Curcumin Nanoformulation Research Articles

Curcumin and its nano-formulations combined with exercise: From molecular mechanisms to clinic.

Curcumin is a strong substance derived from turmeric, a popular spice, renowned for its antioxidant and anti-inflammatory abilities. The study delved deeply into a thorough examination of various sources to evaluate the impact of both regular curcumin and nano-formulated curcumin on elements that impact physical performance, including muscular strain, discomfort, swelling, and oxidative tension. While engaging in exercise, the body experiences a rise in reactive oxygen species and inflammation. As a result, it is important to ensure a proper balance between internal and external sources of antioxidants to maintain stability in the skeletal muscle. Without this balance, there is a risk of muscle soreness, damage, and ultimately, a decline in exercise performance. Curcumin possesses the ability to enhance physical performance and reduce the symptoms of muscle fatigue and injury by virtue of its antioxidative and anti-inflammatory properties. Including curcumin supplements appears to have advantageous effects on various aspects of exercise, such as enhancing performance, assisting with recovery, lessening muscle damage and discomfort, and lowering levels of inflammation and oxidative stress. However, a thorough assessment is necessary to precisely gauge the healing advantages of curcumin in enhancing exercise ability and reducing recovery time.

Curcumin as a Multifunctional Spice Ingredient against Mental Disorders in Humans: Current Clinical Studies and Bioavailability Concerns.

Mental disorders in terms of depression, anxiety, and stress are one of the major causes of burden globally. Over the last two decades, the use of plant-based substances in the treatment of mental disorders in combination or not with medication has increasingly attracted the interest of the scientific research community. However, even if there is a plethora of naturally occurring bioactive compounds, most of them have low bioavailability, rendering them unable to insert into the bloodstream to exert their biological activities. This is a comprehensive narrative review that critically summarizes and scrutinizes the new approaches to the treatment of mental disorders using curcumin, also highlighting its bioavailability properties. The most accurate were searched using effective and relevant keywords. This narrative review reveals substantial evidence that curcumin can exert significant effects on several mental disorders. However, despite the low cost, the extensive and confirmed potency of curcumin and its involvement in signaling pathways and the scientifically confirmed data regarding its molecular mechanisms of action against mental disorders, this naturally occurring compound presents low oral bioavailability. Pharmaceutical technology has provided solutions to increase the bioavailability of curcumin. Combination with piperine, galactomannosides, liposomal formulation or nanoformulation overcomes the bioavailability and solubility disadvantages. Although curcumin demonstrates anti-anxiety, anti-depressive and anti-stress properties, studies on humans are limited and heterogeneous. Further research is highly recommended to determine the most functional formula, dose, duration, and possible side effects of curcumin on mental disorders in humans. Based on the current knowledge, the curcumin nanoformulation and Theracurmin, a form of colloidal submicroscopic particles, seem to be the most effective bioavailable formulations, which may be examined in future clinical human studies.

Microbial fermentation-based synthesis of nano-curcumin suggesting the role of pullulan in nano-formulation

Curcumin is a multitargeting nutraceutical with numerous health benefits, however, its efficacy is limited due to poor aqueous solubility and reduced bioavailability. While nano-formulation has emerged as an alternative to encounter such issues, it often involves use of toxic solvents. Microbial synthesis may be an innovative solution to address this lacuna. Present study, for the first time, reports exploitation of Aureobasidium pullulans RBF4A3 for production of nano-curcumin. For this purpose, Aureobasidium pullulans RBF4A3 was inoculated in YPD media along with curcumin (0.1 mg/mL) and incubated for 24 h, 48 h, and 72 h. Subsequently, residual sugar, biomass, EPS concentration, curcumin concentration, and curcumin nanoparticle size were measured. As a result, nano-curcumin with an average particle size of 31.63 nm and enhanced aqueous solubility was obtained after 72 h. Further, investigations suggested that pullulan, a reducing polysaccharide, played a significant role in curcumin nano-formulation. Pullulan-mediated nano-curcumin formulation, with an average particle size of 24 nm was achieved with conversion rate of around 59.19 %, suggesting improved aqueous solubility. Additionally, the anti-oxidant assay of the resulting nano-curcumin was around 53.7 % per μg. Moreover, kinetics and thermodynamic studies of pullulan-based nano-curcumin revealed that it followed first-order kinetics and was favored by elevated temperature for efficient bio-conversion. Also, various physico-chemical investigations like FT-IR, NMR, and XRD reveal that pullulan backbone remains intact while forming curcumin nanoparticle. This study may open up new avenues for synthesizing nano-polyphenols through a completely green and solvent free process with plausible diverse applications.

