Release Of Curcumin Research Articles

Reactive Oxygen Species-Triggered Curcumin Release from Hollow Mesoporous Silica Nanoparticles for PM2.5-Induced Acute Lung Injury Treatment.

Exposure to fine particulate matter with a diameter ≤2.5 μm (PM2.5) can result in serious inflammation and oxidative stress in lung tissue. However, there is presently very few effective treatments for PM2.5-induced many pulmonary diseases, such as acute lung injury (ALI). Herein, curcumin-loaded reactive oxygen species (ROS)-responsive hollow mesoporous silica nanoparticles (Cur@HMSN-BSA) are proposed for scavenging the intracellular ROS and suppressing inflammatory responses against PM2.5-induced ALI. The prepared nanoparticles were coated with bovine serum albumin (BSA) via an ROS-sensitive thioketal (TK)-containing linker, in which the TK-containing linker would be cleaved by the excessive amounts of ROS in inflammatory sites to induce the detachment of BSA from the nanoparticles surface and thus triggering release of loaded curcumin. The Cur@HMSN-BSA nanoparticles could be used as ROS scavengers because of their excellent ROS-responsiveness, which were able to efficiently consume high concentrations of intracellular ROS. Furthermore, it was also found that Cur@HMSN-BSA downregulated the secretion of several important pro-inflammatory cytokines and promoted the polarization from M1 phenotypic macrophages to M2 phenotypic macrophages for eliminating PM2.5-induced inflammatory activation. Therefore, this work provided a promising strategy to synergistically scavenge intracellular ROS and suppress the inflammation responses, which may serve as an ideal therapeutic platform for pneumonia treatment.

Study of thermal transitions of copolymers based on N‐isopropylacrylamide and acrylic acid with potential for curcumin controlled release

AbstractThermosensitive polymers based on poly(N‐isopropylacrylamide) (pNIPAM) have been widely evaluated in a variety of biomedical applications due to their particular thermal behavior in aqueous solutions. Despite this, few works have focused on the complementary analysis of the thermal transitions of pNIPAM polymers in linear and crosslinked form. In this work, linear and crosslinked poly(N‐isopropylacrylamide‐co‐acrylic acid) p(NIPAM‐co‐AA) copolymers were synthesized at similar NIPAM/AA feed composition and their thermosensitive behavior was studied by turbidimetric methods, FTIR spectroscopy analysis, and temperature‐dependent swelling measurements. The intermolecular crosslinking hindered the hydrophobic aggregation of chain segments, leading to higher transition temperatures of synthesized polymers. AA units promoted the intersegment hydrogen bonds during heating and strengthened the hydrogen bond interactions water‐network. The effect of the thermosensitive behavior of p(NIPAM‐co‐AA) copolymer on curcumin (CUR) release kinetic was also studied. The low uptake level of p(NIPAM‐co‐AA) hydrogel, partially shrunken at 37°C, produced a CUR sustained delivery, reaching the release equilibrium state up to 18 h. Hydrogels of p(NIPAM‐co‐AA) with a suitable composition exhibited a promising performance for the CUR controlled delivery at physiological conditions.

Chitosan-Collagen Electrospun Nanofibers Loaded with Curcumin as Wound-Healing Patches.

Composite chitosan-collagen nanofibrous mats embedded with curcumin were prepared via a single-step electrospinning procedure and explored as wound-healing patches with superior biological activity. A mild crosslinking protocol consisting of a short exposure to ammonia vapor and UV radiation was developed to ensure proper stability in physiological-like conditions without affecting the intrinsic biocompatibility of chitosan and collagen. The fabricated composite patches displayed a highly porous, homogeneous nanostructure consisting of fibers with an average diameter of 200 nm, thermal stability up to 200 °C, mechanical features able to ensure protection and support to the new tissues, and water-related properties in the ideal range to allow exudate removal and gas exchange. The release kinetic studies carried out in a simulated physiological environment demonstrated that curcumin release was sustained for 72 h when the mats are crosslinked hence providing prolonged bioactivity reflected by the displayed antioxidant properties. Remarkably, combining chitosan and collagen not only ensures prolonged stability and optimal physical-chemical properties but also allows for better-promoting cell adhesion and proliferation and enhanced anti-bacteriostatic capabilities with the addition of curcumin, owing to its beneficial anti-inflammatory effect, ameliorating the attachment and survival/proliferation rates of keratinocytes and fibroblasts to the fabricated patches.

