Accelerative effect of topical Zataria multiflora essential oil against infected wound model by modulating inflammation,angiogenesis, and collagen biosynthesis

Abstract

Context

Zataria multiflora Boiss (Lamiaceae) essential oil (ZME) is believed to be a bactericide herbal medicine and might alleviate negative effects of infection.     

磺胺嘧啶银乳膏治疗烧伤创面的临床疗效观察

目的 探讨对烧伤患者行磺胺嘧啶银乳膏治疗对其临床疗效的影响。方法 选择2019年2月～2020年2月本院接收的60例烧伤患者,随机将其进行分组,对照组、研究组各30例。患者入院后,均实施常规创面清洁及针对性药物治疗,对照组在此基础上给予患者纳米银敷料,研究组在对照组治疗基础上,将磺胺嘧啶银乳膏应用其中,观察两组患者各项临床指标（创面愈合时间、住院时间、住院费用）,同时,对比其临床疗效。结果 研究组创面愈合时间、住院时间均显著短于对照组,且住院费用低于对照组,差异有统计学意义（P <0.05）;与对照组73.3%总有效率相比,研究组93.3%治疗总有效率更高,差异具有统计学意义（P <0.05）。结论 对烧伤患者行以磺胺嘧啶银乳膏治疗,可有效促进患者创面愈合,缩短住院时间,降低经济压力,提升整体治疗效果,降低感染率。     

Synthesis of chemically cross-linked polyvinyl alcohol-co-poly (methacrylic acid) hydrogels by copolymerization; a potential graft-polymeric carrier for oral delivery of 5-fluorouracil

Background of the Study

The propose of the present work was to develop chemically cross-linked polyvinyl alcohol-co-poly(methacrylic acid) hydrogel (PVA-MAA hydrogel) for pH responsive delivery of 5-Fluorouracil (5-FU).

Methods

PVA based hydrogels were prepared by free radical copolymerization. PVA has been cross-linked chemically with monomer (methacrylic acid) in aqueous medium, cross-linking agent was ethylene glycol di-methacrylate (EGDMA) and benzoyl peroxide was added as reaction initiator. 5-FU was loaded as model drug. FTIR, XRD, TGA and DSC were performed for characterization of copolymer. Surface morphology was studied by SEM. pH sensitive properties were evaluated by swelling dynamics and equilibrium swelling ratio at low and higher pH.

Results

FTIR, XRD, TGA and DSC studies confirmed the formation of new copolymer. Formulations with higher MAA contents showed maximum swelling at 7.4 pH. High drug loading and higher drug release has been observed at pH 7.4.

Conclusions

The current study concludes that a stable copolymeric network of PVA was developed with MAA. The prepared hydrogels were highly pH responsive. This polymeric network could be a potential delivery system for colon targeting of 5-FU in colorectal cancers.     

Disposition and receptor-site binding of (125)I-EGF after topical administration to skin wounds

The rhEGF topical delivery systems have been hindered by a number of shortcomings which have led to the search of new development strategies. In this study we report the evaluation of cumulative profiles of 10, 5 and 1 microg/ml solutions of (125)I-rhEGF, in a rat full-thickness skin wound model, as well as the drug-induced modulation in the expression of the EGF receptor after lesion. The tissue-associated radioactivity, expressed as the percentage of the dose administered per grams of tissue (%D/g), peaks at 2 h after administration of all doses. (125)I-rhEGF degraded species were detected chromatographically, but no diffusion of the peptide to the surrounding skin was documented. Despite the dose, the EGF receptor expression was increased within 2 h after wounding, followed by a slow decline up to 12 h below baseline. Twelve hours after punch, differences were evident between all treated groups and control. These results demonstrate that (125)I-rhEGF saline solutions are rapidly cleared from application sites, probably by protease-driven cleavage and receptor-mediated endocytosis. Finally, we must be aware that the results herein discussed should be taken into account during the drug delivery system design in order to guarantee the necessary steady-state rhEGF levels upon wound healing process.     

Neem (Azadirachta Indica) and silk fibroin associated hydrogel: Boon for wound healing treatment regimen

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.     

