Topical Treatment Of Wounds Research Articles

WOUND HEALING AND ANTIFUNGAL EVALUATIONS OF SOME SURVEYED PLANTS OF GWADABAWA/ILLELA COMMUNITIES OF SOKOTO STATE-NIGERIA

Objective: This study aimed to evaluate the wound healing and antifungal properties of five earlier surveyed plants of Gwadabawa and Illela communities of Sokoto State-Nigeria cited for their acclaimed therapeutic purpose. Methods: Air-dried plant parts species for each plant were extracted by maceration using methanol. These were concentrated in vacuo to obtain crude methanolic extract (CME). The CME was partly defatted and partitioned with n-butanol to solubilize bioactive compounds in the organic phase, leaving sugars, amino acids, and salty compounds in the aqueous phase. The resulting concentrated n-butanol extracts were then screened by subjecting each extract to in vitro antifungal assay for the determination of the minimum inhibitory concentration (MIC) on Aspergillus niger in a 96-well flat bottom polystyrene microtiter plate using the broth microdilution method as outlined in the 2021 Clinical and Laboratory Standard Institute guideline; while the CME above for each plant, was subjected to wound healing assay using the wound excision model. Results: Our findings showed all five plant extracts were active with variable antifungal properties of MIC values ranging from 250 to 3.9 (mg/ml). The lowest activity was recorded for Waltheria indica, (with a MIC of 125 mg/ml), while the highest activity was indicated for Faidherbia albida (with a MIC of 3.90625 mg/ml). The other three extracts exhibited moderate activity at test concentration with a MIC of 7.8125 mg/ml. Similarly, the CME showed a comparable wound healing effect for all the plant extracts concerning the control groups (5 mg/ml povidone Iodine, PI as positive control and distilled water, DW as negative control). Increased tissue contraction of lesions on the excised skin of rats was observed to significantly differ accordingly based on the applied treatment with the graded doses of the test sample concentrations used (1.25, 2, and 5) mg/ml. Epithelial closure in all the rats occurred after 14 d, and more so, on the 16th 16th-day wounding, the wounds were almost scarless, while those of blank control (DW) had obvious scars. Conclusion: The wound healing and antifungal potentials of the crude extracts of the selected plants were confirmed. Thus, the five screened plant extracts may possibly be further investigated and developed into drugs for topical treatment of fungal-infected wounds, in line with their earlier folklore documentation.

A Designed Host Defense Peptide for the Topical Treatment of MRSA-Infected Diabetic Wounds.

Diabetes mellitus is a chronic disease characterized by metabolic dysregulation which is frequently associated with diabetic foot ulcers that result from a severely compromised innate immune system. The high levels of blood glucose characteristic of diabetes cause an increase in circulating inflammatory mediators, which accelerate cellular senescence and dampen antimicrobial activity within dermal tissue. In diabetic wounds, bacteria and fungi proliferate in a protective biofilm forming a structure that a compromised host defense system cannot easily penetrate, often resulting in chronic infections that require antimicrobial intervention to promote the healing process. The designed host defense peptide (dHDP) RP557 is a synthesized peptide whose sequence has been derived from naturally occurring antimicrobial peptides (AMPs) that provide the first line of defense against invading pathogens. AMPs possess an amphipathic α-helix or β-sheet structure and a net positive charge that enables them to incorporate into pathogen membranes and perturb the barrier function of Gram-positive and Gram-negative bacteria along with fungi. The capacity of skin to resist infections is largely dependent upon the activity of endogenous AMPs that provided the basis for the design and testing of RP557 for the resolution of wound infections. In the current study, the topical application of RP557 stopped bacterial growth in the biofilm of methicillin-resistant Staphylococcus aureus (MRSA) USA300 infected wounds on the flanks of clinically relevant diabetic TALLYHO mice. Topical application of RP557 reduced bacterial load and accelerated wound closure, while wound size in control diabetic mice continued to expand. These studies demonstrate that RP557 reduces or eliminates an infection in its biofilm and restores wound-healing capacity.

Predatory bacterial hydrogels for topical treatment of infected wounds

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 90μm, improving the rapid release of B. bacteriovorus from BG when contacting the aqueous surroundings. BG showed high biosafety with no L929cell toxicity or hemolysis. More importantly, BG exhibited excellent invitro 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.

