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Karthikeyan et al. Nanocurcumin: A Promising Candidate for Therapeutic Applications shielding curcumin from hydrolysis inactivation. Some formulations are targeted for longtime circulation and retention in the body, while reminders have focused on cellular delivery and intracellular release mechanisms. Several curcumin nanoformulations created a great impact on pharmaceutical applications and confirmed to have useful in the diagnosis of various human diseases. They are outlined and discussed here. Liposomes Liposomes are a spherical vesicle comprised of single or multiple phospholipid bilayers surrounding aqueous units that very closely resemble the cell membrane structure (Faraji and Wipf, 2009). Both in vitro and in vivo conditions, liposomes are ideal delivery systems for biologically active substances. Liposomes have many advantages such as high biocompatibility and biodegradability, high stability, low toxicity, better solubility, targeting specific cells, controlled distribution, flexibility, and easy preparation (Moballegh Nasery et al., 2020). Thus, liposomes are strong drug-carrier system to date and preferred by researchers. The diameter of the liposome ranges between 25 to 2.5 mm. The vesicle size is an important factor for deciding the circulation time of liposomes and the quantity of drug capsulation in liposomes is influenced by both size and number of bilayers (Akbarzadeh et al., 2013). Many studies have shown that liposome solubilizes curcumin in the phospholipidic bilayer and allows curcumin to be distributed over aqueous medium and increases the effect of curcumin (Chang et al., 2018). Moreover, liposomal drugs accumulate mainly in the liver, spleen, lung, bone marrow, or other tissues and organs. This helps to improve the drug therapeutic index and decrease the side effect. Extensive studies showed that liposomal curcumin was the most suitable vehicle to treat various cancer diseases. Dhule et al. showed that liposomal curcumin inhibited the growth of the KHOS OS cell line and MCF-7 breast cancer cell line and exhibited a strong anticancer effect in both in vitro and in vivo condition (Dhule et al., 2012). Tian et al. studied the antitumor efficiency and the biochemical mechanisms triggered by curcumin liposomes in PC-3 human prostate cancer cells. The survival rate of curcumin-loaded liposomes treated with PC-3 cells was relatively low and time- depend manner compared with free curcumin (Tian et al., 2014). It was also seen that liposomes could promote the absorption of curcumin into the cell, and the duration of cell fluorescence intensity was higher and longer than the control group. Tefas et al. prepared the liposomes coencapsulating doxorubicin and curcumin, it reduced the cell proliferation in C26 murine colon cancer and showed better cytotoxic activity than its free form (Tefas et al., 2017). Similarly, liposomes co-encapsulating curcumin and resveratrol showed a lower particle size, polydispersity index, and high encapsulation efficiency (Huang et al., 2019). Recently, a combination of curcumin liposome nanocarriers (LIP-CUR) and blue light-emitting diode (BLED) induced photodynamic therapy (BLED-PDT) produced excellent bioactivity and anticancer activity (Vetha et al., 2019). Collectively, the results revealed that the liposomes could be a better carrier for curcumin. Nanoparticles Nanoparticles are particles of approximately 1–100 nm in diameter possess unique physical, chemical, and biological properties that can be useful for drug delivery (Biswas et al., 2014). Nanoparticles are 1,000 times smaller than the average human body cell and consist of materials engineered at the atomic or molecular level. They are also suitable for both controlled and targeted drug delivery systems (Rudramurthy et al., 2016). Encapsulating drugs inside nanoparticles can enhance the pharmacokinetics and solubility of drugs, provide targeted delivery and controlled release of drugs. So far, polymer, solid lipid, magnetic, gold, and albumin-based nanoparticles are extensively used to improve the curcumin therapeutic applications. Polymeric nanoparticles have the advantage of being small and biocompatible, thus being able to circulate a long time in the blood circulation (Ferrari et al., 2018). Many natural and synthetic polymers include N-isopropylacrylamide (NIPAAM), polyvinyl alcohol (PVA), poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol monoacrylate [NIPAAM (VP/PEG A)], N- vinyl-2-pyrrolidone, silk fibroin, hydrophobically modified starch, and chitosan have been identified and utilized for synthesis of curcumin nanoparticles (Shome et al., 2016). Chang et al. studied the molecular mechanisms activated by curcumin loaded-PLGA nanoparticles in CAL27 cisplatin- resistant cancer cells (CAR cells). Experimental data suggested that curcumin loaded-PLGA nanoparticles controlled the activity of multiple drug resistance protein 1 (MDR1) and the development of reactive oxygen species (ROS) in CAR cells by activating the intrinsic apoptotic pathway. Besides, curcumin- loaded PLGA nanoparticle is more effective against the treatment of CAR cells along with enhanced bioactivity at in vitro condition and better bioavailability at in vivo condition compare to the native curcumin (Chang et al., 2013). In another study, curcumin loaded polymeric nanoparticles using Eudragit R E100 cationic copolymer exhibited great binding and cellular uptake of polymeric nanoparticles, therefore increasing cytotoxic activity. Taken together, this nanoparticle formulation suppressed tumor growth and reported a 19-fold higher growth inhibition of Colon-26 cells than curcumin alone (Chaurasia et al., 2016). Also, curcumin silk fibroin (CUR-SF) nanoparticles provided a more stable delivery to colon cancer cells and produced a strong anticancer effect than it’s freeform in HCT116 cells. This study concludes controlled release of CUR-SF can able to improve a curcumin cellular uptake into cancer cells and reduce the cytotoxicity to normal cells (Xie et al., 2017). Solid lipid nanoparticles are the colloidal submicron particles formed through natural or synthetic lipids dispersed in aqueous surfactants or water. They are easily scalable, stable, and biocompatible drug delivery systems with a high drug to lipid ratio which also improves the solubility of poorly soluble drugs (Bhatt et al., 2018). It has been shown that solid lipid curcumin nanoparticles enhanced the solubility over native curcumin and reduced that activity of the lipopolysaccharide (LPS)-induced pro-inflammatory mediators NO, PGE2, and interleukin (IL)-6 by obstructing the activation of NF-kB (Nahar et al., 2015). Sun et al. experimental results indicated that curcumin solid lipid Frontiers in Pharmacology | www.frontiersin.org 6 May 2020 | Volume 11 | Article 487PDF Image | Nanocurcumin Promising Candidate for Therapeutic Applications
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