Formulation Of Curcumin Research Articles

Review: bioavailability and efficacy of 'free' curcuminoids from curcumagalactomannoside (CGM) curcumin formulation.

The golden spice turmeric with its main bioactive component curcumin is one of the most popular and extensively studied nutraceuticals. Despite numerous pre-clinical studies reporting positive pharmacodynamics of turmeric extracts and curcumin, the main issues in translating the pharmacological effects to clinical efficacy have been to overcome its poor pharmacokinetics and to deliver significant amounts of the biologically relevant forms of the actives to various tissues. This review is aimed at providing a first critical evaluation of the current published literature with the novel curcumagalactomannoside (CGM) formulation of curcumin using fenugreek galactomannan dietary fibre, specifically designed to address curcumin poor pharmacokinetics. We describe CGM and its technology as a food-grade formulation to deliver 'free' unconjugated curcuminoids with enhanced bioavailability and improved pharmacokinetic properties. The therapeutic relevance of improving bioavailability of 'free' curcuminoids and some of the technical challenges in the measurement of the 'free' form of curcuminoids in plasma and tissues are also discussed. A total of twenty-six manuscripts are reviewed here, including fourteen pre-clinical and twelve clinical studies that have investigated CGM pharmacokinetics, safety and efficacy in various animal models and human conditions. Overall current scientific evidence suggests CGM formulation has improved bioavailability and tissue distribution of the biologically relevant unconjugated forms of turmeric actives called 'free' curcuminoids that may be responsible for the superior clinical outcomes reported with CGM treatments in comparison with unformulated standard curcumin across multiple studies.

Curcumin for the treatment of COVID-19 patients: A meta-analysis of randomized controlled trials.

Curcumin is a low-cost and easily accessible therapeutic option for COVID-19 patients. We aimed to conduct a meta-analysis to assess the effect of curcumin on clinical outcomes in COVID-19 patients. Various databases, including PubMed, the Cochrane Library and Embase were searched from inception until October 2022 for randomized controlled trials (RCTs) evaluating curcumin use in COVID-19 patients. Results from 13 RCTs were pooled using R software version 4.1.0. Curcumin reduced the risk of all-cause mortality (RR 0.38; 95% CI: 0.20-0.72; moderate certainty of evidence), and patients with no recovery status (RR 0.54; 95% CI: 0.42-0.70; moderate certainty of evidence) but had no effect on the incidence of mechanical ventilation and hospitalization, and the rate of a positive viral PCR test. The results of subgroup analysis suggested a higher benefit with early administration of curcumin (within 5 days of onset of symptoms) and with the use of combination regimens. Curcumin is likely to be of benefit in mild-to-moderate COVID-19 patients, but large-scale RCTs are needed to confirm these findings. The limitations of our meta-analysis include the small sample sizes of the included RCTs and the variable formulations of curcumin used across the studies.

Therapeutic potential of curcumin in ARDS and COVID-19.

Curcumin is a safe, non-toxic, readily available and naturally occurring compound, an active constituent of Curcuma longa (turmeric). Curcumin could potentially treat diseases, but faces poor physicochemical and pharmacological characteristics. To overcome these limitations, we developed a stable, water-soluble formulation of curcumin called cyclodextrin-complexed curcumin (CDC). We have previously shown that direct delivery of CDC to the lung following lipopolysaccharides exposure reduces acute lung injury (ALI) and effectively reduces lung injury, inflammation and mortality in mice following Klebsiella pneumoniae. Recently, we found that administration of CDC led to a significant reduction in angiotensin-converting enzyme 2 and signal transducer and activator of transcription 3 expression in gene and protein levels following pneumonia, indicating its potential in treating coronavirus disease 2019 (COVID-19). In this review, we consider the clinical features of ALI and acute respiratory distress syndrome (ARDS) and the role of curcumin in modulating the pathogenesis of bacterial/viral-induced ARDS and COVID-19.

