RESUMO
Rheumatoid arthritis is a chronic inflammatory disorder of polyarticular tissues, characterised by progressive synovitis. Its prolonged treatment imparts a huge burden on the healthcare system and results in toxicity, which necessitates the search for safe, efficacious and cost-effective therapies. Diospyros malabarica (Desr.) Kostel is traditionally used for anti-inflammatory purposes; however, to the best of our knowledge, there is no detailed study reporting the in vivo anti-inflammatory potential of this plant. Therefore, in the current study, the methanol extract of D. malabarica (Desr.) Kostel fruit (mDMF) was evaluated for its antioxidant, anti-inflammatory and anti-arthritic potentials, along with its underlying mechanisms. The antioxidant activity was evaluated by DPPH assay. Total phenolic and flavonoid contents were estimated via colorimetric and high-performance liquid chromatography (HPLC) methods. Different doses (250, 500 and 750 mg/kg) of mDMF were used to evaluate the anti-inflammatory and anti-arthritis actions in acute inflammatory (carrageenan and histamine-induced paw oedema) and Freund's complete adjuvant (FCA)-induced arthritis rat models. Levels of various pro- and anti-inflammatory biomarkers were estimated using ELISA and RT-PCR techniques. Paw samples were used for different histopathological and radiographic studies. Qualitative phytochemical and HPLC analyses indicated the presence of various polyphenolic compounds in mDMF, which exhibited marked antioxidant activity in the DPPH assay. mDMF showed time-dependent anti-inflammatory and anti-arthritic effects in in vivo models. ELISA assay data showed significant (p < 0.05) reduction in the serum levels of C-reactive protein and rheumatoid factor in the mDMF treatment groups. RT-PCR data showed significant (p < 0.05) down-regulation of various pro-inflammatory markers (TNF-α, NF-κB, COX-2, IL-1ß and IL-6) and up-regulation of anti-inflammatory markers (IκB, IL-4 and IL-10) in serum samples of rats treated with mDMF. The histopathology of the ankle joints showed reduced pannus formation, joint swelling and synovial hyperplasia in mDMF-treated animals when compared with the untreated disease control group. Overall, it may be concluded that the antioxidant, anti-inflammatory and anti-arthritis properties of mDMF are due to its flavonoid and phenolic constituents. Further studies using a stable oral dosage form of D. malabarica (Desr.) Kostel fruits extract are warranted to explore its effects in other inflammatory disorders, including irritable bowel syndrome, appendicitis and hepatitis.
Assuntos
Artrite Experimental , Diospyros , Ratos , Animais , Frutas , Diospyros/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Artrite Experimental/metabolismo , Extratos Vegetais/uso terapêutico , Citocinas/metabolismo , Ratos Sprague-Dawley , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Edema/metabolismo , Flavonoides/uso terapêutico , Biomarcadores/metabolismoRESUMO
Controlled drug delivery is a key strategy aimed at reducing both the frequency of therapeutic dosages and potential systemic side effects, particularly in the case of high drug concentrations. The nanocomposite hydrogel systems presented in this study were synthesized by combining carboxymethyl cellulose, polyvinyl alcohol, and (3-aminopropyl)triethoxysilane-functionalized halloysite nanotubes (fHNTs). This hydrogel system is a potential candidate for the controlled release of cefadroxil monohydrate. These hydrogels are analyzed by Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, and rheological measurements. Additionally, swelling properties, porosity, hydrophilicity, drug release, and in vitro and in vivo analyses were also evaluated. The observed trends in swelling and drug release demonstrated that the outcomes are dependent on the presence of fHNTs in the hydrogel matrix. Notably, fHNTs-loaded hydrogels displayed sustained drug release patterns. This innovative approach eliminates the need for traditional encapsulation and presents promising and translatable strategies for achieving more effective drug release.
RESUMO
Chronic non-healing wounds tender a great challenge to patients, physicians, and wound care professionals. In view of the increasing prevalence of chronic wounds due to ischemia, diabetic foot, venous, and pressure ulcers, their appropriate management requires significant attention. Along with the basic techniques of medical and surgical treatments; an ideal dressing is essential for a speedy recovery and rapid healing of such wounds. Mechanistic understanding of chronic wound pathology will not only help towards future directions for an ideal dressing model but also to resonant advance research related to specific dressings for various wound types. This review provides key insights into causes, pathophysiology, and critical issues pertaining to chronic wounds and their management. It also summarizes the challenges faced for chronic wound treatment and specified factors responsible for delayed healing. Moreover, this review delivers a detailed discussion on available polymeric materials (alginate, chitosan, hyaluronic acid, collagen, polyurethane, cellulose, dextran, gelatin, silk, and polyaniline), their functional characteristics, and usage as chronic wound healing agents for polymeric wound dressing development. Incorporation and comparison of the research studies for their thermal behavior, structural analysis, and microscopic studies by Fourier transform infrared spectroscopy, thermogravimetric analysis and scanning electron microscopy, respectively and swelling studies of different polymeric materials are discussed. Additionally, studies of anatomy cum physiology of wound healing, pathophysiology, tissue engineering and advance healing management approaches makes the content of this review a significant tool for future studies on chronic wounds healing by polymeric wound dressings. In this review, polymeric wound dressings have been explained in terms of their structures, function, chemistry, and key characteristics. These features are directly linked to the polymeric systems' potential in the management of chronic wounds. These polymeric systems have gained promising success in solving real word global health problems. More recently, innovative approaches to fabricate the polymer dressings have been introduced, but their commercial, sustainable, and high-scale production largely remains unexplored. This review also summarizes the promises of polymeric wound dressings and provides a future perspective on how the clinical and commercial landscape could potentially be propelled by utilizing polymers in wound care management.
