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      Drug Design, Development and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the design and development of drugs, as well as the clinical outcomes, patient safety, and programs targeted at the effective and safe use of medicines. Sign up for email alerts here.

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      Paclitaxel-loaded star-shaped copolymer nanoparticles for enhanced malignant melanoma chemotherapy against multidrug resistance

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          Abstract

          Malignant melanoma (MM) is the most dangerous type of skin cancer with annually increasing incidence and death rates. However, chemotherapy for MM is restricted by low topical drug concentration and multidrug resistance. In order to surmount the limitation and to enhance the therapeutic effect on MM, a new nanoformulation of paclitaxel (PTX)-loaded cholic acid (CA)-functionalized star-shaped poly(lactide-co-glycolide) (PLGA)-D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoparticles (NPs) (shortly PTX-loaded CA-PLGA-TPGS NPs) was fabricated by a modified method of nanoprecipitation. The particle size, zeta potential, morphology, drug release profile, drug encapsulation efficiency, and loading content of PTX-loaded NPs were detected. As shown by confocal laser scanning, NPs loaded with coumarin-6 were internalized by human melanoma cell line A875. The cellular uptake efficiency of CA-PLGA-TPGS NPs was higher than those of PLGA NPs and PLGA-TPGS NPs. The antitumor effects of PTX-loaded NPs were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that star-shaped PTX-loaded CA-PLGA-TPGS NPs were significantly superior to commercial PTX formulation Taxol ®. Such drug delivery nanocarriers are potentially applicable to the improvement of clinical MM therapy.

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          PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect.

          Sarbari Acharya, Sanjeeb K Sahoo (2011)
          As mortality due to cancer continues to rise, advances in nanotechnology have significantly become an effective approach for achieving efficient drug targeting to tumour tissues by circumventing all the shortcomings of conventional chemotherapy. During the past decade, the importance of polymeric drug-delivery systems in oncology has grown exponentially. In this context, poly(lactic-co-glycolic acid) (PLGA) is a widely used polymer for fabricating 'nanoparticles' because of biocompatibility, long-standing track record in biomedical applications and well-documented utility for sustained drug release, and hence has been the centre of focus for developing drug-loaded nanoparticles for cancer therapy. Such PLGA nanoparticles have also been used to develop proteins and peptides for nanomedicine, and nanovaccines, as well as a nanoparticle-based drug- and gene-delivery system for cancer therapy, and nanoantigens and growth factors. These drug-loaded nanoparticles extravasate through the tumour vasculature, delivering their payload into the cells by the enhanced permeability and retention (EPR) effect, thereby increasing their therapeutic effect. Ongoing research about drug-loaded nanoparticles and their delivery by the EPR effect to the tumour tissues has been elucidated in this review with clarity. Copyright © 2010 Elsevier B.V. All rights reserved.
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            Cholic acid-functionalized nanoparticles of star-shaped PLGA-vitamin E TPGS copolymer for docetaxel delivery to cervical cancer.

            Shen Feng, Laiqiang Huang, Chunyan Tan … (2013)
            We developed a system of nanoparticles (NPs) of cholic acid functionalized, star-shaped block copolymer consisting of PLGA and vitamin E TPGS for sustained and controlled delivery of docetaxel for treatment of cervical cancer, which demonstrated superior in vitro and in vivo performance in comparison with the drug-loaded PLGA NPs and the linear PLGA-b-TPGS copolymer NPs. The star-shaped block copolymer CA-PLGA-b-TPGS of three branch arms was synthesized through the core-first approach and characterized by (1)H NMR, GPC and TGA. The drug- or coumarin 6-loaded NPs were prepared by a modified nanoprecipitation technique and then characterized in terms of size and size distribution, surface morphology and surface charge, drug encapsulation efficiency, in vitro release profile and physical state of the encapsulated drug. The CA-PLGA-b-TPGS NPs were found to have the highest cellular uptake efficiency, the highest antitumor efficacy compared with PLGA-b-TPGS NPs and PLGA NPs. The results suggest that such a star-shaped copolymer CA-PLGA-b-TPGS could be used as a new molecular biomaterial for drug delivery of high efficiency. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Docetaxel (DTX)-loaded polydopamine-modified TPGS-PLA nanoparticles as a targeted drug delivery system for the treatment of liver cancer.