Curcumin-loaded microemulsion: formulation, characterization, and in vitro skin penetration

Objective Formulation of curcumin in a microemulsion with a high loading capacity and that favors its penetration into the skin. Significance Take advantage of the properties of microemulsions to promote the penetration of curcumin into the skin, with the aim of enhancing its therapeutic effects. Methods Curcumin was formulated in microemulsions based on oleic acid (oil phase), Tween® 80 (surfactant), and Transcutol® HP (cosurfactant). The microemulsion formation area was mapped by constructing pseudo-ternary diagrams for surfactant:co-surfactant ratios 1:1, 1:2, and 2:1. Microemulsions were characterized through measurements of specific weight, refractive index, conductivity, viscosity, droplet size, and in vitro skin permeation studies. Results Nine microemulsions were prepared and characterized, showing clear, stable formulations with globule size dependent on the proportion of the components. The microemulsion with the highest loading capacity (60 mg/mL), based on Tween® 80, Transcutol® HP, oleic acid, and water (40:40:10:10) was able to penetrate the viable epidermis, finding a total amount of curcumin in the receptor medium at 24 h of 10.17 ± 9.7 µg/cm2. The distribution of curcumin in the skin, visualized by confocal laser scanning microscopy, showed that the maximum amount was located between 20 and 30 µm. Conclusion The inclusion of curcumin in a microemulsion allows its passage into and through the skin. The localization of curcumin, especially in the viable epidermis, would be important for those cases where local conditions are sought to be treated.

A primer on common supplements and dietary measures used by patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic disease of the intestines. The pathophysiology of IBD, namely Crohn’s disease and ulcerative colitis, is a complex interplay between environmental, genetic, and immune factors. Physicians and patients often seek complementary and alternative medicines (CAMs) as primary and supplementary treatment modalities. CAMs in IBD span a wide range of plants, herbs, pre/probiotics, and include formulations, such as cannabis, curcumin, fish oil, and De Simone Formulation. Dietary measures are also used to improve symptoms by attempting to target trigger foods and reducing inflammation. Examples include the specific carbohydrate diet, the Mediterranean diet, and a diet low in fermentable oligo-, di- and monosaccharides as well as polyols (FODMAP). We examine and review the most common complementary supplements and diets used by patients with IBD.

Formulation and Development of Curcumin-Piperine-Loaded S-SNEDDS for the Treatment of Alzheimer's Disease.

Curcumin (CUR) and piperine (PIP) are very well-known phytochemicals that claimed to have many health benefits and have been widely used in foods and traditional medicines. This study investigated the therapeutic efficacy of these compounds to treat Alzheimer's disease (AD). However, poor oral bioavailability and permeability of curcumin are a major challenge for formulation scientists. In this research study, the researcher tried to enhance the bioavailability and permeability of curcumin by a nanotechnological approach. In this research study, we developed a CUR-PIP-loaded SNEDDS in various oils. Optimised formulation NF3 was subjected to evaluate its therapeutic effectiveness on AD animal model in comparison with untreated AD model and treated group (by market formulation donepezil). On the basis of characterisation results, it is confirmed that NF3 formulation is the best formulation. The optimised formulation shows a significant dose-dependent manner therapeutic effect on AD-induced model. Novel formulation CUR-PIP solid-SNEDDS was successfully developed and optimised. It is expected that the developed S-SNEDDS can be a potential, safe and effective carrier for the oral delivery of curcumin to the brain. To date, this article is the only study of CUR-PIP-loaded S-SNEDDS for the treatment of AD.

Kinetic and Thermodynamic Behavior of Extraction of Oleoresin Containing Curcuminoids from Turmeric (Curcuma longa L.) in Acetone and Their Bioavailability

