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1.
Silver nanoparticles have attracted wide interest in medicine on account of their antibacterial activity. We report in this paper, the antibacterial activity and biocompatibility of a temperature responsive topical film fabricated from pullulan-g-pNIPAM and impregnated with two different concentrations (15 ppm and 30 ppm) of silver nanoparticles (Ag-NPs). The release of silver from the film under the influence of temperature above the LCST has been studied and the in vitro release profile of the films has been compared with a marketed silver nano formulation, ‘Meganano gel’. The release of silver from the films has a distinctive profile characterized by a sustained release over a period of 48 hrs, which is comparable to the marketed formulation. The films exhibit excellent swelling properties, making them ideal materials for absorption of exudates from wounds. The antibacterial activity of the films has been established at physiological temperature against gram-positive S. aureus and gram-negative E. coli and compared with the marketed formulation. A cytotoxicity evaluation on HeK293 cells has demonstrated their biocompatibility. The nanocomposite films are thus a new therapeutic device for management of non-healing wounds being constructed from temperature responsive polymers that release Ag-NPs when the temperature of the wound exudate is slightly higher than normal.  相似文献   

2.
《药学学报(英文版)》2023,13(1):315-326
Wound infection is becoming a considerable healthcare crisis due to the abuse of antibiotics and the substantial production of multidrug-resistant bacteria. Seawater immersion wounds usually become a mortal trouble because of the infection of Vibrio vulnificus. Bdellovibrio bacteriovorus, one kind of natural predatory bacteria, is recognized as a promising biological therapy against intractable bacteria. Here, we prepared a B. bacteriovorus-loaded polyvinyl alcohol/alginate hydrogel for the topical treatment of the seawater immersion wounds infected by V. vulnificus. The B. bacteriovorus-loaded hydrogel (BG) owned highly microporous structures with the mean pore size of 90 μm, improving the rapid release of B. bacteriovorus from BG when contacting the aqueous surroundings. BG showed high biosafety with no L929 cell toxicity or hemolysis. More importantly, BG exhibited excellent in vitro anti-V. vulnificus effect. The highly effective infected wound treatment effect of BG was evaluated on mouse models, revealing significant reduction of local V. vulnificus, accelerated wound contraction, and alleviated inflammation. Besides the high bacterial inhibition of BG, BG remarkably reduced inflammatory response, promoted collagen deposition, neovascularization and re-epithelization, contributing to wound healing. BG is a promising topical biological formulation against infected wounds.  相似文献   

3.
Background & ObjectivesWound healing is the complex physiological process of replacing damaged cells or tissue layers. The neem (Azadirachta Indica) has a variety of biological activities, which may hasten the rate at which the wound healing mechanism occurs. Silk fibroin is a biomaterial that is reported for its tissue regeneration activity. So, the present study was designed to assess the effectiveness of a hydrogel comprising neem and silk fibroin biomaterials for the treatment of wounds.MethodsTopical neem hydrogels (N-HG) with and without silk fibroin (N-SFB-HG) were prepared using neem extract, silk fibroin, and guar gum, which act by entrapping the components by forming a gel. Evaluation tests such as Fourier transform infrared spectroscopy (FT-IR), visual emergence, pH, rheological behavior, spreading capacity, drug content, skin irritation, anti-microbial action, in vivo wound healing activity, and stability were carried out.ResultsThe FT-IR results showed no chemical interaction between the constituents. The formed hydrogels had pH values of 5.87 ± 0.3 for N-HG and 5.76 ± 0.2 for N-SFB-HG. The preferred topical gel viscosity was observed in the N-HG (54.2 ± 3.2cPs) and N-SFB-HG (59.9 ± 4.8cPs) formulations. The formulated hydrogels were sterile and did not irritate the skin. The in vivo wound healing investigation results reveal that the N-SF-HG treatment speeds up the regeneration of the injured area faster when compared to control and N-HG treated groups.Interpretation & ConclusionThese results support the efficacy of the topical hydrogel formulation, including neem and silk fibroin. Therefore, the neem-silk fibroin hydrogel formulation is a therapeutically viable choice that, following necessary clinical research, might be utilized in novel formulations for managing chronic wounds.  相似文献   

