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      Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles

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          Abstract

          The application of nanomedicines is increasing rapidly with the promise of targeted and efficient drug delivery. Nanomedicines address the shortcomings of conventional therapy, as evidenced by several preclinical and clinical investigations indicating site-specific drug delivery, reduced side effects, and better treatment outcome. The development of suitable and biocompatible drug delivery vehicles is a prerequisite that has been successfully achieved by using simple and functionalized liposomes, nanoparticles, hydrogels, micelles, dendrimers, and mesoporous particles. A variety of drug delivery vehicles have been established for the targeted and controlled delivery of therapeutic agents in a wide range of chronic diseases, such as diabetes, cancer, atherosclerosis, myocardial ischemia, asthma, pulmonary tuberculosis, Parkinson’s disease, and Alzheimer’s disease. After successful outcomes in preclinical and clinical trials, many of these drugs have been marketed for human use, such as Abraxane®, Caelyx®, Mepact®, Myocet®, Emend®, and Rapamune®. Apart from drugs/compounds, novel therapeutic agents, such as peptides, nucleic acids (DNA and RNA), and genes have also shown potential to be used as nanomedicines for the treatment of several chronic ailments. However, a large number of extensive clinical trials are still needed to ensure the short-term and long-term effects of nanomedicines in humans. This review discusses the advantages of various drug delivery vehicles for better understanding of their utility in terms of current medical needs. Furthermore, the application of a wide range of nanomedicines is also described in the context of major chronic diseases.

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          Hydrogels in pharmaceutical formulations.

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          The availability of large molecular weight protein- and peptide-based drugs due to the recent advances in the field of molecular biology has given us new ways to treat a number of diseases. Synthetic hydrogels offer a possibly effective and convenient way to administer these compounds. Hydrogels are hydrophilic, three-dimensional networks, which are able to imbibe large amounts of water or biological fluids, and thus resemble, to a large extent, a biological tissue. They are insoluble due to the presence of chemical (tie-points, junctions) and/or physical crosslinks such as entanglements and crystallites. These materials can be synthesized to respond to a number of physiological stimuli present in the body, such as pH, ionic strength and temperature. The aim of this article is to present a concise review on the applications of hydrogels in the pharmaceutical field, hydrogel characterization and analysis of drug release from such devices.
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            Controlled drug delivery vehicles for cancer treatment and their performance

            Although conventional chemotherapy has been successful to some extent, the main drawbacks of chemotherapy are its poor bioavailability, high-dose requirements, adverse side effects, low therapeutic indices, development of multiple drug resistance, and non-specific targeting. The main aim in the development of drug delivery vehicles is to successfully address these delivery-related problems and carry drugs to the desired sites of therapeutic action while reducing adverse side effects. In this review, we will discuss the different types of materials used as delivery vehicles for chemotherapeutic agents and their structural characteristics that improve the therapeutic efficacy of their drugs and will describe recent scientific advances in the area of chemotherapy, emphasizing challenges in cancer treatments.
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              GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus.

              In healthy humans, the incretin glucagon-like peptide 1 (GLP-1) is secreted after eating and lowers glucose concentrations by augmenting insulin secretion and suppressing glucagon release. Additional effects of GLP-1 include retardation of gastric emptying, suppression of appetite and, potentially, inhibition of β-cell apoptosis. Native GLP-1 is degraded within ~2-3 min in the circulation; various GLP-1 receptor agonists have, therefore, been developed to provide prolonged in vivo actions. These GLP-1 receptor agonists can be categorized as either short-acting compounds, which provide short-lived receptor activation (such as exenatide and lixisenatide) or as long-acting compounds (for example albiglutide, dulaglutide, exenatide long-acting release, and liraglutide), which activate the GLP-1 receptor continuously at their recommended dose. The pharmacokinetic differences between these drugs lead to important differences in their pharmacodynamic profiles. The short-acting GLP-1 receptor agonists primarily lower postprandial blood glucose levels through inhibition of gastric emptying, whereas the long-acting compounds have a stronger effect on fasting glucose levels, which is mediated predominantly through their insulinotropic and glucagonostatic actions. The adverse effect profiles of these compounds also differ. The individual properties of the various GLP-1 receptor agonists might enable incretin-based treatment of type 2 diabetes mellitus to be tailored to the needs of each patient.
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                Author and article information

                Contributors
                pmaiti.mst@itbhu.ac.in
                Journal
                Signal Transduct Target Ther
                Signal Transduct Target Ther
                Signal Transduction and Targeted Therapy
                Nature Publishing Group UK (London )
                2095-9907
                2059-3635
                30 August 2019
                30 August 2019
                2019
                : 4
                : 33
                Affiliations
                GRID grid.467228.d, School of Materials Science and Technology, , Indian Institute of Technology (BHU), ; Varanasi, 221005 India
                Author information
                http://orcid.org/0000-0002-7028-6388
                Article
                68
                10.1038/s41392-019-0068-3
                6799838
                31637012
                91b045bc-e1cf-4270-be98-0012e1282c0c
                © 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
                : 20 June 2019
                : 1 August 2019
                : 1 August 2019
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2019

                cardiovascular diseases,diseases
                cardiovascular diseases, diseases

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