Background: Why this miraculous and amphiphilic compound, the curcumin, which has a very extraordinary therapeutic potential (because can react with many targets in the organism), has a weak bioavailability in the organism and is metabolized in compounds having very weak activity or inactive compounds?. How to improve substantially its bioavailability and therefore its absorption in the organism in order to allow its incorporation in making of pharmaceuticals regardless of its nanoparticles of which obtention is furthermore hardworking?
 Aim: It seems indicated to search the response in the kinetic and thermodynamic behavior of this compound or in its co-administration with the other compounds in vitro in order to understand how to increase its absorption in vivo because bioavailability entails hydrosolubility (hydrophile) of curcuminoids of which the molecules are naturally hydrophobes.
 Objective: So our objective is to make better our understanding of the absorption of natural curcuminoids in the organism without resorting to chemical transformation in nanoparticles that is additionally hardworking.
 Methodology: In this paper, kinetic and thermodynamic study of extraction of oleoresin containing curcuminoids from Turmeric (Curcuma Longa L.), using KUNYIMA’s first law, has been performed in acetone that can be reduced in propan-2-ol which is water-like solvent by catalytic hydrogenating (H2,Ni ) or by chemical reduction (LiAlH4).
 Results: The weak global kinetic constant of extraction of oleoresin containing curcuminoids has been determined at 250 rpm (round per minute) and found the same at 500 rpm (k= 0.1520 ± 0.0005) min-1 for temperature of 27,5°C and constant pressure in acetone in closed system.
 Conclusion: Kunyima’s first law has made possible the kinetic and thermodynamic study of extraction of oleoresin containing curcuminoids from Turmeric. Kinetic constant is a measure of solubility of oleoresin containing curcuminoids and therefore a measure of solubility of curcuminoids in a given solvent, ethanol and acetone being concerned in this paper as solvents. Results show that kinetic constant is inversely proportional to solubility of solvent and it can be a parameter abling the determination of the endothermic or exothermic behavior of extraction of curcuminoids. The endothermic behavior of curcuminoids hereby determined in ethanol and acetone in vitro, increased by magnetic stirring, suggests their weak bioavailability and therefore the weak bioavailability of curcumin. The challenge of this actual research is to improve our understanding of kinetics and thermodynamics of extraction of oleoresin containing curcuminoids from Turmeric in vitro in order to presage their bioavailability still weak for an efficient validated action. The increase of bioavailability will be done whether through improved formulations of curcumin or through new pathways of administration. The conception of curcumin analogous is also a way to promote its effects. More the phenomenon is exothermic in water-like solvents, more the involved chemical compound is bioavailable.
 The study revealed the predominance of keto form of curcumin in acetone and the lack of bioavailability of curcumin (curcuminoids) through the endothermic behavior of extraction of oleoresin containing curcuminoids and through the weak global kinetic constant.
 The variation of entropy in acetone has shown without surprise the disturbance of the system after extraction.
 The values of kinetic constants in acetone and ethanol as water-like solvents have been compared and showed the great solubility of curcuminoids in acetone evidenced by the weak kinetic constant compared to that in ethanol.
 Curcumin predicts anyway hopeful future.

Lipid/Clay-Based Solid Dispersion Formulation for Improving the Oral Bioavailability of Curcumin.

This study was conducted to develop a lipid/clay-based solid dispersion (LSD) formulation to enhance the dissolution and oral bioavailability of poorly soluble curcumin. Krill oil and aminoclay were used as a lipid and a stabilizer, respectively, and LSD formulations of curcumin were prepared by an antisolvent precipitation method combined with freeze-drying process. Based on the dissolution profiles, the optimal composition of LSD was determined at the weight ratio of curcumin: krill oil: aminoclay of 1:5:5 in the presence of 0.5% of D-α-tocopherol polyethylene glycol succinate. The structural and morphological characteristics of the LSD formulation were determined using X-ray powder diffraction, differential scanning calorimetry, and scanning electron microscopy. Crystalline curcumin was changed to an amorphous form in the LSD formulation. At the pH of acidic to neutral, the LSD formulation showed almost complete drug dissolution (>90%) within 1 h, while pure curcumin exhibited minimal dissolution of less than 10%. Furthermore, the LSD formulation had significantly improved oral absorption of curcumin in rats, where Cmax and AUC of curcumin were 13- and 23-fold higher for the LSD formulation than for the pure drug. Taken together, these findings suggest that the krill oil-based solid dispersion formulation of curcumin effectively improves the dissolution and oral bioavailability of curcumin.

The Pharmacological Effects of Curcuma Longa Linn in Wound Healing and Relieving Inflammation

Curcuma Longa is the scientific name of turmeric, a member of the Zingiberaceae family of plants. It has been used in Ayurvedic medicine in different countries since long ago. But now, it is more popularly known for its wound-healing and inflammation-relieving properties. Curcumin is the biologically active ingredient responsible for these actions of Curcuma Longa. It acts at different stages of wound healing and makes it heal more quickly. It prevents inflammation and helps the immune system of the body. It also exhibits more pharmacological properties like anti-cancerous, anti-microbial, anti-diabetic, etc. This review will explain how curcumin heals wounds and acts as an antioxidant and anti-inflammatory. Moreover, this will also shed light on the latest formulations of curcumin, treating wounds and inflammation. Topical formulations are often used for immediate response and effect because they are very strong and provide relief quickly.

