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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.

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      Preparation, Pharmacokinetics, and Antitumor Potential of Miltefosine-Loaded Nanostructured Lipid Carriers

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          Abstract

          Background

          The purpose of this study was to investigate the suitability of nanostructured lipid carriers (NLCs) loaded with miltefosine (HePC) as an anticancer drug for the treatment of breast cancer.

          Methods

          HePC-NLCs were prepared using a microemulsion technique and then evaluated for particle size, polydispersity index (PDI), incorporation efficiency, in vitro release of entrapped drug, and hemolytic potential. Furthermore, pharmacokinetic, biodistribution, and liver toxicity analyses were performed in Sprague–Dawley rats, and antitumor efficacy was evaluated in Michigan Cancer Foundation-7 (MCF-7) and squamous cell carcinoma-7 (SCC-7) cells in vitro and in tumour-bearing BALB/c mice in vivo. Advanced analyses including survival rate, immunohistopathology, and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assays were performed to evaluate apoptosis in vivo.

          Results

          The average particle size of the HePC-NLCs was 143 ± 16 nm, with a narrow PDI (0.104 ± 0.002), and the incorporation efficiency was found to be 91 ± 7%. The NLCs released HePC in a sustained manner, and this release was significantly lower than that of free drug. The in vitro hemolytic assay demonstrated a significantly reduced hemolytic potential (~9%) of the NLCs compared to that of the test formulations. The HePC-NLCs demonstrated enhanced pharmacokinetic behaviour over free drug, including extended blood circulation and an abridged clearance rate in rats. Furthermore, the HePC-NLCs exhibited higher cytotoxicity than the free drug in MCF-7 and SCC-7 cells. Moreover, the HePC-NLCs showed significantly enhanced ( P < 0.005) antitumor activity compared to that of the control and free drug-treated mouse groups. Tumour cell apoptosis was also confirmed, indicating the antitumor potential of the HePC-NLCs.

          Conclusion

          These findings demonstrate the ability of NLCs as a drug delivery system for enhanced pharmacokinetic, antitumor, and apoptotic effects, most importantly when loaded with HePC.

          Most cited references72

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Nanocarriers as an emerging platform for cancer therapy.

            Nanotechnology has the potential to revolutionize cancer diagnosis and therapy. Advances in protein engineering and materials science have contributed to novel nanoscale targeting approaches that may bring new hope to cancer patients. Several therapeutic nanocarriers have been approved for clinical use. However, to date, there are only a few clinically approved nanocarriers that incorporate molecules to selectively bind and target cancer cells. This review examines some of the approved formulations and discusses the challenges in translating basic research to the clinic. We detail the arsenal of nanocarriers and molecules available for selective tumour targeting, and emphasize the challenges in cancer treatment.
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              Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors

              Nanotechnology has recently gained increased attention for its capability to effectively diagnose and treat various tumors. Nanocarriers have been used to circumvent the problems associated with conventional antitumor drug delivery systems, including their nonspecificity, severe side effects, burst release and damaging the normal cells. Nanocarriers improve the bioavailability and therapeutic efficiency of antitumor drugs, while providing preferential accumulation at the target site. A number of nanocarriers have been developed; however, only a few of them are clinically approved for the delivery of antitumor drugs for their intended actions at the targeted sites. The present review is divided into three main parts: first part presents introduction of various nanocarriers and their relevance in the delivery of anticancer drugs, second part encompasses targeting mechanisms and surface functionalization on nanocarriers and third part covers the description of selected tumors, including breast, lungs, colorectal and pancreatic tumors, and applications of relative nanocarriers in these tumors. This review increases the understanding of tumor treatment with the promising use of nanotechnology.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                ijn
                intjnano
                International Journal of Nanomedicine
                Dove
                1176-9114
                1178-2013
                11 May 2021
                2021
                : 16
                : 3255-3273
                Affiliations
                [1 ]Department of Head and Neck Breast, Xinxiang Central Hospital, The Fourth Clinical College of Xinxiang Medical University , Xinxiang City, Henan Province, 453000, People’s Republic of China
                [2 ]Nanomedicine Research Group, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University , Islamabad, 45320, Pakistan
                [3 ]Department of Zoology, Kohat University of Science & Technology , Kohat, Khyber Pakhtunkhwa, Pakistan
                [4 ]Riphah Institute of Pharmaceutical Sciences, Riphah International University , Islamabad, Pakistan
                [5 ]College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University , Ansan, South Korea
                Author notes
                Correspondence: Fakhar ud Din Tel +92 512-90644314Fax +92 512-90644144 Email fudin@qau.edu.pk
                Han-Gon Choi Email hangon@hanyang.ac.kr
                Author information
                http://orcid.org/0000-0003-3753-034X
                http://orcid.org/0000-0002-0915-3527
                http://orcid.org/0000-0002-2514-8306
                http://orcid.org/0000-0001-9537-4897
                Article
                299443
                10.2147/IJN.S299443
                8127833
                34012260
                ac4d1979-61b3-4d8a-8e04-b33f1698641a
                © 2021 Yu et al.

                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
                : 28 December 2020
                : 07 April 2021
                Page count
                Figures: 9, Tables: 9, References: 72, Pages: 19
                Funding
                Funded by: Higher Education Commission of Pakistan via a grant;
                This project was funded by the Higher Education Commission of Pakistan via a grant (No. 21-836/SRGP/R&D/ HEC/2016). Moreover, partial support was provided by Quaid-i-Azam University, Islamabad, Pakistan through the University Research Fund (URF).
                Categories
                Original Research

                Molecular medicine
                breast cancer,miltefosine,nano lipid carriers,bioavailability,pharmacokinetics,antitumor efficacy

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