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      Nanotechnology-based inhalation treatments for lung cancer: state of the art

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          Abstract

          Considering the challenges associated with conventional chemotherapy, targeted and local delivery of chemotherapeutics via nanoparticle (NP) carriers to the lungs is an emerging area of interest. Recent studies and growing clinical application in cancer nanotechnology showed the huge potential of NPs as drug carriers in cancer therapy, including in lung carcinoma for diagnosis, imaging, and theranostics. Researchers have confirmed that nanotechnology-based inhalation chemotherapy is viable and more effective than conventional chemotherapy, with lesser side effects. Recently, many nanocarriers have been investigated, including liposomes, polymeric micelles, polymeric NPs, solid lipid NPs, and inorganic NPs for inhalation treatments of lung cancer. Yet, the toxicity of such nanomaterials to the lungs tissues and further distribution to other organs due to systemic absorption on inhalation delivery is a debatable concern. Here, prospect of NPs-based local lung cancer targeting through inhalation route as well as its associated challenges are discussed.

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          Most cited references65

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          Nanomedicine: current status and future prospects.

          Applications of nanotechnology for treatment, diagnosis, monitoring, and control of biological systems has recently been referred to as "nanomedicine" by the National Institutes of Health. Research into the rational delivery and targeting of pharmaceutical, therapeutic, and diagnostic agents is at the forefront of projects in nanomedicine. These involve the identification of precise targets (cells and receptors) related to specific clinical conditions and choice of the appropriate nanocarriers to achieve the required responses while minimizing the side effects. Mononuclear phagocytes, dendritic cells, endothelial cells, and cancers (tumor cells, as well as tumor neovasculature) are key targets. Today, nanotechnology and nanoscience approaches to particle design and formulation are beginning to expand the market for many drugs and are forming the basis for a highly profitable niche within the industry, but some predicted benefits are hyped. This article will highlight rational approaches in design and surface engineering of nanoscale vehicles and entities for site-specific drug delivery and medical imaging after parenteral administration. Potential pitfalls or side effects associated with nanoparticles are also discussed.
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            Comparative pulmonary toxicity assessment of single-wall carbon nanotubes in rats.

            The aim of this study was to evaluate the acute lung toxicity of intratracheally instilled single-wall carbon nanotubes (SWCNT) in rats. The lungs of rats were instilled either with 1 or 5 mg/kg of the following control or particle types: (1) SWCNT, (2) quartz particles (positive control), (3) carbonyl iron particles (negative control), (4) phosphate-buffered saline (PBS) + 1% Tween 80, or (5) graphite particles (lung tissue studies only). Following exposures, the lungs of PBS and particle-exposed rats were assessed using bronchoalveolar lavage (BAL) fluid biomarkers and cell proliferation methods, and by histopathological evaluation of lung tissue at 24 h, 1 week, 1 month, and 3 months postinstillation. Exposures to high-dose (5 mg/kg) SWCNT produced mortality in ~15% of the SWCNT-instilled rats within 24 h postinstillation. This mortality resulted from mechanical blockage of the upper airways by the instillate and was not due to inherent pulmonary toxicity of the instilled SWCNT particulate. Exposures to quartz particles produced significant increases versus controls in pulmonary inflammation, cytotoxicity, and lung cell parenchymal cell proliferation indices. Exposures to SWCNT produced transient inflammatory and cell injury effects. Results from the lung histopathology component of the study indicated that pulmonary exposures to quartz particles (5 mg/kg) produced dose-dependent inflammatory responses, concomitant with foamy alveolar macrophage accumulation and lung tissue thickening at the sites of normal particle deposition. Pulmonary exposures to carbonyl iron or graphite particles produced no significant adverse effects. Pulmonary exposures to SWCNT in rats produced a non-dose-dependent series of multifocal granulomas, which were evidence of a foreign tissue body reaction and were nonuniform in distribution and not progressive beyond 1 month postexposure (pe). The observation of SWCNT-induced multifocal granulomas is inconsistent with the following: (1) lack of lung toxicity by assessing lavage parameters, (2) lack of lung toxicity by measuring cell proliferation parameters, (3) an apparent lack of a dose response relationship, (4) nonuniform distribution of lesions, (5) the paradigm of dust-related lung toxicity effects, (6) possible regression of effects over time. In addition, the results of two recent exposure assessment studies indicate very low aerosol SWCNT exposures at the workplace. Thus, the physiological relevance of these findings should ultimately be determined by conducting an inhalation toxicity study.
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              The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting.

              H. Maeda (2001)
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                Author and article information

                Journal
                Nanotechnol Sci Appl
                Nanotechnol Sci Appl
                Nanotechnology, Science and Applications
                Nanotechnology, Science and Applications
                Dove Medical Press
                1177-8903
                2015
                19 November 2015
                : 8
                : 55-66
                Affiliations
                [1 ]Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
                [2 ]Nanomedicine Research Lab, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India
                [3 ]Centre de Biophysique Moléculaire(CBM)-CNRS UPR4301, University of Orléans, Orléans Cedex 2, France
                [4 ]Department of Pharmaceutics, Abhilashi College of Pharmacy, Mandi, HP, India
                [5 ]Department of Pharmaceutics, College of Pharmacy, Najran University, Saudi Arabia
                [6 ]Department of Biosciences, Jamia Millia Islamia, New Delhi, India
                [7 ]Metabolomics and Enzymology Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
                Author notes
                Correspondence: Sohail Akhter, Centre de Biophysique Moléculaire (CBM)-CNRS/University of Orléans UPR4301, Rue Charles Sadron, 45071 Orléans Cedex 2, France, Tel +33 6 9990 8746, Email sohailakhtermph@ 123456gmail.com
                [*]

                These authors contributed equally to this work

                Article
                nsa-8-055
                10.2147/NSA.S49052
                4657804
                26640374
                a1a4cd35-560e-4f95-93de-c05e3cf987b9
                © 2015 Ahmad et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. 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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                nanoparticles,lung cancer,inhalational chemotherapy,drug targeting,nanotoxicity

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