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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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      Overcoming multidrug resistance through inhalable siRNA nanoparticles-decorated porous microparticles based on supercritical fluid technology

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          Abstract

          Background

          In recent times, the co-delivery therapeutics have garnered enormous interest from researchers in the treatment of cancers with multidrug resistance (MDR) due to their efficient delivery of multiple agents, which result in synergistic effects and capable of overcoming all the obstacles of MDR in cancer. However, an efficient delivery platform is required for the conveyance of diverse agents that can successfully devastate MDR in cancer.

          Methods

          Initially, short-interfering RNA-loaded chitosan (siRNA-CS) nanoparticles were synthesized using the ionic gelation method. Further, the siRNA-CS nanoparticles and doxorubicin hydrochloride (DOX) were co-loaded in poly-L-lactide porous microparticles (PLLA PMs) (nano-embedded porous microparticles, [NEPMs]) by the supercritical anti-solvent (SAS) process.

          Results and discussion

          The NEPM formulation exhibited an excellent aerodynamic performance and sustained release of DOX, which displayed higher anticancer efficacy in drug-resistant cells (human small cell lung cancer, H69AR cell line) than those treated with either free DOX and DOX-PLLA PMs due to the siRNA from CS nanoparticles silenced the MDR gene to DOX therapy.

          Conclusion

          This eco-friendly process provides a convenient way to fabricate such innovative NEPMs co-loaded with a chemotherapeutic agent and a gene, which can devastate MDR in cancer through the co-delivery system.

          Most cited references52

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          Overcoming ABC transporter-mediated multidrug resistance: Molecular mechanisms and novel therapeutic drug strategies.

          Wen-Wen Li, Han Zhang, Yehuda G. Assaraf … (2016)
          Multidrug resistance is a key determinant of cancer chemotherapy failure. One of the major causes of multidrug resistance is the enhanced efflux of drugs by membrane ABC transporters. Targeting ABC transporters projects a promising approach to eliminating or suppressing drug resistance in cancer treatment. To reveal the functional mechanisms of ABC transporters in drug resistance, extensive studies have been conducted from identifying drug binding sites to elucidating structural dynamics. In this review article, we examined the recent crystal structures of ABC proteins to depict the functionally important structural elements, such as domains, conserved motifs, and critical amino acids that are involved in ATP-binding and drug efflux. We inspected the drug-binding sites on ABC proteins and the molecular mechanisms of various substrate interactions with the drug binding pocket. While our continuous battle against drug resistance is far from over, new approaches and technologies have emerged to push forward our frontier. Most recent developments in anti-MDR strategies include P-gp inhibitors, RNA-interference, nano-medicines, and delivering combination strategies. With the advent of the 'Omics' era - genomics, epigenomics, transcriptomics, proteomics, and metabolomics - these disciplines play an important role in fighting the battle against chemoresistance by further unraveling the molecular mechanisms of drug resistance and shed light on medical therapies that specifically target MDR.
          Article 0 comments Cited 233 times – based on 0 reviews     Review now
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            Targeted delivery of nanoparticles for the treatment of lung diseases.

            W. Roa, Raimar Löbenberg, S. Azarmi (2008)
            Targeted delivery of drug molecules to organs or special sites is one of the most challenging research areas in pharmaceutical sciences. By developing colloidal delivery systems such as liposomes, micelles and nanoparticles a new frontier was opened for improving drug delivery. Nanoparticles with their special characteristics such as small particle size, large surface area and the capability of changing their surface properties have numerous advantages compared with other delivery systems. Targeted nanoparticle delivery to the lungs is an emerging area of interest. This article reviews research performed over the last decades on the application of nanoparticles administered via different routes of administration for treatment or diagnostic purposes. Nanotoxicological aspects of pulmonary delivery are also discussed.
            Article 0 comments Cited 95 times – based on 0 reviews     Review now
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              A review of nanocarriers for the delivery of small interfering RNA.

              Prashant Kesharwani, Virendra Gajbhiye, Narendra Kumar Jain (2012)
              Increasing knowledge about molecular mechanisms of endogenous RNA interference (RNAi) and small interfering RNAs (siRNAs) has been incorporated into innovative nucleic acid medicines for treatment of diseases such as cancers. Although RNAi and siRNA have the potential to become powerful therapeutic drugs, their delivery to the target site represents a major challenge. The design and creation of nanocarriers for the safe and efficient delivery of siRNA towards their potential applications site is one of the challenging and rapidly growing areas of research since they have to overcome the commonly encountered biological barriers. In this review, we discuss the recent nanotechnological strategies for siRNA delivery by using different carriers such as liposomes, dendrimers and carbon nanotubes. Copyright © 2012 Elsevier Ltd. All rights reserved.
              Article 0 comments Cited 90 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Nanomedicine
                Journal ID (iso-abbrev): 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 Collection: 2018
                Publication date (Electronic): 15 August 2018
                Volume: 13
                Pages: 4685-4698
                Affiliations
                [1 ]College of Chemical Engineering, Huaqiao University, Xiamen 361021, P. R. China, azchen@ 123456hqu.edu.cn
                [2 ]Institute of Biomaterials and Tissue Engineering, Huaqiao University, Xiamen 361021, P. R. China, azchen@ 123456hqu.edu.cn
                [3 ]Fujian Provincial Key Laboratory of Biochemical Technology (Huaqiao University), Xiamen 361021, P. R. China, azchen@ 123456hqu.edu.cn
                Author notes
                Correspondence: Ai-Zheng Chen, College of Chemical Engineering, Huaqiao University, Xiamen 361021, P. R. China, Tel +86 592 616 2326, Fax +86 592 616 2326, Email azchen@ 123456hqu.edu.cn
                Article
                Publisher ID: ijn-13-4685
                DOI: 10.2147/IJN.S169399
                PMC ID: 6103603
                PubMed ID: 30154654
                SO-VID: 87f5bcf2-ad61-425a-8180-7c623d63d87b
                Copyright © © 2018 Xu et al. This work is published and licensed by Dove Medical Press Limited
                License:

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Molecular medicine
                Keywords: pulmonary delivery,short-interfering rna,multidrug resistance,doxorubicin,supercritical carbon dioxide
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: pulmonary delivery, short-interfering rna, multidrug resistance, doxorubicin, supercritical carbon dioxide

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