Preparation and Primary Bioactivity Evaluation of Novel Water-Soluble Curcumin-Loaded Polymeric Micelles Fabricated with Chitooligosaccharides and Pluronic F-68.

Curcumin (CU) is a bioactive compound extracted from turmeric and has various advantages. However, the benefit of CU is limited by its low water solubility (11 ng/mL). This research aimed to fabricate a water-soluble CU nano-formulation with chitooligosaccharides (COS) and pluronic F-68 (PF) utilizing the polymeric micelle method. The optimized curcumin-loaded chitooligosaccharides/pluronic F-68 micelles (COSPFCU) exhibited high encapsulation efficiency and loading capacity (75.57 ± 2.35% and 10.32 ± 0.59%, respectively). The hydrodynamic diameter of lyophilized COSPFCU was 73.89 ± 11.69 nm with a polydispersity index below 0.3. The COSPFCU could be completely redispersed in water and showed high DPPH scavenging ability. Meanwhile, COSPFCU could significantly reduce the cytotoxicity of the RAW 264.7 cells compared to native CU. Furthermore, COSPFCU improved the inhibition of NO release activity at 72.83 ± 2.37% but 33.20 ± 3.41% for the CU, with a low cytotoxicity concentration in the RAW 264.7 cells.

Novel curcumin nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cells

Background Curcumin has been used in the treatment of several diseases; however, its low pharmacologic profile reduces its therapeutic use. Towards improving its biological activity, nanoformulations have emerged. Thus, we aimed to determine whether curcumin nanoparticles (Cur-NPs) coated with PEG/chitosan improve the treatment of liver cancer (LC) cells and underpin the molecular mechanisms underlying their anti-cancer activity. Methods Cur-NPs were synthesised in the form of Cur-PLGA-PEG/chitosan NPs. The effect of Cur-NPs was assessed in HepG2 and Huh 7 LC cells and THLE-2 normal liver cells. Results The size of synthesised Cur-NPS was determined in the standard range of 141.2 ± 47.5 nm. Compared to THLE-2 cells, LC cells treated with Cur-NPs exerted cytotoxicity at 6.25 µg/mL after 48h. Treatment of HepG-2 cells with 2.5 µg/mL of Cur-NPs inhibited cell migration and this inhibition was augmented at 10 µg/mL (p < 0.001). Treatment of chicken embryo with 5 µg/mL Cur-NPs reduced angiogenesis (p < 0.001) of 4-day-old embryos. The nanoformulation upregulated Bax and p53 and downregulated Bcl-2 in a concentration-dependent manner and subsequently induce apoptosis in HepG-2 cells. Conclusion Treatment of LC cells with Cur-NPs decreased cell proliferation, migration, and angiogenesis, and induced cell death by promoting the proapoptotic pathway.

Proteomic Modulation in TGF-β-Treated Cholangiocytes Induced by Curcumin Nanoparticles.

Curcumin is a natural polyphenol that exhibits a variety of beneficial effects on health, including anti-inflammatory, antioxidant, and hepato-protective properties. Due to its poor water solubility and membrane permeability, in the present study, we prepared and characterized a water-stable, freely dispersible nanoformulation of curcumin. Although the potential of curcumin nanoformulations in the hepatic field has been studied, there are no investigations on their effect in fibrotic pathological conditions involving cholangiocytes. Exploiting an in vitro model of transforming growth factor-β (TGF-β)-stimulated cholangiocytes, we applied the Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH-MS)-based quantitative proteomic approaches to study the proteome modulation induced by curcumin nanoformulation. Our results confirmed the well-documented anti-inflammatory properties of this nutraceutic, highlighting the induction of programmed cell death as a mechanism to counteract the cellular damages induced by TGF-β. Moreover, curcumin nanoformulation positively influenced the expression of several proteins involved in TGF-β-mediated fibrosis. Given the crucial importance of deregulated cholangiocyte functions during cholangiopathies, our results provide the basis for a better understanding of the mechanisms associated with this pathology and could represent a rationale for the development of more targeted therapies.

