Editorial

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3 pages, 146 KiB

Open AccessEditorial

Microbial Infections and Wound Healing: Medicinal-Chemistry and Technological Based Approaches

by Ivana Cacciatore and Lisa Marinelli

Pharmaceutics 2024, 16(2), 168; https://doi.org/10.3390/pharmaceutics16020168 - 25 Jan 2024

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Abstract

Microbial infections represent a significant global health challenge that impacts all populations [...] Full article

(This article belongs to the Special Issue Microbial Infections and Wound Healing: Medicinal-Chemistry and Technological Based Approaches)

Research

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14 pages, 1962 KiB

Open AccessArticle

Non-Antibiotic Compounds Synergistically Kill Chronic Wound-Associated Bacteria and Disrupt Their Biofilms

by Lucy Coleman, James R. G. Adams, Will Buchanan, Tao Chen, Roberto M. La Ragione and Lian X. Liu

Pharmaceutics 2023, 15(6), 1633; https://doi.org/10.3390/pharmaceutics15061633 - 31 May 2023

Cited by 2 | Viewed by 1389

Abstract

Chronic wounds and their treatment present a significant burden to patients and healthcare systems alike, with their management further complicated by bacterial infection. Historically, antibiotics have been deployed to prevent and treat infections, but the emergence of bacterial antimicrobial resistance and the frequent [...] Read more.

Chronic wounds and their treatment present a significant burden to patients and healthcare systems alike, with their management further complicated by bacterial infection. Historically, antibiotics have been deployed to prevent and treat infections, but the emergence of bacterial antimicrobial resistance and the frequent development of biofilms within the wound area necessitates the identification of novel treatment strategies for use within infected chronic wounds. Here, several non-antibiotic compounds, polyhexamethylene biguanide (PHMB), curcumin, retinol, polysorbate 40, ethanol, and D-α-tocopheryl polyethylene glycol succinate 1000 (TPGS) were screened for their antibacterial and antibiofilm capabilities. The minimum inhibitory concentration (MIC) and crystal violet (CV) biofilm clearance against two bacteria frequently associated with infected chronic wounds, Staphylococcus aureus and Pseudomonas aeruginosa, were determined. PHMB was observed to have highly effective antibacterial activity against both bacteria, but its ability to disperse biofilms at MIC levels was variable. Meanwhile, TPGS had limited inhibitory activity but demonstrated potent antibiofilm properties. The subsequent combination of these two compounds in a formulation resulted in a synergistic enhancement of their capability to kill both S. aureus and P. aeruginosa and disperse their biofilms. Collectively, this work highlights the utility of combinatory approaches to the treatment of infected chronic wounds where bacterial colonization and biofilm formation remains significant issues. Full article

(This article belongs to the Special Issue Microbial Infections and Wound Healing: Medicinal-Chemistry and Technological Based Approaches)

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12 pages, 6385 KiB

Open AccessArticle

Lipoic Acid Conjugated Boron Hybrids Enhance Wound Healing and Antimicrobial Processes

by Hasan Türkez, Özge Çağlar Yıldırım, Sena Öner, Abdurrahim Kadı, Abdulkadir Mete, Mehmet Enes Arslan, İrfan Oğuz Şahin, Ömer Erkan Yapça and Adil Mardinoğlu

Pharmaceutics 2023, 15(1), 149; https://doi.org/10.3390/pharmaceutics15010149 - 31 Dec 2022

Cited by 4 | Viewed by 2119

Abstract

Complications of chronic non-healing wounds led to the emergence of nanotechnology-based therapies to enhance healing, facilitate tissue repair, and prevent wound-related complications like infections. Here, we design alpha lipoic acid (ALA) conjugated hexagonal boron nitride (hBN) and boron carbide (B₄C) nanoparticles [...] Read more.

