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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

      105,621 Monthly downloads/views I 7.033 Impact Factor I 10.9 CiteScore I 1.22 Source Normalized Impact per Paper (SNIP) I 1.032 Scimago Journal & Country Rank (SJR)

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      Nano-vectors for efficient liver specific gene transfer

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          Abstract

          Recent progress in nanotechnology has triggered the site specific drug/gene delivery research and gained wide acknowledgment in contemporary DNA therapeutics. Amongst various organs, liver plays a crucial role in various body functions and in addition, the site is a primary location of metastatic tumor growth. In past few years, a plethora of nano-vectors have been developed and investigated to target liver associated cells through receptor mediated endocytosis. This emerging paradigm in cellular drug/gene delivery provides promising approach to eradicate genetic as well as acquired diseases affecting the liver. The present review provides a comprehensive overview of potential of various delivery systems, viz., lipoplexes, liposomes, polyplexes, nanoparticles and so forth to selectively relocate foreign therapeutic DNA into liver specific cell type via the receptor mediated endocytosis. Various receptors like asialoglycoprotein receptors (ASGP-R) provide unique opportunity to target liver parenchymal cells. The results obtained so far reveal tremendous promise and offer enormous options to develop novel DNA-based pharmaceuticals for liver disorders in near future.

          Most cited references98

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          Regulated portals of entry into the cell.

          Sean D. Conner, Sandra Schmid (2003)
          The plasma membrane is the interface between cells and their harsh environment. Uptake of nutrients and all communication among cells and between cells and their environment occurs through this interface. 'Endocytosis' encompasses several diverse mechanisms by which cells internalize macromolecules and particles into transport vesicles derived from the plasma membrane. It controls entry into the cell and has a crucial role in development, the immune response, neurotransmission, intercellular communication, signal transduction, and cellular and organismal homeostasis. As the complexity of molecular interactions governing endocytosis are revealed, it has become increasingly clear that it is tightly coordinated and coupled with overall cell physiology and thus, must be viewed in a broader context than simple vesicular trafficking.
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            Rapid endo-lysosomal escape of poly(DL-lactide-co-glycolide) nanoparticles: implications for drug and gene delivery.

            Swayam Prabha, Vinod Labhasetwar, S. Sahoo … (2002)
            The endo-lysosomal escape of drug carriers is crucial to enhancing the efficacy of their macromolecular payload, especially the payloads that are susceptible to lysosomal degradation. Current vectors that enable the endo-lysosomal escape of macromolecules such as DNA are limited by their toxicity and by their ability to carry only limited classes of therapeutic agents. In this paper, we report the rapid (<10 min) endo-lysosomal escape of biodegradable nanoparticles (NPs) formulated from the copolymers of poly(DL-lactide-co-glycolide) (PLGA). The mechanism of rapid escape is by selective reversal of the surface charge of NPs (from anionic to cationic) in the acidic endo-lysosomal compartment, which causes the NPs to interact with the endo-lysosomal membrane and escape into the cytosol. PLGA NPs are able to deliver a variety of therapeutic agents, including macromolecules such as DNA and low molecular weight drugs such as dexamethasone, intracellularly at a slow rate, which results in a sustained therapeutic effect. PLGA has a number of advantages over other polymers used in drug and gene delivery including biodegradability, biocompatibility, and approval for human use granted by the U.S. Food and Drug Administration. Hence PLGA is well suited for sustained intracellular delivery of macromolecules.
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              Current status of polymeric gene delivery systems.

              T Park, S. H. Kim, Kyeong-Hoon Jeong (2006)
              Gene therapy provides great opportunities for treating diseases from genetic disorders, infections and cancer. To achieve successful gene therapy, development of proper gene delivery systems could be one of the most important factors. Several non-viral gene transfer methods have been developed to overcome the safety problems of their viral counterpart. Polymer-based non-viral gene carriers have been used due to their merits in safety including the avoidance of potential immunogenecity and toxicity, the possibility of repeated administration, and the ease of the establishment of good manufacturing practice (GMP). A wide range of polymeric vectors have been utilized to deliver therapeutic genes in vivo. The modification of polymeric vectors has also shown successful improvements in achieving target-specific delivery and in promoting intracellular gene transfer efficiency. Various systemic and cellular barriers, including serum proteins in blood stream, cell membrane, endosomal compartment and nuclear membrane, were successfully circumvented by designing polymer carriers having a smart molecular structure. This review explores the recent development of polymeric gene carriers and presents the future directions for the application of the polymer-based gene delivery systems in gene therapy.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Nanomedicine
                Journal ID (publisher-id): International Journal of Nanomedicine
                Title: International Journal of Nanomedicine
                Publisher: Dove Medical Press
                ISSN (Print): 1176-9114
                ISSN (Electronic): 1178-2013
                Publication date (Print): March 2008
                Publication date (Electronic): March 2008
                Volume: 3
                Issue: 1
                Pages: 31-49
                Affiliations
                [1 ]Nucleic Acids Research Laboratory, Institute of Genomics and Integrative Biology, Delhi University Campus Delhi, India
                [2 ]Department of Pharmaceutical Sciences, Dr. Harisingh Gour Vishwavidyalaya Sagar, (M.P.), India
                Author notes
                Correspondence: Kailash C Gupta Institute of Genomics and Integrative Biology, Delhi University Campus, Mall Road, Delhi 110007, India Tel +91 11 27662491 Email kcgupta@ 123456igib.res.in
                Article
                PMC ID: 2526359
                PubMed ID: 18488414
                SO-VID: 158fe5e8-4d10-4281-9b8a-556a7634741f
                Copyright © © 2008 Pathak et al, publisher and licensee Dove Medical Press Ltd.
                History
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular medicine
                Keywords: nanoparticles,hepatocytes,asialoglycoprotein receptors,liposomes,nucleic acids
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: nanoparticles, hepatocytes, asialoglycoprotein receptors, liposomes, nucleic acids

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