Conjugation Of Curcumin Research Articles

Folic Acid‐Mediated Reduction‐Sensitive Curcumin Prodrug Enhances the Delivery Performance of Curcumin in Liver Cancer Cells

AbstractIn order to improve the delivery performance of curcumin (CUR) in liver cancer cells, we prepared a targeted and reduction‐sensitive prodrug, folic acid‐polyethylene glycol‐disulfide bond‐curcumin (FA‐PEG‐SS‐CUR). The synthesis involved the conjugation of CUR with NH2‐PEG‐NH2 through a disulfide bond, followed by the connection of CUR‐SS‐PEG‐NH2 to FA‐COOH via acylation. The resultant FA‐PEG‐SS‐CUR prodrug self‐assembled into nano micelles in aqueous solutions, displaying excellent dispersibility with an approximate particle size of 119 nm. In vitro drug release studies demonstrated the sensitivity of FA‐PEG‐SS‐CUR to glutathione (GSH), displaying sustained release performance. After 72 h, FA‐PEG‐SS‐CUR exhibited a drug release rate of 38% at low GSH concentration and 59% at high GSH concentration. Notably, FA‐PEG‐SS‐CUR micelles exhibited favorable biocompatibility. The hemolysis rate resulting from co‐incubation with red blood cells remained below 3%. Furthermore, cytotoxicity experiments unveiled the substantial cytotoxicity of FA‐PEG‐SS‐CUR micelles against HepG2 tumor cells. Cellular uptake studies confirmed the greater internalization of FA‐PEG‐SS‐CUR by HepG2 cells compared to the non‐targeted PEG‐SS‐CUR. The findings highlight the potential of FA‐PEG‐SS‐CUR as an ideal drug delivery system for CUR due to its facile synthesis and strong self‐assembly performance.

Oral drug delivery vehicle for insulin and curcumin based on egg albumin-dextran conjugate: In vitro and in vivo studies

The increasing desire for oral delivery vehicle systems encouraged the development of micro and nano encapsulation technologies to protect drugs against gastric and enzymatic degradation. This study aimed to develop egg albumin-dextran conjugate as a delivery vehicle for oral administration. For this purpose, insulin was selected as a macromolecule drug and curcumin as a natural lipophilic polyphenol, both show negative absorption kinetics in gastrointestinal tract. Egg albumin-dextran conjugate was prepared by Maillard reaction under mild conditions and subsequently be used to encapsulate insulin and curcumin, respectively. The encapsulation efficiency reached to 97 % and 95.5 % at 300 mg/ml of insulin and curcumin, respectively. The profile of in vitro drug release for the insulin and curcumin indicates that approximately 60 % of the drugs were partially retained by the conjugate in gastric pH environment while a more extensive release was observed under intestinal pH conditions. Application of oral administration of insulin conjugate (IC) and/or curcumin conjugate (CC) to streptozotocin (STZ) induced diabetic rats was investigated for 6 weeks and compared with trade insulin drug. Fifty-four albino rats were separated into nine equivalent groups. Control, insulin conjugate (IC), curcumin conjugate (CC), and IC + CC. The remaining groups injected with STZ and subsequently received vehicle, IC, CC, IC + CC, and trade insulin drug; respectively.Interestingly, insulin conjugate and/or curcumin conjugate significantly reduced hyperglycemia, hyperlipidemia, decreased fructosamine level, decreased HOMA-IR, increased insulin level, increased HOMA-β, increased antioxidant defense molecules, along with modulating morphological pancreatic degeneration caused by STZ. In conclusion, oral insulin-conjugate is more effective than the trade insulin drug. Also, curcumin-conjugate has a promising role as antidiabetic agent as it may contribute in β-cells regeneration. Further, the combination between them may have synergetic antidiabetic effect. But, more detailed studies should be done to investigate the possible mechanisms of their antidiabetic effect.

