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Special Issue "Functional Polymers as Innovative Tools in the Delivery of Antimicrobial Agents"

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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 (30 November 2021) | Viewed by 25877

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Prof. Dr. Umile Gianfranco Spizzirri

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Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Cosenza, Italy
Interests: stimuli-responsive drug delivery systems; munti-functional hydrogels; antioxidant polymers
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Special Issue Information

Dear Colleagues,

Many infectious diseases are induced by omnipresent microorganisms, including bacteria, viruses, protozoa, fungi, and algae, and, consequently, are very common, accounting for a significant share of the global disease burden. Unfortunately, antimicrobial resistance, adverse effects, and the high cost of antimicrobials are crucial health challenges worldwide. One of the common efforts in addressing this issue lies in improving existing antimicrobial delivery systems. In this regard, biocompatible polymeric particles, entrapping these bioactive molecules, are capable of being released over a desired period of time, thereby decreasing the frequency of their administration. At the same time, these systems are able to protect antimicrobial drugs from degradation, enhancing their bioavailability. There are many forms of drug delivery systems based on physical interactions between the polymeric carrier and antimicrobial molecules, namely, nanoparticles and microparticles, capsules and fibres, tablets, pellets, hydrogels, sponges, and many others. They can be synthesized using both natural (gelatin, cellulose, pectin, dextran, or chitosan) and synthetic (silicone latex or acrylates) polymers. Additionally, polymeric devices that are able to undergo morphological modifications in response to an external stimulus (pH, temperature, magnetic field, and light) represent an innovative field in the delivery of antimicrobials. In the effort to further improve delivery device performance, a combination of two or more signals can be developed by incorporating different stimulae’s responsive elements into the same polymeric network. These smart polymeric materials lead to superior in vitro and/or in vivo therapeutic efficacy, with programmed site-specific features and remarkable potential for targeted therapy. This Special Issue welcomes any topics regarding recent progress in the synthesis and characterization of innovative functional polymers suitable as carriers of antimicrobials, to be employed in the pharmaceutical and biomedical fields.

Dr. Umile Gianfranco Spizzirri
Guest Editor

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Keywords

Drug delivery systems
Antimicrobial agents
Polymeric carriers
Site-specific release
Smart polymers

Published Papers (10 papers)

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Editorial

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Open AccessEditorial

Functional Polymers as Innovative Tools in the Delivery of Antimicrobial Agents

Umile Gianfranco Spizzirri

Pharmaceutics 2022, 14(3), 487; https://doi.org/10.3390/pharmaceutics14030487 - 23 Feb 2022

Viewed by 845

Abstract

Ubiquitous microorganisms such as bacteria, viruses, algae, and fungi induce several infectious diseases, representing crucial health challenges worldwide, due to increased antimicrobial resistance, high antimicrobial cost and adverse effects [...] Full article

(This article belongs to the Special Issue Functional Polymers as Innovative Tools in the Delivery of Antimicrobial Agents)

Research

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Open AccessEditor’s ChoiceArticle

Mixed Pluronic—Cremophor Polymeric Micelles as Nanocarriers for Poorly Soluble Antibiotics—The Influence on the Antibacterial Activity

Cristina Scomoroşcenco

Claudia Mihaela Ninciuleanu

Cristina Lavinia Nistor

and

Ludmila Otilia Cinteza

Pharmaceutics 2021, 13(4), 435; https://doi.org/10.3390/pharmaceutics13040435 - 24 Mar 2021

Cited by 20 | Viewed by 2800

Abstract

In this work, novel polymeric mixed micelles from Pluronic F127 and Cremophor EL were investigated as drug delivery systems for Norfloxacin as model antibiotic drug. The optimal molar ratio of surfactants was determined, in order to decrease critical micellar concentration (CMC) and prepare carriers with minimal surfactant concentrations. The particle size, zeta potential, and encapsulation efficiency were determined for both pure and mixed micelles with selected composition. In vitro release kinetics of Norfloxacin from micelles show that the composition of surfactant mixture generates tunable extended release. The mixed micelles exhibit good biocompatibility against normal fibroblasts MRC-5 cells, while some cytotoxicity was found in all micellar systems at high concentrations. The influence of the surfactant components in the carrier on the antibacterial properties of Norfloxacin was investigated. The drug loaded mixed micellar formulation exhibit good activity against clinical isolated strains, compared with the CLSI recommended standard strains (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29213, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922). P. aeruginosa 5399 clinical strain shows low sensitivity to Norfloxacin in all tested micelle systems. The results suggest that Cremophor EL-Pluronic F127 mixed micelles can be considered as novel controlled release delivery systems for hydrophobic antimicrobial drugs. Full article

