Special Issue "Local Antibacterial and Antimicrobial Drug Delivery Systems"

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (10 October 2021).

Special Issue Editor

Dr. Karin Kogermann
E-Mail Website
Guest Editor
Institute of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, 50411 Tartu, Estonia
Interests: electrospinning; nanofibers/microfibers; antibacterial and antimicrobial drugs; delivery systems; wound healing; wound infection; action mechanisms; in vitro/in vivo infection models; solid state characterization; process analytical technology
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Special Issue Information

Dear Colleagues,

Antibiotic resistance is a huge problem for society, and it is rising to dangerously high levels in all parts of the world. Conventional antibiotics are becoming ineffective against microorganisms due to their widespread and often inappropriate use. New treatments are constantly sought in order to successfully fight against microbial infections and biofilms and avoid the development of resistance. In addition to new drug molecules and new action mechanisms, novel local drug delivery systems are being developed that enable the improvement of the specificity and bioactivity of antibacterial/antimicrobial agents and reduction of the probability of possible side-effects.

The design and development of local drug delivery systems need to be conducted considering the biorelevant testing conditions which enable the in vivo conditions to be mimicked. Furthermore, the selection of suitable carrier systems requires thorough analysis in order to improve the therapeutic outcome and achieve the desired safety, biocompatibility, and biodegradability. In several cases, carriers themselves may have additional bioactivity.

This Special Issue aims to cover different aspects of the development of local antibacterial and antimicrobial drug delivery systems, and will include papers describing the design, preparation, and characterization of these systems and the latest developments in this field. Production scale-up and the sterilization of drug delivery systems require a great deal attention. New and promising strategies that allow antibacterial/antimicrobial therapies and patients’ quality of life to be improved are specifically welcome.

Authors are invited to submit original research articles and reviews in this important and exciting research field.

Ass. Prof. Karin Kogermann
Guest Editor

Manuscript Submission Information

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Keywords

  • drug design
  • local drug delivery systems
  • antimicrobial agent delivery
  • antibacterial agent delivery
  • biopolymers
  • biomaterials
  • nanomedicine
  • nanoparticles
  • electrospun fibers/scaffolds
  • drug–polymer–fiber interactions
  • printed systems
  • antibacterial/antimicrobial activity
  • sterility, safety, and efficacy

Published Papers (16 papers)