盐酸莫西沙星静电纺丝膜的制备及性能研究

目的:制备具有抗菌作用的盐酸莫西沙星(MH)静电纺丝膜。方法:以聚乙烯醇(PVA)和海藻酸钠(SA)为载体,MH为模型药物,制备具有优良透气性能的抗菌静电纺丝膜。以溶液可纺性、静电纺丝的形态结构等为指标,筛选12%PVA与2%SA不同体积比(4:1、3.5:1.5、3:2、2.5:2.5、2:3、1:4)的纺丝溶液及静电纺丝膜的加药量以确定最佳处方。测定静电纺丝膜的透气性能并与口罩无纺布比较。结果:最佳处方为12%PVA与2%SA的体积比为3:2,加药量为2%;纺丝溶液可纺性好,所制静电纺丝直径小且均匀,表面光滑,串珠状纺丝少,收率为(86.73±2.92)%,透气性能优于无纺布(P<0.05)。结论:制备的MH静电纺丝膜载药均匀,具有良好的透气性能。     

An alternative approach to wound healing field; new composite films from natural polymers for mupirocin dermal delivery

In this study, novel adhesive films were prepared for Mupirocin dermal delivery. Natural polymers as chitosan, sodium alginate and carbopol were used for films development to evaluate possible interactions and drug release properties. Solvent evaporation method was used for films preparation. Preliminary studies involved FT-IR spectroscopy and Scanning Electron Microscopy to specify interactions and morphology. Thickness, tensile strength and water uptake in phosphate buffer saline were evaluated whereas in vitro release studies were also performed. In vitro drug release studies demonstrated that mupirocin release was improved. Ex vivo bioadhesion and permeation studies using Balb-c mice were performed to check the suitability of the films. Antimicrobial ability was evaluated by agar well diffusion tests. Finally, excisional wound model applied to test the wound healing effect and evaluated macroscopic and histopathologically. One formulation was found more effective compared to the market product for wound healing at Balb-c mice.     

Recent developments in drug-eluting dressings for the treatment of chronic wounds

Introduction: Granulation is a key unit process in the production of pharmaceutical solid dosage forms and involves the agglomeration of fine particles with the aid of a binding agent. Fluidized bed granulation, a classic example of spray granulation, is a technique of particle agglomeration brought about by the spray addition of the binding liquid onto a stationary bed of powder particles that is transformed to a fluid-like state by the passage of air through it.

Areas covered: The basic working principles, equipment set-up, advantages and challenges of fluidized bed granulation are introduced in this review. This is followed by an overview of the formulation and process-related variables affecting granulation performance. Technological advances, particularly in the application of process analytical tools, in the field of fluidized bed granulation research are also discussed.

Expert opinion: Fluidized bed granulation is a popular technique for pharmaceutical production, as it is a highly economical and efficient one-pot process. The research and development of process analytical technologies (PAT) has allowed greater process understanding and control to be achieved, even for the lesser known fluidized bed techniques, such as bottom spray and fluidized hot melt granulation. In view of its consistent mixing, as well as continuous and concurrent wetting and drying occurring throughout processing, fluidized bed granulation shows great potential for continuous production although more research is required to fully implement, validate and integrate the PAT tools in a production line.     

Novel nanostructured supramolecular hydrogels for the topical delivery of anionic drugs

A bis-imidazolium-based amphiphilic molecule was used to form novel supramolecular gels in ethanol–water mixtures. The proportion of solvents, the concentration of gellant and the temperature are factors that strongly influence the gelling process. The physical gels that are formed comprise entangled fibers of around 100 nm in diameter, able to incorporate anionic drugs, whose morphology varies depending on the drug they incorporate. These hydrogels are soft and therefore optimum for skin application. They show good stability when compared to previously reported gels. Suitable drug release and skin permeation profiles were obtained, and, moreover, they seem to promote the retention of the drug inside the skin. Finally, effective in vivo anti-inflammatory activity was observed, especially with the indomethacin-incorporated gel, which indicates that these supramolecular hydrogels are a good option for the delivery of poor water soluble drugs for the treatment of acute inflammation or other skin diseases.     

Pharmaceutical strategies for the treatment of bacterial biofilms in chronic wounds

Biofilms are sessile communities of microorganisms, mainly bacteria, that grow on biotic and abiotic surfaces. These microorganisms are embedded within an extracellular polymeric substance that provides enhanced protection from antimicrobials. Chronic wounds provide an ideal habitat for biofilm formation. Bacteria can easily attach to wound debris and can infect the wound due to an impaired host immune response. This review highlights the mechanism of biofilm formation and the role of biofilms in the pathophysiology of chronic wounds. Our major focus is on various formulation strategies and delivery systems that are employed to eradicate or disperse biofilms, thereby effectively managing acute and chronic wounds. We also discuss clinical research that has studied or is studying the treatment of biofilm-infected chronic wounds.     