Assuntos
Materiais Biocompatíveis , Pé Diabético , Bandagens , Pé Diabético/tratamento farmacológico , Humanos , Polímeros , CicatrizaçãoRESUMO
Controlled drug delivery is a prime stratagem for minimizing both the frequency of therapeutic administration as well as systematic side effects with high drug content. One of the extensively studied approaches for controlling medicament delivery is the encapsulation of drug within polymer chains which sluggish the release on the basis of its crosslinked network. Recent advances in biomedical field have led to the fabrication of chitosan (CS) based biocompatible and biodegradable hydrogels for controlled delivery of encapsulated drug. In this study, CS-PVP based hydrogels are fabricated by varying the concentration of 3-glycidyloxypropyl trimethoxysilane (GPTMS) via solution casting technique. Swelling indices of prepared hydrogel samples were determined in different media including distilled water, different pH and electrolyte solutions. FTIR, TGA and WAXRD are conducted to evaluate the structural, thermal and crystalline properties of prepared hydrogels, respectively. Porosity (71%), hydrophilicity (55°) and mechanical properties (97.56 MPa of UTS and 85.23% E%) were investigated for the fabricated samples. Extensively in vitro biodegradation, antimicrobial performance and cytotoxicity were evaluated for these hydrogels. The drug release analysis was carried out to examine the release response of encapsulated iodopovidone at physiological conditions. These results tender a strategy for the design of structural hydrogel with different crosslinking mechanism like physical and covalent interactions. These insights obviate the demand for encapsulation and offer promising and translatable strategies for more effective release of drugs.
Assuntos
Quitosana/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Hidrogéis/química , Povidona-Iodo/administração & dosagem , Reagentes de Ligações Cruzadas/química , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Eletrólitos , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Porosidade , Difração de Raios XRESUMO
Novel pH-sensitive γ-irradiated low molecular weight (MW) chitosan (CS) (pre-irradiated) and poly (vinyl alcohol) (PVA) blended injectable hydrogels, crosslinked with varying concentrations of glycerol, were fabricated for drug delivery application. The effect of low MW irradiated CS on controlled drug release was evaluated to address the problem of higher viscosity and lower solubility of high MW CS. The FTIR spectra of hydrogels depicted the presence of all the incorporated functional groups and the developed interactions (physical and chemical). The surface morphology of hydrogels assessed by scanning electron microscope exhibited porous microstructure. All hydrogels were subjected to the swelling analysis in different media (water, buffer and electrolytes). The pH sensitive hydrogel samples exhibited less swelling at acidic and neutral pH while higher swelling at basic pH. CPG-0.5 showed the highest swelling at all pH media as compared to other hydrogel samples. CPG-1.0 was selected for the release analysis of drug because of its highest swelling (114.47%) in distilled water having neutral pH. It was loaded with model drug (Montelukast Sodium) during the preparation phase and studied for drug release capability. The in-vitro controlled release evaluation of hydrogel (CPG-1.0) was performed in SGF and SIF using UV-visible spectroscopy. The results confirmed their applications in injectable drug release systems as all the loaded drug was released in 30â¯min in SGF (pHâ¯-1.2) while the release of drug in SIF (pHâ¯-6.8) was in controlled manner (99.62% in 3â¯h). The improved antibacterial activity of these hydrogel films was owing to the fact that the γ-irradiated low MW CS has ruptured the bacterial cell and its metabolism more efficiently by inflowing in the cell.
Assuntos
Acetatos/administração & dosagem , Quinolinas/administração & dosagem , Quitosana/administração & dosagem , Quitosana/química , Quitosana/efeitos da radiação , Reagentes de Ligações Cruzadas/farmacologia , Ciclopropanos , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Liberação Controlada de Fármacos , Escherichia coli/efeitos dos fármacos , Raios gama , Glicerol/farmacologia , Hidrogéis/administração & dosagem , Hidrogéis/química , Hidrogéis/efeitos da radiação , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Varredura , Peso Molecular , Álcool de Polivinil/administração & dosagem , Porosidade , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , SulfetosRESUMO
Graphene oxide (GO) was indigenously synthesized from graphite using standard Hummers method. Chitosan-graphene oxide green composite films were fabricated by mixing aqueous solution of chitosan and GO using dilute acetic acid as a solvent for chitosan. Chitosan of different viscosity and calculated molecular weight was used keeping amount of GO constant in each composite film. The structural properties, thermal stability and mechanical properties of the composite films were investigated using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and tensile test. FTIR studies revealed the successful synthesis of GO from graphite powder and it was confirmed that homogenous blending of chitosan and GO was promising due to oxygenated functional groups on the surface of GO. XRD indicated effective conversion of graphite to GO as its strong peak observed at 11.06° as compared to pristine graphite which appeared at 26°. Moreover, mechanical analysis confirmed the effect of molecular weight on the mechanical properties of chitosan-GO composites showing that higher molecular weight chitosan composite (GOCC-1000) showed best strength (higher than 3GPa) compared to other composite films. Thermal stability of GOCC-1000 was enhanced for which residual content increased up to 56% as compared to the thermal stability of GOCC-200 whose residue was restricted to only 24%. The morphological analysis of the composites sheets by SEM was smooth having dense structure and showed excellent interaction, miscibility, compatibility and dispersion of GO with chitosan. The prepared composite films find their applications as biomaterials in different biomedical fields.