4.
Many chronic wounds exhibit high matrix metalloproteinase (MMP) activity that impedes the normal wound healing process. Intradermal delivery (IDD) of sub-antimicrobial concentrations of doxycycline, as an MMP inhibitor, could target early stages of chronic wound development and inhibit further wound progression. To deliver doxycycline intradermally, the skin barrier must be disrupted. Microneedle rollers offer a minimally invasive technique to penetrate the skin by creating multiple microchannels that act as temporary conduits for drugs to diffuse through. In this study, an innovative and facile approach for delivery of doxycycline across Strat-MTM membrane was investigated using microneedle rollers. The quantity and rate of doxycycline diffusing through the micropores directly correlated with increasing microneedle lengths (250, 500 and 750?μm). Treatment of Strat-MTM with microneedle rollers resulted in a reduction in fibroblast-mediated collagen gel contraction and MMP activity compared with untreated Strat-MTM. Our results show that treatment of an epidermal mimetic with microneedle rollers provides sufficient permeabilization for doxycycline diffusion and inhibition of MMP activity. We conclude that microneedle rollers are a promising, clinically ready tool suitable for delivery of doxycycline intradermally to treat chronic wounds.  相似文献   

5.
Ulmus davidiana var. japonica Rehder (Urticales: Ulmaceae) (UD) is a tree widespread in northeast Asia. It is traditionally used for anticancer and anti-inflammatory therapy. The present study investigated the effect of an ethanol extract of UD on vascular tension and its underlying mechanism in rats. The dried root bark of UD was ground and extracted with 80% ethanol. The prepared UD extract was used in further analysis. The effect of UD on the cell viability, vasoreactivity and hemodynamics were investigated using propidium iodide staining in cultured cells, isometric tension recording and blood pressure analysis, respectively. Low dose of UD (10~100μg/ml) did not affect endothelial cell viability, but high dose of UD reduced cell viability. UD induced vasorelaxation in the range of 0.1~10μg/ml with an ED(50) value of 2μg/ml. UD-induced vasorelaxation was completely abolished by removal of the endothelium or by pre-treatment with L-NAME, an inhibitor of nitric oxide synthase. UD inhibited calcium influx induced by phenylephrine and high K(+) and also completely abolished the effect of L-NAME. Intravenous injection of UD extracts (10~100 mg/kg) decreased arterial and ventricular pressure in a dose-dependent manner. Moreover, UD extracts reduced the ventricular contractility (+dP/dt) in anesthetized rats. However, UD-induced hypotensive actions were minimized in L-NAME-treated rats. Taken together, out results showed that UD induced vasorelaxation and has antihypertensive properties, which may be due the activation of nitric oxide synthase in endothelium.  相似文献   

6.
Objective To characterise the magnitude and distribution of fibroblast growth factor‐2 (FGF‐2) following topical application in hypromellose gel and film formulations or a solution in an animal wound model, in order to assess the potential of this route for treatment of chronic wounds. Method Topical formulations of FGF‐2 were applied to punch biopsy wounds, and FGF‐2 levels within the wound measured. Each 12 mm diameter wound received 0.3 μg FGF‐2 in solution, a 7% (w/w) hypromellose gel, a dried hypromellose film on Melolin‐backing or a saline control. After 2, 5 or 8 h the wounds were horizontally dissected into four sections (surface granulation, subcutaneous fat, superficial muscle and deep muscle) which were then analysed for FGF‐2 concentration using ELISA. Confocal microscopy was used to evaluate the distribution of FGF‐2 within the wound. Key findings There were significant differences in the mean FGF‐2 levels with respect to formulation and time following application (P < 0.05). FGF‐2 penetrated faster into tissue when formulated as a solution than as a gel or a film. There did not appear to be a significant difference between the gel and the film with respect to total concentrations achieved in the tissue, although confocal microscopy showed differences in FGF‐2 distribution within the wound. Conclusions Delivery of FGF‐2 to wounds in a solution gave the greatest increase in tissue FGF‐2 concentration when measured by ELISA and visualised using confocal microscopy. Gel and film formulations prolonged the release of FGF‐2 into the wound, although FGF‐2 levels were not significantly different from controls when measured by ELISA. Confocal microscopy highlighted the differences in the penetration and distribution of the FGF‐2 within the wound when released from different formulations.  相似文献   

