Biocompatibility and potential anticancer activity of gadolinium oxide (Gd2O3) nanoparticles against nasal squamous cell carcinoma.

Chemotherapy as a cornerstone of cancer treatment is slowly being edged aside owing to its severe side effects and systemic toxicity. In this case, nanomedicine has emerged as an effective tool to address these drawbacks. Herein, a biocompatible carrier based on bovine serum albumin (BSA) coated gadolinium oxide nanoparticles (Gd2O3@BSA) was fabricated for curcumin (CUR) delivery and its physicochemical features along with its potential anticancer activity against nasal squamous cell carcinoma were also investigated. It was found that the fabricated Gd2O3@BSA containing CUR (Gd2O3@BSA-CUR) had spherical morphology with hydrodynamic size of nearly 26 nm, zeta-potential of -36 mV and high drug (CUR) loading capacity. Drug release profile disclosed that the release of CUR from the prepared Gd2O3@BSA-CUR nanoparticles occurred in a sustained- and pH-dependent manner. Also, in vitro cytotoxicity analysis revealed that the fabricated Gd2O3@BSA nanoparticles possessed excellent biosafety toward HFF2 normal cells, while Gd2O3@BSA-CUR appeared to display the greatest anticancer potential against RPMI 2650 and CNE-1 cancer cell lines. The results also show that the Gd2O3@BSA nanoparticles were compatible with the blood cells with minor hemolytic effect (< 3%). The manufactured NPs were found to be completely safe for biological applications in an in vivo subacute toxicity study. Taken together, these finding substantiate the potential anticancer activity of Gd2O3@BSA-CUR nanoparticles against nasal squamous cell carcinoma, but the results obtained demand further studies to assess their full potential.

A smartphone-assisted portable dual-mode immunoassay of gentamicin based on curcumin nanoparticles and carbon dots.

A smartphone-assisted portable dual-mode immunoassay was constructed based on curcumin nanoparticles (CNPs) and carbon dots (CDs) for gentamicin (GEN) detection. CNPs were labeled with goat anti-mouse IgG (Ab2) to create a conjugation that coupled dual signals to concentrations of GEN antigens. CNPs were introduced to pH 7.4 water and showed insignificant color and optical responses. When exposed to the high pH environment, the structure of CNPs changed and color and optical properties were restored. Because of the inner filter effect (IFE) between CNPs and CDs, the fluorescence of CNPs at 550 nm quenched the fluorescence of CDs at 450 nm. Colorimetry and ratiometric fluorescence (F550 nm/F450 nm) dual-mode immunoassay linearly correlated with GEN ranged from 10-4 to 100 µg/mL with a detection limit (LOD) of 8.98 × 10-5 µg/mL and 4.66 × 10-5 µg/mL, respectively. This work supplied a portable, sensitive, and specific platform to detect GEN.

Enhanced breast cancer therapy using multifunctional lipid-coated nanoparticles combining curcumin chemotherapy and nitric oxide gas delivery.

The limitations associated with conventional cancer treatment modalities, particularly for breast cancer, underscore the imperative for developing safer and more productive drug delivery systems. A promising strategy that has emerged is the combination of chemotherapy with gas therapy. We synthesized curcumin-loaded amorphous calcium carbonate nanoparticles (Cur-CaCO3) via a gas diffusion reaction in the present study. Subsequently, a "one-step" ethanol injection method was employed to fabricate lipid-coated calcium carbonate nanoparticles (Cur-CaCO3@LA-Lip) loaded with L-arginine, aimed at harnessing the synergistic effects of chemotherapy and nitric oxide to enhance antitumor efficacy. Transmission electron microscopy analysis revealed that Cur-CaCO3@LA-Lip nanoparticles were subspherical with a distinct lipid layer encapsulating the periphery. Fourier transform infrared spectroscopy, X-ray powder diffraction, and differential scanning calorimetry results confirmed the successful synthesis of Cur-CaCO3@LA-Lip. The nanoparticles exhibited significant drug loading capacities of 8.89% for curcumin and 3.1% for L-arginine. In vitro and in vivo assessments demonstrated that Cur-CaCO3@LA-Lip nanoparticles facilitated sustained release of curcumin and exhibited high cellular uptake, substantial tumor accumulation, and excellent biocompatibility. Additionally, the nanoparticles showed robust cytotoxicity and potent antitumor efficacy, suggesting their potential as a formidable candidate for breast cancer therapy.

