle's interaction with blood components before systemic use. An investigation into the interaction of ultrafine AuPs with blood components is must for its clinical application. In present study, the interaction of ultrafine sized AuPs (2⯱â¯0.5â¯nm, 5⯱â¯1â¯nm, and 10⯱â¯2â¯nm) with blood components and its immunogenic property (pro-inflammatory reaction) was investigated. All three sized AuPs did not cause any significant hemolysis. Plasma coagulation study showed significant increase in Prothrombin time (PT) with International Normalized Ratio (INR) value raised to 1.53 with 10â¯nm AuPs. Maximum prolongation of activated partial thromboplastin time (APTT) (3.2â¯s) was seen with 5 &10â¯nm sized AuPs. Maximum thrombin time (TT) prolongation was seen with 2â¯nm (18.3s) with the difference of 1.4â¯s as compared to control. Platelet aggregation was faster in case of 5 & 10â¯nm sized AuPs. All three sized AuPs exhibited in-vitro C3 complement activation whereas they did not stimulate significant proliferation of peripheral blood mononuclear cells (PBMC). These findings further validate the utility of ultrafine AuPs for in-vivo applications.
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Oro/toxicidad , Material Particulado/toxicidad , Animales , Coagulación Sanguínea/efectos de los fármacos , Activación de Complemento/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , Leucocitos Mononucleares/efectos de los fármacos , Ratones , Agregación Plaquetaria/efectos de los fármacosRESUMEN
The study highlights the significance of co-application of bioactive components into liposomal gel formulations and their comparison to azithromycin for treatment of Acne. A Design of Experiments (DoE) approach was utilized to obtain optimized liposomal formulation encapsulating curcumin, with size and zeta potential of â¼100 nm and â¼14 mV, respectively, characterized by DLS, HR-TEM, FESEM, and AFM. The curcumin liposomal dispersion depicted excellent stability over the period of 60 days, which was further converted in gel form using Carbopol. Pharmacokinetics of curcumin-loaded liposomal gel showed that Tmax for curcumin was achieved within 1 h of post application in both stratum corneum and skin, indicating quick penetration of nano-sized liposomes. Stratum corneum depicted Cmax of 688.3 ng/mL and AUC0-t of 5857.5 h × ng/mL, while the skin samples displayed Cmax of 203.3 ng/gm and AUC0-t of 2938.1 h × ng/gm. Lauric acid and azithromycin liposomal gel formulations were prepared as per the optimum parameters obtained by DoE. In antibacterial activity using agar diffusion assay, lauric acid gel formulation revealed â¼1.5 fold improved antibacterial effect than curcumin gel formulation. Interestingly, their co-application (1:1) exhibited significantly enhanced antibacterial effect against both macrolide-sensitive (1.81 versus 1.25 folds) and resistant strains of P. acnes (2.93 versus 1.22 folds) than their individual counterparts. The in vivo studies in rat ear model displayed a â¼2 fold reduction in comedones count and cytokines (TNF-α and IL-1ß) on co-application with curcumin and lauric acid liposomal gel compared to placebo treated group.
Asunto(s)
Acné Vulgar/tratamiento farmacológico , Geles/química , Geles/farmacología , Liposomas/química , Liposomas/farmacología , Animales , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Azitromicina/farmacocinética , Azitromicina/farmacología , Química Farmacéutica/métodos , Curcumina/química , Curcumina/farmacocinética , Curcumina/farmacología , Geles/farmacocinética , Ácidos Láuricos/química , Ácidos Láuricos/farmacocinética , Ácidos Láuricos/farmacología , Liposomas/farmacocinética , Tamaño de la Partícula , Ratas , Ratas Sprague-Dawley , Piel/efectos de los fármacosRESUMEN
In the present work, polymersomes based on self-assembled, folate-targeted, redox-responsive, ATRP-based amphiphilic diblock copolymer poly(polyethylene glycol)-S-S-polylactide with disulfide linkage were developed for efficient doxorubicin (DOX) delivery and compared with marketed DOXIL nanoformulation. The polymersomes formulation was optimized by quality by design approach providing monodisperse nanostructures of â¼110 nm and enhanced DOX loading of â¼20%. Polymersomes showed excellent stability as per the ICH guidelines over the extended storage period of 3 months. The in vitro drug release profile confirmed the redox sensitive behavior of polymersomes providing â¼80% drug release in endosomal pH 5 with 10 mmol GSH as compared to â¼20% release at pH 7.4. The targeted polymersomes achieved enhanced cellular internalization in folate receptor overexpressing cell lines, MDA-MB-231 and HeLa, providing â¼24% higher tumor reduction than DOXIL in Ehrlich ascites tumor bearing Swiss albino mice.
