Alexandra Elena Oprea

Efficiency of Vanilla, Patchouli and Ylang Ylang Essential Oils Stabilized by Iron Oxide@C14 Nanostructures against Bacterial Adherence and Biofilms Formed by Staphylococcus aureus and Klebsiella pneumoniae Clinical Strains

Biofilms formed by bacterial cells are associated with drastically enhanced resistance against most antimicrobial agents, contributing to the persistence and chronicization of the microbial infections and to therapy failure. The purpose of this study was to combine the unique properties of magnetic nanoparticles with the antimicrobial activity of three essential oils to obtain novel nanobiosystems that could be used as coatings for catheter pieces with an improved resistance to Staphylococcus aureus and Klebsiella pneumoniae clinical strains adherence and biofilm development. The essential oils of ylang ylang, patchouli and vanilla were stabilized by the interaction with iron oxide@C14 nanoparticles to be further used as coating agents for medical surfaces. Iron oxide@C14 was prepared by co-precipitation of Fe+2 and Fe+3 and myristic acid (C14) in basic medium. Vanilla essential oil loaded nanoparticles pelliculised on the catheter samples surface strongly inhibited both the initial adherence of S. aureus cells (quantified at 24 h) and the development of the mature biofilm quantified at 48 h. Patchouli and ylang-ylang essential oils inhibited mostly the initial adherence phase of S. aureus biofilm development. In the case of K. pneumoniae, all tested nanosystems exhibited similar efficiency, being active mostly against the adherence K. pneumoniae cells to the tested catheter specimens. The new nanobiosystems based on vanilla, patchouli and ylang-ylang essential oils could be of a great interest for the biomedical field, opening new directions for the design of film-coated surfaces with anti-adherence and anti-biofilm properties.

MAPLE Fabricated Fe3O4@Cinnamomum verum Antimicrobial Surfaces for Improved Gastrostomy Tubes

Cinnamomum verum-functionalized Fe3O4 nanoparticles of 9.4 nm in size were laser transferred by matrix assisted pulsed laser evaporation (MAPLE) technique onto gastrostomy tubes (G-tubes) for antibacterial activity evaluation toward Gram positive and Gram negative microbial colonization. X-ray diffraction analysis of the nanoparticle powder showed a polycrystalline magnetite structure, whereas infrared mapping confirmed the integrity of C. verum (CV) functional groups after the laser transfer. The specific topography of the deposited films involved a uniform thin coating together with several aggregates of bio-functionalized magnetite particles covering the G-tubes. Cytotoxicity assays showed an increase of the G-tube surface biocompatibility after Fe3O4@CV treatment, allowing a normal development of endothelial cells up to five days of incubation. Microbiological assays on nanoparticle-modified G-tube surfaces have proved an improvement of anti-adherent properties, significantly reducing both Gram negative and Gram positive bacteria colonization.

Bioactive ZnO Coatings Deposited by MAPLE—An Appropriate Strategy to Produce Efficient Anti-Biofilm Surfaces

Deposition of bioactive coatings composed of zinc oxide, cyclodextrin and cefepime (ZnO/CD/Cfp) was performed by the Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The obtained nanostructures were characterized by X-ray diffraction, IR microscopy and scanning electron microscopy. The efficient release of cefepime was correlated with an increased anti-biofilm activity of ZnO/CD/Cfp composites. In vitro and in vivo tests have revealed a good biocompatibility of ZnO/CD/Cfp coatings, which recommend them as competitive candidates for the development of antimicrobial surfaces with biomedical applications. The release of the fourth generation cephalosporin Cfp in a biologically active form from the ZnO matrix could help preventing the bacterial adhesion and the subsequent colonization and biofilm development on various surfaces, and thus decreasing the risk of biofilm-related infections.