Curcumin or quercetin loaded nutriosomes as oral adjuvants for malaria infections

Artemisinin, curcumin or quercetin, alone or in combination, were loaded in nutriosomes, special phospholipid vesicles enriched with Nutriose FM06®, a soluble dextrin with prebiotic activity, that makes these vesicles suitable for oral delivery. The resulting nutriosomes were sized between 93 and 146 nm, homogeneously dispersed, and had slightly negative zeta potential (around −8 mV). To improve their shelf life and storability over time, vesicle dispersions were freeze-dried and stored at 25 °C. Results confirmed that their main physico-chemical characteristics remained unchanged over a period of 12 months. Additionally, their size and polydispersity index did not undergo any significant variation after dilution with solutions at different pHs (1.2 and 7.0) and high ionic strength, mimicking the harsh conditions of the stomach and intestine. An in vitro study disclosed the delayed release of curcumin and quercetin from nutriosomes (∼53% at 48 h) while artemisinin was quickly released (∼100% at 48 h). Cytotoxicity assays using human colon adenocarcinoma cells (Caco-2) and human umbilical vein endothelial cells (HUVECs) proved the high biocompatibility of the prepared formulations. Finally, in vitro antimalarial activity tests, assessed against the 3D7 strain of Plasmodium falciparum, confirmed the effectiveness of nutriosomes in the delivery of curcumin and quercetin, which can be used as adjuvants in the antimalaria treatment. The efficacy of artemisinin was also confirmed but not improved. Overall results proved the possible use of these formulations as an accompanying treatment of malaria infections.

Nanocurcumin and viable Lactobacillus plantarum based sponge dressing for skin wound healing

Curcumin loaded solid lipid nanoparticles (CSLNs) and probiotic (Lactobacillus plantarum UBLP-40; L. plantarum) were currently co-incorporated into a wound dressing. The combination with manifold anti-inflammatory, anti-infective, analgesic, and antioxidant properties of both curcumin and L. plantarum will better manage complex healing process. Recent reports indicate that polyphenolics like curcumin improve probiotic effects. Curcumin was nanoencapsulated (CSLNs) to improve its bioprofile and achieve controlled release on the wound bed. Bacteriotherapy (probiotic) is established to promote wound healing via antimicrobial activity, inhibition of pathogenic toxins, immunomodulation, and anti-inflammatory actions. Combination of CSLNs with probiotic enhanced (560%) its antimicrobial effects against planktonic cells and biofilms of skin pathogen, Staphylococcus aureus 9144. The sterile dressing was devised with selected polymers, and optimized for polymer concentration, and dressing characteristics using a central composite design. It exhibited a swelling ratio of 412 ± 36%, in vitro degradation time of 3 h, optimal water vapor transmission rate of 1516.81 ± 155.25 g/m2/day, high tensile strength, low-blood clotting index, case II transport, and controlled release of curcumin. XRD indicated strong interaction between employed polymers. FESEM revealed a porous sponge like meshwork embedded with L. plantarum and CSLNs. It degraded and released L. plantarum, which germinated in the wound bed. The sponge was stable under refrigerated conditions for up to six months. No translocation of probiotic from wound to the internal organs confirmed safety. The dressing exhibited faster wound closure and lowered bioburden in the wound area in mice. This was coupled with a decrease in TNF-α, MMP-9, and LPO levels; and an increase in VEGF, TGF-β, and antioxidant enzymes such as catalase and GSH, establishing multiple healing pathways. Results were compared with CSLNs and probiotic-alone dressings. The dressing was as effective as the silver nanoparticle-based marketed hydrogel dressing; however, the cost and risk of developing resistance would be much lower currently.