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Research

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Article
Evaluation of the Influence of a Hydrogel Containing AMPD on the Stability of Tetracycline Hydrochloride
Pharmaceutics 2021, 13(9), 1381; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091381 - 01 Sep 2021
Viewed by 490
Abstract
Tetracyclines, as beneficial antimicrobial factors in both local and systemic therapy, are characterized by high instability. The aim of the study was the development of the influence of hydrogel formulation on the tetracycline hydrochloride (TC) level under varying storage conditions. The HPLC, XPRD [...] Read more.
Tetracyclines, as beneficial antimicrobial factors in both local and systemic therapy, are characterized by high instability. The aim of the study was the development of the influence of hydrogel formulation on the tetracycline hydrochloride (TC) level under varying storage conditions. The HPLC, XPRD as well as SEM and macroscopic observations were involved in the study. The TC concentration decreased within ca. two months from 9.37 µg/mL to 4.41 µg/mL in the case of the photoprotected TC solution stored at 23 °C, whereas the decrease in storage temperature did not improve the final level of TC. In the presence of AMPD, the TC level in aqueous solution decreased drastically to ca. 1 µg/mL. Application of a polyacrylic acid derivative enabled conservation of the TC level through the ca. two months. Thus, the use of alcoholamine in the preparation of the TC hydrogel may result in the development of a therapeutic product with a dual action against acne, including antimicrobial activity and saponification of free fatty acids deposited in the follicles. Full article
(This article belongs to the Special Issue Local Antibacterial and Antimicrobial Drug Delivery Systems)
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Article
Staphylococcus aureus Specific Electrospun Wound Dressings: Influence of Immobilization Technique on Antibacterial Efficiency of Novel Enzybiotic
Pharmaceutics 2021, 13(5), 711; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13050711 - 13 May 2021
Cited by 1 | Viewed by 637
Abstract
The spread of antimicrobial resistance requires the development of novel strategies to combat superbugs. Bacteriolytic enzymes (enzybiotics) that selectively eliminate pathogenic bacteria, including resistant strains and biofilms, are attractive alternatives to antibiotics, also as a component of a new generation of antimicrobial wound [...] Read more.
The spread of antimicrobial resistance requires the development of novel strategies to combat superbugs. Bacteriolytic enzymes (enzybiotics) that selectively eliminate pathogenic bacteria, including resistant strains and biofilms, are attractive alternatives to antibiotics, also as a component of a new generation of antimicrobial wound dressings. AuresinePlus is a novel, engineered enzybiotic effective against Staphylococcus aureus—one of the most common pathogenic bacteria, found in infected wounds with a very high prevalence of antibiotic resistance. We took advantage of its potent lytic activity, selectivity, and safety to prepare a set of biodegradable PLGA/chitosan fibers generated by electrospinning. Our aim was to produce antimicrobial nonwovens to deliver enzybiotics directly to the infected wound and better control its release and activity. Three different methods of enzyme immobilization were tested: physical adsorption on the previously hydrolyzed surface, and covalent bonding formation using N-hydroxysuccinimide/N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide (NHS/EDC) or glutaraldehyde (GA). The supramolecular structure and functional properties analysis revealed that the selected methods resulted in significant development of nanofibers surface topography resulting in an efficient enzybiotic attachment. Both physically adsorbed and covalently bound enzymes (by NHS/EDC method) exhibited prominent antibacterial activity. Here, we present the extensive comparison between methods for the effective attachment of the enzybiotic to the electrospun nonwovens to generate biomaterials effective against antibiotic-resistant strains. Our intention was to present a comprehensive proof-of-concept study for future antimicrobial wound dressing development. Full article
(This article belongs to the Special Issue Local Antibacterial and Antimicrobial Drug Delivery Systems)
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Article
Development of Cephradine-Loaded Gelatin/Polyvinyl Alcohol Electrospun Nanofibers for Effective Diabetic Wound Healing: In-Vitro and In-Vivo Assessments
Pharmaceutics 2021, 13(3), 349; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13030349 - 07 Mar 2021
Cited by 4 | Viewed by 765
