Ocjena apsorpcije, djelotvornosti protiv bakterije Escherichia coli i citotoksičnosti krutih lipidnih nanočestica s moksifloksacinom

Moxifloxacin (MOX) is an important antibiotic commonly used in the treatment of recurrent Escherichia coli (E. coli) infections. The aim of this study was to investigate its antibacterial efficiency when used with solid lipid nanoparticles (SNLs) and nanostructured lipid carriers (NLCs) as delivery vehicles. For this purpose we designed two SLNs (SLN1 and SLN2) and two NLCs (NLC1 and NLC2) of different characteristics (particle size, size distribution, zeta potential, and encapsulation efficiency) and loaded them with MOX to determine its release, antibacterial activity against E. coli, and their cytotoxicity to the RAW 264.7 monocyte/macrophage-like cell line in vitro. With bacterial uptake of 57.29 %, SLN1 turned out to be significantly more effective than MOX given as standard solution, whereas SLN2, NLC1, and NLC2 formulations with respective bacterial uptakes of 50.74 %, 39.26 %, and 32.79 %, showed similar activity to standard MOX. Cytotoxicity testing did not reveal significant toxicity of nanoparticles, whether MOX-free or MOX-loaded, against RAW 264.7 cells. Our findings may show the way for a development of effective lipid carriers that reduce side effects and increase antibacterial treatment efficacy in view of the growing antibiotic resistance.Moksifloksacin je važan antibiotik koji se često rabi za liječenje rekurentne infekcije bakterijom Escherichia coli (E. coli). Cilj je ovog istraživanja bio ocijeniti njegovu djelotvornost u formulaciji s krutim lipidnim nanočesticama (engl. solid lipid nanoparticles, krat. SNL) i nanostrukturiranim lipidnim nosačima (engl. nanostructured lipid carriers, krat. NLC) kao njegovim vehikulima. U tu smo svrhu osmislili dva SLN-a (SLN1 I SLN2) te dva NLC-a (NLC1 i NLC2) različitih svojstava (veličine čestice, raspodjele veličina, zeta potencijala i sposobnosti enkapsulacije) te ih obogatili moksifloksacinom kako bismo utvrdili njegovo otpuštanje, djelovanje protiv E. coli i citotoksičnost za makrofagnu staničnu liniju RAW 264.7 in vitro. S bakterijskom apsorpcijom od 57,29 %, SLN1 se pokazao značajno djelotvornijim vehikulom moksifloksacina od njegove standardne formulacije (otopine), a formulacije s SLN2, NLC1 odnosno NLC2 s odgovarajućim apsorpcijama od 50,74 %, 39,26 % odnosno 32,79 % iskazale su djelotvornost sličnu onoj standardnog antibiotika. Test citotoksičnosti nije pokazao značajnu toksičnost nanočestica bez obzira na to jesu li sadržavale moksifloksacin ili nisu. Naši rezultati upućuju na mogući smjer razvoja djelotvornih lipidnih nosača kojima bi se mogle smanjiti nuspojave i povećati antibakterijska djelotvornost liječenja s obzirom na sve veću bakterijsku rezistentnost

In vitro and in vivo evaluation of linezolid loaded electrospun PLGA and PLGA/PCL fiber mats for prophylaxis and treatment of MRSA induced prosthetic infections

In this study, it was aimed to formulate linezolid loaded electrospun PLGA and PCL fiber mats doing controlled drug release, to be used in the treatment and prophylaxis of the prosthesis related infections. The effect of PLGA concentration, PLGA to PCL ratio and the amount of linezolid on the fiber and mat properties were examined. Fiber diameter has been shown to increase with increasing amount of PLGA and linezolid. Increase in PLGA amount resulted in reduced linezolid release, whereas increase in linezolid amount resulted in increased drug release. All PLGA fiber mats have shown to have favorable encapsulation efficiency (>= 73%) and mechanical properties. Encapsulation efficiency and the mechanical properties deteriorated with the addition of PCL to the formulations. PLGA fiber mats have shown a biphasic controlled release and in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), pattern up to one month. The formulation selected as the optimum has been evaluated in vivo on the infected rats, which had prosthetic implantation after bone fracture. Consequently, it has been demonstrated microbiologically and histopathologically that a more efficient therapy and prophylaxis have been achieved with a 37-fold lower dose of linezolid

Evaluation of a novel oxiconazole nitrate formulation: The thermosensitive gel

Superficial fungal infections caused by Candida species are common skin diseases. Therefore, this study aimed to develop a new formulation containing oxiconazole nitrate, which is an azole group derivative for antifungal treatment, as a thermosensitive gel since there has been no literature study until now.MIC value of the novel thermosensitive formulation against three Candida species was calculated and time-dependent antifungal activity analysis was performed. Viscosity, transition temperature Tsol-gel (°C) and gelation time of the thermosensitive gel formulation were also determined in the viscometer. The measurements performed on the tensilometer device were analyzed for adhesion hardness and elongation percentages of the formulation. In the FT-IR spectrometer, the spectrum of solution and gel state was compared between 650 and 4000 cm−1 and it was found that there is no difference between them.It was found that the temperature is reversible on the formulation and did not cause any disruption of its components. Characterization parameters of the thermosensitive gel formulation containing oxiconazole nitrate and time-dependent activity against Candida species was observed to be the same as those of the solution containing only oxiconazole nitrate. MIC, MFC and time-dependent antifungal analysis did not show any particular difference between formulation and oxiconazole nitrate itself. Thermosensitive gel formulation containing oxiconazole nitrate was found to be effective on superficial fungal infections. We believe it is also appropriate for in vivo usage, but it is necessary to perform animal and human research. It is also needed to evaluate the formulation against other etiologic agents of superficial fungal infections. Keywords: Oxiconazole nitrate, Thermosensitive gels, Poloxamer 407, Candida, Antifungal activit

Increased oxidative/nitrosative stress and decreased antioxidant enzyme activities in prostate cancer

Objectives The study was aimed to evaluate the oxidative/nitrosative stress status in prostate cancer (CaP) and benign prostatic hyperplasia (BPH). Design and methods 312 men from two different populations were included: 163 men from Macedonia (73 CaP patients, 67 BPH patients and 23 control subjects) and 149 men from Turkey (34 prostate cancer patients, 100 BPH patients and 15 control subjects). We measured erythrocyte malondialdehyde (MDA) levels, erythrocyte activities of superoxide dismutase (CuZn-SOD), glutathione peroxidase (GPX) and catalase (CAT); plasma nitrite/nitrate (NO2−/NO3−), cGMP and 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels. Results A similar pattern of alteration in the oxidative/nitrosative stress-related parameters was found in both, Macedonian and Turkish studied samples: higher MDA concentrations with lower GPX and CuZn-SOD activities in CaP patients versus controls and BPH groups. The CAT activity was decreased in the CaP patients versus controls in the Turkish studied sample. Furthermore, CaP patients had increased plasma NO2−/NO3− and cGMP levels versus controls and BPH groups in both studied samples. Conclusions This study has confirmed an imbalance in the oxidative stress/antioxidant status and revealed an altered nitrosative status in prostate cancer patients