Reprogramming M1-to-M2 Phenotype to Alleviate Inflammation: Using Liposomal Curcumin as a Tool to Redefine Macrophage Functionality.

The versatile nature of macrophages and their ability to switch between various activation states plays a pivotal role in both promoting and inhibiting inflammatory processes. In pathological inflammatory conditions, classically activated M1 macrophages are often associated with initiating and maintaining inflammation, while alternatively activated M2 macrophages are linked to the resolution of chronic inflammation. Achieving a favorable equilibrium between M1 and M2 macrophages is crucial for mitigating inflammatory environments in pathological conditions. Polyphenols are known to have strong inherent antioxidative capabilities, and curcumin has been found to reduce macrophage inflammatory reactions. However, its therapeutic efficacy is compromised due to its poor bioavailability. The present study aims to harness the properties of curcumin by loading it in nanoliposomes and enhancing the M1-to-M2 macrophage polarization. A stable liposome formulation was achieved at 122.1 ± 0.08 nm, and a sustained kinetic release of curcumin was observed within 24 h. The nanoliposomes were further characterized using TEM, FTIR, and XRD, and the morphological changes in macrophage cells, RAW264.7, were observed in SEM, indicating a distinct M2-type phenotype after the treatment with liposomal curcumin. ROS may partially control macrophage polarization and be observed to decrease after treatment with liposomal curcumin. The nanoliposomes were able to successfully internalize in the macrophage cells, and an enhanced expression of ARG-1 and CD206 with a decrease in iNOS, CD80, and CD86 levels suggested the polarization of LPS-activated macrophages toward the M2 phenotype. Also, liposomal curcumin treatment dose-dependently inhibited TNF-α, IL-2, IFN-γ, and IL-17A at secretory levels and simultaneously increased the levels of cytokines like IL-4, IL-6, and IL-10.

ZIF‐8 Based Active Wound Dressing for pH Modulation and pH‐Responsive Delivery of Curcumin and Zn2+: Effect of Acidity on the Drug Release for Antibacterial and Antioxidant Efficacy

AbstractA wound evolves with variable pHs depending on the healing stage, and the maintenance of mild acidic condition can help healing by deterring the formation of a biofilm. Herein, a dual‐layer wound dressing with an acid‐responsive zeolitic imidazolate framework–8 (ZIF‐8) layer and an acid‐modulating layer is designed to control the acid‐dependent release of therapeutic agents for the improved healing process. The outer dressing layer is coated with curcumin‐incorporated ZIF‐8, where curcumin and zinc ions are released upon dissociation of ZIF‐8 in an acidic condition. The inner layer, a pH modulator, is fabricated by electrospinning polyvinylpyrrolidone with addition of acetic acid. In vitro release test shows that the outer layer dressing attains a considerably higher release of curcumin and Zn2+ under an acidic condition. Combined with the inner acidic layer, the dual layer dressing exhibits facilitated release of effective agents regardless of environmental pHs, attributed to the proper pH modulation to about 6.5. The anti‐oxidant activity of curcumin and antibacterial activity of Zn2+ are confirmed. The study highlights the novel proof‐of‐concept design of active wound dressing demonstrating the dual functions of pH regulation and the stimulus‐responsive drug delivery.

Microfluidic-Assisted ZIF-Silk-Polydopamine Nanoparticles as Promising Drug Carriers for Breast Cancer Therapy.

