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A review article published in the journal. Antioxidants provides a detailed overview of nanoparticle-based strategies to improve the bioavailability and bioactivity of curcumin.
Study: Improving the bioavailability and bioactivity of curcumin for disease prevention and treatment. Image Credit: Microgen/Shutterstock
Background
Curcumin, the main bioactive compound in turmeric, is a polyphenol found in long turmeric estate. This compound has numerous health benefits, including anti-cancer, antioxidant, anti-inflammatory, anti-obesity, anti-diabetic, antimicrobial, healing and lipid-lowering properties.
Curcumin has low bioavailability in human organs and is rapidly converted into a series of bioactive metabolites after intestinal absorption. Dried turmeric powder prepared from long turmeric The roots contain about 2-5% curcumin.
Curcumin consumed through dietary sources is sufficient to affect the gut microbiota. However, due to rapid metabolism, the concentration of intact curcumin in the circulation becomes very low (submicromolar concentrations), which is insufficient to trigger cell signaling and gene expression, as observed in in vitro Studies with cultured cells.
Examples of curcumin nanodelivery systems.
Strategies to increase the bioavailability of curcumin
Dietary curcumin is inefficiently absorbed across the intestinal epithelium and undergoes rapid metabolism and systemic elimination. In an aqueous solution with neutral pH, the enol state of curcumin is formed, which reduces the stability of curcumin.
Various nanoformulations have been developed to increase the concentration of curcumin in the circulation as well as in specific cells, tissues and organelles. These nanoformulations have been designed to increase curcumin solubility, improve stability during gastrointestinal absorption, alter absorption pathways, and inhibit detoxification enzymes through the use of adjuvants.
The latest generation of curcumin nanoformulations can increase the bioavailability of free curcumin in plasma by more than 100 times and improve absorption, cellular uptake, permeability across the blood-brain barrier, and tissue distribution.
Factors that enhance the bioavailability of curcumin include the composition, size, and route of administration of the nanoparticles. Curcumin preparations with smaller nanoparticles have been found to increase bioavailability when administered orally. In contrast, larger nanoparticles have been found to increase bioavailability when administered intravenously.
Curcumin nanoformulations can induce senescence in malignant and normal cells, thereby effectively treating various types of cancer and age-related diseases, including cardiometabolic diseases, neurodegenerative diseases, and liver, lung, and gastrointestinal diseases.
Regarding the mode of action, existing evidence indicates that curcumin acts as an antioxidant and anti-inflammatory compound to reduce the production of reactive oxygen species (ROS) and modulate cell signaling and gene expression related to inflammatory pathways. These activities work synergistically to maintain the homeostasis of cellular macromolecules (proteins, DNA, and lipids).
These activities can be increased by incorporating curcumin into nanoparticle-based formulations, such as polymeric curcumin-bioperin-PLGA. Isomerization of curcumin to cis-trans curcumin is known to increase its ability to bind to adenosine receptors. Incorporation of cis-trans curcumin into nanoformulations is considered a valuable strategy to increase its therapeutic efficacy against inflammatory diseases.
Regarding the safety profile, recent clinical trials indicate that most curcumin nanoformulations are well tolerated and safe for use in humans.
Antimicrobial activities
Curcumin is known to exert an antimicrobial effect against Gram-positive and Gram-negative bacteria, and this activity is beneficial for topical applications against skin infections and oral and intestinal applications. Additionally, curcumin can indirectly prevent infections by inhibiting bacterial growth in food.
The antimicrobial activities of curcumin can be improved by incorporating it into nanoformulations. Administration of curcumin with other compounds, such as antibiotics, honey or other polyphenols, can also increase its antimicrobial and biofilm-inhibiting activities.
Effects of curcumin nanoformulations on the gastrointestinal tract.
Various nanotechnology-based systems, such as micelles, liposomes, exosomes, phospholipid complexes, nanoemulsions, nanostructured lipid carriers, and biopolymer nanoparticles, have been found to increase the bioavailability of oral curcumin.
Nanoparticle curcumin called ‘teracurmin’ has been found to suppress colitis in mice by modulating the gut microbiota. An improvement in the composition of the intestinal microbiota has also been achieved using curcumin extract in nanobubbles. Curcumin loaded with nanostructured lipid carriers has been found to reduce colon inflammation in animals.
Incorporation of curcumin into liposomes has been found to increase their anticancer activity by improving gastrointestinal absorption. Furthermore, administration of curcumin with other bioactive compounds, such as piperine and salsalate, has been found to increase the bioavailability and bioactivity of curcumin.
Effects of curcumin nanoformulations on liver and adipose tissue.
Nanoformulations of curcumin with adjuvants, such as piperine and quercetin, have been found to significantly increase its bioavailability and bioactivity. Various nanotechnology-based delivery systems such as micelles, liposomes, polymeric, metallic and solid lipid nanoparticles have been found to increase the bioavailability of curcumin.
The anti-inflammatory, antioxidant, and antifibrotic properties of curcumin make it a potential therapeutic compound for liver diseases. In liver diseases, curcumin nanoformulations have been found to increase its therapeutic efficacy by increasing the solubility, bioavailability and membrane permeability of curcumin and improving its pharmacokinetics, pharmacodynamics and biodistribution.
Effects of curcumin nanoformulations on the cardiovascular system.
Curcumin encapsulated in carboxymethyl chitosan nanoparticles conjugated to a myocyte-specific localizing peptide has been found to increase the cardiac bioavailability of curcumin. The formulation has also been found to improve cardiac function by reducing the expression of hypertrophy marker genes and apoptotic mediators.
Various nanoformulations of curcumin, such as hyaluronic acid-based nanocapsules, PLGA-encapsulated nanoparticles, or nanoemulsion systems, have been found to increase the aqueous solubility of curcumin and subsequently prevent hypertension in animals. Similar cardioprotective effects have been observed using nanocurcumin polymer-based nanoparticles and curcumin- and nisin-based polylactic acid nanoparticles. These formulations have been found to prevent myocardial damage and improve cardiac muscle functions.
Effects of curcumin nanoformulations on the brain.
Curcumin in complex with galactomannans has been found to have improved blood-brain barrier permeability and greater efficacy in preventing neuroinflammation, anxiety, fatigue, and memory loss in both humans and animals.
Curcumin-loaded liposomes have been found to exert anti-amyloidogenic and anti-inflammatory effects in animal and cellular models of Alzheimer’s disease. The preventive activities of curcumin against Alzheimer’s disease are associated with its ability to reduce amyloid beta production and tau aggregation, which are the main characteristics of Alzheimer’s disease.
However, clinical trials involving patients with mild to moderate Alzheimer’s disease failed to find any beneficial effect of curcumin in reducing disease biomarkers and improving cognitive functions.
On the other hand, a recent clinical trial involving non-demented adults has shown that oral curcumin treatment can improve memory and reduce the accumulation of amyloid and tau in the amygdala and hypothalamus.