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.

Curcumin-Based Nanoformulations: A Promising Adjuvant towards Cancer Treatment.

Throughout the United States, cancer remains the second leading cause of death. Traditional treatments induce significant medical toxic effects and unpleasant adverse reactions, making them inappropriate for long-term use. Consequently, anticancer-drug resistance and relapse are frequent in certain situations. Thus, there is an urgent necessity to find effective antitumor medications that are specific and have few adverse consequences. Curcumin is a polyphenol derivative found in the turmeric plant (Curcuma longa L.), and provides chemopreventive, antitumor, chemo-, and radio-sensitizing properties. In this paper, we summarize the new nano-based formulations of polyphenolic curcumin because of the growing interest in its application against cancers and tumors. According to recent studies, the use of nanoparticles can overcome the hydrophobic nature of curcumin, as well as improving its stability and cellular bioavailability in vitro and in vivo. Several strategies for nanocurcumin production have been developed, each with its own set of advantages and unique features. Because the majority of the curcumin-based nanoformulation evidence is still in the conceptual stage, there are still numerous issues impeding the provision of nanocurcumin as a possible therapeutic option. To support the science, further work is necessary to develop curcumin as a viable anti-cancer adjuvant. In this review, we cover the various curcumin nanoformulations and nanocurcumin implications for therapeutic uses for cancer, as well as the current state of clinical studies and patents. We further address the knowledge gaps and future research orientations required to develop curcumin as a feasible treatment candidate.

Development of UV spectrophotometric method for estimation of curcumin in bulk drug and nanogel formulation: A hydrolytic degradation studies

The main purpose of this research was to develop and validate a cost effective UV spectrophotometric method for determination of curcumin in bulk drug and nanogel formulation. The method was validated according to the guideline of International Conference on Harmonisation (ICH). The curcumin was found to be soluble in methanol with λmax of 425 nm. Curcumin over the concentration level of (1-8 µg mL) depicted linear relation in the plot of concentration vs. absorbance. The regression equation of graph was y = 0.1137x - 0.0138 with R value of 0.999. The limits of detection and quantification were 0.23 μg mLand 0.75 μg mL, respectively. The method was accurate, precise, reproducible and robust since all the samples analyzed had relative standard deviation less than 2%. No statistically significant difference between theoretical and measured concentrations was detected. The degradation kinetics of free curcumin (k = 0.042 µg mL.h, 0.53 µg mL.h and 0.068 µg mL.h) and nanogel formulation (k = 0.178 h, 0.003 h and 0.005 h) were zero and first order, respectively. The proposed method was found to be specific while estimating curcumin loaded nanogel formulation without interference of excipients. The developed method was cost effective and can be used for routine quality control analysis of curcumin.

Oral Preparation of Hyaluronic Acid, Chondroitin Sulfate, Curcumin, and Quercetin (Ialuril® Soft Gels) for the Prevention of LUTS after Intravesical Chemotherapy.

Intravesical chemotherapy may cause chemical cystitis and related lower urinary tract symptoms (LUTS). The aims of this study were to evaluate the efficacy and safety of an oral preparation of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin, and quercetin (Ialuril® Soft Gels) to reduce the severity of LUTS in patients with a history of bladder cancer (BCa) undergoing intravesical chemotherapy. We designed a monocentric, randomized, double-blind, placebo-controlled pilot trial. Patients referred to our institute between November 2016 and March 2018 were enrolled. All subjects had non-muscle-invasive BCa and received intravesical chemotherapy with mitomycin C (MMC). Patients were randomized 1:1 in two groups (intervention vs. control). All subjects underwent oral administration (Ialuril® Soft Gels or placebo) starting one week before the first weekly instillation and ending 30 days after the last one, subsequently starting one week before each monthly instillation and ending 14 days after it. International prostate symptom score (IPSS) and 0-100 visual analogue scale (VAS) were used to assess the efficacy of the treatment. Adverse events were also described. Patients were evaluated at baseline and after 1, 4, 7, and 13 months of intravesical chemotherapy. A total of 34 patients were enrolled. The median IPSS score was significantly lower in the intervention group compared to the control group at 4 (13 vs. 17 points; p = 0.038), 7 (10 vs. 18 points; p < 0.001), and 13 (10 vs. 17 points; p = 0.002) months. The median VAS score was significantly lower in the intervention group compared to the control group at 7 (22 vs. 37 points; p = 0.021) and 13 (20 vs. 35 points; p = 0.024) months. No AE specifically related to supplement or placebo was recorded. Oral formulation of HA, CS, quercetin, and curcumin could be an effective and safe supportive therapy against chemical cystitis in patients receiving intravesical chemotherapy for BCa.