Abstract
Diabetic wound infections caused by conventional antibiotic-resistant Staphylococcus aureus strains are fast emerging, leading to life-threatening situations (e.g., high costs, morbidity, and mortality) associated with delayed healing and chronic inflammation. Electrospinning is one of the most widely used techniques for the fabrication of [...] Read more.
Diabetic wound infections caused by conventional antibiotic-resistant Staphylococcus aureus strains are fast emerging, leading to life-threatening situations (e.g., high costs, morbidity, and mortality) associated with delayed healing and chronic inflammation. Electrospinning is one of the most widely used techniques for the fabrication of nanofibers (NFs), induced by a high voltage applied to a drug-loaded polymer solution. Particular attention is given to electrospun NFs for pharmaceutical applications (e.g., original drug delivery systems) and tissue regeneration (e.g., as tissue scaffolds). However, there is a paucity of reports related to their application in diabetic wound infections. Therefore, we prepared eco-friendly, biodegradable, low-immunogenic, and biocompatible gelatin (GEL)/polyvinyl alcohol (PVA) electrospun NFs (BNFs), in which we loaded the broad-spectrum antibiotic cephradine (Ceph). The resulting drug-loaded NFs (LNFs) were characterized physically using ultraviolet-visible (UV-Vis) spectrophotometry (for drug loading capacity (LC), drug encapsulation efficiency (EE), and drug release kinetics determination), thermogravimetric analysis (TGA) (for thermostability evaluation), scanning electron microscopy (SEM) (for surface morphology analysis), and Fourier-transform infrared spectroscopy (FTIR) (for functional group identification). LNFs were further characterized biologically by in-vitro assessment of their potency against S. aureus clinical strains (N = 16) using the Kirby–Bauer test and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, by ex-vivo assessment to evaluate their cytotoxicity against primary human epidermal keratinocytes using MTT assay, and by in-vivo assessment to estimate their diabetic chronic wound-healing efficiency using NcZ10 diabetic/obese mice (N = 18). Thin and uniform NFs with a smooth surface and standard size (<400 nm) were observed by SEM at the optimized 5:5 (GEL:PVA) volumetric ratio. FTIR analyses confirmed the drug loading into BNFs. Compared to free Ceph, LNFs were significantly more thermostable and exhibited sustained/controlled Ceph release. LNFs also exerted a significantly stronger antibacterial activity both in-vitro and in-vivo. LNFs were significantly safer and more efficient for bacterial clearance-induced faster chronic wound healing. LNF-based therapy could be employed as a valuable dressing material to heal S. aureus-induced chronic wounds in diabetic subjects. Full article
(This article belongs to the Special Issue Local Antibacterial and Antimicrobial Drug Delivery Systems)
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Article
Assessment of Antimicrobic, Antivirotic and Cytotoxic Potential of Alginate Beads Cross-Linked by Bivalent Ions for Vaginal Administration
Pharmaceutics 2021, 13(2), 165; https://doi.org/10.3390/pharmaceutics13020165 - 27 Jan 2021
Viewed by 598
Abstract
Antimicrobial agent abuse poses a serious threat for future pharmacotherapy, including vaginal administration. The solution can be found in simple polymeric systems with inherent antimicrobial properties without the need to incorporate drugs, for instance alginate beads cross-linked by bivalent ions. The main goal [...] Read more.
Antimicrobial agent abuse poses a serious threat for future pharmacotherapy, including vaginal administration. The solution can be found in simple polymeric systems with inherent antimicrobial properties without the need to incorporate drugs, for instance alginate beads cross-linked by bivalent ions. The main goal of the presented study was to provide improvement on the well-documented cytotoxicity of Cu2+ cross-linked alginate. Alginate beads were prepared by external ionotropic gelation by cross-linking with Cu2+, Ca2+ and Zn2+ ions, separately and in mixtures. Morphological properties, swelling capacity, ion release and efficacy against the most common vaginal pathogens (C. albicans, E. coli, E. faecalis and virus strain—human herpesvirus type 1) were evaluated. The prepared particles (particle size 1455.68 ± 18.71–1756.31 ± 16.58 µm) had very good sphericity (0.86 ± 0.04–0.97 ± 0.06). In mixture samples, Cu2+ hampered second ion loading, and was also released incompletely (18.75–44.8%) compared to the single ion Cu2+ sample (71.4%). Efficacy against the selected pathogens was confirmed in almost all samples. Although anticipating otherwise, ion mixture samples did not show betterment over a Cu2+ cross-linked sample in cytotoxicity–pathogen efficacy relation. However, the desired improvement was found in a single ion Zn2+ sample whose minimal inhibition concentrations against the pathogens (0.6–6.12 mM) were close to, or in the same mathematical order as, its toxic concentration of 50 (1.891 mM). In summary, these findings combined with alginate’s biocompatibility and biodegradability give the combination solid potential in antimicrobial use. Full article