(This article belongs to the Special Issue Functional Polymers as Innovative Tools in the Delivery of Antimicrobial Agents)

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Open AccessArticle

Antimicrobial Contribution of Chitosan Surface-Modified Nanoliposomes Combined with Colistin against Sensitive and Colistin-Resistant Clinical Pseudomonas aeruginosa

Valentina Laverde-Rojas

Yamil Liscano

Sandra Patricia Rivera-Sánchez

Ivan Darío Ocampo-Ibáñez

Yeiston Betancourt

Maria José Alhajj

Cristhian J. Yarce

Constain H. Salamanca

and

Jose Oñate-Garzón

Pharmaceutics 2021, 13(1), 41; https://doi.org/10.3390/pharmaceutics13010041 - 30 Dec 2020

Cited by 6 | Viewed by 1782

Abstract

Colistin is a re-emergent antibiotic peptide used as a last resort in clinical practice to overcome multi-drug resistant (MDR) Gram-negative bacterial infections. Unfortunately, the dissemination of colistin-resistant strains has increased in recent years and is considered a public health problem worldwide. Strategies to reduce resistance to antibiotics such as nanotechnology have been applied successfully. In this work, colistin was characterized physicochemically by surface tension measurements. Subsequently, nanoliposomes coated with highly deacetylated chitosan were prepared with and without colistin. The nanoliposomes were characterized using dynamic light scattering and zeta potential measurements. Both physicochemical parameters fluctuated relatively to the addition of colistin and/or polymer. The antimicrobial activity of formulations increased by four-fold against clinical isolates of susceptible Pseudomona aeruginosa but did not have antimicrobial activity against multidrug-resistant (MDR) bacteria. Interestingly, the free coated nanoliposomes exhibited the same antibacterial activity in both sensitive and MDR strains. Finally, the interaction of colistin with phospholipids was characterized using molecular dynamics (MD) simulations and determined that colistin is weakly associated with micelles constituted by zwitterionic phospholipids. Full article

(This article belongs to the Special Issue Functional Polymers as Innovative Tools in the Delivery of Antimicrobial Agents)

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Open AccessArticle

Bi-Functional Alginate Oligosaccharide–Polymyxin Conjugates for Improved Treatment of Multidrug-Resistant Gram-Negative Bacterial Infections

and

Pharmaceutics 2020, 12(11), 1080; https://doi.org/10.3390/pharmaceutics12111080 - 11 Nov 2020

Cited by 16 | Viewed by 2198

Abstract

The recent emergence of resistance to colistin, an antibiotic of last resort with dose-limiting toxicity, has highlighted the need for alternative approaches to combat infection. This study aimed to generate and characterise alginate oligosaccharide (“OligoG”)–polymyxin (polymyxin B and E (colistin)) conjugates to improve the effectiveness of these antibiotics. OligoG–polymyxin conjugates (amide- or ester-linked), with molecular weights of 5200–12,800 g/mol and antibiotic loading of 6.1–12.9% w/w, were reproducibly synthesised. In vitro inflammatory cytokine production (tumour necrosis factor alpha (TNFα) ELISA) and cytotoxicity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) of colistin (2.2–9.3-fold) and polymyxin B (2.9–27.2-fold) were significantly decreased by OligoG conjugation. Antimicrobial susceptibility tests (minimum inhibitory concentration (MIC), growth curves) demonstrated similar antimicrobial efficacy of ester- and amide-linked conjugates to that of the parent antibiotic but with more sustained inhibition of bacterial growth. OligoG–polymyxin conjugates exhibited improved selectivity for Gram-negative bacteria in comparison to mammalian cells (approximately 2–4-fold). Both OligoG–colistin conjugates caused significant disruption of Pseudomonas aeruginosa biofilm formation and induced bacterial death (confocal laser scanning microscopy). When conjugates were tested in an in vitro “time-to-kill” (TTK) model using Acinetobacter baumannii, only ester-linked conjugates reduced viable bacterial counts (~2-fold) after 4 h. Bi-functional OligoG–polymyxin conjugates have potential therapeutic benefits in the treatment of multidrug-resistant (MDR) Gram-negative bacterial infections, directly reducing toxicity whilst retaining antimicrobial and antibiofilm activities. Full article

(This article belongs to the Special Issue Functional Polymers as Innovative Tools in the Delivery of Antimicrobial Agents)

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Open AccessArticle

Sustained Release of Linezolid from Prepared Hydrogels with Polyvinyl Alcohol and Aliphatic Dicarboxylic Acids of Variable Chain Lengths

