scholarly journals Bacteriophages for Chronic Wound Treatment: From Traditional to Novel Delivery Systems

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 235 ◽  
Author(s):  
Ana M. Pinto ◽  
Miguel A. Cerqueira ◽  
Manuel Bañobre-Lópes ◽  
Lorenzo M. Pastrana ◽  
Sanna Sillankorva
Keyword(s):  
Chronic Wounds ◽  
Chronic Wound ◽  
Phage Therapy ◽  
Ex Vivo ◽  
Financial Burden ◽  
Delivery Systems ◽  
Efficacy Evaluation ◽  
Antibiotic Resistant

The treatment and management of chronic wounds presents a massive financial burden for global health care systems, with significant and disturbing consequences for the patients affected. These wounds remain challenging to treat, reduce the patients’ life quality, and are responsible for a high percentage of limb amputations and many premature deaths. The presence of bacterial biofilms hampers chronic wound therapy due to the high tolerance of biofilm cells to many first- and second-line antibiotics. Due to the appearance of antibiotic-resistant and multidrug-resistant pathogens in these types of wounds, the research for alternative and complementary therapeutic approaches has increased. Bacteriophage (phage) therapy, discovered in the early 1900s, has been revived in the last few decades due to its antibacterial efficacy against antibiotic-resistant clinical isolates. Its use in the treatment of non-healing wounds has shown promising outcomes. In this review, we focus on the societal problems of chronic wounds, describe both the history and ongoing clinical trials of chronic wound-related treatments, and also outline experiments carried out for efficacy evaluation with different phage-host systems using in vitro, ex vivo, and in vivo animal models. We also describe the modern and most recent delivery systems developed for the incorporation of phages for species-targeted antibacterial control while protecting them upon exposure to harsh conditions, increasing the shelf life and facilitating storage of phage-based products. In this review, we also highlight the advances in phage therapy regulation.

scholarly journals Polymer-Based Smart Drug Delivery Systems for Skin Application and Demonstration of Stimuli-Responsiveness

Polymers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1285
Author(s):  
Louise Van Gheluwe ◽  
Igor Chourpa ◽  
Coline Gaigne ◽  
Emilie Munnier
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Ex Vivo ◽  
Delivery Systems ◽  
Stimuli Responsive ◽  
Stimuli Responsive Polymers ◽  
Smart Drug ◽  
Smart Drug Delivery

Progress in recent years in the field of stimuli-responsive polymers, whose properties change depending on the intensity of a signal, permitted an increase in smart drug delivery systems (SDDS). SDDS have attracted the attention of the scientific community because they can help meet two current challenges of the pharmaceutical industry: targeted drug delivery and personalized medicine. Controlled release of the active ingredient can be achieved through various stimuli, among which are temperature, pH, redox potential or even enzymes. SDDS, hitherto explored mainly in oncology, are now developed in the fields of dermatology and cosmetics. They are mostly hydrogels or nanosystems, and the most-used stimuli are pH and temperature. This review offers an overview of polymer-based SDDS developed to trigger the release of active ingredients intended to treat skin conditions or pathologies. The methods used to attest to stimuli-responsiveness in vitro, ex vivo and in vivo are discussed.

Modelling Staphylococcus aureus biofilms on infected chronic wounds

2020 ◽  
Author(s):  
Yanyan Cheng ◽  
Paul De Bank ◽  
Albert Bolhuis
Keyword(s):  
Staphylococcus Aureus ◽  
Dynamic Model ◽  
Chronic Wounds ◽  
Ex Vivo ◽  
Venous Pressure ◽  
Viable Count ◽  
Major Health Problem ◽  
Single Strain