Review on the Therapeutic Potential of Curcumin and its Derivatives on Glioma Biology.

Gliomas are common and aggressive brain tumors that carry a poor prognosis. The current multimodal therapeutic option for glioma includes surgery subsequently temozolomide chemotherapy and/or radiation; but gliomas are often associated with multidrug resistance, intensive adverse events, and tumor relapse. Thus, novel interventions that can enhance successful chemo-prevention and overcome therapeutic resistance are urgently needed. Phytochemicals have several biological properties with multi-target sites and relatively limited degrees of toxicity. Curcumin is a natural polyphenolic compound with several anti-tumor effects which potentially inhibit tumor growth, development, proliferation, invasion, dissemination, and angiogenesis in different human malignancies. Experimental model studies have demonstrated that curcumin attenuates glioma cell viability by G2/M cell cycle arrest, apoptosis, induction of autophagy, gene expression alteration, and disruption of multi-molecular pathways. Moreover, curcumin has been reported to re-sensitize cancer to chemotherapeutics as well as augment the effect of radiotherapy on glioma cells. In this review, we have provided an update on the in vitro and in vivo effects of curcumin-based therapy on gliomas. We have also discussed the use of curcumin in combination therapies, its effectiveness on drug-resistant cells, and new formulations of curcumin in the treatment of gliomas.

Combined Treatment of Dendrosomal-Curcumin and Daunorubicin Synergistically Inhibit Cell Proliferation, Migration and Induce Apoptosis in A549 Lung Cancer Cells.

Chemotherapy drugs used to treat lung cancer are associated with drug resistance and severe side effects. There have been rising demands for new therapeutic candidates and novel approaches, including combination therapy. Here, we aimed to investigate the combinatorial effect of a dendrosomal formulation of curcumin (DNC) and daunorubicin (DNR) on the A549 lung cancer cell line. We performed cytotoxicity, apoptosis, cell migration, colony-formation capacity, and gene expression analysis to interpret the mechanism of action for a combination of DNC and DNR on A549 cells. Our results revealed that the combination of DNC and DNR could synergistically inhibit the A549 cells' growth. This synergistic cytotoxicity was further approved by flow cytometry, migration assessment, colony-forming capacity and gene expression analysis. DNR combination with DNC resulted in increased apoptosis to necrosis ratio compared to DNR alone. In addition, the migration and colony-forming capacity were at the minimal range when DNC was combined with DNR. Combined treatment decreased the expression level of MDR-1, hTERT and Bcl-2 genes significantly. In addition, the ratio of Bax/Bcl2 gene expression significantly increased. Our analysis by free curcumin, dendrosomes and DNC also showed that dendrosomes do not have any significant cytotoxic effect on the A549 cells, suggesting that this carrier has a high potential for enhancing the curcumin's biological effects. Our observations suggest that the DNC formulation of curcumin synergistically enhances the antineoplastic effect of DNR on the A549 cell line through the modulation of apoptosis/necrosis ratio, as well as Bax/Bcl2 ratio, MDR-1 and hTERT gene expression.

Preclinical studies of the antitumor effect of curcumin-loaded polymeric nanocapsules: A systematic review and meta-analysis.