黄酮类分子印迹互穿聚合物网络水凝胶的制备及性能研究

目的制备以芦丁分子为模板的分子印迹互穿聚合物网络水凝胶,并研究其性能。方法以吸附量为指标,考察黄酮类分子印迹互穿聚合物网络水凝胶合成工艺;以提取率为指标,采用HPLC法考察分子印迹互穿聚合物网络对槲皮素、麻黄碱、芦丁的提取纯化性能。结果当PVA与PAM质量比为1∶1、交联剂25%戊二醛加入量为1.25 m L时,PVA/PAM分子印迹互穿聚合物网络水凝胶对黄酮类分子具有良好的选择性提取纯化性能。结论以芦丁分子为模板的PVA/PAM分子印迹互穿聚合物网络水凝胶对黄酮类有较好的选择性提取纯化性能。     

烧伤止痛膏治疗浅Ⅱ度烧伤创面疗效观察

目的观察应用烧伤止痛膏治疗浅Ⅱ度烧伤创面的临床有效性与安全性。方法 84例浅Ⅱ度烧伤患者随机分为试验组和对照组,各42例。试验组创面选用烧伤止痛膏纱布敷料包扎治疗,对照组选用凡士林油纱布包扎治疗,观察用药后的疗效和安全性指标。并采用视觉模拟评分法（VAS）对患者创面总体疼痛感觉进行评价。结果试验组和对照组的7d创面愈合率分别为（65.39±22.86）%和（41.06±23.10）%,创面愈合时间分别为（10.03±2.38）d和（12.54±2.30）d,两组相比差异有统计学意义（P〈0.01）。试验组创面换药27例患者感轻微疼痛,VAS评分为≤3分;对照组30例创面换药时感到明显疼痛,VAS评分3~6分（P〈0.01）。试验组未见毒副作用和不良反应。结论烧伤止痛膏治疗浅Ⅱ度烧伤创面安全有效,明显减轻患者的疼痛。     

Distribution of fibroblast growth factor‐2 (FGF‐2) within model excisional wounds following topical application

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.     

Composite Alginate-Hyaluronan Sponges for the Delivery of Tranexamic Acid in Postextractive Alveolar Wounds

The management of wounds in patients on anticoagulant therapy who require oral surgical procedures is problematic and often results in a nonsatisfactory healing process. Here, we report a method to prepare an advanced dressing able to avoid uncontrolled bleeding by occluding the postextractive alveolar wounds, and simultaneously, capable of a fast release of tranexamic acid (TA). Composite alginate/hyaluronan (ALG/HA) sponge dressings loaded with TA were prepared by a straightforward internal gelation method followed by a freeze-drying step. Both blank and drug-loaded sponges were soft, flexible, and elegant in appearance and nonbrittle in nature. Scanning electron microscopy analysis confirmed the porous nature of these dressings. The integration of HA influenced the microstructure, reducing the porosity, modifying the water uptake kinetic, and increasing the resistance to compression. TA release from ALG/HA sponges showed a controlled release up to 3 h, and it was faster in the presence of HA. Finally, an in vitro clotting test performed on human whole blood confirmed that the TA-loaded sponges significantly reduce the blood clotting index by 30% compared with ALG/HA₂₀ sponges. These results suggest that, if placed in a socket cavity, these dressings could give a relevant help to the blood hemostasis after dental extractions, especially in patients with coagulation disorders.     

注射用亚叶酸钠的细菌内毒素检查

目的　建立检测注射用亚叶酸钠中内毒素的试验方法。方法　采用《中国药典》2 0 0 0年版附录细菌内毒素检查法。结果　注射用亚叶酸钠在药液稀释浓度 0. 5 5mg·ml-1以下时 ,与鲎试剂反应无干扰。结论　用细菌内毒素检查法检查注射用亚叶酸钠中的内毒素可行。     

Potential benefits of using chitosan and silk fibroin topical hydrogel for managing wound healing and coagulation