Asunto(s)
Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Liposomas/síntesis química , Poliésteres/química , Ácidos Polimetacrílicos/química , Animales , Células HeLa , Humanos , Liposomas/efectos adversos , Ratones , Oxidación-Reducción , Tensoactivos/síntesis químicaRESUMEN
Nanotechnology has revolutionized health care industry in a large scale and its applications are a boon to modern medicine and dental science. It is expected to pervade and further revolutionize the art and science of dentistry and may well have important applications spanning all the aspects of oral diseases, diagnosis, prevention and treatment. Materials science in dentistry has embraced the technology to produce nanomaterials that are being used in caries inhibitors, antimicrobial resins, hard tissue remineralizing agents, targeted drug delivery, scaffolds, bio-membranes, nanocrystalline hydroxyl apatite, restorative cements, adhesion promoters and boosters, bioactive glass, tissue conditioners, reinforced methacrylate resins, root canal disinfectants, friction free orthodontic arch wires and nano composites life. These upcoming technologies have potential to bring about significant benefits in the form of improvement in dental science and to society. The present review presents the latest recent developments in this interdisciplinary field bridging nanotechnology and dental science.
Asunto(s)
Materiales Biocompatibles , Materiales Dentales , Nanoestructuras , Nanotecnología , Odontología , HumanosRESUMEN
Here, we investigated the synergistic effect of electrospun nanofibrous scaffolds made of gelatin /sulfated hyaluronan (sHA) or native hyaluronan (HA)/chondroitin sulfate (CS) and, keratinocytes (HaCaT)-human mesenchymal stem cells (hMSCs) contact co-culture on epithelial differentiation of hMSCs. The hMSCs were co-cultured in contact with HaCaT cells for 5 days on electrospun scaffold. Results show that electrospun scaffolds containing sulfated glycosaminoglycans (GAGs) stimulate epithelial differentiation in terms of various protein expression markers (keratin 14, ΔNp63α and Pan-cytokeratin) and gene expression of several dermal proteins (keratin 14, ΔNp63α). Electrospun scaffold independent of GAGs alone did not affect the epithelial differentiation of hMSCs but combination of keratinocyte-hMSC contact co-culture and electrospun scaffold promotes the epithelial differentiation of hMSCs.
Asunto(s)
Comunicación Celular/fisiología , Queratinocitos/citología , Queratinocitos/fisiología , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/fisiología , Andamios del Tejido , Diferenciación Celular , Células Cultivadas , Técnicas de Cocultivo/instrumentación , Técnicas de Cocultivo/métodos , Galvanoplastia/métodos , Regulación de la Expresión Génica , Humanos , Ensayo de Materiales , Nanofibras/química , Andamios del Tejido/química , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Grafting of quaternary nitrogen atoms into the backbone of polymer is an efficient way of developing new generation antimicrobial polymeric wound dressing. In this study, an elastic, non-adhesive and antimicrobial transparent hydrogel based dressing has been designed, which might be helpful for routine observation of wound area without removing the dressing material along with maintaining a sterile environment for a longer period of time. Green synthesized silver nanoparticles have been loaded into the quaternized PVA hydrogel matrix to improve its antimicrobial property. Silver nanoparticles loaded quaternized PVA hydrogel showed enhanced mechanical and swelling properties compared to native quaternized PVA hydrogel. Release kinetics evaluated by atomic absorption spectroscopy revealed that the release mechanism of silver nanoparticles from the hydrogel follows Fickian diffusion. Antimicrobial efficacy of the hydrogels was evaluated by disk diffusion test on Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. After 96 h of release in phosphate buffer, the growth inhibition zone created by silver nanoparticless loaded quaternized PVA hydrogel is comparable to that created by ampicillin. These observations assert that the silver nanoparticles loaded quaternized PVA hydrogel acts as a reservoir of silver nanoparticles, which helps in maintaining a sterile environment for longer time duration by releasing Ag nanocrystallite in sustained manner.