Free radical-induced soybean protein isolate -curcumin conjugates: Characterization, antioxidant and in vitro digestion characteristics

Natural soybean protein isolate（SPI) is vulnerable to environmental factors that compromise its functionality. One effective method to improve this functionality is through free radical induction. In this study, SPI and curcumin (Cur) were utilized to prepare SPI-Cur conjugates using the free radical induction method. The formation mechanism, structure, and functional properties of these conjugates were subsequently. The results indicated that at pH 9, the SPI-Cur conjugate formed hydroxyquinone dimers, which exhibited higher inhibition of digestive enzymes and increased stability through free radical-induced reactions. Furthermore, the antioxidant properties of SPI-Cur conjugates increased significantly, with increases of 9.17-, 2.3-, and 7.70-fold in DPPH, ABTS, and reducing power, respectively (p < 0.05). Circular dichroism analysis revealed increases in the secondary structure of proteins in SPI-Cur conjugates α-helix from 0.40% to 1.47%, β-sheet from 28.70% to 98.38% (pH 3 to pH 9), β-turns from 70.83% to 0.15%, and Random coils from 0.00% to 81.21%. These results suggest a novel approach for creating SPI-Cur conjugates through free radical-induced reactions, which could aid in the development of a continuous delivery system for polyphenols based on SPI and improve the high-value utilization of SPI.

In Situ Reaction-Generated Aldehyde-Scavenging Polypeptides-Curcumin Conjugate Nanoassemblies for Combined Treatment of Spinal Cord Injury.

The microenvironment after traumatic spinal cord injury (SCI) involves complex pathological processes, including elevated oxidative stress, accumulated reactive aldehydes from lipid peroxidation, excessive immune cell infiltration, etc. Unfortunately, most of current neuroprotection therapies cannot cope with the intricate pathophysiology of SCI, leading to scant treatment efficacies. Here, we developed a facile in situ reaction-induced self-assembly method to prepare aldehyde-scavenging polypeptides (PAH)-curcumin conjugate nanoassemblies (named as PFCN) for combined neuroprotection in SCI. The prepared PFCN could release PAH and curcumin in response to oxidative and acidic SCI microenvironment. Subsequently, PFCN exhibited an effectively neuroprotective effect through scavenging toxic aldehydes as well as reactive nitrogen and oxygen species in neurons, modulating microglial M1/M2 polarization, and down-regulating the expression of inflammation-related cytokines to inhibit neuroinflammation. The intravenous administration of PFCN could significantly ameliorate the malignant microenvironment of injured spinal cord, protect the neurons, and promote the motor function recovery in the contusive SCI rat model.

Comparative study of linear polyglycidol acylhydrazones and curcumin conjugates: Surface activity and targeted antitumor drug delivery

Linear polyglycidol (LPG) has emerged as a polyethylene glycol (PEG) alternative in novel surfactant development due to its unique advantages, such as high bioavailability and multiple functionalization sites. In this study, a series of LPG based acylhydrazones, including copolymers CLPG1–3 with different length (n = 7–11) of alkyl chains and a curcumin (CUR) drug conjugate CLPG4 were synthesized for the first time. CLPG1-4 exhibited a decreasing trend in their surface-active properties as the molecular hydrophobicity increased. Among them, CLPG1 revealed the most powerful foaming ability, emulsion stability than the other analogs and tested commercial references, attributing to its optimal hydrophilic/hydrophobic balance. On the other hand, the drug conjugate CLPG4 revealed significantly enhanced selective tumor cell inhibition and cellular uptake than free CUR in the in vitro experiments. The established structure-property profile in this study provides a useful reference for their practical applications in the chemical and pharmaceutical fields.

Hyaluronic Acid-Curcumin Complex Triggers Apoptotic Pathway in Breast Cancer Cells via CD44 Receptors

