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      Paclitaxel and curcumin coadministration in novel cationic PEGylated niosomal formulations exhibit enhanced synergistic antitumor efficacy

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          Abstract

          Background

          The systemic administration of cytotoxic chemotherapeutic agents for cancer treatment often has toxic side effects, limiting the usage dose. To increase chemotherapeutic efficacy while reducing toxic effects, a rational design for synergy-based drug regimens is essential. This study investigated the augmentation of therapeutic effectiveness with the co-administration of paclitaxel (PTX; an effective chemotherapeutic drug for breast cancer) and curcumin (CUR; a chemosensitizer) in an MCF-7 cell line.

          Results

          We optimized niosome formulations in terms of surfactant and cholesterol content. Afterward, the novel cationic PEGylated niosomal formulations containing Tween-60: cholesterol:DOTAP:DSPE-mPEG (at 59.5:25.5:10:5) were designed and developed to serve as a model for better transfection efficiency and improved stability. The optimum formulations represented potential advantages, including extremely high entrapment efficiency (~ 100% for both therapeutic drug), spherical shape, smooth-surface morphology, suitable positive charge (zeta potential ~ + 15 mV for both CUR and PTX), sustained release, small diameter (~ 90 nm for both agents), desired stability, and augmented cellular uptake. Furthermore, the CUR and PTX kinetic release could be adequately fitted to the Higuchi model. A threefold and 3.6-fold reduction in CUR and PTX concentration was measured, respectively, when the CUR and PTX was administered in nano-niosome compared to free CUR and free PTX solutions in MCF-7 cells. When administered in nano-niosome formulations, the combination treatment of CUR and PTX was particularly effective in enhancing the cytotoxicity activity against MCF-7 cells.

          Conclusions

          Most importantly, CUR and PTX, in both free form and niosomal forms, were determined to be less toxic on MCF-10A human normal cells in comparison to MCF-7 cells. The findings indicate that the combination therapy of PTX with CUR using the novel cationic PEGylated niosome delivery is a promising strategy for more effective breast cancer treatment.

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          Most cited references44

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          Nanoparticle delivery of cancer drugs.

          Nanomedicine, the application of nanotechnology to medicine, enabled the development of nanoparticle therapeutic carriers. These drug carriers are passively targeted to tumors through the enhanced permeability and retention effect, so they are ideally suited for the delivery of chemotherapeutics in cancer treatment. Indeed, advances in nanomedicine have rapidly translated into clinical practice. To date, there are five clinically approved nanoparticle chemotherapeutics for cancer and many more under clinical investigation. In this review, we discuss the various nanoparticle drug delivery platforms and the important concepts involved in nanoparticle drug delivery. We also review the clinical data on the approved nanoparticle therapeutics as well as the nanotherapeutics under clinical investigation.
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            Curcumin nanoformulations: a review of pharmaceutical properties and preclinical studies and clinical data related to cancer treatment.

            Curcumin, a natural yellow phenolic compound, is present in many kinds of herbs, particularly in Curcuma longa Linn. (turmeric). It is a natural antioxidant and has shown many pharmacological activities such as anti-inflammatory, anti-microbial, anti-cancer, and anti-Alzheimer in both preclinical and clinical studies. Moreover, curcumin has hepatoprotective, nephroprotective, cardioprotective, neuroprotective, hypoglycemic, antirheumatic, and antidiabetic activities and it also suppresses thrombosis and protects against myocardial infarction. Particularly, curcumin has demonstrated efficacy as an anticancer agent, but a limiting factor is its extremely low aqueous solubility which hampers its use as therapeutic agent. Therefore, many technologies have been developed and applied to overcome this limitation. In this review, we summarize the recent works on the design and development of nano-sized delivery systems for curcumin, including liposomes, polymeric nanoparticles and micelles, conjugates, peptide carriers, cyclodextrins, solid dispersions, lipid nanoparticles and emulsions. Efficacy studies of curcumin nanoformulations using cancer cell lines and in vivo models as well as up-to-date human clinical trials are also discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.
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              Non-ionic surfactant based vesicles (niosomes) in drug delivery

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                Author and article information

                Contributors
                alemi.ashraf@gmail.com
                jzavar@ssu.ac.ir
                fhaghirosadat@gmail.com
                zarei.j@gmail.com
                mojtabahaghi@ymail.com
                seyedahmadhosseini@yahoo.com
                somayehhaghi72@gmail.com
                Journal
                J Nanobiotechnology
                J Nanobiotechnology
                Journal of Nanobiotechnology
                BioMed Central (London )
                1477-3155
                23 March 2018
                23 March 2018
                2018
                : 16
                : 28
                Affiliations
                [1 ]ISNI 0000 0004 0612 5912, GRID grid.412505.7, Department of Clinical Biochemistry, Faculty of Medicine, , Shahid Sadoughi University of Medical Sciences, ; Yazd, Iran
                [2 ]ISNI 0000 0004 0612 5912, GRID grid.412505.7, Biotechnology Research Center, International Campus, , Shahid Sadoughi University of Medical Science, ; Yazd, Iran
                [3 ]ISNI 0000 0004 0612 7950, GRID grid.46072.37, Department of Life Science Engineering, Faculty of New Sciences & Technologies, , University of Tehran, ; Tehran, Iran
                [4 ]ISNI 0000 0004 0612 5912, GRID grid.412505.7, Protein Engineering Laboratory, Department of Medical Genetics, School of Medicine, , Shahid Sadoughi University of Medical Sciences, ; Yazd, Iran
                [5 ]ISNI 0000 0000 9296 6873, GRID grid.411230.5, Nutrition and Metabolic Diseases Research Center, , Ahvaz Jundishapur University of Medical Sciences, ; Ahvaz, Iran
                [6 ]ISNI 0000 0000 8819 4698, GRID grid.412571.4, Student Research Committee, , Shiraz University of Medical Sciences, ; Shiraz, Iran
                Article
                351
                10.1186/s12951-018-0351-4
                5865280
                29571289
                2306cebc-44af-43df-bebb-0546c15a3246
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 13 November 2017
                : 13 March 2018
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Biotechnology
                niosome,paclitaxel,curcumin,combination therapy,chemotherapy
                Biotechnology
                niosome, paclitaxel, curcumin, combination therapy, chemotherapy

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