Achados clínico-patológicos e imuno-histoquímicos em um caso de angiomatose cutânea bovina em uma novilha Holandesa

ABSTRACT: Bovine cutaneous angiomatosis (BCA) is a rare condition characterized by vasoproliferative skin lesions mainly affecting cattle in the northern hemisphere. An eight-month-old Holstein heifer showed two skin easy-bleeding nodules bulging from the epidermis in the forehead and close to the right prescapular region. Skin lesions were within the dermis and had an irregular surface and a soft heterogeneous reddish parenchyma composed of numerous variable-sized arterioles, veins, and capillaries surrounded by abundant collagenous fibrous tissue. Immunohistochemical assays evidenced endothelial cells lining proliferative vascular structure immunolabeled for CD31 and Von Willebrand factor, and vascular smooth muscle cells immunostained for smooth muscle actin. All clinical, pathological, and immunohistochemical features observed in the Holstein heifer were hallmarks of BCA. Considering its potential for hereditary spread, BCA must be included in the differential diagnosis of easily bleeding skin nodules that do not respond to routine topical wound treatments to prevent its spread in Brazilian herds.

Topical Wound Treatment with a Nitric Oxide-Releasing PDE5 Inhibitor Formulation Enhances Blood Perfusion and Promotes Healing in Mice.

Chronic, non-healing wounds constitute a major health problem, and the current therapeutic options are limited. Therefore, pharmaceuticals that can be locally applied to complicated wounds are urgently needed. Such treatments should directly target the underlying causes, which include diabetes mellitus, chronic local pressure and/or vascular insufficiency. A common consequence of these disorders is impaired wound angiogenesis. Here, we investigated the effect of topical application of a nitric oxide-releasing phosphodiesterase 5 inhibitor (TOP-N53)-containing liquid hydrogel on wound repair in mice. The drug-loaded hydrogel promoted re-epithelialization and angiogenesis in wounds of healthy and healing-impaired diabetic mice. Using a non-invasive label-free optoacoustic microscopy approach combined with automated vessel analysis, we show that the topical application of TOP-N53 formulation increases the microvascular network density and promotes the functionality of the newly formed blood vessels, resulting in enhanced blood perfusion of the wounds. These results demonstrate a remarkable healing-stimulating activity of topically applied TOP-N53 formulation, supporting its further development as a wound therapeutic.

Pentoxifylline/Valsartan co-delivery in liposomal gel alters the inflammatory HMGB-1/ TLR pathway and promotes faster healing in burn wounds: A promising repurposed approach

Burn wounds are one of the most severe complex forms of trauma. Hence, new treatment strategies that facilitate the healing process; reduce the severity and the healing time is the main concern of the health care systems. In this work, pentoxifylline-valsartan, (PTX- VAL), loaded liposomes integrated into gel were designed for the first time as a novel co-delivery carrier for the treatment of burn wounds. The objective of this work was to investigate the ability of the nano-based liposomal system to co-entrap two repurposed drugs; hydrophilic pentoxifylline and lipophilic valsartan for topical treatment of burn wounds. The impact of increasing the phospholipid amount to enhance the co-entrapment of PTX and VAL was investigated and in-vitro evaluation of the prepared formulations was conducted to choose the optimum composition with the highest entrapment of both drugs adopting a simple, reliable derivative spectrophotometric method. Structure elucidation was also performed using a transmission electron microscope. In addition, A simple selected derivative spectrophotometric method was developed for the assay of PTX-VAL novel combination. The proven selectivity, precision and accuracy assured the reliability of this analytical method. Being economic and fast makes routine application of the developed analytical method is recommended in pharmaceutical industry. The selected liposomal formulation integrated into gel matrix (PTX-VAL-LG) showed; nanometric size, acceptable entrapment efficiency of both PTX and VAL as well as sustained release profiles and thus, enhanced action.

Murine macrophages or their secretome delivered in alginate dressings enhance impaired wound healing in diabetic mice

Diabetic foot ulceration is a devastating diabetic complication with unmet needs. We explored the efficacy of calcium-crosslinked alginate dressings in topically delivering primary macrophages and their secretome to diabetic wounds. The alginate bandages had a microporous structure that enabled even cell loading with prolonged cell survival and egress following wound placement. In vitro experiments showed that we could successfully differentiate and polarize primary murine bone marrow derived monocytes into M0, M1, M2a and M2c defined states with distinct gene expression, surface protein and secretome profiles. The primary macrophages were delivered in the bandages, migrated within the wounds and were still present for as long as 16 days post-injury. In wounds of db/db mice, treatment with all macrophage subtypes and their secretome, when compared to control, accelerated wound healing. Bulk RNA sequencing analysis and multiplex protein quantification of wound lysates revealed that M2c macrophages conditioned media had the most impact in wound healing affecting processes like neurogenesis, while M1 conditioned media promoted keratinization and epidermal differentiation. Collectively, our results indicate that alginate dressings can serve as a delivery platform for topical treatment of diabetic wounds and that conditioned media from distinctly polarized macrophages is equally or more effective than their parental cells in advancing wound healing and could therefore be a promising and technically advantageous alternative to cell therapy.