Gustavo Cabrera-Barjas

Johanna Castaño

and

Esteban F. Durán-Lara

Pharmaceutics 2020, 12(10), 982; https://doi.org/10.3390/pharmaceutics12100982 - 17 Oct 2020

Cited by 9 | Viewed by 2264

Abstract

A series of hydrogels with a specific release profile of linezolid was successfully synthesized. The hydrogels were synthesized by cross-linking polyvinyl alcohol (PVA) and aliphatic dicarboxylic acids, which include succinic acid (SA), glutaric acid (GA), and adipic acid (AA). The three crosslinked hydrogels were prepared by esterification and characterized by equilibrium swelling ratio, infrared spectroscopy, thermogravimetric analysis, mechanical properties, and scanning electron microscopy. The release kinetics studies of the linezolid from prepared hydrogels were investigated by cumulative drug release and quantified by chromatographic techniques. Mathematical models were carried out to understand the behavior of the linezolid release. These data revealed that the sustained release of linezolid depends on the aliphatic dicarboxylic acid chain length, their polarity, as well as the hydrogel crosslinking degree and mechanical properties. The in vitro antibacterial assay of hydrogel formulations was assessed in an Enterococcus faecium bacterial strain, showing a significant activity over time. The antibacterial results were consistent with cumulative release assays. Thus, these results demonstrated that the aliphatic dicarboxylic acids used as crosslinkers in the PVA hydrogels were a determining factor in the antibiotic release profile. Full article

(This article belongs to the Special Issue Functional Polymers as Innovative Tools in the Delivery of Antimicrobial Agents)

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Open AccessArticle

Hybrid Nanoparticles of Poly (Methyl Methacrylate) and Antimicrobial Quaternary Ammonium Surfactants

Beatriz Ideriha Mathiazzi

and

Ana Maria Carmona-Ribeiro

Pharmaceutics 2020, 12(4), 340; https://doi.org/10.3390/pharmaceutics12040340 - 10 Apr 2020

Cited by 10 | Viewed by 2847

Abstract

Quaternary ammonium surfactants (QACs) are microbicides, whereas poly (acrylates) are biocompatible polymers. Here, the physical and antimicrobial properties of two QACs, cetyl trimethyl ammonium bromide (CTAB) or dioctadecyl dimethyl ammonium bromide (DODAB) in poly (methyl methacrylate) (PMMA) nanoparticles (NPs) are compared to those of QACs alone. Methyl methacrylate (MMA) polymerization using DODAB or CTAB as emulsifiers and initiator azobisisobutyronitrile (AIBN) yielded cationic, nanometric, homodisperse, and stable NPs. NPs’ physical and antimicrobial properties were assessed from dynamic light scattering (DLS), scanning electron microscopy, and viability curves of Escherichia coli, Staphylococcus aureus, or Candida albicans determined as log(colony-forming unities counting) over a range of [QACs]. NPs were spherical and homodisperse but activity for free QACs was higher than those for QACs in NPs. Inhibition halos against bacteria and yeast were observed only for free or incorporated CTAB in NPs because PMMA/CTAB NPs controlled the CTAB release. DODAB displayed fungicidal activity against C. albicans since DODAB bilayer disks could penetrate the outer glycoproteins fungus layer. The physical properties and stability of the cationic NPs highlighted their potential to combine with other bioactive molecules for further applications in drug and vaccine delivery. Full article

(This article belongs to the Special Issue Functional Polymers as Innovative Tools in the Delivery of Antimicrobial Agents)

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Open AccessArticle

Zein/MCM-41 Nanocomposite Film Incorporated with Cinnamon Essential Oil Loaded by Modified Supercritical CO₂ Impregnation for Long-Term Antibacterial Packaging

and

Pharmaceutics 2020, 12(2), 169; https://doi.org/10.3390/pharmaceutics12020169 - 18 Feb 2020

Cited by 16 | Viewed by 2465

Abstract

Antimicrobial medicine and food packages based on bio-based film containing essential oils have attracted great attention worldwide. However, the controlled release of essential oils from these film nanocomposites is still a big challenge. In this study, a long-term antibacterial film nanocomposite composed of zein film and cinnamon essential oil (CEO) loaded MCM-41 silica nanoparticles was prepared. The CEO was loaded into MCM-41 particles via modified supercritical impregnation efficiently with a high drug load (>40 wt%). The morphologies of the prepared nanoparticles and film nanocomposite were characterized by a scanning electron microscope. The release behaviors of CEO under different temperatures, high humidity, continuous illumination and in phosphate buffer solution (PBS) solution were investigated. The results showed that the film nanocomposite had an outstanding release-control effect. The addition of MCM-41 nanoparticles also improved the mechanical properties of zein films. The antibacterial effect of CEO was significantly prolonged by the film nanocomposite; indicating the CEO film nanocomposite fabricated via modified supercritical CO₂ impregnation was a potential long-term antibacterial medicine or food package material. Full article