PH-controlled release feature of chitosan assembled silica nanoparticles containing nano-formulated curcumin over in vitro gastric and physiological condition

Low water solubility leading to poor bioavailability has an impact on the decreasing of curcumin uptake in the body, resulting in a deficiency of its medicinal benefits. This study aims to overcome the limitations of curcumin by formulating a nano-emulsion called curcumin emulsion (CE). Furthermore, in order to improve the physicochemical properties and drug release features, the CE was encapsulated within chitosan-assembled mesoporous silica nanoparticles (Chi@SiO2@CE). This material was prepared using a one-pot method and was characterized by Attenuated-total reflectance (ATR-FTIR), Particle Size Analyzer (PSA), Thermogravimetric analysis (TGA), N2 adsorption-desorption, Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM). Additionally, antioxidant activity and in vitro drug release were also conducted. The study demonstrated that CE has strong antioxidant activity (IC50 = 14.14 μM) compared to curcumin alone. Additionally, the Chi@SiO2@CE exhibited pH-controlled release behavior, with less than 20% release of curcumin under an artificial gastric environment and 50% release under pH 7.4 conditions within 24 h. Therefore, this research suggest that Chi@SiO2@CE material has potential as a pH-responsive drug delivery material.

Nano formulation approaches for curcumin delivery- a review

Curcumin is a polyphenol molecule derived from Curcuma longa Linn's rhizomes. Curcumin appears to have been the target of substantial research, with cancer, viral, fungal infections, bacterial, arthritis, antioxidant, anti-inflammatory, allergies, Alzheimer's disease, and other chronic diseases and disorders all being explored. Curcumin has undesirable features such as inadequate intake and low aqueous solubility. To resolve these challenges, research has taken numerous attempts to improve its absorption, solubility, and bioavailability. Nanotechnology plays a critical role in the creation of nanostructured devices, nanomedicines, targeted therapy, and nanocarriers. Curcumin nano formulation has alleviated some of the major disadvantages of curcumin-based medication delivery. The emphasis of the study is on nano-based techniques to address therapeutic activity, efficacy, bioavailability, and solubility. Curcumin was localized to a certain cellular and molecular level by combining nano-curcumin with a specific molecule to enhance activity at the target site. A detailed description of solubility and bioavailability enhancement technique using protein carriers, solid dispersions, nanofiber, carbon dots, liposomes, and polymer carrier drug delivery systems is provided in this review.

Evaluation of dietary curcumin nanospheres as phytobiotics on growth performance, serum biochemistry, nutritional composition, meat quality, gastrointestinal health, and fecal condition of finishing pigs.