Evaluation of Wound‐Healing Activity of Securidaca longepedunculata Root Extract in Male Wistar Rats

AbstractWound‐healing is a complex series of well‐coordinated cellular and biochemical happenings that reinstates the skin‘s integrity. Medicinal herbs offer a promising alternative than synthetic medications for wound‐healing because they have fewer adverse effects. This present study aims to evaluate wound‐healing potential of methanol extract of S. longepedunculata root (MESLR) in male rats. Some biological activities as well as phytochemical analysis were also carried out to elucidate the rationale of its wound‐healing potency. Alkaloids, flavonoids and terpenoids were found to be present amongst others with the saponin content being the chief [(22.80±0.87) g/100 g]. MESLR had a greater potential inhibiting the DPPH radicals at IC50 of 5.5 μg/ml and % free radical inhibition of 86.03 % as well as the highest inhibiting potential 54.34 % in the anti‐inflammatory study. 100 % wound closure (p< 0.05) was observed with 2.0 g/10 g MESLR based‐ointment as against the negative control group before the 21st day while the subsequent groups and the standard treatment showed complete closure on the last day of the experiment. The histological examination showed more collagen formation, less inflammatory cell, increased fibroblast distribution, and keratin synthesis in all the groups except for the negative control group, which on the 21st day of the study demonstrated epithelial necrosis and severe epidermal deterioration. The foundational information presented from this study suggests the efficacy of S. longepedunculata for topical management and treatment of wounds in traditional medicine and this report is the earliest study of the use of S. longepedunculata root for wound‐healing.

Topical Wound Therapy Products With Ionic Silver: A Technologic Analysis.

The purpose of this technologic analysis was to review use of ionic silver as a component of topical wound therapy products. Published literature from a variety of fields related to ionic silver and its use in topical wound therapy products was reviewed and a summary of common commercially available wound care products containing ionic silver was generated, along with general recommendations for use. Safety information from both manufacturer guidelines and the Manufacturer and User Facility Device Experience (MAUDE) database is summarized. Various formulations of ionic silver products are used for topical treatment of wounds. Antimicrobial activity varies according to the specific silver formulation and type of microorganisms in the wound bed. In vitro evidence suggests that some bacterial strains may be developing resistance to ionic silver. Improved knowledge of the benefits and safety precautions associated with topical silver preparations can guide its application to topical therapy for wound healing.

Aberrant in physicochemical properties, functional health and medicinal grades of honeys from different sales outlets in Southwest Nigeria

BackgroundHoney is consumed for the derived benefits as sweetener, for healing wounds, skin burns, regulating blood sugar level, treatments of some ailments, etc. In Nigeria, adulteration of honey is a serious concern, and these adulterated or fake honeys have health implications. This research aims to compare and contrast the physicochemical qualities, functional health and medicinal values of honey samples from local honey parkers, supermarkets and beekeepers’ sales outlets in Southwest Nigeria.ResultsThe darkness of the honey from the three sources was significantly different. The honey samples from the beekeepers have ash contents values of 0.25–1.0 in line with CAC and IHC, whereas 7(46.66%) and 2(13.33%) of honey samples from the supermarkets and local handlers/parkers, respectively, deviated from this standard values. The wound healing development after 8 days of topical treatment of incision wounds with honey from beekeepers shows a good development. 93.3% of the honeys sourced from the beekeepers, 58.06 and 66.05% of the honeys sourced from the supermarkets, and the local honey markets were found to be original.ConclusionThe originality of honey for consumers’ satisfaction is dependent on the complimentary factors of physicochemical properties, functional health and medicinal values. These findings provide information for consumers’ awareness on categorization of honey as original/pure, adulterated and fake and the health implications.

