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1.
ACS Appl Bio Mater ; 7(6): 3701-3713, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38748449

RESUMEN

Metal-organic complexes have shown astounding bioactive properties; however, they are rarely explored as biomaterials. Recent studies showed that carboxymethyl-chitosan (CMC) genipin-conjugated zinc biomimetic scaffolds have unique bioselective properties. The biomaterial was reported to be mammalian cell-friendly; at the same time, it was found to discourage microbial biofilm formation on its surface, which seemed to be a promising solution to addressing the problem of trauma-associated biofilm formation and development of antimicrobial resistance. However, the mechanically frail characteristics and zinc overload raise concerns and limit the potential of the said biomaterials. Hence, the present work is focused on improving the strength of the earlier scaffold formulations, testing its in vivo efficacy and reaffirming its action against biofilm-forming microbe Staphylococcus aureus. Scaling up of CMC proportion increased rigidity, and 8% CMC was found to be the ideal concentration for robust scaffold fabrication. Freeze-dried CMC scaffolds with or without genipin (GP) cross-linking were conjugated with zinc using 2 M zinc acetate solution. Characterization results indicated that the CMC-Zn scaffolds, without genipin, showed mechanical properties close to bone fillers, resist in vitro enzymatic degradation until 4 weeks, are porous in nature, and have radiopacity close to mandibular bones. Upon implantation in a subcutaneous pocket of Wistar rats, the scaffolds showed tissue in-growth with simultaneous degradation without any signs of toxicity past 28 days. Neither were there any signs of toxicity in any of the vital organs. Considering many superior properties among the other formulations, the CMC-Zn scaffolds were furthered for biofilm studies. CMC-Zn showed negligible S. aureus biofilm formation on its surface as revealed by an alamar blue-based study. RT-PCR analysis revealed that CMC-Zn downregulated the expression of pro-biofilm effector genes such as icaC and clfB. A protein docking study predicted the inhibitory mechanism of CMC-Zn. Although it binds strongly when alone, at high density, it may cause inactivation of the transmembrane upstream activators of the said genes, thereby preventing their dimerization and subsequent inactivation of the effector genes. In conclusion, zinc-conjugated carboxymethyl-chitosan scaffolds are mechanically robust, porous, yet biodegradable, harmless to the host in the long term, they are radiopaque and prevent biofilm gene expression in notorious microbes; hence, they could be a suitable candidate for bone filler applications.


Asunto(s)
Materiales Biocompatibles , Biopelículas , Ensayo de Materiales , Staphylococcus aureus , Zinc , Biopelículas/efectos de los fármacos , Zinc/química , Zinc/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología , Animales , Porosidad , Ratas , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Tamaño de la Partícula , Quitosano/química , Quitosano/farmacología , Pruebas de Sensibilidad Microbiana , Andamios del Tejido/química
2.
Bioeng Transl Med ; 7(3): e10306, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36176604

RESUMEN

Effective and safe liver-directed gene therapy has great promise in treating a broad range of liver diseases. While adenoviral (Ad) vectors have been widely used for efficacious in vivo gene delivery, their translational utilities are severely limited due to the short duration of transgene expression and solicitation of host immune response. Used as a promising polymeric vehicle for drug release and nucleic acid delivery, carboxymethyl chitosan (CMC) is biocompatible, biodegradable, anti-microbial, inexpensive, and easy accessible. Here, by exploiting its biocompatibility, controlled release capability and anti-inflammatory activity, we investigated whether CMC can overcome the shortcomings of Ad-mediated gene delivery, hence improving the prospect of Ad applications in gene therapy. We demonstrated that in the presence of optimal concentrations of CMC, Ad-mediated transgene expression lasted up to 50 days after subcutaneous injection, and at least 7 days after intrahepatic injection. Histologic evaluation and immunohistochemical analysis revealed that CMC effectively alleviated Ad-induced host immune response. In our proof-of-principle experiment using the CCl4-induced experimental mouse model of chronic liver damage, we demonstrated that repeated intrahepatic administrations of Ad-IL10 mixed with CMC effectively mitigated the development of hepatic fibrosis. Collectively, these results indicate that CMC can improve the prospect of Ad-mediated gene therapy by diminishing the host immune response while allowing readministration and sustained transgene expression.

3.
Gels ; 8(1)2022 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-35049590

RESUMEN

This study aimed to enhance the solubility and release characteristics of docetaxel by synthesizing highly porous and stimuli responsive nanosponges, a nano-version of hydrogels with the additional qualities of both hydrogels and nano-systems. Nanosponges were prepared by the free radical polymerization technique and characterized by their solubilization efficiency, swelling studies, sol-gel studies, percentage entrapment efficiency, drug loading, FTIR, PXRD, TGA, DSC, SEM, zeta sizer and in vitro dissolution studies. In vivo toxicity study was conducted to assess the safety of the oral administration of prepared nanosponges. FTIR, TGA and DSC studies confirmed the successful grafting of components into the stable nano-polymeric network. A porous and sponge-like structure was visualized through SEM images. The particle size of the optimized formulation was observed in the range of 195 ± 3 nm. The fabricated nanosponges noticeably enhanced the drug loading and solubilization efficiency of docetaxel in aqueous media. The drug release of fabricated nanosponges was significantly higher at pH 6.8 as compared to pH 1.2 and 4.5. An acute oral toxicity study endorsed the safety of the system. Due to an efficient preparation technique, as well as its enhanced solubility, excellent physicochemical properties, improved dissolution and non-toxic nature, nanosponges could be an efficient and a promising approach for the oral delivery of poorly soluble drugs.