Curcumin is a bioactive functional feeding stimulant that is widely used as an additive in cuisine and animal feeds. Owing to its hydrophobic nature and low bioavailability, the nanoformulation of curcumin has recently received special attention from researchers. In this study, we investigated the effects of curcumin nanospheres (CN) on the growth performance, serum biochemistry, meat quality, intestinal immunohistochemistry, fecal malodors and microbes in finishing pigs. A total of 90 crossbred pigs (Duroc × [Yorkshire × Landrace]) with an average initial body weight of 73.77 ± 0.08 kg were randomized into 3 dietary groups in triplicate pens (10 pigs in each pen): control (CON) without supplementation of CN and the pigs in the remaining two groups were supplemented with CN at 1.0 (CN1) and 2.0 (CN2) mL/kg diet for a 40-day long experiment. The results showed that pigs fed the higher CN supplemented diet (CN2) had significantly higher final weight (FW) and weight gain (WG) than those fed the CON diet, and no significant differences were observed in the feed conversion ratio (FCR) and average daily feed intake (ADFI) after 28 days. At the end of the experiment, pigs fed the CN supplemented diet showed no significant difference in WG, ADFI or FCR compared to those on the CON diet. Overall, at the termination of the 40-day feeding trial, dietary CN had a significant effect on FW and WG, except for ADFI and FCR, in finishing pigs. After 40 days of the feeding trial, serum biochemical parameters such as glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase, triglycerides, and total cholesterol levels were significantly decreased in pigs fed the CN supplemented diet. However, high density lipoprotein levels were significantly increased in pigs fed the CN diets. Protein and lipid contents, as well as yellowness and lightness of the neck and longissimus dorsi muscles were not significantly affected by CN supplementation; however, there was a tendency to increase the redness of the longissimus dorsi muscle in pigs fed the CN2 supplemented diet compared to the CON diet. Meat grading and carcass weight significantly increased in pigs fed a higher CN supplemented diet. Fecal Escherichia coli and ammonia gas were significantly depleted in pigs fed CN diets. Histomorphological parameters, such as villus height, crypt depth and goblet cells in the jejunum of the intestine were significantly increased in pigs fed CN diet. Immunohistochemical staining showed that pro-inflammatory cytokine like tumor necrosis factor-α expression was reduced in pigs fed CN supplemented diets compared to the CON diet; however, antibodies such as immunoglobulin A and tight junction proteins such as claudin 3 were highly expressed in the intestine of pigs fed the CN diets. Overall, the results demonstrate the potential of dietary curcumin nanospheres as a nanobiotechnology tool as well as an effective feed additive for improving the performance and health status of finishing pigs.

Potential Anti-Proliferative Effect of Nano-formulated Curcumin Through Modulating Micro RNA- 132, Cyclin D1, and hTERT Genes Expression in Breast Cancer Cell Lines

Potential Anti-Proliferative Effect of Nano-formulated Curcumin Through Modulating Micro RNA- 132, Cyclin D1, and hTERT Genes Expression in Breast Cancer Cell Lines

Formation, characterization, and analysis of curcumin nanoformulation for evaluating its in vitro cytotoxicity.

Nanotechnology holds significance in all fields of research, and the formation and surface alterations of nanomaterials are particularly important in this discipline. Nanoformulations synthesized with bioactive plant components play a crucial role in the improvement of several therapeutics and diagnostics. In the present study, we reported the synthesis of a curcumin nanoformulation (CN) by using curcumin and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). The synthesized CN was characterized using dynamic light scattering, UV-Visible spectrophotometry, Fourier-transform infrared spectroscopy, field-emission scanning electron microscopy, and X-ray diffraction. Furthermore, it was evaluated for solubility, drug loading, encapsulation efficiency, stability, in vitro release, and anticancer potentials. The role of TPGS in the synthesis of CN was validated. The synthesized CN exhibited a size of 6.2 ± 1.9 nm, needle-shaped morphology, a polydispersity index of 0.164, and zeta potential of - 10.1 ± 3.21 mV, as determined by characterization techniques. Its water solubility was 2.5 × 104 times higher than that of pure curcumin. The encapsulation efficiency and curcumin loading efficiency of the synthesized CN were found to be 80 and 10%, respectively, with storage stability exceeding 30 days. Moreover, the synthesized CN demonstrated significant in vitro anticancer activity against the colorectal cancer cell line HCT-116, with an IC50 value of 12.74 ± 0.54 μM at 24 h.

Curcumin-Loaded Oil-Free Self-Assembled Micelles Inhibit the Influenza A Virus Activity and the Solidification of Curcumin-Loaded Micelles for Pharmaceutical Applications.

Curcumin, a well-known natural lipophilic phenolic compound, plays a vital role in inhibiting the influenza infection. Currently, many kinds of formulations for the enhancement of a water dispersion of curcumin have been developed; however, the anti-influenza abilities of formulated curcumin have been much less investigated. In this study, the optimized self-assembled micelles of RH 40/Tween 80 loaded with curcumin (Cur-M) in an oil-free-based system were spherical with a hydrodynamic size at 13.55 nm ± 0.208 and polydispersity at 0.144 characterized by atomic force microscopy and dynamic light scattering, respectively. Additionally, Cur-M significantly increased the bioactivity/stability of curcumin and effectively inhibited the influenza A virus infection and its replication after viral entry, indicating the alteration of the inhibition mechanisms of curcumin against virus infection via RH 40/Tween 80 micelle formulation. Furthermore, a solid formulation (Cur-SM) of Cur-M was successfully developed by a one-pot physical adsorption method using a small amount of adsorbent and ~50% of curcumin/Cur-M that could be burst released from Cur-SM in 1 h, facilitating the fast-releasing applications. Ultimately, all of the results show that Cur-SM acts as a good nano-formulation of curcumin with improved solubility/dispersity in aqueous solutions and demonstrate new anti-influenza mechanisms of curcumin for pharmaceutical development.