Complications of chronic non-healing wounds led to the emergence of nanotechnology-based therapies to enhance healing, facilitate tissue repair, and prevent wound-related complications like infections. Here, we design alpha lipoic acid (ALA) conjugated hexagonal boron nitride (hBN) and boron carbide (B₄C) nanoparticles (NPs) to enhance wound healing in human dermal fibroblast (HDFa) cell culture and characterize its antimicrobial properties against Staphylococcus aureus (S. aureus, gram positive) and Escherichia coli (E. coli, gram negative) bacterial strains. ALA molecules are integrated onto hBN and C₄B NPs through esterification procedure, and molecular characterizations are performed by using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and UV-vis spectroscopy. Wound healing and antimicrobial properties are investigated via the use of cell viability assays, scratch test, oxidative stress, and antimicrobial activity assays. Based on our analysis, we observe that ALA-conjugated hBN NPs have the highest wound-healing feature and antimicrobial activity compared to ALA-B₄C. On the other hand, hBN, ALA-B₄C, and ALA compounds showed promising regenerative and antimicrobial properties. Also, we find that ALA conjugation enhances wound healing and antimicrobial potency of hBN and B₄C NPs. We conclude that the ALA-hBN conjugate is a potential candidate to stimulate regeneration process for injuries. Full article

(This article belongs to the Special Issue Microbial Infections and Wound Healing: Medicinal-Chemistry and Technological Based Approaches)

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10 pages, 1792 KiB

Open AccessArticle

Evaluation of Nisin-Loaded PLGA Nanoparticles Prepared with Rhamnolipid Cosurfactant against S. aureus Biofilms

by Ayşe Üstün and Serkan Örtücü

Pharmaceutics 2022, 14(12), 2756; https://doi.org/10.3390/pharmaceutics14122756 - 09 Dec 2022

Cited by 2 | Viewed by 1345

Abstract

In this article, nisin(N)-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) were prepared using the single-solvent evaporation method with a rhamnolipid(R) cosurfactant. The antibacterial–antibiofilm effects of the prepared formulation and free nisin were evaluated against S. aureus (ATCC 25923). The characterization of NPs was [...] Read more.

In this article, nisin(N)-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) were prepared using the single-solvent evaporation method with a rhamnolipid(R) cosurfactant. The antibacterial–antibiofilm effects of the prepared formulation and free nisin were evaluated against S. aureus (ATCC 25923). The characterization of NPs was analyzed using scanning electron microscopy (SEM), Zetasizer and Fourier-transform infrared spectroscopy (FTIR). The drug encapsulation efficiency and loading capacity percentages of NPs were calculated by the spectrophotometric method. The drug release of N-loaded PVA-R-PLGA NPs was determined by the dialysis bag method. The antibacterial and antibiofilm activity of N-PVA-R-PLGA NPs was determined. PVA-R-PLGA-NPs were found to be spherical with sizes of ~140 nm, according to the SEM analysis and surface charge of N-PVA-R-PLGA NPs −53.23 ± 0.42 mV. The sustained release of N (≥72% after 6 h) was measured in PVA-R-PLGA-NPs. The encapsulation efficiency percentage of N-PVA-R-PLGA NP was 78%. The MIC values of free nisin and N-PVA-R-PLGA NPs were 256 μg/mL and 64 μg/mL, respectively. The antibiofilm inhibition percentages of free nisin and N-PVA-R-PLGA NPs were 28% and 72%, respectively. These results reveal that N-PVA-R-PLGA NPs are a promising formulation for use in infections caused by S. aureus compared to free nisin. Full article

(This article belongs to the Special Issue Microbial Infections and Wound Healing: Medicinal-Chemistry and Technological Based Approaches)

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14 pages, 2075 KiB

Open AccessArticle

Development of Biocompatible Ciprofloxacin–Gold Nanoparticle Coated Sutures for Surgical Site Infections

by Sunitha Sampathi, Pankaj Kumar Tiriya, Sujatha Dodoala, Vijayabhaskarreddy Junnuthula and Sathish Dyawanapelly

Pharmaceutics 2022, 14(10), 2130; https://doi.org/10.3390/pharmaceutics14102130 - 07 Oct 2022

Cited by 3 | Viewed by 1982

Abstract

Surgical site infections (SSIs) are mainly observed after surgeries that use biomaterials. The aim of this present work was to develop ciprofloxacin hydrochloride (CPH)-loaded gold nanoparticles. These ciprofloxacin–gold nanoparticles were coated onto a sterile surgical suture using an adsorption technique, followed by rigidization [...] Read more.