Objective: Curcumin (CUR) was modified with hyaluronic acid (HA) to increase its water solubility and bioavailability. Our aim was to increase the uptake of CUR into the cells that express CD44 receptors and to compare the cellular effects in two different human breast carcinoma cells, MCF-7 and MDA-MB-231. &#x0D; Methods: Hyaluronic acid-curcumin complex (HA-CUR) was synthesized and characterized. &#x0D; MCF-7 and MDA-MB-231 cells were grown under appropriate conditions and the effect of CUR and HA-CUR on cell viability was determined. Apoptosis levels of cells after treatment with CUR and HA-CUR were also measured. CD44 receptor levels of both cells were compared and then apoptosis levels were measured in MDA-MB-231 cells after saturation of CD 44 receptors with HA. In both cells expression of caspase-9 and PARP was analyzed to confirm apoptosis. &#x0D; Results: In MCF-7 cells, the percentage apoptosis level of the CUR group was slightly lower than the HA-CUR group. In MDA-MB-231 cells, no statistically significant difference was found in the CUR group compared to the control group, but the apoptosis level of the HA-CUR group was higher than the control group. CD44 receptor levels were higher in MDA-MB-231 cells compared to MCF-7 cells. Blocking the CD44 receptors reversed the apoptotic effect of HA-CUR in MDA-MB-231 cells. Both CUR and HA-CUR had apoptotic effects in MCF-7 and MDA-MB-231 cells. &#x0D; Conclusion: Conjugation of CUR with HA, which is specific for CD44 receptors aids, in its entry to target cells making it a powerful agent for targeted cancer therapy.

"Cytotoxic Activity of Some Water Soluble Curcumin Conjugates on Human Colorectal Adenocarcinoma and Human Hepatocellular Carcinoma Cells"

"Cytotoxic Activity of Some Water Soluble Curcumin Conjugates on Human Colorectal Adenocarcinoma and Human Hepatocellular Carcinoma Cells"

Cover Feature: Polypyridyl CoII‐Curcumin Complexes as Photoactivated Anticancer and Antibacterial Agents (ChemBioChem 10/2023)

Visible light-induced anticancer and antibacterial profiles of Co(II) curcumin complexes. This cover illustrates Co(II)-curcumin conjugates exhibiting remarkable visible light-triggered anticancer activity against breast cancer (MCF-7) cells by ROS-induced apoptosis and the fluorescent nature of curcumin assisting in cell imaging. Also, antibacterial activity against both gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) bacterial strains through the activation of the Co(II)-curcumin conjugates at the targeted site by light exposure, is depicted here. More information can be found in the Research Article by B. Koch, S. Banerjee.

Cerium Oxide Nanoparticles: Synthesis and Characterization Using Curcuma longa (Turmeric Rhizome)

Cerium oxide and turmeric are widely used in the medical field because of their distinctive properties. Turmeric, predominantly used in Asian cuisines, is also an anti-inflammatory element in ayurvedic medicines. The lower bioavailability of turmeric rhizomes has restricted their medical applications to a specific limit, both in vitro and in vivo. Previous investigations have reported that the conjugation of curcumin and cerium oxide nanoparticles improves turmeric’s stability, making them efficient in treating chronic diseases such as cancer. The main objective of this study is to carry out the synthesis of cerium oxide nanoparticles using turmeric rhizomes. Various methods were used to characterize the cerium oxide nanoparticles. Scanning electron microscopy, energy dispersive X-ray spectroscopy, and field emission scanning electron microscopy were used to determine the morphological properties of the cerium oxide nanoparticles. Fourier transform infrared spectroscopy and X-ray diffraction were used to determine the structural properties of those nanoparticles. The BEAS-2B cells were cultured in a controlled environment, and the biocompatibility studies were conducted using an MTT assay to assess their cytotoxicity. Based on toxicity studies of cerium oxide nanoparticles, future research will be performed on their biomedical applications.

Synthesis and Biological Evaluation of Curcumin-NSAIDs Conjugates

The present research work involves the synthesis of a total of four Curcumin-NSAIDs conjugates and their subsequent biological screening for Rheumatoid Arthritis, Anti-inflammatory, and Anti-ulcer activities. Curcumin is a phytochemical having versatile therapeutic potential. The idea of conjugating curcumin with various NSAIDs is somewhat novel in the sense that it helps in obtaining the target of incorporating certain desired properties in the curcumin like enhanced bioavailability, reduction in the side effects and also giving good therapeutic potential in terms of determination of rheumatoid arthritis, anti-inflammatory and anti-ulcer activities of synthesized conjugates using appropriate animal models. Additionally, studies have been done on the in vivo bioavailability of curcumin-NSAIDs conjugates and curcumin in Sprague-Dawley rats and on the antiarthritic efficacy of curcumin-NSAIDs conjugates and curcumin in a modified streptococcal cell wall-induced arthritis model in Balb/c mice to resemble rheumatoid arthritis in human. Curcumin-NSAID conjugates have shown improved stability in all of the studies mentioned when compared to curcumin and curcumin-NSAID conjugates; they also increased curcumin’s bioavailability by more than five folds and significantly reduced arthritis symptoms in a streptococcal cell wall-induced arthritis model when compared to other conjugates and curcumin. The structural features of all the synthesized compounds have been confirmed by appropriate spectral analysis. Other supporting techniques employed for structural and purity aspects include Melting point determination, Thin Layer Chromatography analysis, and Recrystallization. Therefore, conjugating curcumin with medicinal molecules proved to be a creative way to increase its bioavailability and enhance its wide range of pharmacological effects.