VALIDATION, STABILITY STUDIES, AND SIMULTANEOUS ESTIMATION OF CO-ENCAPSULATED CURCUMIN, EPIGALLOCATECHIN GALLATE NANOFORMULATION BY RP-HPLC METHOD

Objective: A new reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed to simultaneously determine curcumin and epigallocatechin gallate (EGCG) in novel nanoformulation. Methods: The high-performance liquid chromatography (HPLC) method was achieved by using a Thermo Scientific Hypersil Base Deactivated Silica (BDS) C18 column (25 cm X 4.6 mm, 5 µm) at 35 °C column oven temperature. The chromatographic procedure was performed with a mobile phase of acetonitrile and 0.025 M (pH 4.0) potassium dihydrogen phosphate (KH2PO4) buffer by gradient mode of elution. The injection volume was 20 µl, and the flow rate was 1.5 ml/min, with ultraviolet (UV) detection using a diode array detector (DAD) at a 268 nm isosbestic wavelength. Results: Drug entrapment efficiency studies were performed with co-encapsulated EGCG and curcumin nanoformulation, which were found to be 94.35 % and 95.12 %, respectively. This shows that the developed method is highly effective. EGCG and curcumin were eluted at 3.9 min and 10.7 min, respectively. The linearity range was 25-175 µg/ml for EGCG and 12.5-100 µg/ml for curcumin. The correlation coefficient was 0.991 for EGCG and 0.999 for curcumin from the linearity curve, which indicates that the method can produce good sensitivity. Forced degradation studies were conducted in acidic, basic, oxidative, thermal, photolytic, and UV stress conditions, where all the degradation peaks were monitored. Conclusion: The developed method was linear, simple, rapid, robust, and precise. It could be used to quantify EGCG and curcumin simultaneously in various nanoformulations for in vivo and in vitro applications.

Phytosomal curcumin alleviates collagen-induced arthritis by downregulating Th17 and upregulating Treg cell responses in rats

Objective: To explore the effects of a nano-formulation of curcumin (phytosomal curcumin) on the clinical and pathological symptoms of collagen-induced arthritis (CIA) in rats. Methods: Forty male Wistar rats were immunized with an emulsion containing bovine type II collagen and incomplete Freund's adjuvant and then administered phytosomal curcumin post-immunization. Clinical symptoms and histological analysis of the synovial tissues were performed. The effect of phytosomal curcumin on Th17 and Treg parameters was also evaluated. Results: Phytosomal curcumin reduced the clinical severity and paw swelling in CIA-induced rats, which was accompanied by a reduction in the number of inflammatory cell infiltration in the synovial tissue. Additionally, treatment with phytosomal curcumin significantly inhibited CIA-associated mediators as well as increased the anti-inflammatory mediators in comparison to the control groups. Conclusions: Phytosomal curcumin could improve CIA autoimmune responses and can be considered a potential candidate for the treatment of rheumatoid arthritis.

Investigation of Curcumin-Loaded OA400 Nanoparticle's Effect on the Expression of E6 and E7 Human Papilloma-Virus Oncogenes and P53 and Rb Factors in HeLa Cell Line.

