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      International Journal of Nanomedicine (submit here)

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      Solid lipid nanoparticles for thermoresponsive targeting: evidence from spectrophotometry, electrochemical, and cytotoxicity studies

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          Abstract

          Thermoresponsive drug delivery systems are designed for the controlled and targeted release of therapeutic payload. These systems exploit hyperthermic temperatures (>39°C), which may be applied by some external means or due to an encountered symptom in inflammatory diseases such as cancer and arthritis. The objective of this paper was to provide some solid evidence in support of the hypothesis that solid lipid nanoparticles (SLNs) can be used for thermoresponsive targeting by undergoing solid–liquid phase transition at their melting point (MP). Thermoresponsive lipid mixtures were prepared by mixing solid and liquid natural fatty acids, and their MP was measured by differential scanning calorimetry (DSC). SLNs (MP 39°C) containing 5-fluorouracil (5-FU) were synthesized by hot melt encapsulation method, and were found to have spherical shape (transmission electron microscopy studies), desirable size (<200 nm), and enhanced physicochemical stability (Fourier transform infrared spectroscopy analysis). We observed a sustained release pattern (22%–34%) at 37°C (5 hours). On the other hand, >90% drug was released at 39°C after 5 hours, suggesting that the SLNs show thermoresponsive drug release, thus confirming our hypothesis. Drug release from SLNs at 39°C was similar to oleic acid and linoleic acid nanoemulsions used in this study, which further confirmed that thermoresponsive drug release is due to solid–liquid phase transition. Next, a differential pulse voltammetry-based electrochemical chemical detection method was developed for quick and real-time analysis of 5-FU release, which also confirmed thermoresponsive drug release behavior of SLNs. Blank SLNs were found to be biocompatible with human gingival fibroblast cells, although 5-FU-loaded SLNs showed some cytotoxicity after 24 hours. 5-FU-loaded SLNs showed thermoresponsive cytotoxicity to breast cancer cells (MDA-MB-231) as cytotoxicity was higher at 39°C (cell viability 72%–78%) compared to 37°C (cell viability >90%) within 1 hour. In conclusion, this study presents SLNs as a safe, simple, and effective platform for thermoresponsive targeting.

          Most cited references29

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          Carbon nanodots featuring efficient FRET for real-time monitoring of drug delivery and two-photon imaging.

          A FRET-based carbon nanodot (CDot) drug delivery platform has been developed. These CDots offer excellent biocompatibility, stable fluorescence, and efficient FRET between CDots and the attached fluorescent drug molecules, such as doxorubicin, enabling enhanced drug delivery, convenient cell imaging, and real-time monitoring of drug release. Moreover, the FRET-based two-photon imaging and drug tracking in deep tissues are also demonstrated. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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            Nanotoxicology applied to solid lipid nanoparticles and nanostructured lipid carriers - a systematic review of in vitro data.

            Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were developed as alternative to other colloidal carriers. They were designed to overcome lipid nanoemulsions and liposomes in stability and ability to control the release of an encapsulated substance, and at the same time to be better tolerated than polymeric nanoparticles. Since the patenting of SLN discovery, large amount of data became available on the behaviour of these systems in vitro. SLN/NLC have many prerequisites to be a well tolerated carrier - the currently available data seem to confirm it, but there are also some contradictory results. In this review, we collected the available data from cytotoxicity, oxidative stress and hemocompatibility studies in vitro and analysed their outcomes. We also provide a summary of the available data in a form of reference table.
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              To heat or not to heat: Challenges with clinical translation of thermosensitive liposomes.

              Thermosensitive liposomes have been put forward as a strategy to improve upon the limited tumor drug availability associated with conventional non-thermosensitive liposomes. ThermoDox® is the first and only thermosensitive liposome formulation to reach clinical development. The initial Phase III clinical trial on ThermoDox® (i.e. HEAT trial) evaluating the combination of ThermoDox® and radiofrequency ablation (RFA) in comparison to RFA alone for treatment of inoperable hepatocellular carcinoma (HCC) failed to reach its primary endpoint in progression-free survival (PFS). Nevertheless, a subgroup analysis demonstrated a marked improvement in PFS and a significant improvement in overall survival (OS) for patients who underwent RFA treatment for at least 45min. Potential reasons for failure of the HEAT trial have been summarized in this review and include issues with clinical trial design, lack of supporting preclinical data, and improvements in the control arm (i.e. RFA alone). In recent years, there have been many developments and improvements in heating infrastructure, thermometry and treatment planning of hyperthermia and ablation treatments. Still, there are many barriers to the clinical implementation and accessibility of heat treatment. This review provides an in-depth analysis of the current status, as well as potential challenges faced by continued clinical translation of thermosensitive liposomes.
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                Author and article information

                Journal
                Int J Nanomedicine
                Int J Nanomedicine
                International Journal of Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2017
                21 November 2017
                : 12
                : 8325-8336
                Affiliations
                [1 ]Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Punjab, Pakistan
                [2 ]Nanobiotech Group, National Institute of Biotechnology and Genetic Engineering, Faisalabad, Punjab, Pakistan
                [3 ]Department of Chemical Engineering, Northeastern University, Boston, MA, USA
                [4 ]Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia
                Author notes
                Correspondence: Ayesha Ihsan, Nanobiotech Group, National Institute of Biotechnology and Genetic Engineering, Jhang Road, Faisalabad 38000, Punjab, Pakistan, Tel +92 41 920 1316, Fax +92 41 920 1472, Email aishaehsan@ 123456gmail.com
                Asadullah Madni, Department of Pharmacy, The Islamia University of Bahawalpur, Railway Road, Bahawalpur 63100, Punjab, Pakistan, Tel +92 62 925 5243, Fax +92 62 925 5565, Email asadpharmacist@ 123456hotmail.com
                Article
                ijn-12-8325
                10.2147/IJN.S147506
                5701611
                29200845
                af4d196e-5111-4522-bc76-d644c7ab218b
                © 2017 Rehman 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.

                History
                Categories
                Original Research

                Molecular medicine
                temperature sensitive,breast cancer,5-fluorouracil,nanostructured lipid carriers,emulsions,fatty acids

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