Research

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14 pages, 2589 KiB

Open AccessArticle

Ciprofloxacin-Loaded Polyvinylpyrrolidone Foils for the Topical Treatment of Wound Infections with Methicillin-Resistant Staphylococcus aureus (MRSA)

by Fiorenza Rancan, Jana Jurisch, Sabrina Hadam, Annika Vogt, Ulrike Blume-Peytavi, Ilker S. Bayer, Marco Contardi and Christoph Schaudinn

Pharmaceutics 2023, 15(7), 1876; https://doi.org/10.3390/pharmaceutics15071876 - 03 Jul 2023

Cited by 2 | Viewed by 1450

Abstract

Bacterial infections are a constant challenge in the management of acute and chronic wounds. Chronic wounds, such as diabetic foot ulcers, have increased significantly in the last few years due to the rise of an aging population. A better understanding of the infectious [...] Read more.

Bacterial infections are a constant challenge in the management of acute and chronic wounds. Chronic wounds, such as diabetic foot ulcers, have increased significantly in the last few years due to the rise of an aging population. A better understanding of the infectious pathophysiological mechanisms is urgently needed along with new options for the treatment of wound infections and wound-healing disorders. New advances in the preparation of biocompatible dressing materials that can be loaded with antimicrobial drugs may improve the topical treatment of infected wounds. In this study, we investigated the antimicrobial activity of polyvinylpyrrolidone (PVP) foils loaded with ciprofloxacin (Cipro-foils) in the presence of acetic acid as a co-solvent. We used ex vivo human wounds that were infected with two bacterial strains: methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa (PAO1). The effectiveness of the treatment was demonstrated by the quantification of the living bacteria extracted from the wound and the detection of released immunological mediators in skin extracts and in the skin culture media. We found that Cipro-foils effectively treated the infection with both PAO1 and MRSA. Other than PAO1, MRSA had no lytic activity toward skin proteins. MRSA infections increased cytokines’ expression and release. Interestingly, treatment with Cipro-foils could partially counteract these effects. Full article

(This article belongs to the Special Issue Wound Care: From Traditional Cotton Wound Dressings to Innovative Wound Dressings)

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13 pages, 2732 KiB

Open AccessArticle

Therapeutic Application of an Ag-Nanoparticle-PNIPAAm-Modified Eggshell Membrane Construct for Dermal Regeneration and Reconstruction

by Emily Briggs, Rosemond A. Mensah, Kapil D. Patel, Nandin-Erdene Mandakhbayar, Nik San Sharifulden, Zalike Keskin Erdogan, Lady V. Barrios Silva, Kawther Salim, Hae-Won Kim, Linh T. B. Nguyen and David Y. S. Chau

Pharmaceutics 2022, 14(10), 2162; https://doi.org/10.3390/pharmaceutics14102162 - 11 Oct 2022

Cited by 6 | Viewed by 2167

Abstract

Current therapeutic treatments for the repair and/or replacement of damaged skin following disease or traumatic injury is severely limited. The chicken eggshell membrane (ESM) is a unique material: its innate physical and mechanical characteristics offer optimal barrier properties and, as a naturally derived [...] Read more.

Current therapeutic treatments for the repair and/or replacement of damaged skin following disease or traumatic injury is severely limited. The chicken eggshell membrane (ESM) is a unique material: its innate physical and mechanical characteristics offer optimal barrier properties and, as a naturally derived extract, it demonstrates inherent biocompatibility/biodegradability. To further enhance its therapeutic and clinical potential, the ESM can be modified with the thermo-responsive polymer, poly(N-isopropylacrylAmide) (PNIPAAm) as well as the incorporation of (drug-loaded) silver nanoparticles (AgNP); essentially, by a simple change in temperature, the release and delivery of the NP can be targeted and controlled. In this study, ESM samples were isolated using a decellularization protocol, and the physical and mechanical characteristics were profiled using SEM, FT-IR, DSC and DMA. PNIPAAm was successfully grafted to the ESM via amidation reactions and confirmed using FT-IR, which demonstrated the distinctive peaks associated with Amide A (3275 cm⁻¹), Amide B (2970 cm⁻¹), Amide I (1630 cm⁻¹), Amide II (1535 cm⁻¹), CH₂, CH₃ groups, and Amide III (1250 cm⁻¹) peaks. Confirmation of the incorporation of AgNP onto the stratified membrane was confirmed visually with SEM, qualitatively using FT-IR and also via changes in absorbance at 380 nm using UV-Vis spectrophotometry during a controlled release study for 72 h. The biocompatibility and cytotoxicity of the novel constructs were assessed using human dermal fibroblast (HDFa) and mouse dermal fibroblast (L929) cells and standard cell culture assays. Metabolic activity assessment (i.e., MTS assay), LDH-release profiles and Live/Dead staining demonstrated good attachment and spreading to the samples, and high cell viability following 3 days of culture. Interestingly, longer-term viability (>5 days), the ESM-PNIPAAm and ESM-PNIPAAm (AgNP) samples showed a greater and sustained cell viability profile. In summary, the modified and enhanced ESM constructs were successfully prepared and characterized in terms of their physical and mechanical profiles. AgNP were successfully loaded into the construct and demonstrated a desirable release profile dependent on temperature modulation. Fibroblasts cultured on the extracted ESM samples and ESM-PNIPAAm demonstrated high biocompatibility in terms of high cell attachment, spreading, viability and proliferation rates. As such, this work summarizes the development of an enhanced ESM-based construct which may be exploited as a clinical/therapeutic wound dressing as well as a possible application as a novel biomaterial scaffold for drug development. Full article