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Antiinfecciosos/química , Vendajes , Hidrogeles/química , Nanopartículas del Metal/química , Plata/química , Difusión , Escherichia coli/efectos de los fármacos , Tecnología Química Verde , Humanos , Cinética , Microscopía Electrónica de Rastreo , Polímeros/química , Pseudomonas aeruginosa/efectos de los fármacos , Espectrofotometría Atómica , Staphylococcus aureus/efectos de los fármacos , Estrés Mecánico , Resistencia a la Tracción , Cicatrización de Heridas/efectos de los fármacos , Difracción de Rayos XRESUMEN
Redox responsive biodegradable polymersomes comprising of poly(ethylene glycol)-polylactic acid-poly(ethylene glycol) [PEG-s-s-PLA-s-s-PLA-s-s-PEG] triblock copolymer with multiple disulfide linkages were developed to improve intracellular delivery and to enhance chemotherapeutic efficacy of doxorubicin in breast cancer with minimal cardiotoxicity. Folic acid and trastuzumab functionalized monodispersed polymersomes of size â¼150 nm were prepared by nanoprecipitation method while achieving enhanced doxorubicin loading of â¼32% in the polymersomes. Multiple redox responsive disulfide linkages were incorporated in the polymer in order to achieve complete disintegration of polymersomes in redox rich environment of cancer cells resulting in enhanced doxorubicin release as observed in in vitro release studies, where â¼90% doxorubicin release was achieved in pH 5.0 in the presence of 10 mM glutathione (GSH) as compared to â¼20% drug release in pH 7.4. Folic acid and trastuzumab mediated active targeting resulted in improved cellular uptake and enhanced apoptosis in in vitro studies in breast cancer cell lines. In vivo studies in Ehrlich ascites tumor bearing Swiss albino mice showed enhanced antitumor efficacy and minimal cardiotoxicity of polymersomes with â¼90% tumor regression as compared to â¼38% tumor regression observed with free doxorubicin. The results highlight therapeutic potential of the polymersomes as doxorubicin delivery nanocarrier in breast cancer therapy with its superior antitumor efficacy and minimal cardiotoxicity.
Asunto(s)
Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Portadores de Fármacos/química , Ácido Fólico/farmacología , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Trastuzumab/farmacología , Animales , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapéutico , Portadores de Fármacos/efectos adversos , Portadores de Fármacos/síntesis química , Liberación de Fármacos , Femenino , Humanos , Células MCF-7 , Ratones , Oxidación-Reducción , Polietilenglicoles/químicaRESUMEN
Naturally occurring antimicrobial peptides (AMPs) display the ability to eliminate a wide variety of bacteria, without toxicity to the host eukaryotic cells. Synthetic polymers containing moieties mimicking lysine and arginine components found in AMPs have been reported to show effectiveness against specific bacteria, with the mechanism of activity purported to depend on the nature of the amino acid mimic. In an attempt to incorporate the antimicrobial activity of both amino acids into a single water-soluble copolymer, a series of copolymers containing lysine mimicking aminopropyl methacrylamide (APMA) and arginine mimicking guanadinopropyl methacrylamide (GPMA) were prepared via aqueous RAFT polymerization. Copolymers were prepared with varying ratios of the comonomers, with degree of polymerization of 35-40 and narrow molecular weight distribution to simulate naturally occurring AMPs. Antimicrobial activity was determined against Gram-negative and Gram-positive bacteria under conditions with varying salt concentration. Toxicity to mammalian cells was assessed by hemolysis of red blood cells and MTT assays of MCF-7 cells. Antimicrobial activity was observed for APMA homopolymer and copolymers with low concentrations of GPMA against all bacteria tested, with low toxicity toward mammalian cells.