Anti-Cancer Properties of Two Intravenously Administrable Curcumin Formulations as Evaluated in the 3D Patient-Derived Cancer Spheroid Model.

Curcumin (Cur) is a heavily used complementary derived drug from cancer patients. Spheroid samples derived from 82 patients were prepared and treated after 48 h with two Cur formulations (CurA, CurB) in mono- and combination therapy. After 72 h, cell viability and morphology were assessed. The Cur formulations had significant inhibitory effects of -8.47% (p < 0.001), CurA of -10.01% (-50.14-23.11%, p = 0.001) and CurB of -6.30% (-33.50-19.30%, p = 0.006), compared to their solvent controls Polyethylene-glycol, ß-Cyclodextrin (CurA) and Kolliphor-ELP, Citrate (CurB). Cur formulations were more effective in prostate cancer (-19.54%) and less effective in gynecological non-breast cancers (0.30%). CurA showed better responses in samples of patients <40 (-13.81%) and >70 years of age (-17.74%). CurB had stronger effects in metastasized and heavily pretreated tumors. Combinations of Cur formulations and standard therapies were superior in 20/47 samples (42.55%) and inferior in 7/47 (14.89%). CurB stimulated chemo-doublets more strongly than monotherapies (-0.53% vs. -6.51%, p = 0.022) and more effectively than CurA (-6.51% vs. 3.33%, p = 0.005). Combinations of Cur formulations with Artesunate, Resveratrol and vitamin C were superior in 35/70 (50.00%) and inferior in 16/70 (22.86%) of samples. Cur formulations were significantly enhanced by combination with Artesunate (p = 0.020). Cur formulations showed a high variance in their anti-cancer effects, suggesting a need for individual testing before administration.

Co-encapsulation of hydrophilic and hydrophobic bioactives stabilized in nanostarch-assisted emulsion for inner core gel of coaxial 3D printing.

3D printing technology, especially coaxial 3D mode of multiple-component shaping, has great potential in the manufacture of personalized nutritional foods. However, integrating and stabilizing functional objectives of different natures remains a challenge for 3D customized foods. Here, we used starch nanoparticle (SNP) to assisted soy protein (SPI) emulsion to load hydrophilic and hydrophobic bioactives (anthocyanin, AC, and curcumin, Cur). The addition of SNP significantly improved the storage stability of the emulsion. Xanthan gum (XG) was also added to the SNP/SPI system to enhance its rheology and form an emulsion gel as inner core of coaxial 3D printing. Low field nuclear magnetic resonance and emulsification analyses showed that AC/Cur@SNP/SPI/XG functional inner core had a strong water binding state and good stability. After printing with outer layer, the SNP/SPI coaxial sample had the lowest deviation rate of 0.8 %. Also, SNP/SPI coaxial sample showed higher AC (90.2 %) and Cur (90.8 %) retention compared to pure starch (S), pure SNP, pure SPI, and S/SPI samples as well as SNP/SPI sample printed without outer layer. In summary, this study provides a new perspective for the manufacture of customized products as multifunctional foods, feeds and even potential delivery of drugs.

Immunomodulatory Antibacterial Hydrogel for Wound Infection Management.

Background: Wound healing has always been a focal point in clinical work. Bacterial infections and immune microenvironment disorders can both hinder normal wound healing. Current wound dressings only serve a covering function. Developing wound dressings with antibacterial and immunomodulatory functions is crucial for aiding wound healing. To address this issue, we have developed a hydrogel with antibacterial and immunomodulatory functions for managing infected wounds. Methods: The present study describes a photo-crosslinked antibacterial hydrogel composed of curcumin, silver nanoparticles-loaded reduced graphene oxide, and silk fibroin methacryloyl for the treatment of infected wounds. The study assessed its antibacterial properties and its capacity to induce macrophage M2 polarization through in vitro and in vivo experiments. Results: The hydrogel demonstrates robust antibacterial properties and enhances macrophage M2 polarization in both in vitro and in vivo settings. Moreover, it accelerates the healing of infected wounds in vivo by stimulating collagen deposition and angiogenesis. Conclusion: Overall, this hydrogel shows great potential in managing wound infections.

Hybrid Organic-Inorganic Copper and Cobalt Complexes for Antimicrobial Potential Applications.