7.
Cetirizine hydrochloride (CTZ), a second-generation anti-histaminic drug, has been recently explored for its effectiveness in the treatment of alopecia. Niosomes are surfactant-based nanovesicular systems that have promising applications in both topical and transdermal drug delivery. The aim of this study was to design topical CTZ niosomes for management of alopecia. Thin film hydration technique was implemented for the fabrication of CTZ niosomes. The niosomes were examined for vesicle size, surface charge, and entrapment efficiency. The optimized niosomal formulation was incorporated into a hydrogel base (HPMC) and explored for physical characteristics, ex vivo permeation, and in vivo dermato-kinetic study. The optimized CTZ-loaded niosomal formulation showed an average size of 403.4 ± 15.6 nm, zeta potential of − 12.9 ± 1.7 mV, and entrapment efficiency percentage of 52.8 ± 1.9%. Compared to plain drug solution, entrapment of CTZ within niosomes significantly prolonged in vitro drug release up to 12 h. Most importantly, ex-vivo skin deposition studies and in vivo dermato-kinetic studies verified superior skin deposition/retention of CTZ from CTZ-loaded niosomal gels, compared to plain CTZ gel. CTZ-loaded niosomal gel permitted higher drug deposition percentage (19.2 ± 1.9%) and skin retention (AUC0-10h 1124.5 ± 87.9 μg/mL.h) of CTZ, compared to 7.52 ± 0.7% and 646.2 ± 44.6 μg/mL.h for plain CTZ gel, respectively. Collectively, niosomes might represent a promising carrier for the cutaneous delivery of cetirizine for the topical management of alopecia.  相似文献   

8.
Acute or chronic wounds are one of the most common health problems worldwide and medicinal drugs or traditional remedies are often used in wound healing. Further studies regarding wound treatment are rapidly continuing. Vitexin is a phenolic compound, which is found in many medicinal plants, has different pharmacological effects such as anti-inflammatory, analgesic and antioxidant. In the present study, it is aimed to investigate the wound healing effect of formulation prepared as chitosan-based gel with vitexin in vivo and in vitro. Cytotoxicity and wound healing assays were used for in vitro and excisional wound model is used for in vivo studies. Extracted tissues from wound area were histologically examined. Wound healing process was monitored on 7, 14 and 21st days. When wound construction was evaluated, chitosan-based gel formulation containing vitexin demonstrated significant effect compared to control group. Histological examinations demonstrated that skin regeneration was promoted by vitexin formulation. Significant cell proliferation was observed with vitexin/chitosan dispersion in the wound healing assay performed with NIH 3T3 and HaCaT cells. In conclusion, our test substance chitosan-based gel formulation containing vitexin significantly accelerated wound healing both in vivo and in vitro.  相似文献   

9.
The objective of the study was to develop a suitable trans-dermal delivery system for propranolol hydrochloride (PPL) via employing chitosan as a film former. Drug concentration uniformity, thickness, moisture uptake capacity and skin bioadhesion of the films were characterized. The effects of chitosan and PPL concentration and different penetration enhancers on the release and permeation profiles from the films were investigated. Skin irritation of the candidate film was evaluated. Chitosan film (PPL 2 mg cm(-2), chitosan 2%, m/m, cineol 10%, m/m) was found nonirritant and achieved 88.2% release after 8 hours in phosphate buffer. Significant high (p < 0.001) permeation of PPL through rat skin was obtained using this film compared to the film without enhancer (about 8 times enhancement factor), making it a promising trans-dermal delivery system for PPL.  相似文献   