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Acrilamidas/química , Aminas/química , Péptidos Catiónicos Antimicrobianos/síntesis química , Guanidinas/química , Peptidomiméticos/síntesis química , Polímeros/síntesis química , Péptidos Catiónicos Antimicrobianos/farmacología , Arginina/química , Supervivencia Celular/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , Lisina/química , Células MCF-7 , Estructura Molecular , Peptidomiméticos/farmacología , Polimerizacion , Polímeros/farmacologíaRESUMEN
Nonspecificity and cardiotoxicity are the primary limitations of current doxorubicin chemotherapy. To minimize side effects and to enhance bioavailability of doxorubicin to cancer cells, a dual-targeted pH-sensitive biocompatible polymeric nanosystem was designed and developed. An ATRP-based biodegradable triblock copolymer, poly(poly(ethylene glycol) methacrylate)-poly(caprolactone)-poly(poly(ethylene glycol) methacrylate) (pPEGMA-PCL-pPEGMA), conjugated with doxorubicin via an acid-labile hydrazone bond was synthesized and characterized. Dual targeting was achieved by attaching folic acid and the AS1411 aptamer through EDC-NHS coupling. Nanoparticles of the functionalized triblock copolymer were prepared using the nanoprecipitation method, resulting in an average particle size of â¼140 nm. The biocompatibility of the nanoparticles was evaluated using MTT cytotoxicity assays, blood compatibility studies, and protein adsorption studies. In vitro drug release studies showed a higher cumulative doxorubicin release at pH 5.0 (â¼70%) compared to pH 7.4 (â¼25%) owing to the presence of the acid-sensitive hydrazone linkage. Dual targeting with folate and the AS1411 aptamer increased the cancer-targeting efficiency of the nanoparticles, resulting in enhanced cellular uptake (10- and 100-fold increase in uptake compared to single-targeted NPs and non-targeted NPs, respectively) and a higher payload of doxorubicin in epithelial cancer cell lines (MCF-7 and PANC-1), with subsequent higher apoptosis, whereas a normal (noncancerous) cell line (L929) was spared from the adverse effects of doxorubicin. The results indicate that the dual-targeted pH-sensitive biocompatible polymeric nanosystem can act as a potential drug delivery vehicle against various epithelial cancers such as those of the breast, ovary, pancreas, lung, and others.
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Antineoplásicos/farmacología , Materiales Biocompatibles/farmacología , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos , Ácido Fólico/farmacología , Nanopartículas/química , Oligodesoxirribonucleótidos/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Aptámeros de Nucleótidos , Materiales Biocompatibles/administración & dosificación , Materiales Biocompatibles/química , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Ensayos de Selección de Medicamentos Antitumorales , Ácido Fólico/administración & dosificación , Ácido Fólico/química , Humanos , Concentración de Iones de Hidrógeno , Células MCF-7 , Estructura Molecular , Nanopartículas/administración & dosificación , Oligodesoxirribonucleótidos/administración & dosificación , Oligodesoxirribonucleótidos/química , Tamaño de la Partícula , Polimerizacion , Relación Estructura-Actividad , Propiedades de SuperficieRESUMEN
The impairment of phenotype switching of pro-inflammatory M1 to pro-healing M2 macrophage induced by hyperglycemic microenvironment often elevates oxidative stress, impairs angiogenesis, and leads to chronic non-healing wounds in diabetic patients. Administration of M2 macrophage-derived exosomes (M2Exo) at wound site is known to polarize M1 to M2 macrophage and can accelerate wound healing by enhancing collagen deposition, angiogenesis, and re-epithelialization. In the present study, M2Exo were conjugated with oxidized hyaluronic acid and mixed with PEGylated silk fibroin to develop self-healing Exo-gel to achieve an efficient therapy for diabetic wounds. Exo-gel depicted porous networked morphology with self-healing and excellent water retention behaviour. Fibroblast cells treated with Exo-gel showed significant uptake of M2Exo that increased their proliferation and migration in vitro. Interestingly, in a diabetic wound model of wistar rats, Exo-gel treatment induced 75 % wound closure within 7 days with complete epithelial layer regeneration by modulating cytokine levels, stimulating fibroblast-keratinocyte interaction and migration, angiogenesis, and organized collagen deposition. Taken together, this study suggests that Exo-gel depict properties of an excellent wound healing matrix and can be used as a therapeutic alternative to treat chronic non-healing diabetic wounds.