Metal-organic frameworks (MOFs) are heralded as potential nanoplatforms for biomedical applications. Zeolitic imidazolate framework-8 (ZIF-8), as one of the most well known MOFs, has been widely applied as a drug delivery carrier for cancer therapy. However, the application of ZIF-8 nanoparticles as a therapeutic agent has been hindered by the challenge of how to control the release behaviour of anti-cancer zinc ions to cancer cells. In this paper, we designed microfluidic-assisted core-shell ZIF-8 nanoparticles modified with silk fibroin (SF) and polydopamine (PDA) for sustained release of zinc ions and curcumin (CUR) and tested these in vitro in various human breast cancer cells. We report that microfluidic rapid mixing is an efficient method to precisely control the proportion of ZIF-8, SF, PDA, and CUR in the nanoparticles by simply adjusting total flow rates (from 1 to 50 mL/min) and flow rate ratios. Owing to sufficient and rapid mixing during microfluidic-assisted nanoprecipitation, our designer CUR@ZIF-SF-PDA nanoparticles had a desired particle size of 170 nm with a narrow size distribution (PDI: 0.08), which is much smaller than nanoparticles produced using traditional magnetic stirrer mixing method (over 1000 nm). Moreover, a properly coated SF layer successfully enhanced the capability of ZIF-8 as a reservoir of zinc ions. Meanwhile, the self-etching reaction between ZIF-8 and PDA naturally induced a pH-responsive release of zinc ions and CUR to a therapeutic level in the MDA-MB-231, SK-BR-3, and MCF-7 breast cancer cell lines, resulting in a high cellular uptake efficiency, cytotoxicity, and cell cycle arrest. More importantly, the high biocompatibility of designed CUR@ZIF-SF-PDA nanoparticles remained low in cytotoxicity on AD-293 non-cancer cells. We demonstrate the potential of prepared CUR@ZIF-SF-PDA nanoparticles as promising carriers for the controlled release of CUR and zinc ions in breast cancer therapy.

Color Stability Enhancement of Curcumin Bioplastic Films Using Natural Hybrid Fillers of Montmorillonite and Revalorized Cellulose

Naturally colored packaging systems with improved color stability are essential as alternatives to mainstay synthetic colored conventional plastics, which typically present high toxicity and environmental pollution challenges. Herein, we report a versatile all green fabrication process for colored bioplastic films. Curcumin (CUR), a model plant-based colorant, was incorporated with newly developed natural hybrid fillers of montmorillonite (MMT) and biomass waste-recovered cellulose (CEL) for improved color stability performance. The CUR-based hybrid fillers were compounded with polylactic acid (PLA) to fabricate sustainable, colored composite films via hot-melt extrusion. Fourier transform infrared (FTIR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA) results indicated good compatibility between the filler counterparts. Macro- and microstructure analysis of the colored films confirmed the good dispersion of the natural hybrid fillers within the PLA matrix. No change was observed in the thermal properties of the colored films, while dynamic mechanical analysis (DMA) results demonstrated a moderate increase in the films’ elastic modulus, from 870 to 970 MPa. The color entrapment efficiency of the hybrid filler-based films was evaluated through a study of CUR release in ethanol. A sustained CUR release profile reaching around 50% after 48 h was observed in the hybrid filler-based films in contrast to 80% in the PLA–CUR film. This was correlated with the significantly improved color stability of the PLA films containing the hybrid fillers under weathering conditions of UV irradiation, high temperature, and humidity. Over a period of 10 days, the CUR-CEL-MMT-based films had relatively consistent color stability, showing a color shift value (ΔE*) of only 1.1 in comparison to 5.1 for the PLA film containing only CUR.

Curcumin nanocrystals self-stabilized Pickering emulsion freeze-dried powder: Development, characterization, and suppression of airway inflammation

