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      Low-Molecular-Weight Heparins: Reduced Size Particulate Systems for Improved Therapeutic Outcomes

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          Abstract

          A wide range of diseases have been treated using low-molecular-weight heparins (LMWHs), the drug of choice for anticoagulation. Owing to their better pharmacokinetic features compared to those of unfractionated heparin (uFH), several systems incorporating LMWHs have been investigated to deliver and improve their therapeutic outcomes, especially through development of their micro- and nano-particles. This review article describes current perspectives on the fabrication, characterization, and application of LMWHs-loaded micro- and nano-particles to achieve ameliorated bioavailability. The valuable applications of LMWH will continue to encourage researchers to identify efficient delivery systems that have specific release characteristics and ameliorated bioavailability, overcoming the challenges presented by biological obstructions and the physicochemical properties of LMWHs.

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          Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

          David Garcia, Trevor P Baglin, Jeffrey Weitz … (2012)
          This article describes the pharmacology of approved parenteral anticoagulants. These include the indirect anticoagulants, unfractionated heparin (UFH), low-molecular-weight heparins (LMWHs), fondaparinux, and danaparoid, as well as the direct thrombin inhibitors hirudin, bivalirudin, and argatroban. UFH is a heterogeneous mixture of glycosaminoglycans that bind to antithrombin via a unique pentasaccharide sequence and catalyze the inactivation of thrombin, factor Xa, and other clotting enzymes. Heparin also binds to cells and plasma proteins other than antithrombin causing unpredictable pharmacokinetic and pharmacodynamic properties and triggering nonhemorrhagic side effects, such as heparin-induced thrombocytopenia (HIT) and osteoporosis. LMWHs have greater inhibitory activity against factor Xa than thrombin and exhibit less binding to cells and plasma proteins than heparin. Consequently, LMWH preparations have more predictable pharmacokinetic and pharmacodynamic properties, have a longer half-life than heparin, and are associated with a lower risk of nonhemorrhagic side effects. LMWHs can be administered once daily or bid by subcutaneous injection, without coagulation monitoring. Based on their greater convenience, LMWHs have replaced UFH for many clinical indications. Fondaparinux, a synthetic pentasaccharide, catalyzes the inhibition of factor Xa, but not thrombin, in an antithrombin-dependent fashion. Fondaparinux binds only to antithrombin. Therefore, fondaparinux-associated HIT or osteoporosis is unlikely to occur. Fondaparinux exhibits complete bioavailability when administered subcutaneously, has a longer half-life than LMWHs, and is given once daily by subcutaneous injection in fixed doses, without coagulation monitoring. Three additional parenteral direct thrombin inhibitors and danaparoid are approved as alternatives to heparin in patients with HIT.
          Article 0 comments Cited 228 times – based on 0 reviews     Review now
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            Biopolymer-Based Nanoparticles for Drug/Gene Delivery and Tissue Engineering

            Sachiko Kaihara Nitta, Keiji Numata (2013)
            There has been a great interest in application of nanoparticles as biomaterials for delivery of therapeutic molecules such as drugs and genes, and for tissue engineering. In particular, biopolymers are suitable materials as nanoparticles for clinical application due to their versatile traits, including biocompatibility, biodegradability and low immunogenicity. Biopolymers are polymers that are produced from living organisms, which are classified in three groups: polysaccharides, proteins and nucleic acids. It is important to control particle size, charge, morphology of surface and release rate of loaded molecules to use biopolymer-based nanoparticles as drug/gene delivery carriers. To obtain a nano-carrier for therapeutic purposes, a variety of materials and preparation process has been attempted. This review focuses on fabrication of biocompatible nanoparticles consisting of biopolymers such as protein (silk, collagen, gelatin, β-casein, zein and albumin), protein-mimicked polypeptides and polysaccharides (chitosan, alginate, pullulan, starch and heparin). The effects of the nature of the materials and the fabrication process on the characteristics of the nanoparticles are described. In addition, their application as delivery carriers of therapeutic drugs and genes and biomaterials for tissue engineering are also reviewed.
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              More than an anticoagulant: Do heparins have direct anti-inflammatory effects?

              Timothy Poterucha, Peter Libby, Samuel Z Goldhaber (2017)
              The heparins, well-known for their anticoagulant properties, may also have anti-inflammatory effects that could contribute to their effectiveness in the treatment of venous thromboembolism and other vascular diseases. This review focuses on the inflammatory pathophysiology that underlies the development of thrombosis and the putative effects of heparin on these pathways. We present evidence supporting the use of heparin for other indications, including autoimmune disease, malignancy, and disseminated intravascular coagulation. These considerations highlight the need for further research to elucidate the mechanisms of the possible pleiotropic effects of the heparins, with a view to advancing treatments based upon heparin derivatives.
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                Author and article information

                Contributors
                Marco Guerrini: Role: Academic Editor
                Edwin Alexander Yates: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Molecules
                Journal ID (iso-abbrev): Molecules
                Journal ID (publisher-id): molecules
                Title: Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
                Publisher: MDPI
                ISSN (Electronic): 1420-3049
                Publication date (Electronic): 18 July 2018
                Publication date Collection: July 2018
                Volume: 23
                Issue: 7
                Electronic Location Identifier: 1757
                Affiliations
                [1 ]School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China; tauriansfairy88@ 123456gmail.com (F.A.); 15951712208@ 123456163.com (X.W.); 18994103736@ 123456163.com (G.W.); 18018027031@ 123456163.com (S.W.)
                [2 ]State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; kessejnr@ 123456yahoo.com
                Author notes
                [* ]Correspondence: 1020040855@ 123456cpu.edu.cn ; Tel.: +86-157-2080-6012
                Article
                Publisher ID: molecules-23-01757
                DOI: 10.3390/molecules23071757
                PMC ID: 6100363
                PubMed ID: 30021958
                SO-VID: b0f0631d-4a09-4afe-a098-c1815ba48df4
                Copyright © © 2018 by the authors.
                License:

                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/).

                History
                Date received : 24 May 2018
                Date accepted : 04 July 2018
                Categories
                Subject: Review

                Keywords: low molecular weight heparins,stability,encapsulation,polymers,bioavailability
                Data availability:
                Keywords: low molecular weight heparins, stability, encapsulation, polymers, bioavailability

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