Effects of whey protein-polyphenol conjugates incorporation on physicochemical and intelligent pH-sensing properties of carboxymethyl cellulose based films

This study aimed to develop carboxymethyl cellulose films functionalized by whey protein and polyphenols (proanthocyanidins and curcumin) conjugates. The physicochemical properties, freshness monitoring and preservation ability of films with conjugates were evaluated. The results showed that the vapor barrier property, tensile strength and contact angle of films incorporated with conjugates were improved 10%–31%, 61%–134%, 4%–19% respectively. Furthermore, the incorporation of conjugates improved the ability to indicate the changes of pH value, inhibit the microbial growth and prevent fat oxidation, when the films were applied for beef preservation. The improvement was attributed to the enhancement of intermolecular interactions and higher binding rate, which helped to form the films with more compact and uniform microstructure. This study suggested that films containing conjugates can be applied for monitoring freshness and extending the shelf-life of beef.

Modified Curcumins as Potential Drug Candidates for Breast Cancer: An Overview.

Breast cancer (BC), the most common malignancy in women, results from significant alterations in genetic and epigenetic mechanisms that alter multiple signaling pathways in growth and malignant progression, leading to limited long-term survival. Current studies with numerous drug therapies have shown that BC is a complex disease with tumor heterogeneity, rapidity, and dynamics of the tumor microenvironment that result in resistance to existing therapy. Targeting a single cell-signaling pathway is unlikely to treat or prevent BC. Curcumin (a natural yellow pigment), the principal ingredient in the spice turmeric, is well-documented for its diverse pharmacological properties including anti-cancer activity. However, its clinical application has been limited because of its low solubility, stability, and bioavailability. To overcome the limitation of curcumin, several modified curcumin conjugates and curcumin mimics were developed and studied for their anti-cancer properties. In this review, we have focused on the application of curcumin mimics and their conjugates for breast cancer.

Synthesis of Cobalt Bis(Dicarbollide)-Curcumin Conjugates for Potential Use in Boron Neutron Capture Therapy.

A series of novel cobalt bis(dicarbollide)—curcumin conjugates were synthesized. Two conjugates were obtained through the nucleophilic ring-opening reaction of the 1,4-dioxane and tetrahydropyran derivatives of cobalt bis(dicarbollide) with the OH group of curcumin, and using two equiv. of the oxonium derivatives, two other conjugates containing two cobalt bis(dicarbollide) units per molecule were obtained. In contrast to curcumin, the conjugates obtained were found to be non-cytotoxic against both tumor and normal cell lines. The analysis of the intracellular accumulation of the conjugates by flow cytometry showed that all cobalt bis(dicarbollide)—curcumin conjugates entered HCT116 colorectal carcinoma cells in a time-dependent manner. New non-cytotoxic conjugates contain a large amount of boron atoms in the biomolecule and can potentially be used for further biological research into boron neutron capture therapy (BNCT).

Design, Synthesis, and Anticancer Studies of a p-Cymene-Ru(II)-Curcumin Organometallic Conjugate Based on a Fluorescent 4-Amino-1,8-naphthalimide Tröger's Base Scaffold.

