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      Paclitaxel-loaded sodium deoxycholate-stabilized zein nanoparticles: characterization and in vitro cytotoxicity

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          Abstract

          Paclitaxel (PTX) is one of the most successful antineoplastic drugs and is widely used for the treatment of many forms of advanced and refractory cancer. Unfortunately, various drawbacks including non-selective cytotoxicity, poor water solubility and low bioavailability limit its clinical use. The aim of this study was to characterize a novel colloidal system made up of the natural protein zein, that would be able to efficiently retain the anticancer compound and increase its in vitro pharmacological effects. In fact, zein has promising characteristics that render it a potential material to be used in drug delivery application. The influences of temperature, pH and serum incubation on the stability of these particles, entrapment efficiency of PTX and in vitro toxicity on different cancer cell lines were evaluated. The nanosystems containing PTX demonstrated suitable storage stability, and were not destabilized by temperatures of up to 50 °C, pH alterations, the freeze-drying process or serum proteins. The encapsulation of PTX did not destabilize the structure of the zein nanoparticles and a suitable drug entrapment efficiency resulted. PTX-loaded zein nanoparticles showed an increased toxicity on different cancer cell lines with respect to the free drug, confirming its potential application in preclinical and clinical investigations.

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          Most cited references42

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          Regulated portals of entry into the cell.

          The plasma membrane is the interface between cells and their harsh environment. Uptake of nutrients and all communication among cells and between cells and their environment occurs through this interface. 'Endocytosis' encompasses several diverse mechanisms by which cells internalize macromolecules and particles into transport vesicles derived from the plasma membrane. It controls entry into the cell and has a crucial role in development, the immune response, neurotransmission, intercellular communication, signal transduction, and cellular and organismal homeostasis. As the complexity of molecular interactions governing endocytosis are revealed, it has become increasingly clear that it is tightly coordinated and coupled with overall cell physiology and thus, must be viewed in a broader context than simple vesicular trafficking.
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            DLS and zeta potential - What they are and what they are not?

            Adequate characterization of NPs (nanoparticles) is of paramount importance to develop well defined nanoformulations of therapeutic relevance. Determination of particle size and surface charge of NPs are indispensable for proper characterization of NPs. DLS (dynamic light scattering) and ZP (zeta potential) measurements have gained popularity as simple, easy and reproducible tools to ascertain particle size and surface charge. Unfortunately, on practical grounds plenty of challenges exist regarding these two techniques including inadequate understanding of the operating principles and dealing with critical issues like sample preparation and interpretation of the data. As both DLS and ZP have emerged from the realms of physical colloid chemistry - it is difficult for researchers engaged in nanomedicine research to master these two techniques. Additionally, there is little literature available in drug delivery research which offers a simple, concise account on these techniques. This review tries to address this issue while providing the fundamental principles of these techniques, summarizing the core mathematical principles and offering practical guidelines on tackling commonly encountered problems while running DLS and ZP measurements. Finally, the review tries to analyze the relevance of these two techniques from translatory perspective.
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              To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine?

              F Danhier (2016)
              Tumor targeting by nanomedicine-based therapeutics has emerged as a promising approach to overcome the lack of specificity of conventional chemotherapeutic agents and to provide clinicians the ability to overcome shortcomings of current cancer treatment. The major underlying mechanism of the design of nanomedicines was the Enhanced Permeability and Retention (EPR) effect, considered as the "royal gate" in the drug delivery field. However, after the publication of thousands of research papers, the verdict has been handed down: the EPR effect works in rodents but not in humans! Thus the basic rationale of the design and development of nanomedicines in cancer therapy is failing making it necessary to stop claiming efficacy gains via the EPR effect, while tumor targeting cannot be proved in the clinic. It is probably time to dethrone the EPR effect and to ask the question: what is the future of nanomedicines without the EPR effect? The aim of this review is to provide a general overview on (i) the current state of the EPR effect, (ii) the future of nanomedicine and (iii) the strategies of modulation of the tumor microenvironment to improve the delivery of nanomedicine.
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                Author and article information

                Contributors
                Journal
                Heliyon
                Heliyon
                Heliyon
                Elsevier
                2405-8440
                06 September 2019
                September 2019
                06 September 2019
                : 5
                : 9
                : e02422
                Affiliations
                [a ]Department of Experimental and Clinical Medicine, University “Magna Græcia” of Catanzaro, Campus Universitario “S. Venuta”, I-88100, Catanzaro, Italy
                [b ]Department of Health Sciences, University “Magna Græcia” of Catanzaro, Campus Universitario “S. Venuta”, I-88100, Catanzaro, Italy
                [c ]Department of Pharmacy, University of Chieti - Pescara “G. d'Annunzio”, via dei Vestini 31, 66100, Chieti, Italy
                Author notes
                []Corresponding author. donatocosco@ 123456unicz.it
                [∗∗ ]Corresponding author. fresta@ 123456unicz.it
                Article
                S2405-8440(19)36082-7 e02422
                10.1016/j.heliyon.2019.e02422
                6734341
                31517130
                84b3a973-baf9-48c9-be2f-54fc5769a6a6
                © 2019 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 4 April 2019
                : 18 July 2019
                : 2 September 2019
                Categories
                Article

                nanotechnology,physical chemistry,nanoparticles,paclitaxel,sodium deoxycholate,turbiscan stability index,zein

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