(This article belongs to the Special Issue Local Antibacterial and Antimicrobial Drug Delivery Systems)
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Article
Au–ZnO Conjugated Black Phosphorus as a Near-Infrared Light-Triggering and Recurrence-Suppressing Nanoantibiotic Platform against Staphylococcus aureus
Pharmaceutics 2021, 13(1), 52; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13010052 - 02 Jan 2021
Cited by 3 | Viewed by 911
Abstract
Antibiotic therapy is the gold standard for bacterial infections treatment. However, the rapid increase in multidrug-resistant (MDR) bacterial infections and its recent use for secondary bacterial infections in many COVID-19 patients has considerably weakened its treatment efficacy. These shortcomings motivated researchers to develop [...] Read more.
Antibiotic therapy is the gold standard for bacterial infections treatment. However, the rapid increase in multidrug-resistant (MDR) bacterial infections and its recent use for secondary bacterial infections in many COVID-19 patients has considerably weakened its treatment efficacy. These shortcomings motivated researchers to develop new antibacterial materials, such as nanoparticle-based antibacterial platform with the ability to increase the chances of killing MDR strains and prevent their drug resistance. Herein, we report a new black phosphorus (BP)-based non-damaging near-infrared light-responsive platform conjugated with ZnO and Au nanoparticles as a synergistic antibacterial agent against Staphylococcus aureus species. First, BP nanosheets containing Au nanoparticles were assembled in situ with the ZnO nanoparticles prepared by a low-temperature solution synthesis method. Subsequently, the antibacterial activities of the resulting Au–ZnO–BP nanocomposite against the non-resistant, methicillin-resistant, and erythromycin-resistant S. aureus species were determined, after its photothermal efficacy was assessed. The synthesized nanocomposite exhibited excellent anti-S. aureus activity and good photothermal characteristics. The non-resistant S. aureus species did not produce drug-resistant bacteria after the treatment of multiple consecutive passages under the pressure of the proposed nanoantibiotic, but rapidly developed resistance to erythromycin. This work clearly demonstrates the excellent photothermal antibacterial properties of Au–ZnO–BP nanocomposite against the MDR S. aureus species. Full article
(This article belongs to the Special Issue Local Antibacterial and Antimicrobial Drug Delivery Systems)
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Article
Liposomes-In-Hydrogel Delivery System Enhances the Potential of Resveratrol in Combating Vaginal Chlamydia Infection
Pharmaceutics 2020, 12(12), 1203; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12121203 - 11 Dec 2020
Cited by 3 | Viewed by 895
Abstract
Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infections and causes serious reproductive tract complications among women. The limitations of existing oral antibiotics and treatment of antimicrobial resistance require alternative treatment options. We are proposing, for the first time, the [...] Read more.
Chlamydia trachomatis is the most common cause of bacterial sexually transmitted infections and causes serious reproductive tract complications among women. The limitations of existing oral antibiotics and treatment of antimicrobial resistance require alternative treatment options. We are proposing, for the first time, the natural polyphenol resveratrol (RES) in an advanced delivery system comprising liposomes incorporated in chitosan hydrogel, for the localized treatment of C. trachomatis infection. Both free RES and RES liposomes-in-hydrogel inhibited the propagation of C. trachomatis in a concentration-dependent manner, assessed by the commonly used in vitro model comprising McCoy cells. However, for lower concentrations, the anti-chlamydial effect of RES was enhanced when incorporated into a liposomes-in-hydrogel delivery system, with inhibition of 78% and 94% for 1.5 and 3 µg/mL RES, respectively for RES liposomes-in-hydrogel, compared to 43% and 72%, respectively, for free RES. Furthermore, RES liposomes-in-hydrogel exhibited strong anti-inflammatory activity in vitro, in a concentration-dependent inhibition of nitric oxide production in the LPS-induced macrophages (RAW 264.7). The combination of a natural substance exhibiting multi-targeted pharmacological properties, and a delivery system that provides enhanced activity as well as applicability for vaginal administration, could be a promising option for the localized treatment of C. trachomatis infection. Full article