<p>Chronic wounds, for instance venous, pressure, arterial and diabetic ulcers, are a major health problem throughout the world. Compared with normal wounds, those that take more than four weeks to heal are defined as chronic. Interestingly, the numbers of patients suffering from chronic wounds and the cost for treatment have been increasing during the past two decades. There is increasing evidence that suggests that bacteria infect those chronic wounds and there exist as a biofilm, which affects wound healing and success of treatment. To study biofilms in infected wounds, both in vitro and in vivo biofilm models are important to be developed.</p> <p> </p> <p>In this project, a dynamic ex vivo chronic wound biofilm model for Staphylococcus aureus using a 3D printed chamber and porcine skin was developed. This dynamic model then used to determine antibiotic treatment by using poly(ε‐caprolactone) (PCL) electrospun fibrous mats containing different antibiotics, e.g. tetracycline, gentamicin and fusidic acid. Furthermore, electrospun PCL/silk fibroin scaffolds were also used as carrier of gentamicin. The killing effect of mature S. aureus MRSA 252 growing in the wound model was tested by both viable count and qPCR.</p> <p> </p> <p>The results indicated that this newly designed dynamic model was successful in mimicking single-strain biofilm on infected chronic wounds. Compared with traditional biofilm assays, the flow system generates an air-liquid-solid interface, which more closely approaches to real conditions. Furthermore, results from using electrospun fibrous scaffolds provided strong evidence for their potential in clinical applications to treat infected skin.</p> <p> </p>

Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) Containing Rice Bran Oil for Enhanced Fenofibrate Oral Delivery: In Vitro Digestion, Ex Vivo Permeability, and In Vivo Bioavailability Studies

2020 ◽  
Vol 21 (6) ◽  
Author(s):  
Christina Karavasili ◽  
Ioannis I. Andreadis ◽  
Maria P. Tsantarliotou ◽  
Ioannis A. Taitzoglou ◽  
Paschalina Chatzopoulou ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Rice Bran ◽  
Oral Delivery ◽  
Drug Delivery Systems ◽  
Rice Bran Oil ◽  
Ex Vivo ◽  
In Vitro Digestion ◽  
Delivery Systems

scholarly journals Antibacterial properties of thioridazine

2019 ◽  
pp. 96-104
Author(s):  
N. Hrynchuk ◽  
N. Vrynchanu
Keyword(s):  
Antibacterial Activity ◽  
Ex Vivo ◽  
Antibacterial Properties ◽  
Antimicrobial Properties ◽  
Antibiotic Resistant ◽  
In Vivo Experiments ◽  
Antistaphylococcal Activity ◽  
The Impact

The emergence and spread of antibiotic-resistant strains of microorganisms reduces the effectiveness of antibiotic therapy and requires finding solutions to problems, one of which is the study of antimicrobial properties in drugs of various pharmacological groups. The purpose of the work was to summarize the data on the antibacterial activity of thioridazine and its derivatives to determine the feasibility and prospects of creating new antibacterial drugs on their basis. The paper presents literature data on the effects of thioridazine on the causative agent of tuberculosis, antistaphylococcal activity, susceptibility of plasmodium and trypanosoma. The antibacterial activity of the drug was established within in vitro studies with the determination of MIC towards gram-positive and gram-negative microorganisms, ex vivo using macrophage lines, as well as within in vivo experiments on mice. It is established that the neuroleptic thioridazine is characterized by pronounced anti-tuberculosis activity, the mechanism of action is associated with the impact on the cell membrane of M. tuberculosis, inactivation by calmodulin and inhibition of specific NADH-dehydrogenase type II. The literature data indicate that thioridazine is able to increase the activity of isoniazid against the strains of mycobacteria that are susceptible and resistant to its action. It has been established that resistance to thioridazine in antibiotic-resistant M. tuberculosis strains is not formed. The drug is characterized by its ability to inhibit the growth and reproduction of both methicylin-sensitive (MSSA) and methicilin-resistant (MRSA) strains of Staphylococcus aureus, which has been proven within in vitro experiments. The effectiveness of thioridazine has been proven within in vivo experiments in case of skin infection and sepsis caused by S. aureus. Antimicrobial effect of the drug is also observed towards to plasmodium (P. falciparum) and trypanosomes (Trypanosoma spp.). Currently, the synthesis of thioridazine derivatives is carried out to identify compounds with a pronounced antibacterial effect. Some of the first synthesized compounds are not inferior or superior to thioridazine by the inhibitory effect. Thus, these data suggest that drugs of different pharmacological groups, including drugs that affect the nervous system - thioridazine and its derivatives, can be a source of replenishment of the arsenal of antimicrobial drugs to control such threatening infections as tuberculosis and diseases caused by polyresistant strains of microorganisms.