(This article belongs to the Special Issue Wound Care: From Traditional Cotton Wound Dressings to Innovative Wound Dressings)

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14 pages, 25865 KiB

Open AccessEditor’s ChoiceArticle

Evaluation of Antioxidant and Wound-Healing Properties of EHO-85, a Novel Multifunctional Amorphous Hydrogel Containing Olea europaea Leaf Extract

by Antonio Casado-Diaz, José Manuel Moreno-Rojas, José Verdú-Soriano, José Luis Lázaro-Martínez, Leocadio Rodríguez-Mañas, Isaac Tunez, Manuel La Torre, Miriam Berenguer Pérez, Feliciano Priego-Capote and Gema Pereira-Caro

Pharmaceutics 2022, 14(2), 349; https://doi.org/10.3390/pharmaceutics14020349 - 01 Feb 2022

Cited by 16 | Viewed by 3571

Abstract

The excess of free radicals in the wound environment contributes to its stagnation during the inflammatory phase, favoring hard-to-heal wounds. Oxidative stress negatively affects cells and the extracellular matrix, hindering the healing process. In this study, we evaluated the antioxidant and wound-healing properties [...] Read more.

The excess of free radicals in the wound environment contributes to its stagnation during the inflammatory phase, favoring hard-to-heal wounds. Oxidative stress negatively affects cells and the extracellular matrix, hindering the healing process. In this study, we evaluated the antioxidant and wound-healing properties of a novel multifunctional amorphous hydrogel-containing Olea europaea leaf extract (OELE). Five assessments were performed: (i) phenolic compounds characterization in OELE; (ii) absolute antioxidant activity determination in OELE and hydrogel (EHO-85); (iii) antioxidant activity measurement of OELE and (iv) its protective effect on cell viability on human dermal fibroblasts (HDFs) and keratinocytes (HaCaT); and (v) EHO-85 wound-healing-capacity analysis on diabetic mice (db/db; BKS.Cg-m+/+Leprdb). The antioxidant activity of OELE was prominent: 2220, 1558, and 1969 µmol TE/g by DPPH, ABTS, and FRAP assays, respectively. Oxidative stress induced with H₂O₂ in HDFs and HaCaT was normalized, and their viability increased with OELE co-treatment, thus evidencing a protective role. EHO-85 produced an early and sustained wound-healing stimulating effect superior to controls in diabetic mice. This novel amorphous hydrogel presents an important ROS scavenger capacity due to the high phenolic content of OELE, which protects skin cells from oxidative stress and contributes to the physiological process of wound healing. Full article

(This article belongs to the Special Issue Wound Care: From Traditional Cotton Wound Dressings to Innovative Wound Dressings)

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18 pages, 4200 KiB

Open AccessArticle

Nitric Oxide-Releasing Bacterial Cellulose/Chitosan Crosslinked Hydrogels for the Treatment of Polymicrobial Wound Infections

by Nurhasni Hasan, Juho Lee, Hye-Jin Ahn, Wook Ryol Hwang, Muhammad Akbar Bahar, Habibie Habibie, Muhammad Nur Amir, Subehan Lallo, Hong-Joo Son and Jin-Wook Yoo

Pharmaceutics 2022, 14(1), 22; https://doi.org/10.3390/pharmaceutics14010022 - 22 Dec 2021

Cited by 13 | Viewed by 3625

Abstract

Polymicrobial wound infections are a major cause of infectious disease-related morbidity and mortality worldwide. In this study, we prepared a nitric oxide (NO)-releasing oxidized bacterial cellulose/chitosan (BC_TO/CHI) crosslinked hydrogel to effectively treat polymicrobial wound infections. Linear polyethyleneimine diazeniumdiolate (PEI/NO) was used [...] Read more.