BACKGROUND/AIMS: The naturally occurring phenolic chemical curcumin (CUR), which was derived from the Curcuma longa plant, has a variety of biological actions, including anti-inflammatory, antimicrobial, antioxidant, and anticancer activities. Curcumin is known for its restricted bioavailability due to its hydrophobicity, poor intestinal absorption, and quick metabolism. To boost the biological effects of these bioactive molecules, it is necessary to raise both their bioavailability and their solubility in water. Aim: The aim of this study is to synthesize and characterize hybrid organic-inorganic complexes of copper and cobalt, and to evaluate their antimicrobial potential against a range of pathogenic microorganisms. METHODS: The synthesis of metal curcumin complexes (Cu-CUR and Co-CUR) was achieved by mixing curcumin with copper acetate monohydrate. The solid residue was isolated, filtered, and dried in an oven. X-ray diffraction analysis was used to identify the structure and phase of the prepared samples. FTIR spectra were recorded using a Shimadzu 2200 module. The antimicrobial activity of the prepared complexes was evaluated against four bacterial strains and two Candida species. The chemical materials were dissolved in DMSO to a final concentration of 20%, and the plates were incubated at 37°C for 24 hours. The results showed that the prepared complexes had antimicrobial activity against the tested microorganisms. RESULTS: The study compared the Powder X-ray diffraction (XRD) patterns of prepared copper and cobalt complexes to pure curcumin, revealing new, isostructural complexes. The FTIR analysis showed that the Cu-CUR and Co-CUR complexes varied in their inhibitory effect against microorganisms, with Co-CUR being more effective. The results are consistent with previous studies showing the cobalt-curcumin complex was effective against various bacterial genera, with inhibition activity varying depending on the species and strains of microorganisms. CONCLUSION: Copper and cobalt curcumin complexes, synthesized at room temperature, exhibit high crystallinity and antimicrobial activity. Co-CUR, with its superior antibacterial potential, outperforms pure curcumin in inhibiting microbes. Further investigation is needed to understand their interaction mechanisms with bacteria and fungi.

Oral enzyme-responsive nanoprobes for targeted theranostics of inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a progressive and debilitating inflammatory disease of the gastrointestinal tract (GIT). Despite recent advances, precise treatment and noninvasive monitoring remain challenging. METHODS: Herein, we developed orally-administered, colitis-targeting and hyaluronic acid (HA)-modified, core-shell curcumin (Cur)- and cerium oxide (CeO2)-loaded nanoprobes (Cur@PC-HA/CeO2 NPs) for computed tomography (CT) imaging-guided treatment and monitoring of IBD in living mice. RESULTS: Following oral administration, high-molecular-weight HA maintains integrity with little absorption in the upper GIT, and then actively accumulates at local colitis sites owing to its colitis-targeting ability, leading to specific CT enhancement lasting for 24 h. The retained NPs are further degraded by hyaluronidase in the colon to release Cur and CeO2, thereby exerting anti-inflammatory and antioxidant effects. Combined with the ability of NPs to regulate intestinal flora, the oral NPs result in substantial relief in symptoms. Following multiple treatments, the gradually decreasing range of the colon with high CT attenuation correlates with the change in the clinical biomarkers, indicating the feasibility of treatment response and remission. CONCLUSION: This study provides a proof-of-concept for the design of a novel theranostic integration strategy for concomitant IBD treatment and the real-time monitoring of treatment responses.

Effect of the presence of berberine/curcumin on the binding of limonin to human serum albumin and antitumor activity in vitro.