Asunto(s)
Exosomas , Ácido Hialurónico , Hidrogeles , Macrófagos , Cicatrización de Heridas , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Animales , Exosomas/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Ratas , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Hidrogeles/química , Hidrogeles/farmacología , Diabetes Mellitus Experimental , Ratas Wistar , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Masculino , Ratones , Seda/química , Seda/farmacología , Microambiente Celular/efectos de los fármacos , Humanos , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacosRESUMEN
PURPOSE: In chronic hyperglycemia, the advanced glycation end product (AGE) interacts with its receptor (RAGE) and contributes to impaired wound healing by inducing oxidative stress, generating dysfunctional macrophages, and prolonging the inflammatory response. Additionally, uncontrolled levels of proteases, including metallomatrix protease-9 (MMP-9), in the diabetic wound bed degrade the extracellular matrix (ECM) and biological cues that augment healing. A multifunctional antimicrobial hydrogel (Immuno-gel) containing RAGE and MMP-9 inhibitors can regulate the wound microenvironment and promote scar-free healing. RESULTS: Immuno-gel was characterized and the wound healing efficacy was determined in vitro cell culture and in vivo diabetic Wistar rat wound model using ELISA, Western blot, and Immunofluorescence staining. The Immuno-gel exhibited a highly porous morphology with excellent in vitro cytocompatibility. AGE-stimulated macrophages treated with the Immuno-gel released higher levels of pro-healing cytokines in vitro. In the hydrogel-wound interface of diabetic Wistar rats, Immuno-gel treatment significantly reduced MMP-9 and NF-κB expression and enhanced pro-healing (M2) macrophage population and pro-healing cytokines. CONCLUSION: Altogether, this study suggests that Immuno-gel simultaneously attenuates macrophage dysfunction through the inhibition of AGE/RAGE signaling and reduces MMP-9 overexpression, both of which favor scar-free healing. The combinatorial treatment with RAGE and MMP-9 inhibitors via Immuno-gel simultaneously modulates the diabetic wound microenvironment, making it a promising novel treatment to accelerate diabetic wound healing.
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Diabetes Mellitus Experimental , Productos Finales de Glicación Avanzada , Hidrogeles , Metaloproteinasa 9 de la Matriz , Ratas Wistar , Receptor para Productos Finales de Glicación Avanzada , Transducción de Señal , Cicatrización de Heridas , Animales , Metaloproteinasa 9 de la Matriz/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/farmacología , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Ratas , Transducción de Señal/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/inmunología , Masculino , RatonesRESUMEN
Polymer-SPION hybrids were investigated for receptor-mediated localization in tumour tissue. Superparamagnetic iron oxide nanoparticles (SPIONs) prepared by high-temperature decomposition of iron acetylacetonate were monodisperse (9.27 ± 3.37 nm), with high saturation magnetization of 76.8 emu g(-1). Amphiphilic copolymers prepared from methyl methacrylate and PEG methacrylate by atom transfer radical polymerization were conjugated with folic acid (for folate-receptor specificity). The folate-conjugated polymer had a low critical micellar concentration (0.4 mg l(-1)), indicating stability of the micellar formulation. SPION-polymeric micelle clusters were prepared by desolvation of the SPION dispersion/polymer solution in water. Magnetic resonance imaging of the formulation revealed very good contrast enhancement, with transverse (T(2)) relaxivity of 260.4 mM(-1) s(-1). The biological evaluation of the SPION micelles included cellular viability assay (MTT) and uptake in HeLa cells. These studies demonstrated the potential use of these nanoplatforms for imaging and targeting.