4.
Materials (Basel) ; 14(21)2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34772099

RESUMEN

This study demonstrated the synthesis of o-carboxymethyl chitosan (CMC)-stabilized zinc oxide nanocomposites (ZnO NCs) combined with aqueous leaves extracts of hydroponically cultured ginseng and used as a photocatalyst for the degradation of hazardous dyes, including malachite green (MG), rhodamine B (RB), and congo red (CR) under ultraviolet illumination. Hydroponic ginseng leaves contain bioactive components, namely ginsenoside and natural polyphenol, which prompt ginseng's biological effect. Besides, the CMC polymer is naturally biodegradable, stabilizes the nanoformation and enhances the solubility of ginsenoside. The hydroponic ginseng leaves zinc oxide CMC nanocomposites (GL-CMC-ZnO NCs) were synthesized using the co-precipitation method and characterized using different analytical methods. The FTIR analysis identified significant phytochemicals in the leaves extracts and cotton-shape morphology observed using FE-TEM analysis. The XRD analysis also determined that the crystallite size was 28 nm. The photocatalyst degraded CR, RB, and MG dyes by approximately 87%, 94%, and 96% within contact times of 10, 20, 25, and 30 min, respectively, when the dye concentration was 15 mg/L. As far as our knowledge, this is the first report on hydroponic ginseng NCs incorporated with the CMC polymer for the degradation of hazardous dyes on wastewater treatment. This study can add significant value to large-scale wastewater treatment.

5.
Materials (Basel) ; 14(12)2021 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-34208787

RESUMEN

In the present work, precipitated calcium carbonate (PCC) and carboxymethyl chitosan (CMC) were prepared to obtain new hybrid materials used in papermaking. In the first step, occurred the precipitation of CaCO3 in solution containing CMC at different levels (0.5%, 1%, and 1.5%). In the second step, PCC-CMC hybrid material (25%) was added to pulp suspension, and the sheets were made. The effect of PCC-CMC on paper properties (mechanical and optical) was systematically investigated. Breaking length, the brightness and opacity of the sheets obtained with the PCC-CMC material were better than the sheets fabricated with the unmodified PCC at similar levels of content.

6.
Int J Biol Macromol ; 166: 1335-1351, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33171183

RESUMEN

Nowadays, treatment to the infected wounds caused by bacterial even multi-resistant bacterial strains and subsequently complete skin regeneration remain a critical clinical challenge. Herein, a novel multi-functional platform (Alg/1.0Ag@CMC-PAMAM/PRP) was prepared as wound dressings by mixing platelet rich plasma (PRP) with the sodium alginate (Alg) based dressing containing nano silver (Ag)-doped carboxymethyl chitosan grafted polyamideamine (Ag@CMC-PAMAM) cationic polymers. The present dressings exhibited high swelling, suitable water vapor transmission rate (WVTR), and good mechanical properties and degradability, as well as sustained release of PRP. Besides, the component of Ag@CMC-PAMAM nanoparticles endow them with excellent antibacterial performance, while the incorporation of PRP promotes the effect of anti-inflammatory and angiogenesis by up-regulating relative activity factor expression of TGF-ß1, CD31 and α-SMA and down-regulating the inflammatory-relative genes including TNF-α, IL-6 and IL-1ß, all of which promote the closure of wound and produce a superior healing effect to the commercial Aquacel Ag group. This work indicates that the prepared Alg/1.0Ag@CMC-PAMAM/PRP wound dressing is a promising biomaterial with synergistic effect of antibacterial property and wound healing.


Asunto(s)
Alginatos/química , Vendas Hidrocoloidales , Quitosano/análogos & derivados , Nanocompuestos/química , Plata/química , Cicatrización de Heridas , Actinas/genética , Actinas/metabolismo , Animales , Línea Celular , Citocinas/genética , Citocinas/metabolismo , Ratones , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/genética , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Plasma Rico en Plaquetas/química , Poliaminas/química , Ratas , Ratas Sprague-Dawley , Piel/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo
7.
J Conserv Dent ; 19(2): 143-6, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27099420

RESUMEN

AIM: The purpose of this study was to evaluate the sealing ability of mineral trioxide aggregate (MTA) and EndoSequence with chitosan and carboxymethyl chitosan (CMC) as retrograde smear layer removing agents using scanning electron microscopy (SEM). MATERIALS AND METHODS: Forty human single rooted teeth were taken. Crowns were decoronated and canals were obturated. Apically roots were resected and retrograde cavities were done. Based on the type of retrograde material placed and the type of smear layer removal agent used for retrograde cavities, they were divided into four groups (N = 10): Group I chitosan with EndoSequence, group II chitosan with MTA, group III CMC with EndoSequence, and Group IV CMC with MTA. All the samples were longitudinally sectioned, and the SEM analysis was done for marginal adaptation. STATISTICAL ANALYSIS: Kruskal-Wallis and Mann-Witney analysis tests. RESULTS: SEM images showed the presence of less gaps in group III, i.e., CMC with EndoSequence when compared to other groups with statistically significant difference. CONCLUSION: Within the limited scope of this study, it was concluded that EndoSequence as retrograde material showed better marginal sealing ability.

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