Poly(lactic-co-glycolic) acid/chitosan microsphere thin films functionalized with Cinnamomi aetheroleum and magnetite nanoparticles for preventing the microbial colonization of medical surfaces

Poly(lactic-co-glycolic) acid/chitosan microsphere coatings containing Cinnamomi aetheroleum-functionalized magnetite nanoparticles (Fe3O4@CA) were deposited by matrix-assisted pulsed laser evaporation in order to improve the surface resistance to microbial colonization. The obtained surface proved a very good biocompatibility and demonstrates that bacterial colonization is impaired on the nanomodified bioactive surfaces and also Staphylococcus aureus biofilm formation is significantly altered.Graphical Abstract

Extended release of vitamins from magnetite loaded polyanionic polymeric beads

Here we explore a novel approach of increasing the release duration of folic and ascorbic acid from magnetite entrapped into calcium-alginate beads. Synthesis and characterization of magnetite-vitamins complexes are reported. The magnetite-vitamins complexes were characterized by FT-IR, XRD, SEM, BET and DTA-TG. Also calcium-alginate magnetic beads were prepared by dripping a mixture of sodium alginate with magnetite-vitamins complexes into calcium chloride solution. Extended release profile of the two experimental models was evaluated and quantified by UV-vis.

Chapter 2 – Toxicity of inorganic nanoparticles against prokaryotic cells

Nowadays, drug-resistant bacteria are a serious problem concerning the international health organizations, as high-dose treatments are necessary to overcome these infections, inducing higher toxicity, longer hospital stays, and increased mortality. Due to the progress that has been made in nanotechnology, some inorganic materials, that have already been known to possess antimicrobial properties, have been transformed into nanoparticles. Thus, silver, copper, or titanium dioxide nanoparticles were developed and administered as drinkable colloids, or transformed into nanostructured coatings in medical devices. Some of these are clinically approved and the mechanisms of toxicity are almost clearly elucidated, however, newly improved systems are continuously being developed, in order to overcome the shortcomings of the existing ones and to improve living standards. This chapter makes a summary of the existing studies regarding the mechanisms of toxicity for some inorganic nanoparticles against prokaryote cells. Also, some newly developed model systems are described, focusing on the biosynthesized nanoparticles, which are clearly a trend in this field.

Antibiotic Drug Delivery Systems for the Intracellular Targeting of Bacterial Pathogens

Intracellular bacterial pathogens are hard to treat because of the inability of conventional antimicrobial agents belonging to widely used classes, like aminoglycosides and β-lac‐ tams, fluoroquinolones, or macrolides to penetrate, accumulate, or be retained in the mammalian cells. The increasing problem of antibiotic resistance complicates more the treatment of the diseases caused by these agents. In many cases, the increase in therapeu‐ tic doses and treatment duration is accompanied by the occurrence of severe side effects. Taking into account the huge financial investment associated with bringing a new antibi‐ otic to the market and the limited lifetime of antibiotics, the design of drug delivery sys‐ tems to enable the targeting of antibiotics inside the cells, to improve their activity in different intracellular niches at different pH and oxygen concentrations, and to achieve a reduced dosage and frequency of administration could represent a prudent choice. An ideal drug delivery system should possess several properties, such as antimicrobial activ‐ ity, biodegradability, and biocompatibility, making it suitable for use in biomedical and pharmaceutical formulations. This approach will allow reviving old antibiotics rendered useless by resistance or toxicity, rescuing the last line therapy antibiotics by increasing the therapeutic index, widening the antimicrobial spectrum of antibiotics scaffolds that failed due to membrane permeability problems, and thus reducing the gap between in‐ creasingly drug-resistant pathogens and the development of new antibiotics. Different improved drug carriers have been developed for treating intracellular pathogens, includ‐ ing antibiotics loaded into liposomes, microspheres, polymeric carriers, and nanoplexes. The purpose of this chapter is to present the limitations of each class of antibiotics in tar‐ geting intracellular pathogens and the main research directions for the development of drug delivery systems for the intracellular release of antibiotics.

Nanoarchitectonics Used in Antiinfective Therapy

Although multiple approaches have emerged for reducing the microbial resistance and morbidity and mortality associated with persistent infections, current statistics reveal their poor efficiency. In this context, recent nanotechnological progress offers a new perspective in infection control, supported by highly specialized and efficient nanomaterials that can control the delivery, release, and efficiency of antimicrobial drugs in particular infections, thus reducing side effects and probably resistance rates. This chapter presents and discusses the current microbial resistance situation, which affects the entire world population and the perspective imposed by magnetite-based nanomaterials in developing alternative therapeutic and preventive antipathogenic approaches. Antimicrobial-functionalized magnetite nanoparticles, polymeric magnetite-based biomaterials, and enzyme-immobilization procedures in magnetic nanosystems with a great impact on antiinfectious therapies are also highlighted.