10.
The hypothesis that ozonated oil has wound healing property was investigated in an excision wound model using Sprague Dawley rats. The animals were divided into four groups, which were treated with sesame oil (vehicle), framycetin (standard), or two doses of ozonated sesame oil (peroxide values 500 and 700 mEq/1000 g, respectively). The formulations were topically applied on the excision wounds once daily for 11 consecutive days and the animals were euthanized on the 12th day. Wound healing was assessed by measuring the wound contracture, tensile strength, collagen content and superoxide dismutase activity of skin of the excised wound area. On the terminal day, areas of the wounds of the group receiving high dose ozonated oil were significantly smaller than those of the group treated with vehicle. Ozonated oil treated wounds had significantly higher tensile strength, collagen content and superoxide dismutase activity than that of the vehicle treated wounds. Histopathological analysis of skin of the excised wound area treated with ozonated oil revealed better healing activity vis-à-vis vehicle-treated wounds. Thus, it can be concluded that ozonated oil can be of potential therapeutic use for healing wounds.  相似文献   

11.
Epidermal growth factor (EGF) and zinc promote re-epithelization and reparative tissue strength by enhancing deposition of collagen at the site of the wound. In this study two EGF dosage forms were chosen to assess the effect of zinc levels on wound healing and for comparison with wound tear strengths. A solution of EGF in 0.9% w/v NaCl and an EGF gel in 0.2% Carbopol 940 polymer (5 μL) were applied to full-thickness skin wounds of mice twice a day for 7 and 15 days. Wound zinc levels were higher on day 7 than on day 15, especially in wounds treated with EGF. The wound zinc levels of the gel + EGF group on day 15 were similar to those of normal control skin. These results imply that there is a close connection, but no direct relationship, between EGF application in both dosage forms and wound zinc levels during healing.  相似文献   

12.
Prolonged inflammation and increased oxidative stress impairs healing in diabetics and application of curcumin, a well known antioxidant and anti-inflammatory agent, could be an important strategy in improving impaired healing in diabetics. So, the present study was conducted to evaluate the cutaneous wound healing potential of topically applied curcumin in diabetic rats. Open excision skin wound was created in streptozotocin induced diabetic rats and wounded rats were divided into three groups; i) control, ii) gel-treated and iii) curcumin-treated. Pluronic F-127 gel (25%) and curcumin (0.3%) in pluronic gel were topically applied in the gel- and curcumin-treated groups, respectively, once daily for 19 days. Curcumin application increased the wound contraction and decreased the expressions of inflammatory cytokines/enzymes i.e. tumor necrosis factor-alpha, interleukin (IL)-1beta and matrix metalloproteinase-9. Curcumin also increased the levels of anti-inflammatory cytokine i.e. IL-10 and antioxidant enzymes i.e. superoxide dismutase, catalase and glutathione peroxidase. Histopathologically, the curcumin-treated wounds showed better granulation tissue dominated by marked fibroblast proliferation and collagen deposition, and wounds were covered by thick regenerated epithelial layer. These findings reveal that the anti-inflammatory and antioxidant potential of curcumin caused faster and better wound healing in diabetic rats and curcumin could be an additional novel therapeutic agent in the management of impaired wound healing in diabetics.  相似文献   

13.
The use of green solvents in extraction processes, especially for applications of lignocellulosic biomass, has been extensively studied over the last years. Among the range of different green solvents, deep eutectic solvents (DES) show promising results for extraction processes. Therefore, the aim of this work was the use of DES as additives in aqueous mixtures for the selective extraction of flavonoid compounds from the bark of Larix decidua. For this purpose, bark has been treated using different solvent ratios consisting of a DES/H2O mixture (0, 25, 50 and 75 wt%). Two DES were studied, choline chloride:urea and choline chloride:1,4-butanediol. In order to study the success of the extractions, the extracts and the remaining solid fraction were characterised. From the results, it was concluded that the choline chloride:1,4-butanediol (75 wt%) gave the best results, obtaining the richest extracts in flavonoids (383 mg CE/g dried bark extract), as well as those with the highest antioxidant capacity. These good results confirm the capacity of this DES to obtain active biomolecules for further application.  相似文献   