Surgical site infections (SSIs) are mainly observed after surgeries that use biomaterials. The aim of this present work was to develop ciprofloxacin hydrochloride (CPH)-loaded gold nanoparticles. These ciprofloxacin–gold nanoparticles were coated onto a sterile surgical suture using an adsorption technique, followed by rigidization via ionotropic crosslinking using sodium alginate. Furthermore, UV-visible spectroscopy, infrared spectroscopy, and scanning electron microscopy were used to characterize the samples. The particle size of the nanoparticles was 126.2 ± 13.35 nm with a polydispersity index of 0.134 ± 0.03, indicating nanosize formation with a monodispersed system. As per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, stability studies were performed for 30 days under the following conditions: 2–8 °C, 25 ± 2 °C/60 ± 5% RH, and 40 ± 2 °C/75 ± 5% RH. For both Gram-negative and Gram-positive bacteria, the drug-coupled nanoparticle-laden sutures showed a twofold higher zone of inhibition compared with plain drug-coated sutures. In vitro drug release studies showed a prolonged release of up to 180 h. Hemolysis and histopathology studies displayed these sutures’ acceptable biocompatibility with the healing of tissue in Albino Swiss mice. The results depict that the use of antibiotic-coated sutures for preventing surgical site infection for a long duration could be a viable clinical option. Full article

(This article belongs to the Special Issue Microbial Infections and Wound Healing: Medicinal-Chemistry and Technological Based Approaches)

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14 pages, 3675 KiB

Open AccessArticle

Wound-Healing Promotion and Anti-Inflammatory Properties of Carvacrol Prodrugs/Hyaluronic Acid Formulations

by Lisa Marinelli, Ivana Cacciatore, Erica Costantini, Marilisa Pia Dimmito, Federica Serra, Antonio Di Stefano and Marcella Reale

Pharmaceutics 2022, 14(7), 1468; https://doi.org/10.3390/pharmaceutics14071468 - 14 Jul 2022

Cited by 3 | Viewed by 1915

Abstract

Background. Wound healing (WH) is a complex process involving several stages, such as hemostasis, inflammation, re-epithelialization, and remodeling. Many factors can impair WH, and different pharmacological approaches were studied to date, but the increase in antibiotic resistance, invasiveness, treatment duration, and high cost, [...] Read more.

Background. Wound healing (WH) is a complex process involving several stages, such as hemostasis, inflammation, re-epithelialization, and remodeling. Many factors can impair WH, and different pharmacological approaches were studied to date, but the increase in antibiotic resistance, invasiveness, treatment duration, and high cost, have often hampered the resolution of the wound. In this study, we investigated the possible application of water-soluble carvacrol prodrugs (WSCPs) and hyaluronic acid (HA) and their formulations (WSCPs/HA) to improve WH and regulate the inflammatory response. Materials and methods. Firstly, the cytotoxicity of 0.1, 1 and 10 µg/mL of HA, WSCPs and WSCPs/HA formulations were evaluated on HaCaT cells and THP-1 cell lines. The ability of WSCPs/HA formulations to modulate wound repair was evaluated in an in vitro model of WH, using HaCaT cells at 6, 18, and 24 h. The expression of WH mediators, after wound closure was determined by qRT-PCR. Following, we polarized THP-1 cells in M1/M2-like macrophages and tested the anti-inflammatory properties of WSCPs/HA formulations. After, we tested the in vitro WH model for the effects of conditioned medium (CM) from M1/M2-like cells cultured in the presence of WSCPs/HA. Results. Results showed that WSCPs/HA formulations were able to significantly raise the wound closure rate, compared to the single constituents, promoting a complete wound closure after 18 h for WSCP1/HA (10 µg/mL) and after 24 h for WSCP2/HA (10 µg/mL), modulating the MMPs, TGFβ, and COX-2 gene expression. The effects of CM derived from M1/M2 polarized cells cultured in the presence of WSCPs/HA determined WH regulation, with a better ability of the WSCP2/HA formulation to modulate the time-dependent expression of reparative and inflammatory mediators. Conclusion. Our data underline the possible application of WSCPs/HA formulations as bioactive agents for the regulation of the wound repair process by the modulation of inflammatory and remodeling phases, affecting the activity of immune cells. Full article