The competition among drugs for binding to plasma proteins is regarded as a pharmacokinetic drug interaction. Competition between antitumor agents and other drugs for plasma protein binding can alter the free concentration of the drug, potentially impacting its efficacy and increasing the risk of toxic side effects. Through a range of spectroscopic techniques, this study examined the interaction between limonin and human serum albumin (HSA) in the context of berberine (Ber) and curcumin (Cur) under physiological conditions to clarify the binding mechanisms of binary and ternary systems at the molecular level. As demonstrated by fluorescence quenching experiments, Static quenching was identified as the mechanism of interaction between HSA and limonin. The results of site competition experiments indicated that the binding site between limonin and HSA was site I, a result further supported by molecular docking simulations. Through the use of thermodynamic data calculations, it was determined that limonin forms a stable complex with HSA by establishing hydrogen bonds and van der Waals forces. Circular dichroism (CD) spectroscopy, three-dimensional (3D) fluorescence spectroscopy, and synchronous fluorescence spectroscopy (SFS) employed to validate the notion that limonin perturbed the microenvironment of amino acids and induced conformational changes in HSA. What's more, the presence of Ber or Cur was found to have further modified the alterations observed in the interaction between the original HSA-limonin binary system. In vitro cellular experiments showed that interaction with HSA reduced the antitumor activity of limonin. In contrast, adding Ber or Cur increased the inhibition rate of tumor cells. The coexistence of both Ber and Cur significantly diminished limonin's binding affinity to HSA. The current investigation enhances comprehension regarding the binding characteristics and interaction mechanisms involving limonin, Ber, Cur, and HSA. It explores the potential of HSA as a versatile drug carrier and furnishes theoretical underpinnings for co-administrative strategies.

Development of modular polymeric nanoparticles for drug delivery using amine reactive chemistry.

Curcumin has been explored for its anti-cancer potential, but is severely limited by its hydrophobicity and sensitivity to light and water. In this study, poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were synthesized to encapsulate curcumin via single emulsion method to improve curcumin stability and bioavailability. The PLGA NPs were coated with oligomeric chitosan (COS) and RGD peptide (a peptide consisting of Arg-Gly-Asp) using amine-reactive chemistry (NHS and EDC). Both COS and RGD had been previously shown to accumulate and target many different types of cancer cells. NPs were characterised based on size distribution, zeta potential, and binding efficiency of RGD peptide. They were also evaluated on encapsulation efficiency, and stability, of curcumin within the NPs. OVCAR-3 cancer cells were treated with COS and RGD-coated PLGA NPs loaded with Coumarin-6 dye for fluorescent imaging of cell uptake. They were also treated with curcumin-loaded NPs to determine cytotoxicity and effectiveness of delivery. The NPs exhibited size distribution and zeta potential within expected values, though binding efficiency of RGD was low. Curcumin-loaded NPs showed significant increase in cytotoxicity over free (unencapsulated) curcumin, and void (empty) NPs, suggesting successful delivery of curcumin as an anti-cancer agent; the performance of COS and RGD coated NPs over bare PLGA NPs was inconclusive, however, optimization will be required to improve formulation during the coating steps. This method of NP synthesis serves as proof of concept for a modular solution to the development of various coated polymeric NPs for other drugs or applications.

Discovery of Curcuminoids as Pancreatic Lipase Inhibitors from Medicine-and-Food Homology Plants.

Researchers are increasingly interested in discovering new pancreatic lipase inhibitors as anti-obesity ingredients. Medicine-and-food homology plants contain a diverse set of natural bioactive compounds with promising development potential. This study screened and identified potent pancreatic lipase inhibitors from 20 commonly consumed medicine-and-food homology plants using affinity ultrafiltration combined with spectroscopy and docking simulations. The results showed that turmeric exhibited the highest pancreatic lipase-inhibitory activity, and curcumin, demethoxycurcumin, and bisdemethoxycurcumin were discovered to be potent pancreatic lipase inhibitors within the turmeric extract, with IC50 values of 0.52 ± 0.04, 1.12 ± 0.05, and 3.30 ± 0.08 mg/mL, respectively. In addition, the enzymatic kinetics analyses demonstrated that the inhibition type of the three curcuminoids was the reversible competitive model, and curcumin exhibited a higher binding affinity and greater impact on the secondary structure of pancreatic lipase than found with demethoxycurcumin or bisdemethoxycurcumin, as observed through fluorescence spectroscopy and circular dichroism. Furthermore, docking simulations supported the above experimental findings, and revealed that the three curcuminoids might interact with amino acid residues in the binding pocket of pancreatic lipase through non-covalent actions, such as hydrogen bonding and π-π stacking, thereby inhibiting the pancreatic lipase. Collectively, these findings suggest that the bioactive compounds of turmeric, in particular curcumin, can be promising dietary pancreatic lipase inhibitors for the prevention and management of obesity.

Bone Marrow Mesenchymal Stem Cell-Derived Nanovesicles Containing H8 Improve Hepatic Glucose and Lipid Metabolism and Exert Ameliorative Effects in Type 2 Diabetes.