Polymicrobial wound infections are a major cause of infectious disease-related morbidity and mortality worldwide. In this study, we prepared a nitric oxide (NO)-releasing oxidized bacterial cellulose/chitosan (BC_TO/CHI) crosslinked hydrogel to effectively treat polymicrobial wound infections. Linear polyethyleneimine diazeniumdiolate (PEI/NO) was used as the NO donor. The aldehyde group of BC_TO and the amine of CHI were used as crosslinked hydrogel-based materials; their high NO loading capacity and antibacterial activity on the treatment of polymicrobial-infected wounds were investigated. The blank and NO-loaded crosslinked hydrogels, namely BC_TO-CHI and BC_TO-CHI-PEI/NO, were characterized according to their morphologies, chemical properties, and drug loading. BC_TO-CHI-PEI/NO exhibited sustained drug release over four days. The high NO loading of BC_TO-CHI-PEI/NO enhanced the bactericidal efficacy against multiple bacteria compared with BC_TO-CHI. Furthermore, compared with blank hydrogels, BC_TO-CHI-PEI/NO has a favorable rheological property due to the addition of a polymer-based NO donor. Moreover, BC_TO-CHI-PEI/NO significantly accelerated wound healing and re-epithelialization in a mouse model of polymicrobial-infected wounds. We also found that both crosslinked hydrogels were nontoxic to healthy mammalian fibroblast cells. Therefore, our data suggest that the BC_TO-CHI-PEI/NO developed in this study improves the efficacy of NO in the treatment of polymicrobial wound infections. Full article

(This article belongs to the Special Issue Wound Care: From Traditional Cotton Wound Dressings to Innovative Wound Dressings)

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18 pages, 3796 KiB

Open AccessArticle

Development of Spanish Broom and Flax Dressings with Glycyrrhetinic Acid-Loaded Films for Wound Healing: Characterization and Evaluation of Biological Properties

by Angela Abruzzo, Concettina Cappadone, Valentina Sallustio, Giovanna Picone, Martina Rossi, Fiore Pasquale Nicoletta, Barbara Luppi, Federica Bigucci and Teresa Cerchiara

Pharmaceutics 2021, 13(8), 1192; https://doi.org/10.3390/pharmaceutics13081192 - 03 Aug 2021

Cited by 6 | Viewed by 2370

Abstract

The selection of an appropriate dressing for each type of wound is a very important procedure for a faster and more accurate healing process. So, the aim of this study was to develop innovative Spanish Broom and flax wound dressings, as alternatives to [...] Read more.

The selection of an appropriate dressing for each type of wound is a very important procedure for a faster and more accurate healing process. So, the aim of this study was to develop innovative Spanish Broom and flax wound dressings, as alternatives to cotton used as control, with polymeric films containing glycyrrhetinic acid (GA) to promote wound-exudate absorption and the healing process. The different wound dressings were prepared by a solvent casting method, and characterized in terms of drug loading, water uptake, and in vitro release. Moreover, biological studies were performed to evaluate their biocompatibility and wound-healing efficacy. Comparing the developed wound dressings, Spanish Broom dressings with GA-loaded sodium hyaluronate film had the best functional properties, in terms of hydration ability and GA release. Moreover, they showed a good biocompatibility, determining a moderate induction of cell proliferation and no cytotoxicity. In addition, the wound-healing test revealed that the Spanish Broom dressings promoted cell migration, further facilitating the closure of the wound. Full article

(This article belongs to the Special Issue Wound Care: From Traditional Cotton Wound Dressings to Innovative Wound Dressings)

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17 pages, 9078 KiB

Open AccessArticle

Bacterial Cellulose Containing Combinations of Antimicrobial Peptides with Various QQ Enzymes as a Prototype of an “Enhanced Antibacterial” Dressing: In Silico and In Vitro Data

by Aysel Aslanli, Ilya Lyagin, Nikolay Stepanov, Denis Presnov and Elena Efremenko

Pharmaceutics 2020, 12(12), 1155; https://doi.org/10.3390/pharmaceutics12121155 - 27 Nov 2020

Cited by 15 | Viewed by 2084

Abstract

To improve the action of already in use antibiotics or new antimicrobial agents against different bacteria, the development of effective combinations of antimicrobial peptides (AMPs) with enzymes that can quench the quorum (QQ) sensing of bacterial cells was undertaken. Enzymes hydrolyzing N-acyl [...] Read more.