QS66. The Safety of Elution of Multiple Antibiotics From Collagen-rich Hydrogel for Topical Treatment of Chronic Wounds

Purpose: Chronic wounds pose a significant challenge to modern healthcare systems, affecting 1-2% of the population in developed countries with costs ranging between $28.1 and $96.8 billion annually. Overtime chronic wounds tend to become colonized or infected with multiple different bacteria resulting in patients being treated with several rounds of systemic oral and IV antibiotics. Subsequently, antibiotic resistance develops, and wounds become harder to treat. Comorbidities, such as diabetes and peripheral vascular disease, also make treatment more challenging. Ideally chronic wounds would be treated topically with customized antimicrobial combinations unique to each patient’s wound.In vivo, we have previously shown that a topical collagen-rich hydrogel (cHG) can provide controlled elution of single antibiotics leading to inhibition of bacterial growth while avoiding cytotoxicity towards host cells in a stented wound model. We hypothesize that the elution of multiple antibiotics from collagen-rich hydrogel will also be well-tolerated in mammalian cells. Methods: Antibiotic Selection: We performed a literature search to determine the antibiograms bacteria isolated from chronic diabetic wounds; the most common microbes were Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., and beta-hemolytic streptococci. This informed our choice of antibiotics. We tested four antibiotic combinations from six antibiotics. While there are 15 two-antibiotic permutations, these combinations provided the most extensive coverage. Collagen hydrogel formation: 2.5% collagen-rich thermoresponsive hydrogel (cHG) was synthesized according to a previously established protocol. After confirmation of composition and gelation, cHG-antibiotic solutions were prepared by determining 100x the minimum inhibitory concentration of each antibiotic and adjusting the final volume of hydrogel to 100 mL per well. The antibiotic concentrations used were 400 ug/mL vancomycin, 400 ug/mL imipenem, 200 ug/mL ciprofloxacin, 500 ug/mL ceftazidime, 1.0 mg/mL gentamicin, and 100 ug/mL clindamycin.Mammalian cell cytotoxicity: Human adipose-derived stem cells (ASCs), mouse ASCs, human fibroblasts (FBs), and mouse FBs were used to study cytotoxicity in both differentiated and undifferentiated mammalian cells. Cells were seeded onto 24-well culture plates at a density of 2 × 104 cells/ml, allowed to attach overnight, and treated with cHG+antibiotic, incubated until 24, 48, and 72-hour time points.A live/dead viability/cytotoxicity assay was used according to the manufacturer’s instructions, and images were analyzed using MATLAB. All experiments were performed in triplicates. Results: We observed no significant cell death in differentiated and undifferentiated cells in both mouse and human cell lines treated with antibiotic-eluting hydrogel with multiple combinations of antibiotics. All cell lines had >90% survival at all timepoints. Conclusion: This study demonstrates that the application of a topical drug-eluting hydrogel with a combination of antibiotics in the hydrogel is safe for use in mammalian cells. This could transform the treatment of chronic diabetic wounds, which are often polymicrobial with unique resistance patterns requiring multiple antibiotics.

Antidiabetic Wound Dressing Materials Based on Cellulosic Fabrics Loaded with Zinc Oxide Nanoparticles Synthesized by Solid-State Method.

The current study aims for the use of the solid-state technique as an efficient way for the preparation of zinc oxide nanoparticles (ZnONPs) as an antimicrobial agent with high concentration using sodium alginate as stabilizing agent. ZnONPs were prepared with three different concentrations: ZnONPs-1, ZnONPs-2, and ZnONPs-3 (attributed to the utilized different concentrations of zinc acetate, 1.5, 3 and 4.5 g, respectively). The as-fabricated ZnONPs (ZnONPs-1, ZnONPs-2, and ZnONPs-3) were used for the treatment of cellulosic fabrics as dressing materials for the diabetic wounds. DLS findings illustrated that the as-prepared ZnONPs exhibited average particle size equal to 78, 117, and 144 nm, respectively. The data also showed that all the formulated ZnONPs were formed with good stability (above −30 mv). The topographical images of cellulosic fabrics loaded with ZnONPs that were obtained by SEM confirmed the deposition of nanoparticles onto the surface of cellulosic fabrics with no noticeable agglomeration. The findings also outlined that the treated cellulosic fabrics dressings were proven to have enhanced bactericidal characteristics against the pathogenic microorganisms. The finding of wound contraction for the diabetic rats was measured after 21 days and reached 93.5% after treating the diabetic wound with cotton fabrics containing ZnONPs-2. Ultimately, the generated wound dressing (cellulosic fabrics loaded with ZnONPs) offers considerable promise for treating the wound infections and might be examined as a viable alternative to antibiotics and topical wound treatments.