Purpose: Nanovesicles (NVs) derived from bone mesenchymal stem cells (BMSCs) as drug delivery systems are considered an effective therapeutic strategy for diabetes. However, its mechanism of action remains unclear. Here, we evaluated the efficacy and molecular mechanism of BMSC-derived NVs carrying the curcumin analog H8 (H8-BMSCs-NVs) on hepatic glucose and lipid metabolism in type 2 diabetes (T2D). Subjects and Methods: Mouse BMSCs were isolated by collagenase digestion and H8-BMSCs-NVs were prepared by microvesicle extrusion. The effects of H8-BMSCs-NVs on hepatic glucose and lipid metabolism were observed in a T2D mouse model and a HepG2 cell insulin resistance model. To evaluate changes in potential signaling pathways, the PI3K/AKT/AMPK signaling pathway and expression levels of G6P and PEPCK were assessed by Western blotting. Results: H8-BMSCs-NVs effectively improved lipid accumulation in liver tissues and restored liver dysfunction in T2D mice. Meanwhile, H8-BMSCs-NVs effectively inhibited intracellular lipid accumulation in the insulin resistance models of HepG2 cells. Mechanistic studies showed that H8-BMSCs-NVs activated the PI3K/AKT/AMPK signaling pathway and decreased the expression levels of G6P and PEPCK. Conclusion: These findings demonstrate that H8-BMSCs-NVs improved hepatic glucose and lipid metabolism in T2D mice by activating the PI3K/AKT/AMPK signaling pathway, which provides novel evidence suggesting the potential of H8-BMSCs-NVs in the clinically treatment of T2D patients.

Synthesis of curcumin derivatives targeting androgen receptor for castration-resistant prostate cancer therapy.

In this work, a series of curcumin derivatives (1a-1h, 2a-2g, and 3a-3c) were synthesized for the suppression of castration-resistant prostate cancer cells. All synthesized compounds were characterized by 1H NMR, 13C NMR, HRMS, and melting point. The in vitro cytotoxicity study shows that compounds 1a, 1e, 1f, 1h, 2g, 3a, and 3c display similar or enhanced cytotoxicity against 22Rv1 and C4-2 cells as compared to ASC-J9, other synthesized compounds display reduced cytotoxicity against 22Rv1 and C4-2 cells as compared to ASC-J9. Molecular docking simulation was performed to study the binding affinity and probable binding modes of the synthesized compounds with androgen receptor. The results show that all synthesized compounds exhibit higher cdocker interaction energies as compared to ASC-J9. Compounds 1h, 2g, and 3c not only show strong cytotoxicity against 22Rv1 and C4-2 cells but also exhibit high binding affinity with androgen receptor. In androgen receptor suppression study, compounds 1f and 2g show similar androgen receptor suppression effect as compared to ASC-J9 on C4-2 cells, compound 3c displays significantly enhanced AR suppression effect as compared to ASC-J9, 1f and 2g. Compounds 1a, 1e, 1f, 1h, 2g, 3a and 3c prepared in this work have significant potential for castration-resistant prostate cancer therapy.

A pH-triggered N-oxide polyzwitterionic nano-drug loaded system for the anti-tumor immunity activation research.

Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.

Integrating Network Pharmacology, Transcriptomics to Reveal Neuroprotective of Curcumin Activate PI3K / AKT Pathway in Parkinson's Disease.

Background: Parkinson's disease (PD) is the most prevalent movement disorder. Curcumin, a polyphenol with hydrophobic properties, has been proved against Parkinson. Our previous study suggested that curcumin's effectiveness in treating Parkinson's disease may be linked to the gut-brain axis, although the specific mechanism by which curcumin exerts neuroprotective effects in the brain remains unknown. Methods: The therapeutic efficacy of curcumin was evaluated using behavioral tests, immunofluorescence of tyrosine hydroxylase (TH). Network pharmacology and transcriptomics predicted the mechanisms of curcumin in PD. Activation of the phosphatidylinositol 3-kinase PI3K/AKT pathway was confirmed by quantitative polymerase chain reaction (qPCR) and immunofluorescence. Results: Curcumin restored the dyskinesia and dopaminergic neurons damage of MPTP-induced mice. Curcumin against Parkinson's disease by regulating inflammation, oxidative stress, and aging. The mechanisms of these were associated with activation of PI3K / AKT pathway. Conclusion: In conclusion, the neuroprotective mechanisms of curcumin activate PI3K / AKT pathway in Parkinson's disease was revealed by our study.