A unique V-shaped "chiral" supramolecular scaffold, N-(4-pyridyl)-4-amino-1,8-naphthalimide Tröger's base (TBNap), was synthesized in good yield from a precursor N-(4-pyridyl)-4-amino-1,8-naphthalimide (Nap). TBNap was characterized using different spectroscopic methods and the molecular structure was elucidated by diffraction analysis. A new p-cymene-Ru(II)-curcumin conjugate (TB-Ru-Cur) was designed by reacting TBNap dipyridyl donor and ruthenium-curcuminato acceptor [RuCur = (p-cymene)Ru-(curcuminato)Cl] in the presence of silver triflate. TB-Ru-Cur was isolated in quantitative yield and characterized using Fourier transform infrared (FT-IR), NMR (1H, 13C, and 19F), and electrospray ionization mass spectrometry (ESI-MS), and the molecular structure has been predicted using a computational study. Both TBNap and TB-Ru-Cur exhibited intramolecular charge transfer (ICT)-based fluorescence emission. Furthermore, the anticancer properties of TBNap, Ru-Cur, and TB-Ru-Cur were assessed in different cancer cell lines. Gratifyingly, the conjugate TB-Ru-Cur displayed fast-cellular internalization and good cytotoxicity against HeLa, HCT-116, and HepG2 cancer cells and the estimated IC50 value was much lower than that of the precursors (TBNap and Ru-Cur) and the well-known chemotherapeutic drug cisplatin.

5-Fluorouracil and Curcumin Combination Coated with Pectin and Its Strategy towards Titanium Dioxide, Dimethylhydrazine Colorectal Cancer Model with the Evaluation of the Blood Parameters.

Colorectal cancer is considered the third most common cancer and the second leading cause of death globally. It has been proven that titanium dioxide nanoparticles produce oxidative stress and can lead to chronic inflammation, which could turn into diseases like cancer, cardiovascular disorders, diabetes, and so on. To evaluate the effect of 5-fluorouracil (5-FU) curcumin (CUR) conjugate coated with pectin on colorectal cancer induced by titanium dioxide nanoparticles (TiO2-NPs) and dimethylhydrazine (DMH), male rats were administered TiO2-NPs (5 mg/kg) orally and DMH (1 mg/kg) peritoneally for 70 days and treated with 5-FU (60 mg/kg) and CUR (240 mg/kg) conjugate (1:4 ratio) coated with pectin. The bodyweight of the animals was evaluated, and the blood sugar level was calculated. Further blood and plasma analyses were conducted. Hematological parameters, antioxidant parameters, and biochemical estimation were taken into consideration. The TiO2-NPs level in the blood and colorectal region was also calculated. With the induction of colon cancer using TiO2-NPs and DMH, a significant increase in the body weight of the animals was seen; eventually, with treatment, it was reduced. The bodyweight increase was due to an increase in the blood sugar level. There were also significant changes in the hematological parameters and biochemical estimation reports when comparing those of the positive control, negative control, and treated groups. No significant effect on biochemical estimation reports was seen. Conclusions: These reports suggest that 5-FU CUR conjugate coated with pectin helps in the management of colorectal cancer induced by TiO2-NPs and DMH.

Potential therapeutic effects of curcumin coated silver nanoparticle in the treatment of cutaneous leishmaniasis due to Leishmania major in-vitro and in a murine model