Inflammatory skin diseases and wounds.

Inflammatory wounds of the skin can be caused by many different diseases. Of particular importance here are the very heterogeneous groups of vasculitides and vasculopathies. These are usually interdisciplinary relevant diseases that require extensive diagnostics in specialized centres. Clinically, these inflammatory wounds present as very painful ulcers that develop from necrosis and are surrounded by erythematous livid borders. The healing process is often difficult and protracted. Moreover, it considerably impairs the quality of life of the affected patients. In addition to clinical evaluation, histopathological examination of biopsies taken as early as possible is particularly important in diagnosis. Numerous differential diagnoses must be ruled out. Therapeutically, in addition to the often necessary systemic therapies, which include immunosuppressants (immunomodulating drugs and/or rheologics), appropriate topical wound treatment, usually in combination with compression therapy, should always be considered. Whenever possible, the causative factors should be diagnosed early and avoided or treated.

Effective Treatment of Skin Wounds Co-Infected with Multidrug-Resistant Bacteria with a Novel Nanoemulsion.

ABSTRACTWound infections with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are particularly difficult to treat and present a great challenge to clinicians. Nanoemulsions (NE) are novel oil-in-water emulsions formulated from soybean oil, water, solvent, and surfactants such as benzalkonium chloride (BZK). An optimal ratio of those components produces nanometer-sized particles with the positive-charged surfactant at their oil-water interface. We sought to investigate antimicrobial NE as a novel treatment to address wounds co-infected by MRSA and VRE. Swine split-thickness skin wounds were first infected with MRSA and/or VRE, then treated with the nanoemulsion formulation (X-1735) or placebo controls. Bacterial viability after treatment were determined by nutrient agar plates for total, MRSA-specific, and VRE-specific loads. In addition, inflammation indexes were scored by histopathology. When VRE infected wounds were treated with X-1735, they contained 103 lower VRE CFU counts across a 2-week period compared with placebo. Once co-infected MRSA and VRE split-thickness wounds were successfully established, topical treatment of co-infected wounds with X-1735 resulted in a reduction of bacteria by 2 to 3 logs (compared with placebo) at 3- and 14-day postinfection time points. Importantly, X-1735 was effective in significantly alleviating multilevel inflammation in the treated wounds. X-1735 is a new antimicrobial that is safe to apply to open wounds and effectively kills MRSA and VRE. It appears to also reduce inflammation in these co-infected wounds. The data suggest that this approach offers promise as an antimicrobial for open wounds with MRSA and VRE co-infection.IMPORTANCE Infections, specifically polymicrobial, can cause serious consequences when it comes to wound treatment. Prolonged treatment with antibiotics can lead to an increased risk of bacterial resistance; co-infections can complicate treatment options even further. Our research proposes a novel nanoemulsion treatment for two of the most common antibiotic resistant bacteria: methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant enterococci (VRE). This optimized topical treatment formulation not only significantly reduces inflammation and infection in MRSA or VRE infected wounds, but also in MRSA and VRE co-infected wounds as well. The work aims to provide an alternative treatment approach for multidrug-resistant organisms and decrease dependence on systemic treatments.

Photopolymerized Zwitterionic Hydrogels with a Sustained Delivery of Cerium Oxide Nanoparticle-miR146a Conjugate Accelerate Diabetic Wound Healing.

In the United States, $87 billion per year is spent on the care of diabetic ulcers alone. Although the pathophysiology of diabetic wound healing is multifaceted, high systemic levels of inflammation and increased reactive oxygen species are often implicated in the wound healing impairment. Zwitterionic materials have been demonstrated to reduce inflammation and increase extracellular matrix deposition in wound beds, and here, we demonstrate a fabrication method for photopolymerized zwitterionic hydrogels that also enables sustained drug delivery over time. A therapeutic molecule of interest that is examined in this work is cerium oxide nanoparticle tagged with microRNA-146a (CNP-miR146a) to combat both oxidative stress and inflammation. The hydrogels are composed of zwitterionic and nonzwitterionic monomers, and the hydrogel formation occurs in the absence of a crosslinker. The hydrogels exhibit a wide range of stiffness and mechanical properties depending on their monomer content. Additionally, these hydrogels exhibit sustained release of nanoparticles and proteins. Finally, when employed in an in vivo diabetic mouse wound healing model, the zwitterionic hydrogels alone and laden with the CNP-miR146a conjugate significantly improved the rate of diabetic wound healing. Overall, these materials have excellent potential to be used as a topical treatment for chronic diabetic wounds.

