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Karthikeyan et al. Nanocurcumin: A Promising Candidate for Therapeutic Applications physicochemical properties that make nanocurcumin effective than native curcumin. Previous studies demonstrated that these properties can lead to an increased rate of solubility and higher oral bioavailability, including high pharmacokinetic profile, and active targeting (Biswas et al., 2014). Characteristics of curcumin vary with particle size change in the nanoscale. It was found that particle size reduction considerably improves the effectiveness of nanocurcumin and makes it superior to native curcumin. Mostly, 10–100 nm size nanoparticles have been used for various medicinal applications and clinical trials (Flora et al., 2013). Owing to its size, nanocurcumin is considered as an ideal choice to use as a drug compares to normal curcumin because of its larger surface area. Nanocurcumin enters organs that are almost cannot able to enter by curcumin. It was found that nanocurcumin may have a higher intracellular absorption capacity compared to normal curcumin. This property is also important to target intracellular pathogens for infectious diseases (Flora et al., 2013). It has been seen that nanocurcumin contains high systemic bioavailability in plasma and tissues compared to free curcumin (Zou et al., 2015). As per Ma et al. there is an increase in the in vivo bioavailability and distribution of the tissues due to nanocurcumin which offers 60 folds of increase in the biological half-life when compared as to the treatment of native curcumin in an experiment with rat models (Ma et al., 2007). Dende et al. reported nanocurcumin is better bioavailability than native curcumin and obstructing degenerative changes in cerebral malaria studies. There have been three folds of increase in the concentration of curcumin in the tissues of the brain when an oral dose of 5mg PLGA- curcumin with 350 mg of curcumin was delivered than that accumulated with 5 mg of native curcumin (Dende et al., 2017). It was also found that nanoformulation of curcumin strengthens its circulation time, retention time, and mean residence time inside the body (Mythri et al., 2007). The surface area is also a paramount feature of nanoparticles. Primarily, materials made up of nanoparticles have a relatively larger surface area, and it increases the rate of degradation and aqueous solubility, which leads to enrichment of the bioavailability of drugs. Nevertheless, a large surface area enhances a drug response to a specific molecular target and improves its pharmacological activity (Mohanty and Sahoo, 2010). Due to the larger surface area, the drug injected into nanoparticles will be exposed to the particle surface encouraging to fast drug release. Also, the large surface area makes nanoparticles distinctive and suitable applicants for various applications. Brunauer–Emmett–Teller (BET) theorem is the simple and best method to determine the surface area of nanoparticle materials. The role of the surface charges is established in curcumin nanoparticles. In general, the electric potential for the nanoparticles defines by surface charge, and it is completely related to nanoparticles chemical composition. Muller and Keck found that negative and positive zeta potential prevents the aggregation of nanoparticles. Thus, nanoparticles are extremely stable in suspension. Curcumin is forming aggregates and susceptible to opsonization because of its low solubility in water, while nanocurcumin dissolves completely in aqueous media forming no aggregates due to the presence of zeta potential (Muller and Keck, 2004). The positive charge obtained on the surface of nanoparticles is always considered being perfect because it can enter deep into cell membranes and have a high absorption rate compare to negatively charged particles. Also, nanoparticles along with a slight positive charge to improve its internalization capacity while a higher positive charge leads the toxicity to cells (Yallapu et al., 2015). On the other hand, the negative charge does not enter the cell wall at all but prevents it from breaking down under certain conditions and promotes a particle’s stability in circulation. No et al. described a relationship between surface charge and antimicrobial activity of nanocurcumin. Experimental data confirmed that positively charged curcumin nanoparticles showed better antimicrobial activity against Listeria monocytogenes (No et al., 2017). Many biological processes such as protein adsorption and denaturation (Gessner et al., 2000), activation of immune cells, interaction with biological membranes or cellular uptake, and higher toxicity depend on the surface hydrophobicity (Chompoosor et al., 2010). Previous studies showed that the hydrophobicity of nanomaterials had a direct influence on the stability and bio-distribution of nanocarriers (Gessner et al., 2000; Jones et al., 2014). Therefore, it is a major object being controlled in the drug delivery systems. Due to hydrophobic nature,curcumin struggles to reach the cell membrane and bind through hydrogen bonding and hydrophobic interactions to the fatty acyl chains of membrane lipids. Thus, curcumin present inside the cytoplasm is very low. Nanoformulations of curcumin hold promise as a drug delivery system and overwhelmed these difficulties and increased its bioavailability. Loading efficiency and entrapment efficiency of nanodrug are highly depend on the preparation method and type of carrier system used to produce nanodrugs. Both play a vital role in drug delivery and had a great impact on the amount and level of drug release from the carrier. When loading efficiency is associated with the ratio of the drug to that of the carrier system, the entrapment efficiency tells of how much percentage of the drug in the nanoparticles that are being efficiently adsorbed or entrapped (Prokop and Davidson, 2008). NANOCURCUMIN THERAPEUTIC APPLICATIONS Nanocurcumin is a promising therapeutic candidate with useful therapeutic properties viz., anti-inflammatory, anticancer, antiamyloid, antioxidant, antimicrobial antifibrosis and it has potential in the prevention and treatment of many human diseases. In the following section successful therapeutic applications of nanocurcumin are discussed. Anti-Inflammatory Effects Curcumin is a potential anti-inflammatory agent and its anti- inflammatory activities mediated by the obstruction of enzymes activity, cytokines production, and activation of transcription factors. Wang et al. synthesized the curcumin-solid lipid nanoparticles (C-SLNs) and enhanced their effectiveness in an Frontiers in Pharmacology | www.frontiersin.org 11 May 2020 | Volume 11 | Article 487PDF Image | Nanocurcumin Promising Candidate for Therapeutic Applications
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