Curcumin, a plant-derived compound, has various well-known biological effects (anti-inflammatory, antioxidant, antitumor, among others) as well as some important limitations for formulators, such as poor water solubility and low oral bioavailability. Its nanoencapsulation is reported to overcome these drawbacks and to improve its in vivo efficacy. Here, data from preclinical in vivo studies evaluating the antitumor efficacy of curcumin-loaded polymeric nanocapsules are collected, analyzed, and discussed as a systematic review. Meta-analyses are performed to assess the contribution of this nanoencapsulation compared with nonencapsulated curcumin. Eighteen studies (116 animals) meet the inclusion criteria. The evidence that curcumin-loaded polymeric nanocapsules inhibits tumor growth (SMD: -3.03; 95% CI: -3.84, -2.21; p < 0.00001) and decreases tumor weight (SMD: -3.96; 95% CI: -6.22, -1.70; p=0.0006) in rodents is established, regardless of the solid tumor model. To assess the quality of the studies included in the review a bias risk analysis was performed using the SYRCLE's RoB tool. Therefore, encapsulation in polymeric nanocapsules represents an important tool to improve the antitumor effects of curcumin, and this systematic review paves the way for future clinical studies and the translation of curcumin formulations into novel nanomedicines for human cancer treatment.

Gemini Curcumin Suppresses Gastric Cancer AGS Cell Proliferation Through Modulation of lncRNA CCAT2 and c-Myc Genes.

Gemini surfactant nanocurcumin (Gemini-Cur) is a novel formulation of Curcumin (Cur) with dramatic suppressive effects on cancer cells. Here, we investigated the cancer effects of Gemini-Cur in a human gastric adenocarcinoma cell-line (AGS) through the evaluation of the expression of long non-coding RNAs colon cancer-associated transcript-2 (CCAT2) and its downstream c-Myc as known oncogenic modulators of tumorigenesis. The AGS cells were treated with Gemini-Cur and pure Cur in a time- and dose-dependent manner. The toxicity of Gemini-Cur was studied using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and scratch tests. Furthermore, real-time polymerase chain reaction and Western blotting techniques were employed to evaluate the expression of genes. Gemini-Cur significantly affected the viability of AGS cells in a dose- and time-dependent manner with inhibitory concentration 50 values of 59.32, 40.88, and 19.63 µM during 24, 48, and 72 h, respectively. Our findings showed that Gemini-Cur effectively decreased the expression levels of lnc-CCAT2 and c-Myc genes. Western blotting analysis also confirmed the down-regulation of c-Myc in treated samples compared to controls. Gemini-Cur attenuates the proliferation of AGS cells partly through modulation of the lncCCAT2-related pathway.

Curcumin Plant for Colorectal Cancer Prediction and Prevention Using In Silico Molecular Analysis; HOT-MELT Extrusion.

The impact of a soluble complex (SC) of curcumin (CuR) synthesized using hot melt (HM) and hot-melt extrusion (HE) technologies on adenocarcinoma cells for the treatment of colorectal cancer by enhancing CuR solubility is investigated in this work. In silico molecular modelling, solubility, drug release, and physicochemical analysis were all part of the phase solubility (PS) study, which featured a novel dyeing test and a central composite design to optimize the best complex (CDD). The optimal HE-SC (1 : 5) enhances solubility (0.8521 ± 0.016 mg·mL−1) and dissolution (91.87 ± 0.208% at 30 min), and it has an ideal stability constant (309 and 377 M−1) at 25 and 37°C and an AL type of isotherm, implying 1 : 1 stoichiometry according to the findings. An intermolecular hydrogen bond that has not undergone any chemical change and has resulted in the complete conversion of the amorphous form aids in the creation of SC. In vitro cytotoxicity was measured at IC50 on the SW480 (72 M·mL−1) and Caco-2 (40 M·mL−1) cells. According to apoptotic studies, apoptosis was responsible for the vast majority of cell death, with necrosis accounting for a small proportion of the total. In vivo toxicity was established using a zebrafish model, and a western blot examination revealed apoptosis at the molecular level. It was argued that the novel formulations developed using HE technology are more significant and effective than existing pure CuR formulations.