Asunto(s)
Medios de Contraste , Dextranos/síntesis química , Diagnóstico por Imagen/métodos , Receptor 1 de Folato/metabolismo , Imagen por Resonancia Magnética , Micelas , Neoplasias/diagnóstico , Muerte Celular/efectos de los fármacos , Dextranos/química , Dextranos/toxicidad , Dextranos/ultraestructura , Endocitosis/efectos de los fármacos , Células HeLa , Humanos , Espacio Intracelular/efectos de los fármacos , Espacio Intracelular/metabolismo , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/toxicidad , Nanopartículas de Magnetita/ultraestructura , Microscopía Confocal , Microscopía Electrónica de Transmisión , Neoplasias/patología , Polimerizacion , Polímeros/síntesis química , Polímeros/química , Pirenos/química , Espectrofotometría Ultravioleta , Difracción de Rayos XRESUMEN
Faster and predictable osseointegration is crucial for the success of dental implants, especially in patients with compromised local or systemic conditions. Despite various surface modifications on the commercially available Titanium (Ti) dental implants, the bioactivity of Ti is still low. Thus, to achieve both biological and therapeutic activity on titanium surfaces, surface modification techniques such as titanium nanotubes have been studied as nanotube surfaces can hold therapeutic drugs and molecules. The main aim of the present research work is to study the early osseointegration around the novel Simvastatin drug eluting nanotubular dental implant. In the present research, the titanium nanotubes were fabricated on the screw-shaped dental implant surface and the Simvastatin drug was loaded into the nanotubes using the ultrasonication dip method. In vitro and In vivo studies were carried out on the modified dental implants. In vitro cell culture study reported enhanced osteogenic activity on the drug-loaded nanotube surface implants. The invivo animal studies were evaluated by micro-CT, histopathology, and reverse torque removal analysis methods. The test results showed faster osseointegration with the strong interface on the Simvastatin drug-loaded implant surface at 4 weeks of healing as compared to the control implants.
RESUMEN
Antimicrobial peptides (AMPs) show great potential as alternative therapeutic agents to conventional antibiotics as they can selectively bind and eliminate pathogenic bacteria without harming eukaryotic cells. It is of interest to develop synthetic macromolecules that mimic AMPs behavior, but that can be produced more economically at commercial scale. Herein, we describe the use of aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization to prepare primary and tertiary amine-containing polymers with precise molecular weight control and narrow molecular weight distributions. Specifically, N-(3-aminopropyl)methacrylamide (APMA) was statistically copolymerized with N-[3-(dimethylamino)propyl]methacrylamide (DMAPMA) or N-[3-(diethylamino)propyl]methacrylamide (DEAPMA) to afford a range of (co)polymer compositions. Analysis of antimicrobial activity against E. coli (Gram-negative) and B. subtilis (Gram-positive) as a function of buffer type, salt concentration, pH, and time indicated that polymers containing large fractions of primary amine were most effective against both strains of bacteria. Under physiological pH and salt conditions, the polymer with the highest primary amine content caused complete inhibition of bacterial growth at low concentrations, while negligible hemolysis was observed over the full range of concentrations tested, indicating exceptional selectivity. The cytotoxicity of select polymers was evaluated against MCF-7 cells.
Asunto(s)
Antibacterianos/síntesis química , Polimerizacion , Ácidos Polimetacrílicos/síntesis química , Antibacterianos/farmacología , Antibacterianos/toxicidad , Bacillus subtilis/efectos de los fármacos , Cationes , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Pruebas Antimicrobianas de Difusión por Disco , Eritrocitos/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Hemólisis/efectos de los fármacos , Humanos , Concentración de Iones de Hidrógeno , Peso Molecular , Ácidos Polimetacrílicos/farmacología , Ácidos Polimetacrílicos/toxicidadRESUMEN
BACKGROUND: A weak implant-soft tissue interface may lead to bacterial ingression, breakdown of underlying tissues, and eventually implant failure. This study proposes a surface modification technique of titanium alloy (Ti), using a nano-biopolymer scaffold to enhance soft tissue attachment in dental implants. METHODS: Gelatin (20% w/v) embedded with 10 ± 2 nm silver nanoparticles (AgNPs) was electrospun to form a gelatin electrospun mat (GEM) scaffold, bonded to Ti alloy surface using chemical surface functionalization. Antimicrobial activity of AgNPs was tested against representative Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli) at 4, 24, and 48 hours and after embedding in scaffold at 48 hours. Cytotoxicity analysis (MTT assay) was performed using the 3T3 mouse fibroblast cell line at 24 and 72 hours for two groups: control (unmodified Ti disc) and experimental (GEM embedded with AgNPs); and further validated by scanning electron microscopy. RESULTS: The AgNPs-embedded GEM showed good antimicrobial activity at 48 hours, with the AgNPs showing complete (99.99%) inhibition of bacterial colony counts at 24 and 48 hours. Cell viability and proliferation over the GEM modified Ti discs were seen to be significantly increased (P < 0.05) at 72 hours as compared with control. SEM images revealed intimate spreading of fibroblasts, with differentiated cell morphology and pseudopodial processes, indicative of enhanced fibroblastic adhesion, growth, and differentiation over the scaffold. CONCLUSION: Results show good antifouling properties and biocompatibility of the fabricated coating, making it a promising strategy to reduce postoperative infections and peri-implant diseases in Ti dental implants.