Curcumin, a diketone compound extracted from turmeric's rhizome, is an effective anti-inflammatory drug with multiple pharmacological activities. However, its low oral bioavailability due to its low water solubility and permeability severely limits its clinical applications. Therefore, to enhance the oral bioavailability of curcumin, further enhance its anti-inflammatory effects, and improve its potential in the treatment of airway inflammation, a curcumin nanocrystalline self-stabilizing Pickering emulsion (Cur-NSSPE) was prepared through high-pressure homogenization. Next, Cur-NSSPE was dried using a freeze-drying method to produce Cur-NSSPE-FDP. The prepared Cur-NSSPE and Cur-NSSPE-FDP were physically characterized. The release behavior and transmembrane transport capability of Cur-NSSPE-FDP in vitro were evaluated. Pharmacokinetic study was performed to evaluate its oral bioavailability. The anti-inflammatory effects of Cur-NSSPE-FDP in vivo and in vitro were investigated using RAW 264.7 macrophage inflammation model induced by LPS and IFN-γ and asthma model in BALB/c mice induced by OVA. The average particle size of Cur-NSSPE was (163.66 ± 6.78) nm, and the average drug content was (2.78 ± 0.01) mg/mL. The transmission electron microscopy results showed that the droplets were spherical in shape with a relatively uniform size, and the curcumin nanocrystals formed a spherical core-shell structure wrapped at the interface of the droplets. The scanning electron microscopy showed that Cur-NSSPE-FDP was a neatly arranged, having loose and porous network structure. Furthermore, it can significantly improve the cumulative release of curcumin in vitro and improve oral bioavailability in rats, increase the uptake of RAW264.7 and Caco-2 cells, promote the transport of curcumin across Caco-2 cells, significantly inhibit the expression of inflammatory factors NO, IL-6, TNF-a, MDA, IgE and ICAM-1, and improve the expression of IL-10 and SOD. These results indicated that the curcumin nanocrystalline self-stabilizing Pickering emulsion-freeze dried powder improved the oral bioavailability of curcumin and enhanced its therapeutic effect in airway inflammation.

Fabrication of curcumin−loaded foxtail millet prolamin−based nanoparticle: Impact of curdlan sulfate on the particle properties

The sulfation of curdlan was achieved by modification of curdlan with sulfur trioxide–pyridine complex. Curcumin−loaded curdlan sulfate−sodium caseinate stabilized foxtail millet prolamin nanoparticles were fabricated using pH-driven method. Under the optimal conditions, two kinds of foxtail millet prolamin−based nanoparticles were fabricated using different preparation processes for the first time. The mean diameters and zeta-potentials of co−assembled foxtail millet prolamin−sodium caseinate−curdlan sulfate nanoparticles and curdlan sulfate coated co−assembled foxtail millet prolamin−sodium caseinate nanoparticles were 84.7 nm, 136.4 nm and − 45.7 mV, − 41.5, respectively. Molecular docking and infrared spectroscopy indicated that the curcumin was retained in the hydrophobic region of foxtail millet prolamin though four hydrogen bonds and ten hydrophobic interactions, and amino residues of proline, arginase, cysteine, glycine, and alanine served as the main binding sites for curcumin. The deposition and co−assembly of curdlan sulfate enhanced the curcumin encapsulation efficiency from 78.3% to 81.8% and 85.9%, respectively, and slightly reduced the release of curcumin under physiological and endosomal pH conditions. Consequently, the intake of curdlan sulfate−sodium caseinate stabilized composite nanoparticles encapsulated−curcumin by MCF-7 cells was lower than that of sodium caseinate stabilized nanoparticles entrapped−curcumin, and increased the IC50 value from 5.3 μg/mL to 10.5 and 9.0 μg/mL, respectively. This study showed that the biopolymeric nanoparticles have the potential to encapsulate hydrophobic bioactives, and the incorporation of curdlan sulfate exhibited a significant effect on the physicochemical properties, encapsulation, and release profile of foxtail millet prolamin particles.

Mechanism underlying joint loading and controlled release of β-carotene and curcumin by octenylsuccinated Gastrodia elata starch aggregates

This study aimed to fabricate a novel codelivery system to simultaneously load β-carotene and curcumin in a controlled and synergistic manner. We hypothesized that the aggregates of octenylsuccinated Gastrodia elata starch (OSGES) could efficiently load and control the release of β-carotene and curcumin in combination. Mechanisms underlying the self-assembly of OSGES, coloading, and corelease of β-carotene and curcumin by relevant aggregates were studied. The OSGES could form aggregates with a size of 120.2 nm containing hydrophobic domains surrounded by hydrophilic domains. For coloading, the increased solubilities were attributed to favorable interactions between β-carotene and curcumin as well as interactions with octenyl and starch moieties via hydrophobic and hydrogen-bond interactions, respectively. The β-carotene and curcumin molecules occupied the interior and periphery of hydrophobic domains of OSGES aggregates, respectively, and they did not exist in isolation but interacted with each other. The β-carotene and curcumin combination-loaded OSGES aggregates with a size of 310.5 nm presented a more compact structure than β-carotene-only and curcumin-only loaded OSGES aggregates with sizes of 463.5 and 202.9 nm respectively, suggesting that a transition from a loose cluster to a compact cluster was accompanied by coloading. During in vitro digestion, the joint effect of β-carotene and curcumin prolonged their release and increased their bioaccessibility due to competition between favorable hydrophobic and hydrogen-bond interactions and the unfavorable structure erosion and relaxation of the loaded aggregates. Therefore, OSGES aggregates were designed for the codelivery of β-carotene and curcumin, indicating their potential to be applied in functional foods and dietary supplements.