Epigallocatechin gallate and curcumin inhibit Bcl-2: a pharmacophore and docking based approach against cancer.

The protein Bcl-2, well-known for its anti-apoptotic properties, has been implicated in cancer pathogenesis. Identifying the primary gene responsible for promoting improved cell survival and development has provided compelling evidence for preventing cellular death in the progression of malignancies. Numerous research studies have provided evidence that the abundance of Bcl-2 is higher in malignant cells, suggesting that suppressing Bcl-2 expression could be a viable therapeutic approach for cancer treatment. In this study, we acquired a compound collection using a database that includes constituents from Traditional Chinese Medicine (TCM). Initially, we established a pharmacophore model and utilized it to search the TCM database for potential compounds. Compounds with a fitness score exceeding 0.75 were selected for further analysis. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis identified six compounds with favorable therapeutic characteristics. The compounds that successfully passed the initial screening process based on the pharmacodynamic model were subjected to further evaluation. Extra-precision (XP) docking was employed to identify the compounds with the most favorable XP docking scores. Further analysis using the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method to calculate the overall free binding energy. The binding energy between the prospective ligand molecule and the target protein Bcl-2 was assessed by a 100 ns molecular dynamics simulation for curcumin and Epigallocatechin gallate (EGCG). The findings of this investigation demonstrate the identification of a molecular structure that effectively inhibits the functionality of the Bcl-2 when bound to the ligand EGCG. Consequently, this finding presents a novel avenue for the development of pharmaceuticals capable of effectively addressing both inflammatory and tumorous conditions.

Curcumin's membrane localization and disruptive effects on cellular processes - insights from neuroblastoma, leukemic cells, and Langmuir monolayers.

In therapies, curcumin is now commonly formulated in liposomal form, administered through injections or creams. This enhances its concentration at the cellular level compared to its natural form ingestion. Due to its hydrophobic nature, curcumin is situated in the lipid part of the membrane, thereby modifying its properties and influencing processes The aim of the research was to investigate whether the toxicity of specific concentrations of curcumin, assessed through biochemical tests for the SK-N-SH and H-60 cell lines, is related to structural changes in the membranes of these cells, caused by the localization of curcumin in their hydrophobic regions. Biochemical tests were performed using spectrophotometric methods. Langmuir technique were used to evaluate the interaction of the curcumin with the studied lipids. Direct introduction of curcumin into the membranes alters their physicochemical parameters. The extent of these changes depends on the initial properties of the membrane. In the conducted research, it has been demonstrated that curcumin may exhibit toxicity to human cells. The mechanism of this toxicity is related to its localization in cell membranes, leading to their dysfunction. The sensitivity of cells to curcumin presence depends on the saturation level of their membranes; the more rigid the membrane, the lower the concentration of curcumin causes its disruption.

Development and Characterization of Curcumin-Loaded TPGS/F127/P123 Polymeric Micelles as a Potential Therapy for Colorectal Cancer.

Colorectal cancer (CRC) is the third most prominent cancer worldwide, and the second leading cause of cancer death. Poor outcomes and limitations of current treatments fuel the search for new therapeutic options. Curcumin (CUR) is often presented as a safer alternative for cancer treatment with a staggering number of molecular targets involved in tumor initiation, promotion, and progression. Despite being promising, its therapeutic potential is hindered due to its hydrophobic nature. Hence, the ongoing development of optimal delivery strategies based on nanotechnology, such as polymeric micelles (PMs), to overcome issues in CUR solubilization and delivery to tumor cells. In this sense, this study aimed to optimize the development and stability of CUR-loaded P123:F127:TPGS PMs (PFT:CUR) based on the thin-film approach and evaluate their therapeutic potential in CRC. Overall, the results revealed that the solubility of CUR was improved when room temperature was used to hydrate the film. The PFT-CUR hydrated at room temperature presents an average hydrodynamic diameter of 15.9 ± 0.3 nm with a polydispersity index (PDI) of 0.251 ± 0.103 and a zeta potential of -1.5 ± 1.9 mV, and a 35.083 ± 1.144 encapsulation efficiency (EE%) and 3.217 ± 0.091 drug loading (DL%) were observed. To ensure the stability of the optimized PFT-CUR nanosystems, different lyophilization protocols were tested, the use of 1% of glycine (GLY) being the most promising protocol. Regarding the critical micellar concentration (CMC), it was shown that the cryoprotectant and the lyophilization process could impact it, with an increase from 0.064 mg/mL to 0.119 mg/mL. In vitro results showed greater cytotoxic effects when CUR was encapsulated compared to its free form, yet further analysis revealed the heightened cytotoxicity could be attributed to the system itself. Despite challenges, the developed CUR-loaded PM shows potential as an effective therapeutic agent for CRC. Nonetheless, the system must undergo refinements to enhance drug entrapment as well as improve overall stability.