To improve the action of already in use antibiotics or new antimicrobial agents against different bacteria, the development of effective combinations of antimicrobial peptides (AMPs) with enzymes that can quench the quorum (QQ) sensing of bacterial cells was undertaken. Enzymes hydrolyzing N-acyl homoserine lactones (AHLs) and peptides that are signal molecules of Gram-negative and Gram-positive bacterial cells, respectively, were estimated as “partners” for antibiotics and antimicrobial peptides in newly designed antimicrobial–enzymatic combinations. The molecular docking of six antimicrobial agents to the surface of 10 different QQ enzyme molecules was simulated in silico. This made it possible to choose the best variants among the target combinations. Further, bacterial cellulose (BC) was applied as a carrier for uploading such combinations to generally compose prototypes of effective dressing materials with morphology, providing good absorbance. The in vitro analysis of antibacterial activity of prepared BC samples confirmed the significantly enhanced efficiency of the action of AMPs (including polymyxin B and colistin, which are antibiotics of last resort) in combination with AHL-hydrolyzing enzymes (penicillin acylase and His₆-tagged organophosphorus hydrolase) against both Gram-negative and Gram-positive cells. Full article

(This article belongs to the Special Issue Wound Care: From Traditional Cotton Wound Dressings to Innovative Wound Dressings)

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Review

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47 pages, 6340 KiB

Open AccessReview

In Vitro and In Vivo Characterization Methods for Evaluation of Modern Wound Dressings

by Naveed Ahmad

Pharmaceutics 2023, 15(1), 42; https://doi.org/10.3390/pharmaceutics15010042 - 22 Dec 2022

Cited by 14 | Viewed by 5910

Abstract

Chronic wound management represents a major challenge in the healthcare sector owing to its delayed wound-healing process progression and huge financial burden. In this regard, wound dressings provide an appropriate platform for facilitating wound healing for several decades. However, adherent traditional wound dressings [...] Read more.

Chronic wound management represents a major challenge in the healthcare sector owing to its delayed wound-healing process progression and huge financial burden. In this regard, wound dressings provide an appropriate platform for facilitating wound healing for several decades. However, adherent traditional wound dressings do not provide effective wound healing for highly exudating chronic wounds and need the development of newer and innovative wound dressings to facilitate accelerated wound healing. In addition, these dressings need frequent changing, resulting in more pain and discomfort. In order to overcome these issues, a wide range of affordable and innovative modern wound dressings have been developed and explored recently to accelerate and improve the wound healing process. However, a comprehensive understanding of various in vitro and in vivo characterization methods being utilized for the evaluation of different modern wound dressings is lacking. In this context, an overview of modern dressings and their complete in vitro and in vivo characterization methods for wound healing assessment is provided in this review. Herein, various emerging modern wound dressings with advantages and challenges have also been reviewed. Furthermore, different in vitro wound healing assays and in vivo wound models being utilized for the evaluation of wound healing progression and wound healing rate using wound dressings are discussed in detail. Finally, a summary of modern wound dressings with challenges and the future outlook is highlighted. Full article

(This article belongs to the Special Issue Wound Care: From Traditional Cotton Wound Dressings to Innovative Wound Dressings)

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25 pages, 2602 KiB

Open AccessReview

Electrospun Asymmetric Membranes as Promising Wound Dressings: A Review

by Mariana F. P. Graça, Duarte de Melo-Diogo, Ilídio J. Correia and André F. Moreira

Pharmaceutics 2021, 13(2), 183; https://doi.org/10.3390/pharmaceutics13020183 - 30 Jan 2021

Cited by 36 | Viewed by 4634

Abstract

Despite all the efforts that have been done up to now, the currently available wound dressings are still unable to fully re-establish all the structural and functional properties of the native skin. To overcome this situation, researchers from the tissue engineering area have [...] Read more.

Despite all the efforts that have been done up to now, the currently available wound dressings are still unable to fully re-establish all the structural and functional properties of the native skin. To overcome this situation, researchers from the tissue engineering area have been developing new wound dressings (hydrogels, films, sponges, membranes) aiming to mimic all the features of native skin. Among them, asymmetric membranes emerged as a promising solution since they reproduce both epidermal and dermal skin layers. Wet or dry/wet phase inversion, scCO₂-assisted phase inversion, and electrospinning have been the most used techniques to produce such a type of membranes. Among them, the electrospinning technique, due to its versatility, allows the development of multifunctional dressings, using natural and/or synthetic polymers, which resemble the extracellular matrix of native skin as well as address the specific requirements of each skin layer. Moreover, various therapeutic or antimicrobial agents have been loaded within nanofibers to further improve the wound healing performance of these membranes. This review article provides an overview of the application of asymmetric electrospun membranes as wound dressings displaying antibacterial activity and as delivery systems of biomolecules that act as wound healing enhancers. Full article

(This article belongs to the Special Issue Wound Care: From Traditional Cotton Wound Dressings to Innovative Wound Dressings)

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