(This article belongs to the Special Issue Local Antibacterial and Antimicrobial Drug Delivery Systems)
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Article
Efficacy of Local Minocycline Agents in Treating Peri-Implantitis: An Experimental In Vivo Study in Beagle Dogs
Pharmaceutics 2020, 12(11), 1016; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12111016 - 23 Oct 2020
Viewed by 710
Abstract
Background: Local delivery agents (LDA) have the advantage of delivering the antibiotics at high concentrations to the targeted sites. However, the constant flow of gingival crevicular fluids and saliva may restrict their efficacy. Therefore, the drug sustainability and pharmacodynamic properties of any proposed [...] Read more.
Background: Local delivery agents (LDA) have the advantage of delivering the antibiotics at high concentrations to the targeted sites. However, the constant flow of gingival crevicular fluids and saliva may restrict their efficacy. Therefore, the drug sustainability and pharmacodynamic properties of any proposed LDA should be evaluated. Methods: Four dental implants were placed unilaterally in the edentulous mandible of six beagle dogs. Peri-implantitis were experimentally induced using silk-ligatures. Each implant was randomly allocated to receive one of the following four treatments: (i) MC (Chitosan-alginate (CA) minocycline), (ii) MP (CA-without minocycline), (iii) PG (Polyacrylate-glycerin minocycline), and (iv) Control (mechanical debridement only). Mechanical therapies and LDAs were administered into the gingival sulcus two times at a 4-week interval. Drug sustainability as well as clinical, radiographical, and immunohistochemical (IHC) analyses were conducted to evaluate the efficacies of treatments. Results: Reduced mean probing depth was observed in all of the test groups after the second delivery. A minimal marginal bone level change was observed during the treatment period (MP (−0.06 ± 0.53 mm) to PG (−0.25 ± 0.42 mm)). The distribution of IHC cell marker analysis of all targeted antibodies ranged from 6.34% to 11.33%. All treatment outcomes between the test groups were comparable. A prolonged retention of LDA was observed from CA microspheres (MC and MP) at both administrations (p < 0.017) and prolonged sustainability of bacteriostatic effect was observed from MC compared to PG after the second administration (p < 0.05). Conclusions: Prolonged retention of CA microspheres was observed and the longer bacteriostatic effect was observed from the MC group. Mechanical debridement with adjunct LDA therapy may impede peri-implantitis progression, however, prolonged drug action did not lead to improved treatment outcome. Full article
(This article belongs to the Special Issue Local Antibacterial and Antimicrobial Drug Delivery Systems)
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Article
Poly(Aspartic Acid) Functionalized Poly(ϵ-Caprolactone) Microspheres with Enhanced Hydroxyapatite Affinity as Bone Targeting Antibiotic Carriers
Pharmaceutics 2020, 12(9), 885; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12090885 - 17 Sep 2020
Cited by 4 | Viewed by 947
Abstract
Bone infection is a feared complication for patients with surgically fixed bone fractures and local antibiotic delivery is important in prophylaxis and treatment of these infections. Recent studies indicated that Staphylococcus aureus can penetrate bone tissue through micron-sized canaliculi and evade systemic and [...] Read more.
Bone infection is a feared complication for patients with surgically fixed bone fractures and local antibiotic delivery is important in prophylaxis and treatment of these infections. Recent studies indicated that Staphylococcus aureus can penetrate bone tissue through micron-sized canaliculi and evade systemic and currently available local antibiotic treatments. Targeting bacteria within the bone requires highly efficient delivery of antimicrobials to the infected bone tissue. In this work, a biodegradable microsphere carrier loaded with antibiotics and with specific affinity to bone mineral was developed. Two widely used antibiotics, i.e., Gentamicin-dioctyl sulfosuccinate (GM-AOT) and Ciprofloxacin (CF) were embedded in poly(ϵ-caprolactone) (PCL) microspheres fabricated by oil-in-water emulsion techniques with carboxylated poly(vinyl alcohol) (cPVA) as surfactant. The carboxylic acid groups present at the Poly(ϵ-caprolactone)/cPVA (PCL-cPVA) microsphere surface were functionalized with aspartic acid oligomers (ASP) granting bone targeting properties. We report on cPVA synthesis, microsphere formulation, and antibiotic loading of PCL/cPVA-ASP microspheres. Antibiotic loaded PCL/cPVA-ASP microspheres show sustained release of its antibiotic load and can inhibit bacterial growth in vitro for up to 6 days. PCL/cPVA-ASP microspheres show enhanced affinity to mineralized substrates compared to non-functionalized PCL/cPVA microspheres. These findings support further development of these bone targeting antibiotic carriers for potential treatment of persistent bone infections. Full article
