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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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      Anti-tumor efficacy of folate modified PLGA-based nanoparticles for the co-delivery of drugs in ovarian cancer

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background: Ovarian cancer is a leading cause of death in gynecologic malignancies. The high mortality is mainly caused by advanced stage at presentation in most patients. Even after the combination of cytoreductive surgery and systemic platinum and taxane treatment, most patients relapse and eventually succumb to the disease. Therefore, there is an urgent need for new treatments.

          Purpose: A novel folate (FA)-targeted co-delivery of docetaxel (DTX) and gemcitabine (GEM) nanoparticles (NPs) was developed to overcome ovarian cancer.

          Materials and methods: Physicochemical characteristics of NPs such as size, morphology, and release profiles were explored. In vitro and in vivo studies were carried out to assess the efficacy of their antitumor activity in target cells.

          Results: FA modified DTX and GEM co-loaded NPs were prepared using the solvent evaporation method. The NPs with a particle size of ~120nm were stable in the observation period. The hemolysis results indicated that FA-PEG 2000-PLGA was potentially feasible for targeted antitumor drug delivery through blood circulation. In vitro release study suggested that in comparison with the free drug, PLGA-DTX/GEM NPs and FA-PEG 2000-PLGA-DTX/GEM NPs had sustained-release properties. However, there was no obvious difference between the two NPs with the same drug in the release profile. Ovarian cancer cells in vitro efficiently took up the non-targeted and FA-targeted NPs; improved cytotoxicity was observed in the FA-targeted NPs, showing a 3.59- fold drop in the IC 50 in SKOV-3 cells as compared to DTX/GEM alone. Cellular uptake showed that through surface modification, more drugs entered the cell successfully. Pharmacodynamics results showed a statistically significant effect on the rate of reduction of tumor volume for FA-PEG 2000-PLGA-DTX/GEM NPs than other groups and no toxicity of organs.

          Conclusion: The present study indicates that the FA-PEG 2000-PLGA-DTX/GEM NPs provides a promising platform for the treatment of ovarian cancer.

          Most cited references16

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          Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer.

          W McGuire, W J Hoskins, M Brady … (1996)
          Chemotherapy combinations that include an alkylating agent and a platinum coordination complex have high response rates in women with advanced ovarian cancer. Such combinations provide long-term control of disease in few patients, however. We compared two combinations, cisplatin and cyclophosphamide and cisplatin and paclitaxel, in women with ovarian cancer. We randomly assigned 410 women with advanced ovarian cancer and residual masses larger than 1 cm after initial surgery to receive cisplatin (75 mg per square meter of body-surface area) with either cyclophosphamide (750 mg per square meter) or paclitaxel (135 mg per square meter over 24 hours). Three hundred eighty-six women met all the eligibility criteria. Known prognostic factors were similar in the two treatment groups. Alopecia, neutropenia, fever, and allergic reactions were reported more frequently in the cisplatin-paclitaxel group. Among 216 women with measurable disease, 73 percent in the cisplatin-paclitaxel group responded to therapy, as compared with 60 percent in the cisplatin-cyclophosphamide group (P = 0.01). The frequency of surgically verified complete response was similar in the two groups. Progression-free survival was significantly longer (P < 0.001) in the cisplatin-paclitaxel group than in the cisplatin-cyclophosphamide group (median, 18 vs. 13 months). Survival was also significantly longer (P < 0.001) in the cisplatin-paclitaxel group (median, 38 vs. 24 months). Incorporating paclitaxel into first-line therapy improves the duration of progression-free survival and of overall survival in women with incompletely resected stage III and stage IV ovarian cancer.
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            Physicochemical characteristics of nanoparticles affect circulation, biodistribution, cellular internalization, and trafficking.

            Xiaopin Duan, Yaping Li (2013)
            Nanoparticles have many potential applications in tumor therapy. Systemically administered nanoparticles should remain in circulation for a long time to increase their accumulation in targeted tissues before being cleared by the reticuloendothelial system, and be effectively internalized by the targeted cells, which can be influenced significantly by the physicochemical characteristics of nanoparticles, such as particle size, surface properties, and particle shape. This review highlights the impact of the main affects of physicochemical properties on nanoparticle transport behavior in blood, their uptake and clearance by macrophages and their consequent biodistribution, as well as their interaction with targeted cells.
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              The Role of Micelle Size in Tumor Accumulation, Penetration, and Treatment.

              Jinqiang Wang, Weiwei Mao, Lye Lock … (2015)
              The specific sizes that determine optimal nanoparticle tumor accumulation, penetration, and treatment remain inconclusive because many studies compared nanoparticles with multiple physicochemical variables (e.g., chemical structures, shapes, and other physical properties) in addition to the size. In this study, we synthesized amphiphilic block copolymers of 7-ethyl-10-hydroxylcamptothecin (SN38) prodrug and fabricated micelles with sizes ranging from 20 to 300 nm from a single copolymer. The as-prepared micelles had exactly the same chemical structures and similar physical properties except for size, which provided an ideal platform for a systematic investigation of the size effects in cancer drug delivery. We found that the micelle's blood circulation time and tumor accumulation increased with the increase in their diameters, with optimal diameter range of 100 to 160 nm. However, the much higher tumor accumulation of the large micelles (100 nm) did not result in significantly improved therapeutic efficacy, because the large micelles had poorer tumor penetration than the small ones (30 nm). An optimal size that balances drug accumulation and penetration in tumors is critical for improving the therapeutic efficacy of nanoparticulate drugs.
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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): DDDT
                Journal ID (pmc): dddt
                Title: Drug Design, Development and Therapy
                Publisher: Dove
                ISSN (Electronic): 1177-8881
                Publication date (Electronic): 18 April 2019
                Publication date Collection: 2019
                Volume: 13
                Pages: 1271-1280
                Affiliations
                [1 ]Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine , Shanghai, People’s Republic of China
                Author notes
                Correspondence: Xiaoqing Guo; Lingfei HanShanghai First Maternity and Infant Hospital, Tongji University School of Medicine , 2699 West Gaoke Road, Shanghai201204, People’s Republic of ChinaTel +86 212 026 1000Fax +86 212 026 1000Email xiaoqing_guo1001@ 123456sina.com ; lingfei_han2018@ 123456163.com
                [*]

                These authors contributed equally to this work

                Article
                Publisher ID: 195493
                DOI: 10.2147/DDDT.S195493
                PMC ID: 6497857
                SO-VID: 12bc0515-519d-41a6-967b-bf60b6579800
                Copyright statement: © 2019 Li et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. 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. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 21 November 2018
                Date accepted : 14 March 2019
                Page count
                Figures: 6, Tables: 1, References: 20, Pages: 10
                Categories
                Subject: Original Research

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: folate,co-delivery,docetaxel,gemcitabine,nanoparticles
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: folate, co-delivery, docetaxel, gemcitabine, nanoparticles

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