Targeting Spike Glycoprotein S1 Mediated by NLRP3 Inflammasome Machinery and the Cytokine Releases in A549 Lung Epithelial Cells by Nanocurcumin.

Chronic inflammation and tissue damage can result from uncontrolled inflammation during SARS-CoV-2 or COVID-19 infections, leading to post-acute COVID conditions or long COVID. Curcumin, found in turmeric, has potent anti-inflammatory properties but limited effectiveness. This study developed nanocurcumin, a curcumin nanoparticle, to enhance its physical and chemical stability and investigate its in vitro anti-inflammatory properties upon CoV2-SP induction in lung epithelial cells. Nanocurcumin was prepared by encapsulating curcumin extract in phospholipids. The particle size, polydispersity index, and zeta potential of nanocurcumin were measured using dynamic light scattering. The encapsulated curcumin content was determined using HPLC analysis. The encapsulation efficiency of curcumin was 90.74 ± 5.35% as determined by HPLC. Regarding the in vitro release of curcumin, nanocurcumin displayed a higher release content than non-nanoparticle curcumin. Nanocurcumin was further investigated for its anti-inflammatory properties using A549 lung epithelial cell line. As determined by ELISA, nanocurcumin showed inhibitory effects on inflammatory cytokine releases in CoV2-SP-stimulated conditions, as evidenced by a significant decrease in IL-6, IL-1β and IL-18 cytokine secretions compared with the spike-stimulated control group (p < 0.05). Additionally, as determined by RT-PCR, nanocurcumin significantly inhibited the CoV2-SP-stimulated expression of inflammatory genes (IL-6, IL-1β, IL-18, and NLRP3) compared with the spike-stimulated control group (p < 0.05). Regarding the inhibition of NLRP3 inflammasome machinery proteins by Western blot, nanocurcumin decreased the expressions of inflammasome machinery proteins including NLRP3, ASC, pro-caspase-1, and the active form of caspase-1 in CoV2-SP-stimulated A549 cells compared with the spike-stimulated control group (p < 0.05). Overall, the nanoparticle formulation of curcumin improved its solubility and bioavailability, demonstrating anti-inflammatory effects in a CoV2-SP-induced scenario by inhibiting inflammatory mediators and the NLRP3 inflammasome machinery. Nanocurcumin shows promise as an anti-inflammatory product for preventing COVID-19-related airway inflammation.

Efficient synergistic combination effect of curcumin with piperine by polymeric magnetic nanoparticles for breast cancer treatment

