Alexandru Mihai Grumezescu

Hybrid magnetite nanoparticles/Rosmarinus officinalis essential oil nanobiosystem with antibiofilm activity

Biofilms formed by fungal organisms are associated with drastically enhanced resistance against most antimicrobial agents, contributing to the persistence of the fungi despite antifungal therapy. The purpose of this study is to combine the unique properties of nanoparticles with the antimicrobial activity of the Rosmarinus officinalis essential oil in order to obtain a nanobiosystem that could be pelliculised on the surface of catheter pieces, in order to obtain an improved resistance to microbial colonization and biofilm development by Candida albicans and C. tropicalis clinical strains. The R. officinalis essential oils were extracted in a Neo-Clevenger type apparatus, and its chemical composition was settled by GC-MS analysis. Functionalized magnetite nanoparticles of up to 20 nm size had been synthesized by precipitation method adapted for microwave conditions, with oleic acid as surfactant. The catheter pieces were coated with suspended core/shell nanoparticles (Fe3O4/oleic acid:CHCl3), by applying a magnetic field on nanofluid, while the CHCl3 diluted essential oil was applied by adsorption in a secondary covering treatment. The fungal adherence ability was investigated in six multiwell plates, in which there have been placed catheters pieces with and without hybrid nanoparticles/essential oil nanobiosystem pellicle, by using culture-based methods and confocal laser scanning microscopy (CLSM). The R. officinalis essential oil coated nanoparticles strongly inhibited the adherence ability and biofilm development of the C. albicans and C. tropicalis tested strains to the catheter surface, as shown by viable cell counts and CLSM examination. Due to the important implications of Candida spp. in human pathogenesis, especially in prosthetic devices related infections and the emergence of antifungal tolerance/resistance, using the new core/shell/coated shell based on essential oil of R. officinalis to inhibit the fungal adherence could be of a great interest for the biomedical field, opening new directions for the design of film-coated surfaces with antibiofilm properties.

Laser deposition of poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) – lysozyme microspheres based coatings with anti-microbial properties

The purpose of this study was to obtain, characterize and evaluate the cytotoxicity and antimicrobial activity of coatings based on poly(3-hydroxybutyric acid-co-3-hydroxyvaleric acid) - Lysozyme (P(3HB-3HV)/Lys) and P(3HB-3HV) - Polyethylene glycol - Lysozyme (P(3HB-3HV)/PEG/Lys) spheres prepared by Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique, in order to obtain functional and improved Ti-based implants. Morphological investigation of the coatings by Infrared Microscopy (IRM) and SEM revealed that the average diameter of P(3HB-3HV)/Lys spheres is around 2μm and unlike the drop cast samples, IRM recorded on MAPLE films revealed a good distribution of monitored functional groups on the entire scanned surface. The biological evaluation of MAPLE structured surfaces revealed an improved biocompatibility with respect to osteoblasts and endothelial cells as compared with Ti substrates and an enhanced anti-biofilm effect against Gram positive (Staphylococcus aureus) and Gram negative (Pseudomonas aeruginosa) tested strains. Thus, we propose that the fabricated P(3HB-3HV)/PEG/Lys and P(3HB-3HV)/Lys microspheres may be efficiently used as a matrix for controlled local drug delivery, with practical applications in developing improved medical surfaces for the reduction of implant-associated infections.

Preparation and Antimicrobial Activity of Inorganic Nanoparticles

Abstract Nanotechnology provides unique alternatives to control the biological and medical processes to achieve benefits for biology and medicine. Nanoparticles provide appealing properties such as high stability and the possibility of changing their surface characteristics very easily. Metal oxide nanoparticles are promising antimicrobial agents because they do not cause resistance and have good microbicidal activity. This review is focused on applications and properties of inorganic nanostructured materials and discusses the main advantages and risks of using different metal and metal oxide nanoparticles, such as silver nanoparticles, gold nanoparticles, zinc oxide nanoparticles, magnetite nanoparticles, and copper oxide nanoparticles as antimicrobial agents.

Applications of nanoscale drugs carriers in the treatment of chronic diseases

Nanomedicine plays an important role in the medical field for applications as drug delivery and diagnosis. The requirement for the development of multiple systems, which can precisely and specifically deliver the pharmaceutical agent into the desired site, has increased over the last decade. These systems have a great impact in medical fields, such as oncology, cardiology, and immunology. In this regard, smart drug delivery systems with response to stimuli, such as pH, temperature, light, ultrasounds, electrical, and magnetical fields have been developed. Many nanoparticles have been investigated for drug targeting as nanocarriers, including gold NPs, silver NPs, magnetic NPs, quantum dots, and mesoporous silica NPs.

Bioactive mesoporous silica nanostructures with anti-microbial and anti-biofilm properties

The increasing rate of antibiotic resistant bacteria associated with nosocomial infections in severely ill patients has urged the need for new antibacterial therapies. Nanostructured materials represent emerging innovative approaches to controlled delivery of different antimicrobial drugs. Delivery systems encapsulating natural compounds with antibacterial effects, such as essential oils have shown a great potential. Herein we report the development of SiO2 mesoporous nanosystems loaded with eucalyptus (EUC), orange (ORA), and cinnamon (CIN) essential oils. These systems were characterized with respect to morphology (using scanning electron microscopy, SEM, and transmission electron microscopy, TEM), porosity (by BET and TEM analysis), chemical composition (by X-ray diffraction, XRD, and Fourier transform infrared spectrometry, FTIR) and loading capacity (by thermogravimetric analysis, TGA). The anti-bacterial and anti-adherence effects were tested against clinically relevant microbial species (Staphylococcus aureus ATCC 25923; Escherichia coli ATCC 25922; and Candida albicans ATCC 10231), while the biocompatibility was evaluated by in vitro tests with L929 mouse fibroblast cells.

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.

Renoprotective Effects of Shout Camphor Medicinal Mushroom ( Taiwanofungus camphorates , Basidiomycetes) Mycelia on Several Media in Mice with Chronic Kidney Disease

Taiwanofungus camphoratus has been widely used in Taiwan as a folk medicine to prevent and treat liver diseases, diarrhea, abdominal pain, itchy skin, and hypertension. Recent studies have shown that T. camphoratus mycelia extracts exert anti-inflammatory and antioxidant effects on some types of renal disease, but the effect of T. camphoratus mycelia on chronic kidney disease (CKD) remains unclear. In this study we used the Bioresource Collection and Research Center (BCRC) medium and modified media (e.g., BCRC+A, HKS1, and HKS1+A media) to incubate T. camphorates mycelia and detect the feasible benefits of renal protection in mice with CKD. Five groups of mice with a partial nephrectomy (each mouse weighed approximately 30 g) received a daily administration of different media-treated T. camphoratus mycelia water solutions (3 mg dried mycelia dissolved in 0.3 mL water) by oral gavage for 30 days, while a control group received distilled water. The results show that progressive increased blood urea nitrogen and serum creatinine were significantly inhibited in the HKS1+A group on days 10 and 30. Plasma total protein was effectively increased in the HKS1 and HKS1+A groups. The BCRC and BCRC+A groups exhibited no obvious improvement in renal function. The results suggest that the HKS1+A medium provides the optimal effect in preventing the deterioration of kidney function and might have a renoprotective effect on CKD.