Asunto(s)
Antiinfecciosos , Implantes Dentales , Nanopartículas del Metal , Nanofibras , Ratones , Animales , Plata/química , Plata/farmacología , Nanopartículas del Metal/química , Biomimética , Gelatina , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Titanio , Aleaciones , Escherichia coli , Propiedades de Superficie , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacologíaRESUMEN
Assessment of biocompatibility for the developed wound dressing plays a significant role in translational studies. In the present research work, a wound dressing has been developed using gelatin, hyaluronic acid and chondroitin sulfate using EDC as crosslinker in a specific manner. The characterized hydrogel wound dressing was evaluated for its biocompatibility studies by means of ISO-10993-11 medical device rules and standards. Various parameters like skin sensitization test, acute systemic toxic test, implantation study, intracutaneous reactivity test,in vitrocytotoxicity test and bacterial reverse mutation test, were evaluated and the results demonstrated its safety for the pre-clinical investigation.
Asunto(s)
Vendajes , Hidrogeles , Gelatina , Ácido HialurónicoRESUMEN
The surface of dental implants plays a vital role in early and more predictable osseointegration. SLA (sandblasted large grit and acid-etched) represents the most widely accepted, long-term clinically proven surface. Primarily, dental implants are manufactured by either commercially pure titanium (CP-Ti) or Ti6Al4V ELI alloy. The acid etch behavior of CP-Ti is well known and its effects on the surface microstructure and physicochemical properties have been studied by various researchers in the past. However, there is a lack of studies showing the effect of acid etching parameters on the Ti6Al4V alloy surface. The requirement of the narrow diameter implants necessitates implant manufacturing from alloys due to their high mechanical properties. Hence, it is necessary to have an insight on the behavior of acid etching of the alloy surface as it might be different due to changed compositions and microstructure, which can further influence the osseointegration process. The present research was carried out to study the effect of acid etching parameters on Ti6Al4V ELI alloy surface properties and the optimization of process parameters to produce micro- and nanotopography on the dental implant surface. This study shows that the Ti6Al4V ELI alloy depicts an entirely different surface topography compared to CP-Ti. Moreover, the surface topography of the Ti6Al4V ELI alloy was also different when etching was done at room temperature compared to high temperature, which in turn affected the behavior of the cell on these surfaces. Both microns and nano-level topography were achieved through the optimized parameters of acid etching on Ti6Al4V ELI alloy dental implant surface along with improved roughness, hydrophilicity, and enhanced cytocompatibility.
RESUMEN
Development of scaffold from biopolymers can ease the requirements for donor skin autograft and plays an effective role in the treatment of burn wounds. In the current study, a porous foam based, bilayered hydrogel scaffold was developed using gelatin, hyaluronic acid and chondroitin sulfate (G-HA-CS). The fabricated scaffold was characterized physicochemically for pre- and post-sterilization efficacy by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA).In-vitrostudies proved that the scaffold promoted cellular proliferation. The efficacy of G-HA-CS scaffold was compared with Integra™ at different time points (7, 14, 21 and 42 days), in a swine second degree burn wound model. Remarkable healing potential of the scaffold was evident from the wound contraction rate, reduction of IL-6, TNF-αand C3. The expression of healing markers TGF-ß1 and collagen 1 revealed significant skin regeneration with regulated fibroblast activation towards the late phase of healing (p< 0.001 at day 21 and 42 vs. control). Expression of Vascular Endothelial Growth Factor A (VEGFA), vimentin and N-cadherin were found to favor angiogenesis and skin regeneration. Mechanistically, scaffold promoted wound healing by modulation of CD-45, cyclooxygenase-2 and MMP-2. Thus, the promising results with foam based scaffold, comparable to Integra™ in swine burn injury model offer an innovative lead for clinical translation for effective management of burn wound.