Accelerated Wound Healing Induced by a Novel Amphibian Peptide (OA-FF10)

2019 ◽  
Vol 26 (4) ◽  
pp. 261-270 ◽  
Author(s):  
Naixin Liu ◽  
Zhe Li ◽  
Buliang Meng ◽  
Wenxin Bian ◽  
Xiaojie Li ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Low Cost ◽  
Financial Burden ◽  
Human Keratinocytes ◽  
Critical Issue ◽  
Disulfide Bridge ◽  
Toxic Activity

Background: Despite the continued development of modern medicine, chronic wounds are still a critical issue in clinical treatment, placing a great physiological, psychological, and financial burden on patients. Researchers have investigated many methods to solve this problem, with bioactive peptides gaining increasing attention due to their considerable advantages and diverse functions, as well as low cost, simple storage, and easy transportation. Methods: In this research, a novel peptide (named OA-FF10) was identified from the skin secretions of the odorous frog species Odorrana andersonii. The sequence of mature OA-FF10 was “FFTTSCRSGC”, which was produced by the post-translational processing of a 61-residue prepropeptide. Results: Similar to most frog peptides, OA-FF10 showed an intramolecular disulfide bridge at the C-terminus. OA-FF10 demonstrated no antibacterial, antioxidant, hemolytic, or acute toxic activity, but promoted wound healing and proliferation of human keratinocytes (HaCaT) both time- and dose-dependently. Furthermore, while OA-FF10 had no effect on wound healing of Human Skin Fibroblasts (HSF), it did accelerate healing in a full-thickness skin-wound mouse model. Conclusion: Our research revealed the strong wound-healing activity of OA-FF10 in vivo and in vitro, thus providing a new candidate for the development of novel wound-healing drugs.

scholarly journals Ex Vivo and In Vivo Characterization of Interpolymeric Blend/Nanoenabled Gastroretentive Levodopa Delivery Systems

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Ndidi C. Ngwuluka ◽  
Yahya E. Choonara ◽  
Girish Modi ◽  
Lisa C. du Toit ◽  
Pradeep Kumar ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Ex Vivo ◽  
Delivery Systems ◽  
Pharmacokinetic Parameters ◽  
Gastric Residence Time ◽  
Systemic Bioavailability ◽  
Absorption Window

One approach for delivery of narrow absorption window drugs is to formulate gastroretentive drug delivery systems. This study was undertaken to provide insight into in vivo performances of two gastroretentive systems (PXLNETand IPB matrices) in comparison to Madopar® HBS capsules. The pig model was used to assess gastric residence time and pharmacokinetic parameters using blood, cerebrospinal fluid (CSF), and urine samples. Histopathology and cytotoxicity testing were also undertaken. The pharmacokinetic parameters indicated that levodopa was liberated from the drug delivery systems, absorbed, widely distributed, metabolized, and excreted.Cmaxwere 372.37, 257.02, and 461.28 ng/mL and MRT were 15.36, 14.98, and 13.30 for Madopar HBS capsules,PXLNET, and IPB, respectively. In addition, X-ray imaging indicated that the gastroretentive systems have the potential to reside in the stomach for 7 hours. There was strong in vitro-in vivo correlation for all formulations withr2values of 0.906, 0.935, and 0.945 for Madopar HBS capsules,PXLNET, and IPB, respectively. Consequently,PXLNETand IPB matrices have pertinent potential as gastroretentive systems for narrow absorption window drugs (e.g., L-dopa) and, in this application specifically, enhanced the central nervous system and/or systemic bioavailability of such drugs.

In vivo, ex vivo and in vitro assessment of buccal permeation of drugs from delivery systems

2019 ◽  
Vol 17 (1) ◽  
pp. 33-48 ◽  
Author(s):  
Soraia Pinto ◽  
Manuela E Pintado ◽  
Bruno Sarmento
Keyword(s):  
Ex Vivo ◽  
Delivery Systems ◽  
In Vitro Assessment

scholarly journals The safety profile of Bald’s eyesalve for the treatment of bacterial infections