Сучасні хірургічні методи лікування постраждалих з вогнепальними пораненнями кінцівок

Подано можливості етапного лікування вогнепальних ран у 254 пацієнтів з використанням терапії негативним тиском, ультразвукової кавітації і мікробіологічного дослідження ранового вмісту. Розглянуто підходи в комплексному лікуванні на підставі бактеріологічних властивостей вогнепальних поранень. Аналіз результатів лікування показав, що метод комплексного лікування вогнепальних ран м’яких тканин кінцівок з використанням апарату вакуумної аспірації, ультразвукової кавітації для очищення ран, збагаченої тромбоцитами плазми, для локальної стимуляції репаративних процесів дає можливість скоротити тривалість лікування до 8,0 ± 2,8 дня, знизити кількість ускладнень на 30,0 ± 1,2 %, що дозволяє рекомендувати цей метод лікування даної патології.

DELOS Nanovesicles-Based Hydrogels: An Advanced Formulation for Topical Use.

Topical delivery has received great attention due to its localized drug delivery, its patient compliance, and its low risk for side effects. Recent developments have focused on studying new drug delivery systems as a strategy for addressing the challenges of current topical treatments. Here we describe the advances on an innovative drug delivery platform called DELOS nanovesicles for topical drug delivery. Previously, the production of DELOS nanovesicles demonstrated potentiality for the topical treatment of complex wounds, achieving well-tolerated liquid dispersions by this route. Here, research efforts have been focused on designing these nanocarriers with the best skin tolerability to be applied even to damaged skin, and on exploring the feasibility of adapting the colloidal dispersions to a more suitable dosage form for topical application. Accordingly, these drug delivery systems have been efficiently evolved to a hydrogel using MethocelTM K4M, presenting proper stability and rheological properties. Further, the integrity of these nanocarriers when being gellified has been confirmed by cryo-transmission electron microscopy and by Förster resonance energy transfer analysis with fluorescent-labeled DELOS nanovesicles, which is a crucial characterization not widely reported in the literature. Additionally, in vitro experiments have shown that recombinant human Epidermal Growth Factor (rhEGF) protein integrated into gellified DELOS nanovesicles exhibits an enhanced bioactivity compared to the liquid form. Therefore, these studies suggest that such a drug delivery system is maintained unaltered when hydrogellified, becoming the DELOS nanovesicles-based hydrogels, an advanced formulation for topical use.

Antidiabetic of Mango (Mangifera longipes Griff.) Leves: Methanol Extract, Water Fraction, and Ethyl Acetate

Mango leaves (Mangifera longipes Griff.) are used for diabetic, malaria, gastrointestinal, kidney, as well as topical treatment of wounds. The aim of this study was to determine the antidiabetic activity of methanol extract, water fraction and ethyl acetate fraction from mango leaves (Mangifera longipes Griff.). Oral Glucose Tolerance Test (OGTT) on 24 rats divided into 6 groups, namely normal; negative; positive (given acarbose 1.8 mg/200 g BW rats); methanol extract (EM), water fraction (FA), ethyl acetate fraction (FEA) with a dose of 58.8 mg/200 g BW rats. Induction of 1.35 g/200 g BW of rats glucose was carried out 30 minutes before the dosage administration. Data analysis with Paired T Test (95% confidence level). Results: In crude extract standardization, the water content was 2%, the ash content was 12.6% and the water soluble extract content was 19.5%. In crude extract and EM, flavonoids, saponins, and phenols were identified; in FA identified saponins and phenols; FEA identified flavonoids and phenols. A significant decrease in blood glucose levels at T0 and T120 in all groups (significant 2-tailed <0.05). The percentage of decline in the positive and FEA groups compared to the negative was 85.5% and 16.9%, respectively. Discussion:. Flavonoids are thought to increase antioxidant activity and inhibit α-glucosidase enzymes. Conclusion: EM, FA and FEA have antidiabetic activity with the best percentage reduction in glucose levels was FEA (16.9%). Keywords: Antidiabetic, OGTT, Mangifera longipes Griff