Curcumin, a compound derived from the root of the Curcuma longa, has been confirmed as an anticancer, chemoprotective, and gene/protein regulatory agent. Nanoformulation of curcumin has been developed to increase its targeting efficiency, solubility, controlled release, and physical and chemical stability. This study investigated the effect of new nano-type curcumin, oleic acid-derived dendrosome (OA400 nanoparticles), on the expression of E6 and E7 human papillomavirus oncogenes and P53 and Rb factors in the HeLa cell line. After preparing nano-curcumin by mixing OA400 nano-carrier and curcumin, its effect was considered on the human cervical cancer cell line (HeLa cell line RRID: CVCL_003) and normal fibroblast cells. MTT assay and flow cytometry were used to evaluate cell viability and apoptosis. Furthermore, real-time RT-PCR and western blot analyses assessed RNA and protein expression of E6, E7, P53, and Rb. Statistical analyses were performed by GraphPad Prism 7 software. The nanoformulation of curcumin could reduce the expression of E6 and E7 oncogenes and increase P53 and Rb tumor suppressors in HeLa cancerous cells at 15 μM concentration; however, it had no significant effect on the viability of normal fibroblast cells. On the other hand, curcumin altered the expression of these genes at a 50-μM concentration. Gene and protein expression analysis indicated the up-regulation of P53 and Rb factors and the down-regulation of E6 and E7 under the influence of nano-curcumin treatment more than curcumin. These data indicate the potential of curcumin-loaded OA400 nanoparticles to be considered as a treatment option in cervical cancer investigations.

Efficient expression of hydrophobin HGFII-his via POT1-mediated δ integration strategy and its potential in curcumin nanoformulation

In this study, we first developed an efficient and eco-friendly expression system of the recombinant hydrophobin HGFII-his by introducing the POT1-mediated δ sequences site-specific integration strategy in Saccharomyces cerevisiae. Furthermore, according to the physical measurements, Sc-HGFII-his (expressed by S. cerevisiae) and Pp-HGFII-his (expressed by Pichia pastoris strain GS115) revealed identical selfassembly and surface modification properties. Subsequently, we confirmed that the Sc-HGFII-his self-assembled to globular morphology instead the classic rodlets of class I hydrophobins. Additionally, the HGFII-his-based curcumin nanoformulations revealed the nanoparticle profile and were capable of sustained release of curcumin for at least 72 h. As expected, they exhibited satisfied cell uptake profiles and dramatically cytotoxic activity against HeLa cells in antitumor assays. These findings indicate that HGFII-his was suitable for pharmaceutical emulsion formulations. Herein, we pushed the boundaries of an efficient method for the HGFII-his production, realized sustained curcumin release, and boosted the bioavailability and efficacy with HGFII-his-based curcumin nanoformulations.

Surface stabilization determines macrophage uptake, cytotoxicity, and bioactivity of curcumin nanocrystals

Pharmaceutical nanocrystals represent a promising new formulation that combines the benefits of bulk crystalline materials and colloidal nanoparticles. To be applied in vivo, nanocrystals must meet several criteria, namely colloidal stability in physiological media, non-toxicity to healthy cells, avoidance of macrophage clearance, and bioactivity in the target tissue. In the present work, curcumin, a naturally occurring poorly water-soluble molecule with a broad spectrum of bioactivity has been considered a candidate substance for preparing pharmaceutical nanocrystals. Curcumin nanocrystals in the size range of 40–90 nm were prepared by wet milling using the following combination of steric and ionic stabilizers: Tween 80, sodium dodecyl sulfate, Poloxamer 188, hydroxypropyl methylcellulose, phospholipids (with and without polyethylene glycol), and their combination. Nanocrystals stabilized by a combination of phospholipids enriched with polyethylene glycol proved to be the most successful in all evaluated criteria; they were colloidally stable in all media, exhibited low macrophage clearance, and proved non-toxic to healthy cells. This curcumin nanoformulation also exhibited outstanding anticancer potential comparable to commercially used cytostatics (IC50 = 73 µM; 24 h, HT-29 colorectal carcinoma cell line) which represents an improvement of several orders of magnitude when compared to previously studied curcumin formulations. This work shows that the preparation of phospholipid-stabilized nanocrystals allows for the conversion of poorly soluble compounds into a highly effective “solution-like” drug delivery system at pharmaceutically relevant drug concentrations.

Utility of Intravenous Curcumin Nanodelivery Systems for Improving In Vivo Pharmacokinetics and Anticancer Pharmacodynamics.

