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      Carriers for the targeted delivery of aerosolized macromolecules for pulmonary pathologies

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          ABSTRACT

          Introduction: Macromolecules with unique effects and potency are increasingly being considered for application in lung pathologies. Numerous delivery strategies for these macromolecules through the lung have been investigated to improve the targeting and overall efficacy.

          Areas covered: Targeting approaches from delivery devices, formulation strategies and specific targets are discussed.

          Expert opinion: Although macromolecules are a heterogeneous group of molecules, a number of strategies have been investigated at the macro, micro, and nanoscopic scale for the delivery of macromolecules to specific sites and cells of lung tissues. Targeted approaches are already in use at the macroscopic scale through inhalation devices and formulations, but targeting strategies at the micro and nanoscopic scale are still in the laboratory stage. The combination of controlling lung deposition and targeting after deposition, through a combination of targeting strategies could be the future direction for the treatment of lung pathologies through the pulmonary route.

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          Most cited references80

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          Small RNAs in transcriptional gene silencing and genome defence.

          Small RNA molecules of about 20-30 nucleotides have emerged as powerful regulators of gene expression and genome stability. Studies in fission yeast and multicellular organisms suggest that effector complexes, directed by small RNAs, target nascent chromatin-bound non-coding RNAs and recruit chromatin-modifying complexes. Interactions between small RNAs and nascent non-coding transcripts thus reveal a new mechanism for targeting chromatin-modifying complexes to specific chromosome regions and suggest possibilities for how the resultant chromatin states may be inherited during the process of chromosome duplication.
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            Liposomes as vaccine delivery systems: a review of the recent advances.

            Liposomes and liposome-derived nanovesicles such as archaeosomes and virosomes have become important carrier systems in vaccine development and the interest for liposome-based vaccines has markedly increased. A key advantage of liposomes, archaeosomes and virosomes in general, and liposome-based vaccine delivery systems in particular, is their versatility and plasticity. Liposome composition and preparation can be chosen to achieve desired features such as selection of lipid, charge, size, size distribution, entrapment and location of antigens or adjuvants. Depending on the chemical properties, water-soluble antigens (proteins, peptides, nucleic acids, carbohydrates, haptens) are entrapped within the aqueous inner space of liposomes, whereas lipophilic compounds (lipopeptides, antigens, adjuvants, linker molecules) are intercalated into the lipid bilayer and antigens or adjuvants can be attached to the liposome surface either by adsorption or stable chemical linking. Coformulations containing different types of antigens or adjuvants can be combined with the parameters mentioned to tailor liposomal vaccines for individual applications. Special emphasis is given in this review to cationic adjuvant liposome vaccine formulations. Examples of vaccines made with CAF01, an adjuvant composed of the synthetic immune-stimulating mycobacterial cordfactor glycolipid trehalose dibehenate as immunomodulator and the cationic membrane forming molecule dimethyl dioctadecylammonium are presented. Other vaccines such as cationic liposome-DNA complexes (CLDCs) and other adjuvants like muramyl dipeptide, monophosphoryl lipid A and listeriolysin O are mentioned as well. The field of liposomes and liposome-based vaccines is vast. Therefore, this review concentrates on recent and relevant studies emphasizing current reports dealing with the most studied antigens and adjuvants, and pertinent examples of vaccines. Studies on liposome-based veterinary vaccines and experimental therapeutic cancer vaccines are also summarized.
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              Mucosal BCG Vaccination Induces Protective Lung-Resident Memory T Cell Populations against Tuberculosis

              ABSTRACT Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only licensed vaccine against tuberculosis (TB), yet its moderate efficacy against pulmonary TB calls for improved vaccination strategies. Mucosal BCG vaccination generates superior protection against TB in animal models; however, the mechanisms of protection remain elusive. Tissue-resident memory T (TRM) cells have been implicated in protective immune responses against viral infections, but the role of TRM cells following mycobacterial infection is unknown. Using a mouse model of TB, we compared protection and lung cellular infiltrates of parenteral and mucosal BCG vaccination. Adoptive transfer and gene expression analyses of lung airway cells were performed to determine the protective capacities and phenotypes of different memory T cell subsets. In comparison to subcutaneous vaccination, intratracheal and intranasal BCG vaccination generated T effector memory and TRM cells in the lung, as defined by surface marker phenotype. Adoptive mucosal transfer of these airway-resident memory T cells into naive mice mediated protection against TB. Whereas airway-resident memory CD4+ T cells displayed a mixture of effector and regulatory phenotype, airway-resident memory CD8+ T cells displayed prototypical TRM features. Our data demonstrate a key role for mucosal vaccination-induced airway-resident T cells in the host defense against pulmonary TB. These results have direct implications for the design of refined vaccination strategies.
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                Author and article information

                Journal
                Expert Opin Drug Deliv
                Expert Opin Drug Deliv
                IEDD
                iedd20
                Expert Opinion on Drug Delivery
                Taylor & Francis
                1742-5247
                1744-7593
                2018
                26 July 2018
                : 15
                : 8
                : 821-834
                Affiliations
                [a ]School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University , Liverpool, UK
                Author notes
                CONTACT Imran Saleem i.saleem@ 123456ljmu.ac.uk Liverpool John Moores University, School of Pharmacy & Biomolecular Sciences , Byrom Street, Liverpool, L3 3AF, UK
                [*]

                These authors contributed equally to this article

                Article
                1502267
                10.1080/17425247.2018.1502267
                6110405
                30021074
                38e1281b-8613-44a9-8989-5135ecd96f0f
                © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 April 2018
                : 16 July 2018
                Page count
                Figures: 6, Tables: 3, References: 97, Pages: 14
                Funding
                Funded by: Medical Research Council 10.13039/501100000265
                Award ID: MR/P022758/1
                Funding was received from Medical Research Council [Grant Ref: MR/P022758/1].
                Categories
                Review

                aerosol devices,inhaled macromolecules,lung delivery,microcarrier,nanocarrier,nanomedicine,lipid-based systems,passive and active targeting,pulmonary pathologies

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