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      Polymer based dual drug delivery system for targeted treatment of fluoroquinolone resistant Staphylococcus aureus mediated infections

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          Abstract

          The present study attempts to treat S. aureus-induced soft skin infections using a combinatorial therapy with an antibiotic, Ciprofloxacin (CIP), and an efflux pump inhibitor 5-Nitro-2-(3-phenylpropoxy) pyridine (5-NPPP) through a smart hydrogel delivery system. The study aims to reduce the increasing rates of infections and antimicrobial resistance; therefore, an efflux pump inhibitor molecule is synthesized and delivered along with an antibiotic to re-sensitize the pathogen towards antibiotics and treat the infections. CIP-loaded polyvinyl alcohol (PVA) hydrogels at varying concentrations were fabricated and optimized by a chemical cross-linking process, which exhibited sustained drug release for 5 days. The compound 5-NPPP loaded hydrogels provided linear drug release for 2 days, necessitating the need for the development of polymeric nanoparticles to alter the release drug pattern. 5-NPPP loaded Eudragit RSPO nanoparticles were prepared by modified nanoprecipitation—solvent evaporation method, which showed optimum average particle size of 230–280 nm with > 90% drug entrapment efficiency. The 5-NPPP polymeric nanoparticles loaded PVA hydrogels were fabricated to provide a predetermined sustained release of the compound to provide a synergistic effect. The selected 7% PVA hydrogels loaded with the dual drugs were evaluated using Balb/c mice models induced with S. aureus soft skin infections. The results of in vivo studies were evidence that the dual drugs loaded hydrogels were non-toxic and reduced the bacterial load causing re-sensitization towards antibiotics, which could initiate re-epithelization. The research concluded that the PVA hydrogels loaded with CIP and 5-NPPP nanoparticles could be an ideal and promising drug delivery system for treating S. aureus-induced skin infections.

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          Applications of nanoparticle systems in drug delivery technology

          The development of nanoparticle-based drug formulations has yielded the opportunities to address and treat challenging diseases. Nanoparticles vary in size but are generally ranging from 100 to 500 nm. Through the manipulation of size, surface characteristics and material used, the nanoparticles can be developed into smart systems, encasing therapeutic and imaging agents as well as bearing stealth property. Further, these systems can deliver drug to specific tissues and provide controlled release therapy. This targeted and sustained drug delivery decreases the drug related toxicity and increase patient’s compliance with less frequent dosing. Nanotechnology has proven beneficial in the treatment of cancer, AIDS and many other disease, also providing advancement in diagnostic testing.
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            Overcoming ABC transporter-mediated multidrug resistance: Molecular mechanisms and novel therapeutic drug strategies.

            Multidrug resistance is a key determinant of cancer chemotherapy failure. One of the major causes of multidrug resistance is the enhanced efflux of drugs by membrane ABC transporters. Targeting ABC transporters projects a promising approach to eliminating or suppressing drug resistance in cancer treatment. To reveal the functional mechanisms of ABC transporters in drug resistance, extensive studies have been conducted from identifying drug binding sites to elucidating structural dynamics. In this review article, we examined the recent crystal structures of ABC proteins to depict the functionally important structural elements, such as domains, conserved motifs, and critical amino acids that are involved in ATP-binding and drug efflux. We inspected the drug-binding sites on ABC proteins and the molecular mechanisms of various substrate interactions with the drug binding pocket. While our continuous battle against drug resistance is far from over, new approaches and technologies have emerged to push forward our frontier. Most recent developments in anti-MDR strategies include P-gp inhibitors, RNA-interference, nano-medicines, and delivering combination strategies. With the advent of the 'Omics' era - genomics, epigenomics, transcriptomics, proteomics, and metabolomics - these disciplines play an important role in fighting the battle against chemoresistance by further unraveling the molecular mechanisms of drug resistance and shed light on medical therapies that specifically target MDR.
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              Freeze-drying of nanoparticles: formulation, process and storage considerations.

              Freeze-drying has been considered as a good technique to improve the long-term stability of colloidal nanoparticles. The poor stability in an aqueous medium of these systems forms a real barrier against the clinical use of nanoparticles. This article reviews the state of the art of freeze-drying nanoparticles. It discusses the most important parameters that influence the success of freeze-drying of these fragile systems, and provides an overview of nanoparticles freeze-drying process and formulation strategies with a focus on the impact of formulation and process on particle stability.
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                Author and article information

                Contributors
                adlineprinzy@sastra.ac.in
                ramya@scbt.sastra.ac.in
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                14 July 2023
                14 July 2023
                2023
                : 13
                : 11373
                Affiliations
                [1 ]GRID grid.412423.2, ISNI 0000 0001 0369 3226, Quorum Sensing Laboratory, Centre for Research in Infectious Diseases (CRID), School of Chemical and Biotechnology, , SASTRA Deemed to be University, ; Thanjavur, 613401 India
                [2 ]GRID grid.412423.2, ISNI 0000 0001 0369 3226, Pharmaceutical Technology Laboratory, School of Chemical and Biotechnology, , SASTRA Deemed to be University, ; Thanjavur, 613401 India
                Article
                38473
                10.1038/s41598-023-38473-3
                10349073
                14a026b5-f9f7-434a-b846-561fcbe2a65b
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 18 February 2023
                : 9 July 2023
                Categories
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                © Springer Nature Limited 2023

                Uncategorized
                microbiology,health care
                Uncategorized
                microbiology, health care

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