Formulated Curcumin Prevents Paclitaxel-Induced Peripheral Neuropathy through Reduction in Neuroinflammation by Modulation of α7 Nicotinic Acetylcholine Receptors

Paclitaxel is widely used in the treatment of various types of solid malignancies. Paclitaxel-induced peripheral neuropathy (PIPN) is often characterized by burning pain, cold, and mechanical allodynia in patients. Currently, specific pharmacological treatments against PIPN are lacking. Curcumin, a polyphenol of Curcuma longa, shows antioxidant, anti-inflammatory, and neuroprotective effects and has recently shown efficacy in the mitigation of various peripheral neuropathies. Here, we tested, for the first time, the therapeutic effect of 1.5% dietary curcumin and Meriva (a lecithin formulation of curcumin) in preventing the development of PIPN in C57BL/6J mice. Curcumin or Meriva treatment was initiated one week before injection of paclitaxel and continued throughout the study (21 days). Mechanical and cold sensitivity as well as locomotion/motivation were tested by the von Frey, acetone, and wheel-running tests, respectively. Additionally, sensory-nerve-action-potential (SNAP) amplitude by caudal-nerve electrical stimulation, electronic microscopy of the sciatic nerve, and inflammatory-protein quantification in DRG and the spinal cord were measured. Interestingly, a higher concentration of curcumin was observed in the spinal cord with the Meriva diet than the curcumin diet. Our results showed that paclitaxel-induced mechanical hypersensitivity was partially prevented by the curcumin diet but completely prevented by Meriva. Both the urcumin diet and the Meriva diet completely prevented cold hypersensitivity, the reduction in SNAP amplitude and reduced mitochondrial pathology in sciatic nerves observed in paclitaxel-treated mice. Paclitaxel-induced inflammation in the spinal cord was also prevented by the Meriva diet. In addition, an increase in α7 nAChRs mRNA, known for its anti-inflammatory effects, was also observed in the spinal cord with the Meriva diet in paclitaxel-treated mice. The use of the α7 nAChR antagonist and α7 nAChR KO mice showed, for the first time in vivo, that the anti-inflammatory effects of curcumin in peripheral neuropathy were mediated by these receptors. The results presented in this study represent an important advance in the understanding of the mechanism of action of curcumin in vivo. Taken together, our results show the therapeutic potential of curcumin in preventing the development of PIPN and further confirms the role of α7 nAChRs in the anti-inflammatory effects of curcumin.

A Novel Formulation of Curcumin and 3-O-Acetyl-11-Keto-Beta-Boswellic Acid Enriched Boswellia Extract Ameliorates Experimentally Induced Osteoarthritis in Rats

ObjectivesOsteoarthritis (OA) is a chronic musculoskeletal disorder of knee joint, characterized by inflammation and cartilage damage. Current therapeutic approaches for osteoarthritis directed at amelioration of symptoms are associated with clinically significant adverse events upon long-term use. We evaluated a formulation provided by OmniActive Health Technologies that contained combination of highly bioavailable form of curcumin (Curcuwin ultra+) and 3-O-Acetyl-11-keto-beta-Boswellic acid (AKBA) enriched Boswellia extract in monosodium iodoacetate (MIA)-induced knee OA in rats. MethodsThirty-five female rats were distributed into five groups groups: Control, OA, OA + CA (Curcuminoids + AKBA 15 mg/kg), OA + UCII (4 mg/kg) and OA + Move Free advanced Glucosamine and Chondroitin (197 mg/kg). OA was induced by a single administration of MIA into right knee joint through the infrapatellar ligament and followed by treatment for 4 weeks. Animals were evaluated for various biochemical, radiological, histopathological and protein expression for various inflammatory and catabolic markers involved in the biology of OA. ResultsMonosodium iodoacetate induced OA in rats after two weeks of administration. All the three treatment CA, UCII and Move Free formula exhibited an anti-arthritic effect after 4 weeks of treatment with significant (P< 0.05) reduction of both serum and joint tissue TNF-α, IL-1β, IL-10, cartilage oligomeric matrix protein and additionally C-reactive protein in the serum of OA rats. We also observed an overall reduction of oxidative stress with significant (P< 0.05) reduction of lipid peroxidation, and increased antioxidant activities with SOD, GSH-Px and CAT levels in response to treatment in OA animals associated with improved histological structure of the knee joint of OA rats along gross improvement of joint architecture. ConclusionsThe novel formulation of Curcuwin ultra+ and AKBA provided protective effect against osteoarthritis possibly due to anti-inflammatory and anti-oxidant activity in experimentally induced OA in rats with comparable activity to extensivley used supplements against OA in the market such as UCII and Move Free formula and could serve an effective alternative treatment option against OA. Funding SourcesOmniActive Health Technologies (India) and partially by Turkish Academy of Sciences (Turkey)