14.
Topical film-forming solutions (FFSs) show considerable potential for dermal delivery of an API. Through a mechanism of in situ film formation upon solvent evaporation, they may improve skin delivery by prolonging substantivity on the skin, by establishing a transient supersaturation, and/or by enhancing solubility through the formation of a solid dispersion in the resulting film.This work aimed at developing an FFS for topical application with enhanced skin delivery. The tested FFSs were composed of the lipophilic retinoid tazarotene and the hydrophobic polyamide-3 polymers.The residual films cast from FFSs were examined by DSC and their release mechanism was investigated. Additionally, ex vivo skin penetration of tazarotene was explored.In comparison to a physical mixture, the glass transition (Tg) was significantly increased (p < 0.01) in in-situ generated polyamide-3 (11,500 Da)/tazarotene films with ratios 5:1 and 10:1, indicating a molecular distribution of tazarotene within the polymer. Stress testing at 32°C and 40°C further indicated that these films were kinetically stabilized for at least two weeks. Tazarotene release from solid solution films was notably increased as compared to the crystalline and the amorphous tazarotene. A ten-times higher skin penetration of the ratio 10:1 film (containing 0.1% tazarotene) was observed as compared to a commercial 0.1% tazarotene cream.Hence, topical solid solutions may represent an option for improved dermal API delivery.  相似文献   

15.
Bisphenol A (BPA) in vitro skin permeation studies have shown inconsistent results, which could be due to experimental conditions. We studied the impact of in vitro parameters on BPA skin permeation using flow-through diffusion cells with ex-vivo human skin (12 donors, 3–12 replicates). We varied skin status (viable or frozen skin) and thickness (200, 400, 800 μm), BPA concentrations (18, 250 mg/l) and vehicle volumes (10, 100 and 1000 μl/cm2). These conditions led to a wide range of BPA absorption (2%–24% after 24 h exposure), peak permeation rates (J = 0.02–1.31 μg/cm2/h), and permeability coefficients (Kp = 1.6–5.2 × 10−3 cm/h). This is the first time steady state conditions were reached for BPA aqueous solutions in vitro (1000 μl/cm2 applied at concentration 250 mg/l). A reduction of the skin thickness from 800 and 400 μm to 200 μm led to a 3-fold increase of J (P < 0.05). A reduction of the vehicle volume from 1000 to 100 led to a 2-fold decrease in J (P > 0.05). Previously frozen skin led to a 3-fold increase in J compared to viable skin (P < 0.001). We found that results from published studies were consistent when adjusting J according to experimental parameters. We propose appropriate J values for different exposure scenarios to calculate BPA internal exposures for use in risk assessment.  相似文献   

16.

Objective:

To develop topical gel preparations of astemizole and terfenadine and to investigate the actions of the gels on the healing of incision and excision wounds in male albino rats.

Materials and Methods:

Gels containing 1% astemizole, with varying concentrations of carbopol 934 (polymer), were prepared. Similarly, 1% terfenadine gels were made. The formulations were evaluated for release rate and stability. Incision and excision wounds were inflicted on male albino rats under ketamine anesthesia, taking aseptic precautions. The animals were divided into two groups. They were given a topical application of either astemizole or terfenadine gel, at a dose of 100 mg per wound, once daily, for 10 days in the case of incision wounds and till the time of complete closure in the case of excision wounds. On the 11th day, breaking strength of the incision wound was measured. In the excision wound model, wound closure rate, epithelization time, scar features and hydroxyproline content of scar tissue were studied from the day of wounding till the day of the scab falling off, with no residual raw area.

Results:

Gels prepared using 0.8% carbopol 934 and 1% of drug in gel base were found to be stable. The gels of astemizole and terfenadine significantly (P < 0.05) promoted the phases of healing such as collagenation (in incision wounds), wound contraction and epithelization (in excision wounds).