(This article belongs to the Special Issue Local Antibacterial and Antimicrobial Drug Delivery Systems)
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Article
Saturated Fatty Acid-Based In Situ Forming Matrices for Localized Antimicrobial Delivery
Pharmaceutics 2020, 12(9), 808; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12090808 - 25 Aug 2020
Cited by 3 | Viewed by 889
Abstract
In recent years, the world has faced the issue of antibiotic resistance. Methicillin-resistant Staphylococcus aureus (MRSA) is a significant problem in various treatments and control of infections. Biocompatible materials with saturated fatty acids of different chain lengths (C8–C18) were [...] Read more.
In recent years, the world has faced the issue of antibiotic resistance. Methicillin-resistant Staphylococcus aureus (MRSA) is a significant problem in various treatments and control of infections. Biocompatible materials with saturated fatty acids of different chain lengths (C8–C18) were studied as matrix formers of localized injectable vancomycin HCl (VCM)-loaded antisolvent-induced in situ forming matrices. The series of fatty acid-based in situ forming matrices showed a low viscosity (5.47–13.97 cPs) and pH value in the range of 5.16–6.78, with high injectability through a 27-G needle (1.55–3.12 N). The preparations exhibited low tolerance to high concentrations of KH2PO4 solution (1.88–5.42% v/v) and depicted an electrical potential change during phase transformation. Their phase transition and matrix formation at the microscopic and macroscopic levels depended on the chain length of fatty acids and solvent characteristics. The VCM release pattern depended on the nucleation/crystallization and solvent exchange behaviors of the delivery system. The 35% w/v of C12–C16 fatty acid-based in situ forming matrix prolonged the VCM release over seven days in which C12, C14, C16 –based formulation reached 56, 84, and 85% cumulative drug release at 7th day. The release data fitted well with Higuchi’s model. The developed formulations presented efficient antimicrobial activities against standard S. aureus, MRSA, Escherichia coli, and Candida albicans. Hence, VCM-loaded antisolvent-induced fatty acid-based in situ forming matrix is a potential local delivery system for the treatment of local Gram-positive infection sites, such as joints, eyes, dermis of surgery sites, etc., in the future. Full article
(This article belongs to the Special Issue Local Antibacterial and Antimicrobial Drug Delivery Systems)
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Article
Biogenic Silver Nanoparticles Decorated with Methylene Blue Potentiated the Photodynamic Inactivation of Pseudomonas aeruginosa and Staphylococcus aureus
Pharmaceutics 2020, 12(8), 709; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12080709 - 29 Jul 2020
Cited by 8 | Viewed by 959
Abstract
The persistence of multidrug resistance among microorganisms has directed a mandate towards a hunt for the development of alternative therapeutic modalities. In this context, antimicrobial photodynamic therapy (aPDT) is sprouted as a novel strategy to mitigate biofilms and planktonic cells of pathogens. Nanoparticles [...] Read more.
The persistence of multidrug resistance among microorganisms has directed a mandate towards a hunt for the development of alternative therapeutic modalities. In this context, antimicrobial photodynamic therapy (aPDT) is sprouted as a novel strategy to mitigate biofilms and planktonic cells of pathogens. Nanoparticles (NPs) are reported with unique intrinsic and antimicrobial properties. Therefore, silver NPs (AgNPs) were investigated in this study to determine their ability to potentiate the aPDT of photosensitizer against Staphylococcus aureus and Pseudomonas aeruginosa. Biologically synthesized AgNPs were surface coated with methylene blue (MB) and studied for their aPDT against planktonic cells and biofilms of bacteria. The nano-conjugates (MB-AgNPs) were characterized for their size, shape and coated materials. MB-AgNPs showed significant phototoxicity against both forms of test bacteria and no toxicity was observed in the dark. Moreover, activity of MB-AgNPs was comparatively higher than that of the free MB, which concludes that MB-AgNPs could be an excellent alternative to combat antibiotic resistant bacteria. Full article
