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      Nanoformulations of curcumin: an emerging paradigm for improved remedial application

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          Abstract

          Curcumin is a natural polyphenol and essential curcuminoid derived from the rhizome of the medicinal plant Curcuma longa ( L.) is universally acknowledged as “ Wonder drug of life”. It is a vital consumable and restorative herb, commonly keened for several ailments such as cancer, arthritis, pain, bruises, gastrointestinal quandaries, swelling and much more. Despite its enormous curative potential, the poor aqueous solubility and consequently, minimal systemic bioavailability with rapid degradation are some of the major factors which restrict the utilization of curcumin at medical perspective. However, to improve its clinically relevant parameters, nanoformulation of curcumin is emerging as a novel substitute for their superior therapeutic modality. It enhances its aqueous solubility and targeted delivery to the tissue of interest that prompts to enhance the bioavailability, better drug conveyance, and more expeditious treatment. Subsequent investigations are endeavored to enhance the bio-distribution of native curcumin by modifying with felicitous nano-carriers for encapsulation. In this review, we specifically focus on the recent nanotechnology based implementations applied for overcoming the innate constraints of native curcumin and additionally the associated challenges which restrict its potential therapeutic applications both in vivo and in-vitro studies, as well as their detailed mechanism of action, have additionally been discussed.

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          Most cited references 99

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          Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research.

          Curcuma longa (turmeric) has a long history of use in Ayurvedic medicine as a treatment for inflammatory conditions. Turmeric constituents include the three curcuminoids: curcumin (diferuloylmethane; the primary constituent and the one responsible for its vibrant yellow color), demethoxycurcumin, and bisdemethoxycurcumin, as well as volatile oils (tumerone, atlantone, and zingiberone), sugars, proteins, and resins. While numerous pharmacological activities, including antioxidant and antimicrobial properties, have been attributed to curcumin, this article focuses on curcumin's anti-inflammatory properties and its use for inflammatory conditions. Curcumin's effect on cancer (from an anti-inflammatory perspective) will also be discussed; however, an exhaustive review of its many anticancer mechanisms is outside the scope of this article. Research has shown curcumin to be a highly pleiotropic molecule capable of interacting with numerous molecular targets involved in inflammation. Based on early cell culture and animal research, clinical trials indicate curcumin may have potential as a therapeutic agent in diseases such as inflammatory bowel disease, pancreatitis, arthritis, and chronic anterior uveitis, as well as certain types of cancer. Because of curcumin's rapid plasma clearance and conjugation, its therapeutic usefulness has been somewhat limited, leading researchers to investigate the benefits of complexing curcumin with other substances to increase systemic bioavailability. Numerous in-progress clinical trials should provide an even deeper understanding of the mechanisms and therapeutic potential of curcumin.
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            Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma

            Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. Curcumin has been used extensively in Ayurvedic medicine for centuries, as it is nontoxic and has a variety of therapeutic properties including anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer activities via its effect on a variety of biological pathways involved in mutagenesis, oncogene expression, cell cycle regulation, apoptosis, tumorigenesis and metastasis. Curcumin has shown anti-proliferative effect in multiple cancers, and is an inhibitor of the transcription factor NF-κB and downstream gene products (including c-myc, Bcl-2, COX-2, NOS, Cyclin D1, TNF-α, interleukins and MMP-9). In addition, curcumin affects a variety of growth factor receptors and cell adhesion molecules involved in tumor growth, angiogenesis and metastasis. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and treatment protocols include disfiguring surgery, platinum-based chemotherapy and radiation, all of which may result in tremendous patient morbidity. As a result, there is significant interest in developing adjuvant chemotherapies to augment currently available treatment protocols, which may allow decreased side effects and toxicity without compromising therapeutic efficacy. Curcumin is one such potential candidate, and this review presents an overview of the current in vitro and in vivo data supporting its therapeutic activity in head and neck cancer as well as some of the challenges concerning its development as an adjuvant chemotherapeutic agent.
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              Role of particle size in phagocytosis of polymeric microspheres.

              Polymeric microspheres are extensively researched for applications in drug and vaccine delivery. However, upon administration into the body, microspheres are primarily cleared via phagocytosis by macrophages. Although numerous studies have reported on the biochemical pathways of phagocytosis, relatively little is known about the dependence of phagocytosis on particle size. Here, we investigate the previously unexplained dependence of phagocytosis on particle size. Rat alveolar macrophages and IgG-opsonized and non-opsonized polystyrene microspheres were used as model macrophages and drug delivery particles. Phagocytosis, attachment and internalization were measured by flow cytometry and time-lapse video microscopy. Particles possessing diameters of 2-3 microm exhibited maximal phagocytosis and attachment. Rate of internalization, however, was not affected significantly by particle size. Maximal attachment of 2-3 microm microspheres is hypothesized to originate from the characteristic features of membrane ruffles in macrophages. Elimination of ruffles via osmotic swelling nearly eliminated the peculiar size-dependence of phagocytosis. A simple mathematical model is presented to describe the dependence of phagocytosis on particle size. The dependence of phagocytosis on particle size originated primarily from the attachment step. These results reveal the importance of controlling drug delivery particle size distribution and selecting the size appropriate for avoiding or encouraging phagocytosis.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                12 September 2017
                11 July 2017
                : 8
                : 39
                : 66680-66698
                Affiliations
                1 Department of Animal Biotechnology, Faculty of Biotechnology, Jeju National University, Jeju, Republic of Korea
                2 Division of Veterinary Medicine, Faculty of Veterinary Science and Animal Husbandry, Sher-e-Kashmi University of Agricultural Sciences and Technology, R.S. Pura, Jammu, India
                3 Department of Animal Biotechnology, College of Animal Bioscience and Technology, Kangwon National University, Gangwon-do, Republic of Korea
                4 Laboratory of Animal Genetic Engineering and Stem Cell Biology, Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju, Republic of Korea
                Author notes
                Correspondence to: Dong Kee Jeong, ngejeong@ 123456gmail.com , dkjeong@ 123456jejunu.ac.kr
                [*]

                These authors contributed equally to this work

                Article
                19164
                10.18632/oncotarget.19164
                5630447
                f6be1b51-edb8-4f71-bd69-adc5031e1855
                Copyright: © 2017 Gera et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Categories
                Review

                Oncology & Radiotherapy

                curcumin, herb, nano, nanoformulation, nanotechnology

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