Human adipose-derived stem cells in fibrin glue carrier modulate wound healing phases in rats

Cell-based therapy using human adipose-derived stem cells (ADSCs) is a new approach for enhancing wound healing. Therefore, in this study, we aimed to evaluate the immunomodulatory effect and wound healing process based on xenografted human ADSCs in a fibrin glue matrix carrier during the wound healing process in a full-thickness excisional model in rats. Two excisional wounds were made in the dorsum of 60 rats using a dermatological punch (1.5 cm diameter), and the rats were randomly assigned to three groups: control (untreated group), FG (topical treatment of both wounds with fibrin glue), and ADSC+FG (topical treatment of both wounds with 2.0 × 10 5 ADSCs in fibrin glue carrier). On the 2nd, 7th, 14th, and 21st days after the wounding surgical process, re-epithelialization was assessed by imaging the skin/wound/scar, and samples were harvested for histomorphometric analyses (quantification of inflammatory cells, blood vessels, fibroblasts, and collagen); biochemical quantification of myeloperoxidase (neutrophil), N-acetylglucosaminidase (macrophage), hydroxyproline (total collagen), and glycosaminoglycans; immunohistochemistry to detect IL-10 and IL-17; and western blot analysis of TNF-α, TGF-β1, and VEGF. ADSC+FG therapy stimulated the anti-inflammatory response up to the 7th day, where the IL-10 levels were higher compared with the control group. This treatment induced angiogenesis, fibroblast proliferation, and collagen formation faster than the other treatments to enhance re-epithelialization. ADSC and FG therapy could be suitable for modulating the inflammatory response and enhancing re-epithelialization, as well as the formation of new blood vessels during wound healing.

Экспериментальная оценка лечебных свойств мази на основе меланинов из природного сырья и глубинной культуры чаги

Introduction. Due to the acquisition of antibiotic resistance by pyogenic microbiota, the problem of topical (drug) treatment of wounds has worsened. Aim. Experimental evaluation of the antibiotic properties of melanin from natural raw material and a submerged culture of chaga (Inonotus obliquus) in vitro and the therapeutic properties of ointments prepared on the basis of these melanins in vivo. Materials and Methods. Melanins were obtained by alkaline hydrolysis. The antibiotic activity of melanins was determined by co-cultivation in a liquid medium of the studied samples with six cultures of test strains of gram-negative and gram-positive bacteria and two of yeast fungi. Ointments based on melanin from natural raw material and the submerged culture of chaga (Inonotus obliquus F-1244 strain) were obtained using two compositions of ointment base. The wound-healing efficacy of ointments was evaluated on three groups of mice. The control groups were mice untreated and treated with a comparison drug (Levomikon-TFF). The treatment of mice was continued until their incised skin wounds healed. Wound areas, motor activity, appetite, dynamics and character of wound healing were assessed daily in mice of all groups, as well as changes in their body weight every three days. Results. Melanins from natural raw materials and the submerged culture of chaga completely suppressed the growth of gram-positive spore-forming Bacillus cereus bacterium in a co-culture. Melanin from natural raw material of chaga on average suppressed the growth of the Staphylococcus aureus ATCC 6538 strain by an order of magnitude. Melanin from the submerged chaga culture completely suppressed the growth of a clinical isolate of the highly pathogenic Candida sp. Ft-5 strain from a deceased patient with generalized candida infection and, on average, inhibited the growth of the collection strain of yeast Candida albicans 620 by two orders of magnitude more intensively. It was found that ointments based on melanin from natural raw materials and the submerged culture of chaga, as well as ointment containing a fivefold increased concentration of melanin from natural chaga, do not have toxicity to experimental animals. Ointments containing 0.4 mg of melanin from natural raw material and the submerged chaga culture per 0.2 g of a single dose of ointment had the same wound healing efficacy, while not only were not inferior in this indicator to the combined antimicrobial comparison drug Levomikon-TFF, but also showed a tendency to more accelerated wound healing (on the 15–18th day of observation) compared with the process of wound regeneration in the group of animals treated with the drug of comparison. A more accelerated wound healing effect was demonstrated in experimental animals (already on the 12th day of observation) treated with a fivefold increased content of melanin from natural raw material of chaga, compared with mice treated with the comparison drug. Conclusion. Ointments containing melanin of chaga (Inonotus obliquus) have anti-inflammatory, regenerative properties and can be considered promising for topical treatment of wounds.