(This article belongs to the Special Issue Microbial Infections and Wound Healing: Medicinal-Chemistry and Technological Based Approaches)

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Review

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28 pages, 3196 KiB

Open AccessReview

Natural Compounds and Biopolymers-Based Hydrogels Join Forces to Promote Wound Healing

by Federica Falbo, Umile Gianfranco Spizzirri, Donatella Restuccia and Francesca Aiello

Pharmaceutics 2023, 15(1), 271; https://doi.org/10.3390/pharmaceutics15010271 - 12 Jan 2023

Cited by 7 | Viewed by 2215

Abstract

Rapid and complete wound healing is a clinical emergency, mainly in pathological conditions such as Type 2 Diabetes mellitus. Many therapeutic tools are not resolutive, and the research for a more efficient remedial remains a challenge. Wound dressings play an essential role in [...] Read more.

Rapid and complete wound healing is a clinical emergency, mainly in pathological conditions such as Type 2 Diabetes mellitus. Many therapeutic tools are not resolutive, and the research for a more efficient remedial remains a challenge. Wound dressings play an essential role in diabetic wound healing. In particular, biocompatible hydrogels represent the most attractive wound dressings due to their ability to retain moisture as well as ability to act as a barrier against bacteria. In the last years, different functionalized hydrogels have been proposed as wound dressing materials, showing encouraging outcomes with great benefits in the healing of the diabetic wounds. Specifically, because of their excellent biocompatibility and biodegradability, natural bioactive compounds, as well as biomacromolecules such as polysaccharides and protein, are usually employed in the biomedical field. In this review, readers can find the main discoveries regarding the employment of naturally occurring compounds and biopolymers as wound healing promoters with antibacterial activity. The emerging approaches and engineered devices for effective wound care in diabetic patients are reported and deeply investigated. Full article

(This article belongs to the Special Issue Microbial Infections and Wound Healing: Medicinal-Chemistry and Technological Based Approaches)

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41 pages, 22144 KiB

Open AccessReview

Hybrid Azine Derivatives: A Useful Approach for Antimicrobial Therapy

by Dorina Amariucai-Mantu, Violeta Mangalagiu, Iustinian Bejan, Aculina Aricu and Ionel I. Mangalagiu

Pharmaceutics 2022, 14(10), 2026; https://doi.org/10.3390/pharmaceutics14102026 - 23 Sep 2022

Cited by 6 | Viewed by 1367

Abstract

Nowadays, infectious diseases caused by microorganisms are a major threat to human health, mostly because of drug resistance, multi-drug resistance and extensive-drug-resistance phenomena to microbial pathogens. During the last few years, obtaining hybrid azaheterocyclic drugs represents a powerful and attractive approach in modern [...] Read more.

Nowadays, infectious diseases caused by microorganisms are a major threat to human health, mostly because of drug resistance, multi-drug resistance and extensive-drug-resistance phenomena to microbial pathogens. During the last few years, obtaining hybrid azaheterocyclic drugs represents a powerful and attractive approach in modern antimicrobial therapy with very promising results including overcoming microbial drug resistance. The emphasis of this review is to notify the scientific community about the latest recent advances from the last five years in the field of hybrid azine derivatives with antimicrobial activity. The review is divided according to the main series of six-member ring azaheterocycles with one nitrogen atom and their fused analogs. In each case, the main essential data concerning synthesis and antimicrobial activity are presented. Full article

(This article belongs to the Special Issue Microbial Infections and Wound Healing: Medicinal-Chemistry and Technological Based Approaches)

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