              Dunwan Zhu, Wei Tao, Hongling Zhang … (2016)
              Polydopamine-based surface modification is a simple way to functionalize polymeric nanoparticle (NP) surfaces with ligands and/or additional polymeric layers. In this work, we developed DTX-loaded formulations using polydopamine-modified NPs synthesized using D-α-tocopherol polyethylene glycol 1000 succinate-poly(lactide) (pD-TPGS-PLA/NPs). To target liver cancer cells, galactosamine was conjugated on the prepared NPs (Gal-pD-TPGS-PLA/NPs) to enhance the delivery of DTX via ligand-mediated endocytosis. The size and morphology of pD-TPGS-PLA/NPs and Gal-pD-TPGS-PLA/NPs changed obviously compared with TPGS-PLA/NPs. In vitro studies showed that TPGS-PLA/NPs, pD-TPGS-PLA/NPs and Gal-pD-TPGS-PLA/NPs had similar release profiles of DTX. Both confocal laser scanning microscopy and flow cytometric results showed that coumarin 6-loaded Gal-pD-TPGS-PLA/NPs had the highest cellular uptake efficiency in liver cancer cell line HepG2. Moreover, DTX-loaded Gal-pD-TPGS-PLA/NPs inhibited the growth of HepG2 cells more potently than TPGS-PLA/NPs, pD-TPGS-PLA/NPs, and a clinically available DTX formulation (Taxotere®). The in vivo biodistribution experiments show that the Gal-pD-TPGS-PLA/NPs are specifically targeted to the tumor. Furthermore, the in vivo anti-tumor effects study showed that injecting DTX-loaded Gal-pD-TPGS-PLA/NPs reduced the tumor size most significantly on hepatoma-bearing nude mice. These results suggest that Gal-pD-TPGS-PLA/NPs prepared in the study specifically interacted with the hepatocellular carcinoma cells through ligand-receptor recognition and they may be used as a potentially eligible drug delivery system targeting liver cancers.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Drug Des Devel Ther
                Journal ID (iso-abbrev): Drug Des Devel Ther
                Journal ID (publisher-id): Drug Design, Development and Therapy
                Title: Drug Design, Development and Therapy
                Publisher: Dove Medical Press
                ISSN (Electronic): 1177-8881
                Publication date Collection: 2017
                Publication date (Electronic): 06 March 2017
                Volume: 11
                Pages: 659-668
                Affiliations
                [1 ]Department of Burn and Plastic Surgery, The People’s Hospital of Baoan Shenzhen Affiliated to Southern Medical University
                [2 ]Core Laboratory, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China
                Author notes
                Correspondence: Hui Liu, Department of Burn and Plastic Surgery, The People’s Hospital of Baoan Shenzhen Affiliated to Southern Medical University, Shenzhen 518101, People’s Republic of China, Tel/fax +86 755 2778 8311, Email huiliu22@ 123456163.com
                Ni Xie, Core Laboratory, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, People’s Republic of China, Tel/fax +86 755 8300 3435, Email kejiaoke100@ 123456163.com
                Article
                Publisher ID: dddt-11-659
                DOI: 10.2147/DDDT.S127328
                PMC ID: 5345981
                PubMed ID: 28293102
                SO-VID: 70198838-73a2-4f17-916c-f2f898f3371c
                Copyright © © 2017 Su 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.

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                Subject: Original Research

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: malignant melanoma,paclitaxel,nanoparticles,enhanced therapeutic effects,drug delivery
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: malignant melanoma, paclitaxel, nanoparticles, enhanced therapeutic effects, drug delivery

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