(This article belongs to the Special Issue Local Antibacterial and Antimicrobial Drug Delivery Systems)
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Article
Polymeric Nanoparticle Associated with Ceftriaxone and Extract of Schinopsis Brasiliensis Engler against Multiresistant Enterobacteria
Pharmaceutics 2020, 12(8), 695; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12080695 - 23 Jul 2020
Cited by 4 | Viewed by 789
Abstract
Bacterial resistance has become an important public health problem. Bacteria have been acquiring mechanisms to resist the action of antimicrobial active pharmaceutical ingredients (API). Based on this, a promising alternative is the use of nanotechnology, since when the systems are presented in nanometric [...] Read more.
Bacterial resistance has become an important public health problem. Bacteria have been acquiring mechanisms to resist the action of antimicrobial active pharmaceutical ingredients (API). Based on this, a promising alternative is the use of nanotechnology, since when the systems are presented in nanometric size, there is an increase in the interaction and concentration of the action at the target site improving the activity. Thus, this study aims to develop a polymeric nanoparticle (PN) composed of chitosan and hydroxypropylmethylcellulose, as an innovative strategy for the administration of an association between ceftriaxone and extract of S. brasiliensis, for the treatment of Enterobacteriaceae. From a Box–Behnken design, nanoparticles were obtained and evaluated using the DLS technique, obtaining the particle size between 440 and 1660 nm, IPD from 0.42 to 0.92, and positive charges. Morphological characteristics of PN by SEM revealed spherical morphology and sizes similar to DLS. Infrared spectroscopy showed no chemical interaction between the components of the formulation. The broth microdilution technique evaluated their antimicrobial activity, and a considerable improvement in the activity of the extract and the API compared to the free compounds was found, reaching an improvement of 133 times in the minimum inhibitory activity CRO. Full article
(This article belongs to the Special Issue Local Antibacterial and Antimicrobial Drug Delivery Systems)
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Article
“Smart” Antimicrobial Nanocomplexes with Potential to Decrease Surgical Site Infections (SSI)
Pharmaceutics 2020, 12(4), 361; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12040361 - 15 Apr 2020
Cited by 11 | Viewed by 1352
Abstract
The emergence of resistant pathogens is a burden on mankind and threatens the existence of our species. Natural and plant-derived antimicrobial agents need to be developed in the race against antibiotic resistance. Nanotechnology is a promising approach with a variety of products. Biosynthesized [...] Read more.
The emergence of resistant pathogens is a burden on mankind and threatens the existence of our species. Natural and plant-derived antimicrobial agents need to be developed in the race against antibiotic resistance. Nanotechnology is a promising approach with a variety of products. Biosynthesized silver nanoparticles (AgNP) have good antimicrobial activity. We prepared AgNPs with trans-cinnamic acid (TCA) and povidone–iodine (PI) with increased antimicrobial activity. We synthesized also AgNPs with natural cinnamon bark extract (Cinn) in combination with PI and coated biodegradable Polyglycolic Acid (PGA) sutures with the new materials separately. These compounds (TCA-AgNP, TCA-AgNP-PI, Cinn-AgNP, and Cinn-AgNP-PI) and their dip-coated PGA sutures were tested against 10 reference strains of microorganisms and five antibiotics by zone inhibition with disc- and agar-well-diffusion methods. The new compounds TCA-AgNP-PI and Cinn-AgNP-PI are broad spectrum microbicidal agents and therefore potential coating materials for sutures to prevent Surgical Site Infections (SSI). TCA-AgNP-PI inhibits the studied pathogens stronger than Cinn-AgNP-PI in-vitro and on coated sutures. Dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-Vis), Fourier Transform infrared spectroscopy (FT-IR), Raman, X-ray diffraction (XRD), microstructural analysis by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS) confirmed the composition of TCA-AgNP-PI and Cinn-AgNP-PI. Smart solutions involving hybrid materials based on synergistic antimicrobial action have promising future perspectives to combat resistant microorganisms. Full article
(This article belongs to the Special Issue Local Antibacterial and Antimicrobial Drug Delivery Systems)
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Review