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Blessing O. Anonye ◽  
Valentine Nweke ◽  
Jessica Furner-Pardoe ◽  
Rebecca Gabrilska ◽  
Afshan Rafiq ◽  
...  
Keyword(s):  
Safety Profile ◽  
Bacterial Infections ◽  
Chronic Wounds ◽  
Ex Vivo ◽  
Corneal Opacity ◽  
In Vivo Models ◽  
Eye Infections ◽  
Early Medieval Period

Abstract The rise in antimicrobial resistance has prompted the development of alternatives to combat bacterial infections. Bald’s eyesalve, a remedy used in the Early Medieval period, has previously been shown to have efficacy against Staphylococcus aureus in in vitro and in vivo models of chronic wounds. However, the safety profile of Bald’s eyesalve has not yet been demonstrated, and this is vital before testing in humans. Here, we determined the safety potential of Bald’s eyesalve using in vitro, ex vivo, and in vivo models representative of skin or eye infections. We also confirmed that Bald’s eyesalve is active against an important eye pathogen, Neisseria gonorrhoeae. Low levels of cytotoxicity were observed in eyesalve-treated cell lines representative of skin and immune cells. Results from a bovine corneal opacity and permeability test demonstrated slight irritation to the cornea that resolved within 10 min. The slug mucosal irritation assay revealed that a low level of mucus was secreted by slugs indicating moderate mucosal irritation. We obtained promising results from mouse wound closure experiments; no visible signs of irritation or inflammation were observed. Our results suggest that Bald’s eyesalve could be tested further on human volunteers to assess safety for topical application against bacterial infections.

scholarly journals THE POSSIBILITIES OF USING PHAGE THERAPY IN DENTISTRY

2018 ◽  
Vol 22 (2) ◽  
pp. 107-110
Author(s):  
Maria Vladimirovna Kuchmina ◽  
A. Yu Turkina ◽  
Yu. O Paramonov
Keyword(s):  
Bacterial Cell ◽  
Phage Therapy ◽  
Periodontal Diseases ◽  
Resistant Bacteria ◽  
Clinical Use ◽  
Antibiotic Resistant ◽  
Domestic Literature ◽  
Advantages And Disadvantages

The article is devoted to the possibilities of using bacteriophages in dentistry. The main characteristics of bacteriophages and mechanisms of their interaction with a bacterial cell as well as the data of microbiological studies and the results of clinical use of bacteriophages in periodontal diseases are discussed. Bacteriophages have been shown to be effective against periodontopathogenic microorganisms, including antibiotic resistant bacteria in vitro and in vivo. There were reflected the advantages and disadvantages of phage therapy, the main of which for today is a small experience of clinical use of this method. Objective. To analyze the data of foreign and domestic literature and publications in the field of phagotherapy effectiveness in dentistry.

scholarly journals Evaluation of Phage Therapy in the Context of Enterococcus faecalis and Its Associated Diseases

Viruses ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 366 ◽  
Author(s):  
Bolocan ◽  
Upadrasta ◽  
Bettio ◽  
Clooney ◽  
Draper ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Antimicrobial Agents ◽  
Phage Therapy ◽  
Domain Architecture ◽  
The Body ◽  
In Vivo Studies ◽  
Resistant Bacteria ◽  
Antibiotic Resistant

Bacteriophages (phages) or bacterial viruses have been proposed as natural antimicrobial agents to fight against antibiotic-resistant bacteria associated with human infections. Enterococcus faecalis is a gut commensal, which is occasionally found in the mouth and vaginal tract, and does not usually cause clinical problems. However, it can spread to other areas of the body and cause life-threatening infections, such as septicemia, endocarditis, or meningitis, in immunocompromised hosts. Although E. faecalis phage cocktails are not commercially available within the EU or USA, there is an accumulated evidence from in vitro and in vivo studies that have shown phage efficacy, which supports the idea of applying phage therapy to overcome infections associated with E. faecalis. In this review, we discuss the potency of bacteriophages in controlling E. faecalis, in both in vitro and in vivo scenarios. E. faecalis associated bacteriophages were compared at the genome level and an attempt was made to categorize phages with respect to their suitability for therapeutic application, using orthocluster analysis. In addition, E. faecalis phages have been examined for the presence of antibiotic-resistant genes, to ensure their safe use in clinical conditions. Finally, the domain architecture of E. faecalis phage-encoded endolysins are discussed.

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