BackgroundLeishmaniasis is a destructive protozoan parasitic and vector-borne infection characterized as a neglected tropical disease (NTD) that is currently endemic in more than 100 countries. Herbal compounds such as curcumin derived from turmeric with complex and extensive structures have a wide range of applications in the treatment of parasitic infections; however, its usage has a major challenge due to low water solubility and bioavailability. Besides, metal nanoparticles such as silver have been applied for parasitic infection treatment. Synthesis of curcumin and silver nanoparticles conjugate facilitates in enhancing curcumin solubility and bioavailability. Here curcumin-coated silver nanoparticles (Cur@AgNPs) were synthesized, characterized, and then their cell cytotoxicity and antileishmanial activities were investigated both in-vitro and in mouse models. Materials and methodsCurcumin coated silver nanoparticles (Cur@AgNPs) synthesized by a simple one-pot green chemistry technique. After confirming their stability, in vitro cell cytotoxicity and leishmanicidal activity against promastigotes and amastigotes of the protozoan parasite, Leishmania major (L. major) was evaluated by using colourimetric yellow methyl thiazole tetrazolium (MTT) assay. Furthermore, antiparasitic properties of Cur@AgNPs in the mouse model were studied through quantifying footpads (FPs) lesion size and determining parasite burden in lymph nodes (LNs) and FPs of infected BALAB/c mice with L. major. ResultsCur@AgNPs represent a plasmonic peak of silver nanoparticles at 420 nm in UV–Vis spectra. The size of synthesized NPs was 29.1 ± 5.6 nm based on the analyzing TEM micrographs. The hydrodynamic diameter of the synthesized particles is 32.4 ± 2.3 nm. The zeta potential of washed Cur@AgNPs (4 rounds of washing) was −19.8 ± 1.5 mV. The stability of Cur@AgNPs at different time intervals (up to two months) in PBS buffer media has been investigated thoroughly. We confirmed that Cur@AgNPs decreased significantly in both forms of promastigotes and amastigotes of Leishmania parasite in a single treatment. The nanoparticle elucidated potent antileishmanial activity with IC50 of 58.99 μg/ml for promastigotes and EC50 58.99 μg/ml for amastigotes at 48 h post-infection with no harmful negative toxicity on the mice macrophages. In the treated infected BALB/c mice using Cur@AgNPs, the cutaneous leishmania (CL) lesion size in the FPs and Leishmania burden in both LNs and FPs were decreased significantly. ConclusionThe results of this study revealed that Cur@AgNPs could be, novel, safe, and effective promising candidates as an antileishmanial agent in the treatment of CL infection.

Photoactivated multifunctional nanoplatform based on lysozyme-Au nanoclusters-curcumin conjugates with FRET effect and multiamplified antimicrobial activity

Photodynamic therapy is a promising alternative to antibiotics in the treatment of bacterial infection, which has the advantages of less side effects, no drug resistance and accurate treatment. However, most photosensitizers (PSs) have some disadvantages, such as poor water solubility, serious self-quenching, poor stability and so on. Therefore, solving the limitations of traditional photosensitizers has become a hot issue in photodynamic therapy. On this basis, the lysozyme (Lys)-gold nanocluster (AuNCs)-curcumin (Cur) conjugate was used as a new type of water-soluble photosensitizer and combined with the bacterial surface through electrostatic interaction to form a bacterial surface enriched in PSs. At the same time, real-time bacterial imaging can be achieved by using the fluorescence properties of Lys-AuNCs-Cur. Under 405 nm light and dark conditions, the inactivation effect of Lys-AuNCs-Cur on Staphylococcus aureus and Escherichia coli was higher than that of free Cur. Moreover, Lys-AuNCs-Cur can also produce enough ROS to kill methicillin-resistant Staphylococcus aureus. The excellent antibacterial properties of nanoparticles may be attributed to the synergism of antibacterial protein lysozyme and AuNCs-Cur nanocomplexes and the increase of 1O2 production. The results of scanning electron microscope and fluorescence microscopic imaging showed that the cell membrane of E. coli and S. aureus was seriously damaged, and facilitated penetration of Lys-AuNCs-Cur nanocomplexes into the bacteria through the damaged cell membrane, and improve the photoinactivation efficiency of bacteria. More importantly, nanoparticles exhibited almost negligible dark cytotoxicity. The coupling of Cur and gold nanoclusters can significantly improve the stability of free curcumin molecules and the ability to generate ROS. Therefore, this work is of great significance for the development of new antimicrobial agents against bacterial infection.

The Potential Anti-Photoaging Effect of Photodynamic Therapy Using Chlorin e6-Curcumin Conjugate in UVB-Irradiated Fibroblasts and Hairless Mice.

Photodynamic therapy (PDT) has been used to treat cancers and non-malignant skin diseases. In this study, a chlorin e6–curcumin conjugate (Ce6-PEG-Cur), a combination of chlorin e6 (Ce6) and curcumin via a PEG linker, was used as a photosensitizer. The in vitro and in vivo effects of PDT using Ce6-PEG-Cur were analyzed in UVB-irradiated fibroblasts and hairless mice. The UVB-induced expression of MMPs was reduced in Hs68 fibroblast cells, and procollagen type Ⅰ expression was enhanced by Ce6-PEG-Cur-mediated PDT on a Western blotting gel. Moreover, UVB-induced collagen levels were restored upon application of Ce6-PEG-Cur-mediated PDT. Ce6-PEG-Cur-mediated PDT inhibited the expression of phosphorylated p38 in the MAPK signaling pathway, and it reduced the expression of phosphorylated NF-κB. In animal models, Ce6-PEG-Cur-mediated PDT inhibited the expression of MMPs, whereas procollagen type Ⅰ levels were enhanced in the dorsal skin of UVB-irradiated mice. Moreover, UVB-induced dorsal roughness was significantly reduced following Ce6-PEG-Cur-mediated PDT treatment. H&E staining and Masson’s trichrome staining showed that the thickness of the epidermal region was reduced, and the density of collagen fibers increased. Taken together, Ce6-PEG-Cur-mediated PDT might delay and improve skin photoaging by ultraviolet light, suggesting its potential for use as a more effective photo-aging treatment.