Background & ObjectivesThe intricate process of wound healing involves replacing the cellular or tissue structure that has been destroyed. In recent years various wound dressings were launched but reported several limitations. The topical gel preparations are intended for certain skin wound conditions for local action. Chitosan-based hemostatic materials are the most effective in halting acute hemorrhage, and naturally occurring silk fibroin is widely utilized for tissue regeneration. So, this study was conducted to evaluate the potential of chitosan hydrogel(CHI-HYD) and chitosan silk fibroin hydrogel (CHI-SF-HYD) on blood clotting and wound healing.MethodsHydrogel was prepared using various concentrations of silk fibroin with guar gum as a gelling agent. The optimized formulations were evaluated for visual appearance, Fourier transforms infrared spectroscopy (FT-IR), pH, spreadability, viscosity, antimicrobial activity, HR-TEM analysis, ex vivo skin permeation, skin irritation, stability studies, and in vivo studies by using adult male Wistar albino rats.ResultsBased on the outcome of FT-IR, no chemical interaction between the components was noticed. The developed hydrogels exhibited a viscosity of 79.2 ± 4.2 Pa.s (CHI-HYD), 79.8 ± 3.8 Pa.s (CHI-SF-HYD), and pH of 5.87 ± 0.2 (CHI-HYD), 5.96 ± 0.1 (CHI-SF-HYD). The prepared hydrogels were sterile and non-irritant to the skin. The in vivo study outcomes show that the CHI-SF-HYD treated group has significantly shortened the span of tissue reformation than other groups. This demonstrated that the CHI-SF-HYD could consequently accelerate the regeneration of the damaged area.Interpretation & ConclusionOverall, the positive outcomes revealed improved blood coagulation and re-epithelialization. This indicates that the CHI-SF-HYD could be used to develop novel wound-healing devices.     

注射用泮托拉唑钠的细菌内毒素检查

目的建立注射用泮托拉唑钠细菌内毒素的检查方法。方法按《中国药典》2005年版(二部)附录ⅪE进行实验和结果判断。结果用标示量灵敏度0.25EU.mL-1的鲎试剂,注射用泮托拉唑钠的有效检测浓度为0.13mg.L-1,3批注射用泮托拉唑钠内毒素均小于1.88EU.mL-1。结论本品可以用细菌内毒素检查法代替家兔热源检查法。     

外用抗菌离子膜喷雾剂联合甲硝唑栓治疗细菌性阴道病的效果观察

目的 探讨外用抗菌离子膜喷雾剂联合甲硝唑栓治疗细菌性阴道病的临床效果。方法 选取本院2012年2月～2013年5月收治的200例细菌性阴道病患者,采用随机双盲的研究方法 分为两组．试验组给予外用抗菌离子膜喷雾剂联合甲硝唑栓治疗,对照组给予甲硝唑栓治疗,观察两组患者的治疗效果,并于治疗结束后及治愈后3个月内进行复查,观察两组患者的复发情况。结果 两组治疗后线索细胞、pH等指标差异有统计学意义（P〈0．05）;两组治疗后白带多、外阴痒等临床症状差异有统计学意义（P〈0．05）;两组治疗后总有效率比较差异有统计学意义（P〈0．05）;试验组患者治疗后随访复发9例（9．0％）,对照组复发31例（31．0％）,两组差异有统计学意义（χ^2=5．196,P〈0．05）。结论 外用抗菌离子膜喷雾剂联合甲硝唑栓治疗细菌性阴道病的疗效安全、可靠,值得进一步研究和推广应用。     

Mucosal co-delivery of ketorolac and lidocaine using polymeric wafers for dental application

The current study aimed to investigate the effectiveness of a developed sodium alginate and polyvinylpyrrolidone K-25 (PVP K-25) polymeric wafer for the co-delivery of ketorolac and lidocaine to soft tissues for healing and pain control following gingivectomy. Nine ketorolac/lidocaine lyophilized wafers were formulated and assessed for their hydration capacity, mucoadhesion ability and in vitro release profile to select the optimum system for further clinical investigation. Wafer F6 containing 2:1 sodium alginate to PVP K-25 and 10% glycerol showed optimum properties and was selected for the clinical study. Twenty patients were included in the study and the ketorolac/lidocaine wafer was assessed versus a market product. Visual pain analog was evaluated daily for the first week and wound healing index was evaluated for one week, two weeks and one month following the procedure. The developed ketorolac/lidocaine polymeric wafer proved to be an effective method of reducing pain and discomfort together with enhancing wound healing following gingivectomy.