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Karthikeyan et al. Nanocurcumin: A Promising Candidate for Therapeutic Applications TABLE 4 | Details of registered patents on curcumin nanoformulation. S. No 1 2 3 4 5 6 7 8 9 12 13 14 15 16 17 Title of the patent Nanoparticle targeted drug delivery to the lungs using extra-testicular Sertoli cells Topical formulation(s) for the treatment of inflammation, skin and mucosal disorders, and other diseases Curcumin nanoparticles with improved bioavailability and methods of producing the same patent Preparation method and application of curcumin chitosan-stearic acid graft micelle Magnetic nanoparticle formulations, methods for making such formulations, and methods for their use Nanocrystalline solid dispersion compositions and process of preparation Curcumin coated magnetite nanoparticles for biomedical applications Nanoparticles for mitochondrial trafficking of agents Curcumin-er, a liposomal-PLGA sustained release nanocurcumin for minimizing qt prolongation for cancer therapy Novel highly bioavailable, water soluble and sustained release nanoformulations hydrophobic plant derived compounds and extracts Nanomicelles for the treatment of cancer Curcumin-sophorolipid complex Curcumin long-circulating nanoliposome carrier of enoxolone mediation and preparation method Phospholipid/chitosan drug delivery system, preparation method, and uses Production of curcumin and piperine loaded double-layered biopolymer based nano-delivery systems by using electrospray/coating method Patent/application number WO2009105278A2 US 8535693 B2 WO2010013224A2 CN102743336A US 20130245357Al WO 2013132457 A2 WO2013108270A1 WO 2013123298 A1 US 20140065061A1 US 20150072012 A1 WO2016167730A1 WO2016013026A1 CN104689321B WO2017186065A1 EP3142702B1 Reference Kumar et al., 2009 Chaniyilparampu et al., 2010 Santosh Kumar et al., 2010 Xianwang et al., 2012 Chauhan et al., 2013 Bansal et al., 2013 Pattayil and Jayphraba, 2013 Dhar and Marrache, 2013 Ranjan et al., 2014 Sripathy et al., 2015 Oguz et al, 2016 Singh et al., 2016 Li, 2017 Liu et al., 2017 Sezgin and Bayraktar, 2018 Source: Curcumin nanoformulation patents information obtained from Google Patents website The invention of patent WO2016167730A1 described the curcumin nanoparticles and their effectiveness for the treatment of cancer (Oguz et al., 2016). The patent of WO2016013026A1 consisting of acidic sophorolipid and curcumin [SL (A) +Cur], in which, curcumin is solubilized and nano-encapsulated in acidic sophorolipid to improve curcumin’s bioavailability and solubility to increase its therapeutic activity including cancer (Singh et al., 2016). In the patent of CN104689321B, the preparation of glycyrrhetinic acid-mediated curcumin long-circulating nanostructured lipid carrier dispersion liquid was reported. This nanolipid carrier consists of glycyrrhetinic acid-phospholipid derivative, soybean lecithin and polyoxyethylene 40 stearate, caprylic/capric triglyceride, and glyceryl monostearate (Li, 2017). Liu et al. registered the patent of WO2017186065A1 curcumin delivery system based on nanoparticles such as phospholipid and chitosan (Liu et al., 2017). Recently, European patent EP3142702B1 describes the preparation of curcumin and piperine loaded biopolymer-based nano-delivery systems using electrospray/coating techniques with improved curcumin bioavailability (Sezgin Veliddin and Bayraktar, 2018). RESEARCH GAP AND FUTURE PERSPECTIVES Curcumin has been received broad attention over the decades for its potential therapeutic applications. With in-depth review of the literature, it is worth mentioning that nanoencapsulation techniques enhanced the pharmacokinetic properties of the drug packed with curcumin and offered better therapeutic value. In the various sections of this review, according to the content mentioned, numerous curcumin nanoformulation has been developed and used to treat many diseases in human as well as enormous progress has been achieved by curcumin nanoformulation over the past decades. However, the dictum “there is always room for improvement” is precisely in agreement with the pace of the ongoing developments to make curcumin as an effective drug candidate. Hence, many challenges and questions still exist to propose nanocurcumin as a promising candidate for therapeutic applications in human diseases. So far, numerous curcumin nanoformulations have been introduced to improve the cellular uptake, tissue specificity, and effectiveness of curcumin. In this review, some of the curcumin nanoformulations discussed potently challenge many signaling pathways that are linked to various human diseases. Most of these formulations, however, remained at the proof of concept stage and experiments were performed only in the pre-clinical models, and therefore our lack of understanding of the risks of curcumin nanoformulation in humans is a major issue. Thus, always question the toxicological safety of curcumin applications. Unfavorable toxicity arising through the nanomedicine based drug delivery methods result in DNA damage, allergic responses, neuroinflammation, and excitotoxicity. For this peculiar reason, the biocompatibility and biodegradability of the nanomedicines have to be researched and recorded with accuracy. So far, very limited clinical studies only conducted, they confirm that nanocurcumin has better characteristics such as bioavailability, chelating property, and retention time compare to bulk curcumin as well as systematically safe. However, substantial gaps in research have been identified due to the limited number of clinical trials to assess the safety and efficacy of curcumin nanoformulations in humans. Thus, it is necessary to conduct the many clinical trials with a large group of patients before introducing the curcumin nanoformulations to the pharmaceutical market. Curcumin nanoparticles are not tissue Frontiers in Pharmacology | www.frontiersin.org 16 May 2020 | Volume 11 | Article 487PDF Image | Nanocurcumin Promising Candidate for Therapeutic Applications
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