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      Drug Design, Development and Therapy (submit here)

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      Optimization of nebulized delivery of linezolid, daptomycin, and vancomycin aerosol


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          At this time, several antibiotics have been investigated as possibilities for aerosol administration, but local therapy has been found to be more efficient in several diseases.

          Materials and methods

          The drugs linezolid (Zyvox), vancomycin (Voncon), and daptomycin (Cubicin) were tested with three jet nebulizers with seven different residual cups and different loadings. Moreover, three ultrasound nebulizers were again tested with these drugs, with different loadings and mouthpiece attachments.


          When drugs are combined with particular cup designs, they significantly lower the droplet size to 1.60 and 1.80 μm, which represents the best combination of Zyvox and cup G and Cubicin and cup D, respectively. Cup design D is suggested as the most effective cup for lowering the droplet size (2.30 μm) when considering a higher loading level (8 mL).


          Modification of current drugs from dry powder to solution is possible, and the residual cup design plays the most important role in droplet size production when the nebulization systems have the same properties.

          Most cited references35

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          Vancomycin: a 50-year reassessment.

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            Inhaled chemotherapy in lung cancer: future concept of nanomedicine

            Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects.
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              Daptomycin: mechanisms of action and resistance, and biosynthetic engineering.

              Daptomycin is a lipopeptide antibiotic used clinically to treat infections caused by Gram-positive bacteria. Laboratory studies have shown that Staphylococcus aureus resistance to daptomycin occurs stepwise and slowly. Mutations associated with decreased susceptibility were mapped in mprF, yycG, rpoB, and rpoC, each giving about twofold increases in the minimal inhibitory concentration (MIC) and combinations giving higher MICs. The mprF gene encodes a dual functional enzyme that couples lysine to phosphatidylglycerol (PG) and transfers the lysyl-PG (LPG) to the outer leaflet of the membrane. LPG is less acidic than PG, and thus reduces the binding of Ca(++)-bound daptomycin to bacterial membranes. The mprF mutants have higher LPG/PG ratios in the membrane outer leaflet and bind less daptomycin than the wild-type strain. YycG is a sensor histidine kinase of a two component signal transduction system required for viability in many low G+C Gram-positive bacteria. The observation of DapR mutations in yycG suggests that YycG may be a target for daptomycin antibacterial activity. Daptomycin inserts into PG rich membrane at the cell division septum, but also inserts into lung surfactant, explaining why it failed to meet non-inferiority criteria in clinical trials for community acquired pneumonia (CAP). Recent advances in biosynthetic engineering have provided new tools to generate novel lipopeptides with modifications in the core peptide: several were very potent antibiotics against Gram-positive pathogens, and some were active in the presence of surfactant.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                12 August 2014
                : 8
                : 1065-1072
                [1 ]Pulmonary Department-Oncology Unit, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
                [2 ]Department of Food Technology, School of Food Technology and Nutrition, Alexander Technological Educational Institute, Thessaloniki, Greece
                [3 ]Department of Respiratory Diseases, Shanghai Hospital, II Military University Hospital, Shanghai, People’s Republic of China
                [4 ]Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA
                [5 ]II Medical Department, “Coburg” Regional Hospital, Coburg, Germany
                [6 ]Surgery Department, Private Cabinet, Serres, Greece
                Author notes
                Correspondence: Paul Zarogoulidis, Pulmonary Department, “G Papanikolaou” General Hospital, Aristotle University of Thessaloniki, Thessaloniki 55236, Greece, Tel +30 231 034 0370, Fax +30 213 099 2433, Email pzarog@ 123456hotmail.com
                © 2014 Zarogoulidis et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research

                Pharmacology & Pharmaceutical medicine
                vancomycin,linezolid,daptomycin,aerosol,jet nebulizers,ultrasound nebulizers


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