Curcumin nanoformulations for intravenous injection have been developed to offset poor absorption, biotransformation, degradation, and excessive clearance associated with parenteral delivery. This review investigates (1) whether intravenous nanoformulations improve curcumin pharmacokinetics (PK) and (2) whether improved PK yields greater therapeutic efficacy. Standard PK parameters (measured maximum concentration [Cmax], area under the curve [AUC], distribution volume [Vd], and clearance [CL]) of intravenously administered free curcumin in mice and rats were sourced from literature and compared to curcumin formulated in nanoparticles, micelles, and liposomes. The studies that also featured analysis of pharmacodynamics (PD) in murine cancer models were used to determine whether improved PK of nanoencapsulated curcumin resulted in improved PD. The distribution and clearance of free and nanoformulated curcumin were very fast, typically accounting for >80% curcumin elimination from plasma within 60 min. Case-matched analysis demonstrated that curcumin nanoencapsulation generally improved curcumin PK in terms of measured Cmax (n = 27) and AUC (n = 33), and to a lesser extent Vd and CL. However, when the data were unpaired and clustered for comparative analysis, only 5 out of the 12 analyzed nanoformulations maintained a higher relative curcumin concentration in plasma over time compared to free curcumin. Quantitative analysis of the mean plasma concentration of free curcumin versus nanoformulated curcumin did not reveal an overall marked improvement in curcumin PK. No correlation was found between PK and PD, suggesting that augmentation of the systemic presence of curcumin does not necessarily lead to greater therapeutic efficacy.

Radiosensitizing effect of dendrosomal nanoformulation of curcumin on cancer cells.

Curcumin was found to possess numerous pharmacological activities in clinical research, however, its biological effects together with radiation are yet to be addressed. The present study investigated whether the combined treatment of dendrosomal nanoformulation of curcumin (DNC) and gamma radiation can enhance the radiosensitivity of U87MG and MDA-MB-231 cell lines. U87MG and MDA-MB-231 cell lines were exposed to 2 Gray (Gy) and 10μM DNC determined by MTT assay, then subjected to clonogenic assay, cell cycle assay, and flow cytometric apoptosis analysis. Acridine Orange/Ethidium Bromide (AO/EB) and 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) stained cells were used to study morphologic changes. The expression evaluation of putative cell cycle genes, i.e., P53, P21, CCND1, and CCNB1 was carried out by RT-qPCR. Our findings indicated that the combined treatment with DNC and radiation might cooperatively augment the efficacy of ionizing radiation in the cancer cells and notably decrease the survival and viability of the cells in a time- and concentration-dependent manner. In addition to a synergistic effect deducted by sensitizer enhancement ratio (SER) assessment, co-treatment resulted in greater apoptotic cells than the individual treatments. Further experiments then indicated that DNC could effectively induce G2/M phase cell cycle arrest and apoptosis following irradiation. Conformably, there was a decrement of CCND1 and CCNB1 expression, and an increment of P53, P21 expression. The data implied that DNC as a radiosensitizer can enhance the lethal effect of ionizing radiation on cancer cells which could be a promising adjuvant therapy in clinical treatments.

Apoptotic Effect of Gemini Curcumin on MDA-MB-468 Breast Cancer Cell Line.

Gemini Curcumin (Gemini-Cur) is the latest nanoformulation of curcumin with a significant apoptotic effect on cancer cell lines. This in vitro study aims to evaluate the apoptotic effects of Gemini-Cur toward MDA-MB-468 breast cancer cell lines and further the related mechanism of apoptosis. The cytotoxicity of Gemini-Cur toward MDA-MB-468 cell lines was tested using MTT assay. Furthermore, the expression ratio of Bax/Bcl-2 was evaluated by qRT-PCR. Consequently, the protein expression of Bax/Bcl-2, survivin, and caspase-3 was measured using western blotting. Having treated MDA-MB-468 cell lines with Gemini-Cur, the IC50 values were found to be 44.44 and 31.63 μM at 24 and 48 h, respectively. Our findings showed that Gemini-Cur significantly suppresses cancer cell proliferation in a time- and dose-dependent manner. Furthermore, the data revealed that curcumin nanoformulation induces apoptosis in MDA-MB-468 cells through modulation of the expression of Bax, Bcl-2, Survivin, and Caspase-3. The data of the current study propose that Gemini-Cur can be considered a promising candidate against triple-negative breast cancer.