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      Self-assembled hyaluronan nanocapsules for the intracellular delivery of anticancer drugs

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          Abstract

          Preparation of sophisticated delivery systems for nanomedicine applications generally involve multi-step procedures using organic solvents. In this study, we have developed a simple self-assembling process to prepare docetaxel-loaded hyaluronic acid (HA) nanocapsules by using a self-emulsification process without the need of organic solvents, heat or high shear forces. These nanocapsules, which comprise an oily core and a shell consisting of an assembly of surfactants and hydrophobically modified HA, have a mean size of 130 nm, a zeta potential of −20 mV, and exhibit high docetaxel encapsulation efficiency. The nanocapsules exhibited an adequate stability in plasma. Furthermore, in vitro studies performed using A549 lung cancer cells, showed effective intracellular delivery of docetaxel. On the other hand, blank nanocapsules showed very low cytotoxicity. Overall, these results highlight the potential of self-emulsifying HA nanocapsules for intracellular drug delivery.

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          Green chemistry for nanoparticle synthesis.

          The application of the twelve principles of green chemistry in nanoparticle synthesis is a relatively new emerging issue concerning the sustainability. This field has received great attention in recent years due to its capability to design alternative, safer, energy efficient, and less toxic routes towards synthesis. These routes have been associated with the rational utilization of various substances in the nanoparticle preparations and synthetic methods, which have been broadly discussed in this tutorial review. This article is not meant to provide an exhaustive overview of green synthesis of nanoparticles, but to present several pivotal aspects of synthesis with environmental concerns, involving the selection and evaluation of nontoxic capping and reducing agents, the choice of innocuous solvents and the development of energy-efficient synthetic methods.
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            Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile.

            We describe the development and clinical translation of a targeted polymeric nanoparticle (TNP) containing the chemotherapeutic docetaxel (DTXL) for the treatment of patients with solid tumors. DTXL-TNP is targeted to prostate-specific membrane antigen, a clinically validated tumor antigen expressed on prostate cancer cells and on the neovasculature of most nonprostate solid tumors. DTXL-TNP was developed from a combinatorial library of more than 100 TNP formulations varying with respect to particle size, targeting ligand density, surface hydrophilicity, drug loading, and drug release properties. Pharmacokinetic and tissue distribution studies in rats showed that the NPs had a blood circulation half-life of about 20 hours and minimal liver accumulation. In tumor-bearing mice, DTXL-TNP exhibited markedly enhanced tumor accumulation at 12 hours and prolonged tumor growth suppression compared to a solvent-based DTXL formulation (sb-DTXL). In tumor-bearing mice, rats, and nonhuman primates, DTXL-TNP displayed pharmacokinetic characteristics consistent with prolonged circulation of NPs in the vascular compartment and controlled release of DTXL, with total DTXL plasma concentrations remaining at least 100-fold higher than sb-DTXL for more than 24 hours. Finally, initial clinical data in patients with advanced solid tumors indicated that DTXL-TNP displays a pharmacological profile differentiated from sb-DTXL, including pharmacokinetics characteristics consistent with preclinical data and cases of tumor shrinkage at doses below the sb-DTXL dose typically used in the clinic.
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              Nano-emulsions

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                Author and article information

                Contributors
                dolores.torres@usc.es
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                9 August 2019
                9 August 2019
                2019
                : 9
                : 11565
                Affiliations
                [1 ]ISNI 0000000109410645, GRID grid.11794.3a, Nanobiofar Group, IDIS, CIMUS, , University of Santiago de Compostela, ; Santiago de Compostela, Spain
                [2 ]ISNI 0000000109410645, GRID grid.11794.3a, Department of Pharmaceutics and Pharmaceutical Technology, School of Pharmacy, , University of Santiago de Compostela, ; Santiago de Compostela, Spain
                [3 ]ISNI 0000 0000 8814 392X, GRID grid.417555.7, Sanofi-Global R&D, Sanofi US, ; Waltham, USA
                [4 ]ISNI 0000 0001 2181 4263, GRID grid.9983.b, Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, , Universidade de Lisboa, ; Lisbon, Portugal
                [5 ]ISNI 0000 0001 2248 3363, GRID grid.7252.2, Micro et Nanomedecines Translationnelles, MINT, , Université Angers, INSERM 1066, CNRS 6021, 4 rue Larrey, ; Angers, France
                [6 ]ISNI 0000 0000 9403 4738, GRID grid.420359.9, Nano-Oncology Unit, Translational Medical Oncology Group, , Health Research Institute of Santiago de Compostela (IDIS), SERGAS, ; Santiago de Compostela, Spain
                [7 ]Cancer Network Research (CIBERONC), Madrid, Spain
                Author information
                http://orcid.org/0000-0002-6799-2740
                http://orcid.org/0000-0002-6393-6469
                Article
                47995
                10.1038/s41598-019-47995-8
                6689112
                31399627
                e096a3f5-5f1a-4cdb-991f-2852e652bf56
                © The Author(s) 2019

                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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 18 April 2019
                : 22 July 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100000785, EC | Education, Audiovisual and Culture Executive Agency (EACEA);
                Funded by: Grant attributed under the Nanofar Program, Erasmus Mundus Joint Doctorate (EMJD)
                Funded by: FundRef https://doi.org/10.13039/501100008425, Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (Ministry of Culture, Education and University Planning, Government of Galicia);
                Award ID: GRC2013-043
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized
                cell delivery,chemical modification,drug delivery,nanoparticles
                Uncategorized
                cell delivery, chemical modification, drug delivery, nanoparticles

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