(This article belongs to the Special Issue Functional Polymers as Innovative Tools in the Delivery of Antimicrobial Agents)

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Review

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Open AccessReview

Bromelain and Nisin: The Natural Antimicrobials with High Potential in Biomedicine

Urška Jančič

and

Selestina Gorgieva

Pharmaceutics 2022, 14(1), 76; https://doi.org/10.3390/pharmaceutics14010076 - 29 Dec 2021

Cited by 14 | Viewed by 3948

Abstract

Infectious diseases along with various cancer types are among the most significant public health problems and the leading cause of death worldwide. The situation has become even more complex with the rapid development of multidrug-resistant microorganisms. New drugs are urgently needed to curb the increasing spread of diseases in humans and livestock. Promising candidates are natural antimicrobial peptides produced by bacteria, and therapeutic enzymes, extracted from medicinal plants. This review highlights the structure and properties of plant origin bromelain and antimicrobial peptide nisin, along with their mechanism of action, the immobilization strategies, and recent applications in the field of biomedicine. Future perspectives towards the commercialization of new biomedical products, including these important bioactive compounds, have been highlighted. Full article

(This article belongs to the Special Issue Functional Polymers as Innovative Tools in the Delivery of Antimicrobial Agents)

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Open AccessReview

Polymeric Nanomaterials for Efficient Delivery of Antimicrobial Agents

Yin Wang

and

Hui Sun

Pharmaceutics 2021, 13(12), 2108; https://doi.org/10.3390/pharmaceutics13122108 - 07 Dec 2021

Cited by 16 | Viewed by 3495

Abstract

Bacterial infections have threatened the lives of human beings for thousands of years either as major diseases or complications. The elimination of bacterial infections has always occupied a pivotal position in our history. For a long period of time, people were devoted to finding natural antimicrobial agents such as antimicrobial peptides (AMPs), antibiotics and silver ions or synthetic active antimicrobial substances including antimicrobial peptoids, metal oxides and polymers to combat bacterial infections. However, with the emergence of multidrug resistance (MDR), bacterial infection has become one of the most urgent problems worldwide. The efficient delivery of antimicrobial agents to the site of infection precisely is a promising strategy for reducing bacterial resistance. Polymeric nanomaterials have been widely studied as carriers for constructing antimicrobial agent delivery systems and have shown advantages including high biocompatibility, sustained release, targeting and improved bioavailability. In this review, we will highlight recent advances in highly efficient delivery of antimicrobial agents by polymeric nanomaterials such as micelles, vesicles, dendrimers, nanogels, nanofibers and so forth. The biomedical applications of polymeric nanomaterial-based delivery systems in combating MDR bacteria, anti-biofilms, wound healing, tissue engineering and anticancer are demonstrated. Moreover, conclusions and future perspectives are also proposed. Full article

(This article belongs to the Special Issue Functional Polymers as Innovative Tools in the Delivery of Antimicrobial Agents)

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Open AccessReview

Nanotechnologies: An Innovative Tool to Release Natural Extracts with Antimicrobial Properties

Umile Gianfranco Spizzirri

and

Pharmaceutics 2021, 13(2), 230; https://doi.org/10.3390/pharmaceutics13020230 - 06 Feb 2021

Cited by 12 | Viewed by 2624

Abstract

Site-Specific release of active molecules with antimicrobial activity spurred the interest in the development of innovative polymeric nanocarriers. In the preparation of polymeric devices, nanotechnologies usually overcome the inconvenience frequently related to other synthetic strategies. High performing nanocarriers were synthesized using a wide range of starting polymer structures, with tailored features and great chemical versatility. Over the last decade, many antimicrobial substances originating from plants, herbs, and agro-food waste by-products were deeply investigated, significantly catching the interest of the scientific community. In this review, the most innovative strategies to synthesize nanodevices able to release antimicrobial natural extracts were discussed. In this regard, the properties and structure of the starting polymers, either synthetic or natural, as well as the antimicrobial activity of the biomolecules were deeply investigated, outlining the right combination able to inhibit pathogens in specific biological compartments. Full article

(This article belongs to the Special Issue Functional Polymers as Innovative Tools in the Delivery of Antimicrobial Agents)

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