Conclusion:

The gels of astemizole and terfenadine might play an important role in wound management program.  相似文献   

17.
目的回顾性总结我院在应用烧伤湿性医疗技术(MEBT/MEBO)治疗特殊部位冻伤的120例的临床疗效。方法对MEBT/MEBO综合治疗的冻伤患者的疗效进行总结分析,皮肤创面清创后,创面暴露,并用MEBO外涂于创面。结果湿润烧伤膏具有较好的止痛、止痒作用,抗感染力较强,促进创面皮肤再生修复,深度创面无瘢痕愈合,小面积深度创面不需植皮,亦可自行愈合。结论 MEBT/MEBO治疗皮肤冻伤疗效显著。  相似文献   

18.
Diabetic wounds are difficult to treat due to multiple causes, including reduced blood flow and bacterial infections. Reduced blood flow is associated with overexpression of prostaglandin transporter (PGT) gene, induced by hyperglycaemia which causing poor vascularization and healing of the wound. Recently, gold nanoparticles (AuNPs) have been biosynthesized using cold and hot sclerotium of Lignosus rhinocerotis extracts (CLRE and HLRE, respectively) and capped with chitosan (CS) to produce biocompatible antibacterial nanocomposites. The AuNPs have shown to produce biostatic effects against selected gram positive and negative bacteria. Therefore, in this study, a dual therapy for diabetic wound consisting Dicer subtract small interfering RNA (DsiRNA) and AuNPs was developed to improve vascularization by inhibiting PGT gene expression and preventing bacterial infection, respectively. The nanocomposites were incorporated into thermoresponsive gel, made of pluronic and polyethylene glycol. The particle size of AuNPs synthesized using CLRE (AuNPs-CLRE) and HLRE (AuNPs-HLRE) was 202 ± 49 and 190 ± 31 nm, respectively with positive surface charge (+30 to + 45 mV). The thermoresponsive gels containing DsiRNA-AuNPs gelled at 32 ± 1 °C and released the active agents in sufficient amount with good texture and rheological profiles for topical application. DsiRNA-AuNPs and those incorporated into thermoresponsive pluronic gels demonstrated high cell viability, proliferation and cell migration rate via in vitro cultured cells of human dermal fibroblasts, indicating their non-cytotoxicity and wound healing properties. Taken together, the thermoresponsive gels are expected to be useful as a potential dressing that promotes healing of diabetic wounds.  相似文献   

19.
The limited source of human nail plate for studying drug permeation inspired us to develop a nail plate model made of human hair keratin. The manufacturing process consisted of keratin extraction, dialysis, molding, solvent evaporation, and curing, producing a water-resistant film. The permeability of the film was examined using three markers: sodium fluorescein, rhodamine B, and fluorescein isothiocyanate-dextran as water-soluble, lipid-soluble, and large molecule models, respectively. Bovine hoof was used for comparison. First investigation showed that keratin films (thickness 120 μm) resembled hooves (thickness 100 μm) except that these films were more permeable to rhodamine B compared with hooves (1.8-fold, < 0.01). Subsequent investigations using ungual penetration enhancers (urea, thioglycolic acid, and papain) showed that keratin films were generally more susceptible than hooves. This study revealed that the produced keratin film offers a possibility as a human nail plate substitute. However, inclusion of the penetration enhancer must be carefully interpreted.  相似文献   

20.
Purpose  To develop and demonstrate a rapid and simple colorimetric film assay for evaluating lipid interactions of pharmaceutical compounds and gel formulations. Methods  The colorimetric assay comprises glass-supported films of phospholipids and polydiacetylene, which undergo visible and quantifiable blue–red transformations induced by interactions with amphiphilic molecules applied in very small volumes on the film surface. The color transitions are recorded by scanning of the films, and quantified through a simple image analysis algorithm. Results  We show that pharmaceutical molecules and gel formulations induce blue–red transformations after short incubation with the lipid/polydiacetylene (PDA) films. Colorimetric dose–response curves exhibit dependence upon the lipid affinity and extent of membrane binding of the pharmaceutical compounds examined. The colorimetric lipid/PDA film assay was employed for distinguishing the contributions of individual molecular components within gel formulations. Conclusions  The colorimetric data yield insight into the degree of lipid binding of the molecules tested. The film assay is particularly advantageous for analysis of semi-solid (gel or lotion) formulations, elucidating the lipid interaction characteristics of specific molecular components within the mixtures. The new colorimetric film assay constitutes a generic, rapid, and easily applicable platform for predicting and screening interactions of pharmaceutical compounds and complex formulations with lipid barriers. Izek Ben-Shlush and Roman Volinsky contributed equally.  相似文献   

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