Although it has been reported that the co-delivery of drugs can be beneficial to patients to kill breast cancer cells, the delivery methods could only be employed to effectively encapsulate individual curcumin (CUR) or piperine (PIP) molecules due to their different molecular polarities. Therefore, in the current research, an attempt was made to overcome the limitation of the co-delivery of CUR and PIP nanoparticles for breast cancer therapy. To manage locoregional breast cancer recurrence, a magnetic co-delivery system of CUR and PIP against MCF-7 breast cancer cells was examined. CUR and PIP demonstrated synergistic effects for breast cancer therapy when utilized together. However, due to the different polarities of CUR and PIP, it was difficult to co-encapsulate them in conventional delivery systems. Moreover, their low bioavailability, hydrophobic nature, and low cellular uptake limit its usage for cancer therapy. In the current study, to overcome the issues and improves its therapeutic efficacy, CUR and PIP-loaded zein/chitosan-coated iron oxide (Chit-PIP/CUR-zein@Fe3O4) were prepared via a combination of anti-solvent precipitation and layer-by-layer deposition. X-ray diffraction (XRD) analysis revealed magnetite cores and also showed that the binding process did not change the Fe3O4 phase. A vibrational sample magnetometer confirmed that the saturation of sample magnetization was 60 and 40 emu/g for pure Fe3O4 and nanocomposite, respectively. Nanoparticles with an average size of 20 nm were prepared. The drug-loading content of CUR and PIP was approximately 18% and 16%, respectively. CUR and PIP release from Chit-PIP/CUR-zein@Fe3O4 was faster at the extracellular pH of around tumors (6.5) than in normal tissues (7.4), an interesting degree of pH sensitivity. The MTT assay exhibited that PIP/CUR-loaded polymeric magnetic nanoparticles had significant synergistic cytotoxicity against MCF-7 cells compared with other groups. These results demonstrate that the combination of dual-drug loaded polymeric magnetic nanoparticles holds promise for the targeted treatment of cancer cells.

Multifunctional polydopamine – Zn2+-curcumin coated additively manufactured ceramic bone grafts with enhanced biological properties

The lack of site-specific chemotherapeutic agents after osteosarcoma surgeries often induces severe side effects. We propose the utilization of curcumin as an alternative natural chemo-preventive drug for tumor-specific delivery systems with 3D printed tricalcium phosphate (TCP) based artificial bone grafts. The poor bioavailability and hydrophobic nature of curcumin restrict its clinical use. We have used polydopamine (PDA) coating with Zn2+ functionalization to enhance the curcumin release in the biological medium. The obtained PDA–Zn2+ complex is characterized by X-ray photoelectron spectroscopy (XPS). The presence of PDA–Zn2+ coating leads to ~2 times enhancement in curcumin release. We have computationally predicted and validated the optimized surface composition by a novel multi-objective optimization method. The experimental validation of the predicted compositions indicates that the PDA–Zn2+ coated curcumin immobilized delivery system leads to a ~12 folds decrease in osteosarcoma viability on day 11 as compared to only TCP. The osteoblast viability shows ~1.4 folds enhancement. The designed surface shows the highest ~90 % antibacterial efficacy against gram-positive and gram-negative bacteria. This unique strategy of curcumin delivery with PDA–Zn2+ coating is expected to find application in low-load bearing critical-sized tumor-resection sites.

Dual stimuli-responsive gelatin-based hydrogel for pH and temperature-sensitive delivery of curcumin anticancer drug

Stimuli-sensitive drug delivery enables transporting therapeutic agents to diseased areas and then releasing their cargo in response to external or internal stimuli. Here, we report on the synthesis and characterization of dual stimuli-responsive hydrogel for pH and temperature-sensitive delivery of curcumin (CUR) anticancer drug. CUR-loaded chitosan nanocapsules (CURNCs) were embedded in glucose-crosslinked gelatin hydrogel containing polydopamine nanoparticles (PDA NPs) (denoted as GGPDNCs). The result showed that CUR release from CURNCs was higher at acidic pH values. Glucose-crosslinked gelatin hydrogel was stable at 37 °C. To enable thermal responsivity under NIR laser irradiation, PDA NPs were embedded in the glucose-crosslinked gelatin hydrogel. The GGPDNCs hydrogel is, thus, engineered to respond to both pH and temperature stimuli. Under the optimum conditions, the release of CUR from the GGPDNCs-hydrogel under NIR irradiation (940 nm, 1.5 W/cm2) at pH = 5.0 was 1.43-fold higher than pH = 7.4 which is a promising progress in smart drug delivery systems for cancer therapy.