Multifunctional curcumin-based polymer coating: A promising platform against bacteria, inflammation and coagulation.

The extensive use of polymers in the medical field has facilitated the development of various devices and implants, contributing to the restoration of organ function. However, despite their advantages such as biocompatibility and robustness, these materials often face challenges like bacterial contamination and subsequent inflammation, leading to implant-associated infections (IAI). Integrating implants effectively is crucial to prevent bacterial colonization and reduce inflammatory responses. To overcome these major issues, surface chemical modifications have been extensively explored. Indeed, click chemistry, and particularly, copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has emerged as a promising approach for surface functionalization without affecting material bulk properties. Curcumin, known for its diverse biological activities, suffers from low solubility and stability. To enhance its bioavailability, bioconjugation strategy has garnered attention in recent years. This study represents pioneering work in immobilizing curcumin derivative onto polyethylene terephthalate (PET) surfaces, aiming to combat bacterial adhesion, inflammation and coagulation. Before curcumin derivative bioconjugation, a fluorophore, dansyl derivative, was employed in order to monitor and determine the efficiency of the proposed methodology. Previous surface chemical modifications were required for the immobilization of both dansyl and curcumin derivatives. Ultraviolet-Visible (UV-Vis) demonstrated the amidation functionalization of PET surface. Other surface characterization techniques including X-ray Photoelectron Spectroscopy (XPS), Attenuated Total Reflectance Fourier Transformed Infrared (ATR-FTIR), Scanning Electron Microscopy (SEM) and contact angle, among others, confirmed also the conjugation of both dansyl and curcumin derivatives. On the other hand, different biological assays corroborated that curcumin derivative immobilized PET surfaces do not exhibit cytotoxicity effect. Additionally, corresponding inflammation test were performed, indicating that these polymeric surfaces do not produce inflammation and, when curcumin derivative is immobilized, they decrease the inflammation marker level (IL-6). Moreover, the bacterial growth of both Gram positive and Gram negative bacteria were measured, demonstrating that the immobilization of curcumin derivative on PET provided antibacterial properties to the material. Finally, hemolysis rate analysis and whole blood clotting assay demonstrated the antithrombogenic effect of PET-Cur surfaces as well as no hemolysis concern in the fabricated functional surfaces.

Development and characterization of curcumin nanosuspension-embedded genipin-crosslinked chitosan/polyvinylpyrrolidone hydrogel patch for effective wound healing.

This study investigated the development of a genipin-crosslinked chitosan (CS)-based polyvinylpyrrolidone (PVP) hydrogel containing curcumin nanosuspensions (Cur-NSs) to promote wound healing in an excisional wound model. Cur-NSs were prepared, and a simplex centroid mixture design was employed to optimize hydrogel properties for high water absorption, degree of crosslinking, and sufficient toughness. The in vivo wound healing effect was tested in Wistar rats. The optimized hydrogel consisted of a 70:30 ratio of CS:PVP, crosslinked with a 2 % w/w genipin solution. It exhibited high swelling capability (486 %) while maintaining solidity, robustness, and durability. Incorporating 5 % w/w Cur-NSs resulted in a more compact structure, although with a reduction in swelling properties. The release kinetics of Cur from the hydrogel followed the Korsmeyer-Peppas Fickian diffusion model. In vitro biocompatibility studies demonstrated that the hydrogel was non-toxic to skin fibroblast cells. The in vivo experiment revealed a desirable wound healing rate with over 80 % recovery by day 7. Cur-NSs likely aided wound healing by reducing the inflammatory response and stimulating fibroblast proliferation. Additionally, the CS-based hydrogel provided a moist wound environment with hydration and gas transfer, further accelerating wound closure. These findings suggest that the Cur-NS-embedded hydrogel shows promise as a wound dressing material.