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Review
Antibacterial Layer-by-Layer Coatings for Medical Implants
Pharmaceutics 2021, 13(1), 16; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13010016 - 24 Dec 2020
Cited by 7 | Viewed by 1135
Abstract
The widespread occurrence of nosocomial infections and the emergence of new bacterial strands calls for the development of antibacterial coatings with localized antibacterial action that are capable of facing the challenges posed by increasing bacterial resistance to antibiotics. The Layer-by-Layer (LbL) technique, based [...] Read more.
The widespread occurrence of nosocomial infections and the emergence of new bacterial strands calls for the development of antibacterial coatings with localized antibacterial action that are capable of facing the challenges posed by increasing bacterial resistance to antibiotics. The Layer-by-Layer (LbL) technique, based on the alternating assembly of oppositely charged polyelectrolytes, can be applied for the non-covalent modification of multiple substrates, including medical implants. Polyelectrolyte multilayers fabricated by the LbL technique have been extensively researched for the development of antibacterial coatings as they can be loaded with antibiotics, antibacterial peptides, nanoparticles with bactericide action, in addition to being capable of restricting adhesion of bacteria to surfaces. In this review, the different approaches that apply LbL for antibacterial coatings, emphasizing those that can be applied for implant modification are presented. Full article
(This article belongs to the Special Issue Local Antibacterial and Antimicrobial Drug Delivery Systems)
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Review
Electrospinning Proteins for Wound Healing Purposes: Opportunities and Challenges
Pharmaceutics 2021, 13(1), 4; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13010004 - 22 Dec 2020
Cited by 9 | Viewed by 1827
Abstract
With the growth of the aging population worldwide, chronic wounds represent an increasing burden to healthcare systems. Wound healing is complex and not only affected by the patient’s physiological conditions, but also by bacterial infections and inflammation, which delay wound closure and re-epithelialization. [...] Read more.
With the growth of the aging population worldwide, chronic wounds represent an increasing burden to healthcare systems. Wound healing is complex and not only affected by the patient’s physiological conditions, but also by bacterial infections and inflammation, which delay wound closure and re-epithelialization. In recent years, there has been a growing interest for electrospun polymeric wound dressings with fiber diameters in the nano- and micrometer range. Such wound dressings display a number of properties, which support and accelerate wound healing. For instance, they provide physical and mechanical protection, exhibit a high surface area, allow gas exchange, are cytocompatible and biodegradable, resemble the structure of the native extracellular matrix, and deliver antibacterial agents locally into the wound. This review paper gives an overview on cytocompatible and biodegradable fibrous wound dressings obtained by electrospinning proteins and peptides of animal and plant origin in recent years. Focus is placed on the requirements for the fabrication of such drug delivery systems by electrospinning as well as their wound healing properties and therapeutic potential. Moreover, the incorporation of antimicrobial agents into the fibers or their attachment onto the fiber surface as well as their antimicrobial activity are discussed. Full article
(This article belongs to the Special Issue Local Antibacterial and Antimicrobial Drug Delivery Systems)
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Review
Clinical Efficacy of Single Application Local Drug Delivery and Adjunctive Agents in Nonsurgical Periodontal Therapy: A Systematic Review and Network Meta-Analysis
Pharmaceutics 2020, 12(11), 1086; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12111086 - 12 Nov 2020
Cited by 2 | Viewed by 748
Abstract
This review aimed to rank the clinical efficacy of commercially available single-application local drug delivery and adjunctive agents (LDAs) compared with subgingival mechanical debridement (SMD) in nonsurgical periodontal therapy (NSPT). Randomized controlled clinical trials that compared LDAs against SMD alone or with placebo [...] Read more.
This review aimed to rank the clinical efficacy of commercially available single-application local drug delivery and adjunctive agents (LDAs) compared with subgingival mechanical debridement (SMD) in nonsurgical periodontal therapy (NSPT). Randomized controlled clinical trials that compared LDAs against SMD alone or with placebo in adults (aged at least 18 years) diagnosed with periodontitis with a minimum of 6 months follow-up were included. A frequentist approach to random-effects network meta-analysis was implemented. The efficacies of the LDAs measured by probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain were reported as mean difference (MD) with 95% confidence intervals (CIs). The treatments were ranked according to their P-score. Four network meta-analyses suggested that sulfonic/sulfuric acid gel (PPD MD −1.13 mm, 95% CI −1.74 to −0.53, P-score 0.91; CAL MD −1.09 mm, 95% CI −1.58 to −0.61, P-score 0.95) and doxycycline hyclate gel (PPD MD −0.90 mm, 95% CI −1.50 to −0.30, P-score 0.93; CAL MD −0.84 mm, 95% CI −1.40 to −0.28, P-score 0.92) were the most effective in reducing PPD and gaining CAL in split-mouth and parallel studies, respectively (moderate certainty of evidence). LDAs have differing efficacies, but they present with possible clinical significance over SMD alone in NSPT. Full article
(This article belongs to the Special Issue Local Antibacterial and Antimicrobial Drug Delivery Systems)
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Review
Bactericidal Antibacterial Mechanism of Plant Synthesized Silver, Gold and Bimetallic Nanoparticles
Pharmaceutics 2020, 12(11), 1044; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12111044 - 30 Oct 2020
Cited by 5 | Viewed by 963
Abstract
As the field of nanomedicine develops and tackles the recent surge in antibiotic resistance, there is a need to have an in-depth understanding and a synergistic view of research on the effectiveness of a metal nanoparticle (NP) as an antibacterial agent especially their [...] Read more.
As the field of nanomedicine develops and tackles the recent surge in antibiotic resistance, there is a need to have an in-depth understanding and a synergistic view of research on the effectiveness of a metal nanoparticle (NP) as an antibacterial agent especially their mechanisms of action. The constant development of bacterial resistance has led scientists to develop novel antibiotic agents. Silver, gold and its bimetallic combination are one of the most promising metal NPs because they show strong antibacterial activity. In this review we discuss the mode of synthesis and the proposed mechanism of biocidal antibacterial activity of metal NPs. These mechanisms include DNA degradation, protein oxidation, generation of reactive oxygen species, lipid peroxidation, ATP depletion, damage of biomolecules and membrane interaction. Full article
(This article belongs to the Special Issue Local Antibacterial and Antimicrobial Drug Delivery Systems)
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