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

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

Ultrasound‒treated soy protein fibrils: A potential vehicle for curcumin with improved water solubility, antioxidant activity and sustained‒release property

Plant protein fibrils have recently attracted considerable attention as delivery vehicles for hydrophobic bioactive compounds. In this work, ultrasound treatment was applied to improve the structure of protein fibrils. The aim of this work was to investigate the impacts of ultrasound treatment on the structure of soy protein fibrils (SPF), and further explore the interaction between ultrasound‒treated SPF (USPF) and curcumin (Cur) to clarify the impacts of ultrasound on SPF as delivery vehicles. Thioflavin T fluorescence, SDS‒PAGE, Fourier transform infrared (FTIR) spectroscopy, and far‒UV circular dichroism spectroscopy revealed no significant changes in the primary and secondary structure of SPF after ultrasound treatment. Compared with SPF, USPF presented a more uniform particle size and higher surface hydrophobicity. Fluorescence quenching, ultraviolet–visible spectroscopy, isothermal titration calorimetry, and FTIR spectroscopy indicated USPF10 (ultrasonication for 10 min) possessed a high affinity toward curcumin via hydrophobic interactions and hydrogen bonds. The curcumin solubility in USPF10-Cur (133.19 μg/mL) complex was much higher than SPI-Cur (78.26 μg/mL) and SPF-Cur (116.22 μg/mL) complexes. The USPF10‒Cur complex exhibited good colloidal stability and thermal stability. The DPPH and ABTS scavenging capacities of the USPF10‒Cur complex were approximately 1.4 and 2.7 folds higher than those of free curcumin, respectively. An In vitro digestion assay suggested that the USPF10‒Cur complex showed a much more stable and sustainable release of curcumin and provided chances for curcumin release in the intestine. This study indicated that USPF might be promising delivery vehicles for hydrophobic bioactives as stable and functional ingredients in acidic food systems.

Exploring the effect of different linkers on self-assembly, ROS-sensitivity and anticancer efficacy of hydroxyethyl starch-curcumin prodrug

Curcumin is a BCPR inhibitor, antiproliferative agent and apoptotic inducer to cancer cells, which is poorly soluble in water. In order to broaden the application of curcumin, conjugations of quaternary ammonium substituted hydroxyethyl starch (QHES) with curcumin by thioether bond (QHES-2S-CUR), disulfide bond (QHES-SS-CUR), and carbon-carbon bond (QHES-CC-CUR) were implemented, respectively. The effect of above three linkers on the self-assembly behavior of QHES-curcumin prodrugs was evaluated. QHES-2S-CUR and QHES-SS-CUR could facilely self-assemble into spherical micelles in water, while QHES-CC-CUR was lack of conformational stability. In vitro drug release profiles of prodrug micelles were further investigated. Concretely, QHES-2S-CUR presented ROS-sensitive drug release, with 73.57 ± 4.22% of curcumin released under the addition of H2O2 over 24 h. The release of curcumin from QHES-SS-CUR lasted for 54 h due to the slower oxidization of disulfide bonds, and QHES-CC-CUR was insensitive to ROS. In addition, QHES-2S-CUR prodrug micelles demonstrated superior cytotoxicity to murine colonic adenocarcinoma (CT-26) cells compared to QHES-SS-CUR and QHES-CC-CUR, which were internalized by CT-26 cells with high efficiency. These results reveal the potential of QHES-2S-CUR prodrug micelles as tumor microenvironment-responsive anticarcinogen.

Characterization, Formation Mechanism, and Curcumin Delivery of Buckwheat Peptide-Based Emulsion Gels.

This study aimed to construct a natural peptide-based emulsion gel (PG) using small peptides (∼2.2 kDa) by mild enzymatic hydrolysis of buckwheat proteins. The obtained PG presented a porous and tight texture and solid-gel viscoelasticity compared with its parent protein-based emulsion gel. Meanwhile, it exhibited good resistance against heating and freeze-thawing. Furthermore, peptide-oil interaction analysis revealed that the gel matrix was enhanced by the hydrophobic aggregation between peptides and oil molecules, H-bonding interaction of peptide molecules, and peptide-oil aggregate repulsion force. Finally, in vitro intestinal digestion experiments demonstrated that PG could embed and pH-responsively release curcumin in the gastrointestinal tract at a release rate of 53.9%. The findings unfold promising opportunities for using natural PG in a range of applications relying on large proteins or other synthesized molecules.