The development of a redox-sensitive curcumin conjugated chitosan oligosaccharide nanocarrier for the efficient delivery of docetaxel to glioma cells.

BackgroundA redox-sensitive nanoscale delivery system was developed, based on the hydrophilic chitosan oligosaccharide-ss-hydrophobic curcumin conjugate (CSO-ss-CUR) loaded with docetaxel (DTX), for the targeting and synergistic treatment of gliomas.MethodsRedox-sensitive nanoparticles were loaded with DTX (DTX/CSO-ss-CUR) using the improved ultrasonic-dialysis approach. The morphology and particle size of the loaded nanoparticles were examined by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. The cytotoxicity and cellular uptake of the nanoparticles were assessed in vitro using the C6 glial cell line. The in vivo antitumor efficacy and in vivo biodistribution studies were evaluated using the C6 tumor-bearing Balb/c female mouse model.ResultsThe DTX/CSO-ss-CUR nanoparticles were generally spherical in shape and exhibited desirable particle size (under 250 nm) with high drug loading efficiency (DL) (8.96%±0.56%) and encapsulation efficiency (EE) (35.23%±3.26%). In vitro, the drug was released from the nanoparticles in a redox-sensitive manner. The DTX/CSO-ss-CUR nanoparticles exhibited superior hemocompatibility in the hemolytic test and in vitro cytotoxicity and live/dead cell staining experiments revealed a higher cytotoxicity to glioma cells compared to the free drug. Furthermore, in vitro uptake experiments using C6 glioma cells demonstrated that the CSO-ss-CUR nanoparticles had good cell penetration ability. The in vivo antitumor efficacy and in vivo biodistribution studies suggested that the CSO-ss-CUR nanoparticles could effectively inhibit C6 tumor growth. More importantly, after intravenous injection, more CSO-ss-CUR nanoparticles were concentrated in the brain of the mice than free 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR) group.ConclusionsA unique drug delivery system formed by the self-assembly of CSO-ss-CUR was developed and shown to effectively cross the blood-brain barrier (BBB), enriching the abundance of the drug in the brain tissues. This may represent a potential therapeutic strategy for the treatment of gliomas.KeywordsChitosan oligosaccharide (CSO); curcumin (CUR); docetaxel (DTX); glioma

Conjugation of Curcumin and Metformin for Improved Pharmacological Profile in Cancer Therapy: An In Silico Approach

Curcumin has been shown to possess high cytotoxicity towards various cell lines. But its low aqueous solubility and bioavailability limit its use as an effective cytotoxic agent. It has been reported that metformin selectively kills cancer stem cells and blocks tumor growth. Preclinical studies show the effectiveness of both curcumin and metformin in breast cancer. Conjugation of metformin and curcumin may result in synergistic cancer therapy by improving the aqueous solubility of curcumin and hence its bioavailability. In the present study, curcumin-metformin conjugate and the free drugs curcumin and metformin were subjected to docking analysis against the breast cancer targets such as epidermal growth factor receptor, kinesin spindle protein, cyclin-dependent kinase, human placental aromatase, and human estrogen receptor. Docking studies were performed using Autodock Vina. The results signify that curcumin-metformin conjugate showed higher binding energy ranging between -7.4 to -9.7 Kcal/mol than curcumin and metformin. The stability of the conjugate-receptor complex and interactions between them was further evaluated by molecular dynamics simulation. The results showed that the conjugate can interact effectively with human placental aromatase and can be considered for further studies.