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      Nanomedicines for the Delivery of Biologics


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          A special symposium of the Academy of Pharmaceutical Sciences Nanomedicines Focus Group reviewed the current status of the use of nanomedicines for the delivery of biologics drugs. This meeting was particularly timely with the recent approval of the first siRNA-containing product Onpattro™ (patisiran), which is formulated as a lipid nanoparticle for intravenous infusion, and the increasing interest in the use of nanomedicines for the oral delivery of biologics. The challenges in delivering such molecules were discussed with specific emphasis on the delivery both across and into cells. The latest developments in Molecular Envelope Technology ® (Nanomerics Ltd, London, UK), liposomal drug delivery (both from an academic and industrial perspective), opportunities offered by the endocytic pathway, delivery using genetically engineered viral vectors (PsiOxus Technologies Ltd, Abingdon, UK), Transint™ technology (Applied Molecular Transport Inc., South San Francisco, CA, USA), which has the potential to deliver a wide range of macromolecules, and AstraZeneca’s initiatives in mRNA delivery were covered with a focus on their uses in difficult to treat diseases, including cancers. Preclinical data were presented for each of the technologies and where sufficiently advanced, plans for clinical studies as well as early clinical data. The meeting covered the work in progress in this exciting area and highlighted some key technologies to look out for in the future.

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          Most cited references55

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          Chaotic mixer for microchannels.

          It is difficult to mix solutions in microchannels. Under typical operating conditions, flows in these channels are laminar-the spontaneous fluctuations of velocity that tend to homogenize fluids in turbulent flows are absent, and molecular diffusion across the channels is slow. We present a passive method for mixing streams of steady pressure-driven flows in microchannels at low Reynolds number. Using this method, the length of the channel required for mixing grows only logarithmically with the Péclet number, and hydrodynamic dispersion along the channel is reduced relative to that in a simple, smooth channel. This method uses bas-relief structures on the floor of the channel that are easily fabricated with commonly used methods of planar lithography.
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            Engineered nanoparticles for drug delivery in cancer therapy.

            In medicine, nanotechnology has sparked a rapidly growing interest as it promises to solve a number of issues associated with conventional therapeutic agents, including their poor water solubility (at least, for most anticancer drugs), lack of targeting capability, nonspecific distribution, systemic toxicity, and low therapeutic index. Over the past several decades, remarkable progress has been made in the development and application of engineered nanoparticles to treat cancer more effectively. For example, therapeutic agents have been integrated with nanoparticles engineered with optimal sizes, shapes, and surface properties to increase their solubility, prolong their circulation half-life, improve their biodistribution, and reduce their immunogenicity. Nanoparticles and their payloads have also been favorably delivered into tumors by taking advantage of the pathophysiological conditions, such as the enhanced permeability and retention effect, and the spatial variations in the pH value. Additionally, targeting ligands (e.g., small organic molecules, peptides, antibodies, and nucleic acids) have been added to the surface of nanoparticles to specifically target cancerous cells through selective binding to the receptors overexpressed on their surface. Furthermore, it has been demonstrated that multiple types of therapeutic drugs and/or diagnostic agents (e.g., contrast agents) could be delivered through the same carrier to enable combination therapy with a potential to overcome multidrug resistance, and real-time readout on the treatment efficacy. It is anticipated that precisely engineered nanoparticles will emerge as the next-generation platform for cancer therapy and many other biomedical applications.
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              Vaccine Adjuvants: from 1920 to 2015 and Beyond

              The concept of stimulating the body’s immune response is the basis underlying vaccination. Vaccines act by initiating the innate immune response and activating antigen presenting cells (APCs), thereby inducing a protective adaptive immune response to a pathogen antigen. Adjuvants are substances added to vaccines to enhance the immunogenicity of highly purified antigens that have insufficient immunostimulatory capabilities, and have been used in human vaccines for more than 90 years. While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit. Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable. Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects. Activated effectors (such as APCs) then move to draining lymph nodes where they direct the type, magnitude and quality of the adaptive immune response. Thus, the right match of antigens and adjuvants can potentiate downstream adaptive immune responses, enabling the development of new efficacious vaccines. Many infectious diseases of worldwide significance are not currently preventable by vaccination. Adjuvants are the most advanced new technology in the search for new vaccines against challenging pathogens and for vulnerable populations that respond poorly to traditional vaccines.

                Author and article information

                03 May 2019
                May 2019
                : 11
                : 5
                [1 ]The Academy of Pharmaceutical Sciences, 4 Heydon Road, Great Chishill, Royston SG8 8SR, UK
                [2 ]Advanced Drug Delivery, Pharmaceutical Sciences, IMED Biotech Unit, AstraZeneca, Granta Park, Cambridge CB21 6GH, UK; Arpan.Desai@ 123456astrazeneca.com
                [3 ]Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AP, UK; f.greco@ 123456reading.ac.uk
                [4 ]Global Product Development, Pharmaceutical Technology and Development, Operations, AstraZeneca, Macclesfield SK10 2NA, UK; Kathryn.Hill@ 123456astrazeneca.com
                [5 ]Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, UK; JonesAT@ 123456cardiff.ac.uk
                [6 ]Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK; r.j.mrsny@ 123456bath.ac.uk
                [7 ]Pharmaceutical and Pharmacological Sciences Department, University of Padova, F. Marzolo 5, 35131 Padova, Italy; gianfranco.pasut@ 123456unipd.it
                [8 ]Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK; yvonne.perrie@ 123456strath.ac.uk (Y.P.); philipp.seib@ 123456strath.ac.uk (F.P.S.)
                [9 ]Department of Oncology, Old Road Campus Research Building, Oxford OX3 7DQ, UK; len.seymour@ 123456oncology.ox.ac.uk
                [10 ]UCL School of Pharmacy, London WC1N 1AX, UK; ijeoma.f.uchegbu@ 123456pharmacy.ac.uk
                Author notes
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                Meeting Report

                nanomedicines,drug delivery,sirna,mrna,dna,proteins,lipid nanoparticles,liposomes,viral vectors,endocytosis


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