Curcumin Loading Research Articles

Curcumin-loaded proniosomal gel as a biofreindly alternative for treatment of ocular inflammation: In-vitro and in-vivo assessment.

Ocular inflammation is a natural defensive phenomenon, but, it results in discomfort in the eye; as well as makes the eye vulnerable to other diseases. The aim of this work is to investigate that Curcumin (CUR) could be an effective safer biofreindly alternative for treatment of ocular inflammation. Complete in-vitro characterization of proniosomal gel loading-CUR using different surfactants was studied. A comparative in-vivo evaluation of selected formulation to a marketed corticosteroid drops in induced-eye inflammation model in rabbits was assessed. The selected formulation (FCr 300) composed of Cremophore RH surfactant, lecithin and cholesterol (9:9:1) loading CUR (1.2% w/w). The formulation showed mean PS(212.0±0.1)nm, PDI (0.3±0.1) , ZP(-5.1±0.2)mV and % EE (96.0±0.1). TEM showed multilamellar circular shaped niosomes with smooth surface. SEM showed ruptured vesicles for the lyophilized formula. Selected proniosomal gel showed enhanced permeability 3.22-fold and 1.76-fold higher than CUR dispersion and its lyophilized form respectively. Both proniosomal gel (FCr300) and corticosteroid drops reduced the induced inflammatory signs effectively by 40% on day-one and complete recovery on day-four. This anti-inflammatory result was confirmed by histopathological analysis after treatment. Assessment of cumulative IOP as a predicted side effect verified the goal of this work. In conclusion, the use of CUR as a natural biofreindly alternative to the current chemical conventional ocular anti-inflammatory treatment protocols is comparable as an anti-inflammatory drug with much less side effects.

The Effect of Calcination Temperature on the Anticancer Activity of CaFe2O4@PVA Nanocarriers: Photodynamic Therapy and Drug Delivery Study

In this project, Calcium ferrite/polyvinyl alcohol (CaFe2O4@PVA) nanocarriers were prepared by a thermal-treatment method at three different temperatures (773, 823 and 923 K). The nanocarriers were used as drug delivery systems (DDS) to deliver curcumin (CUR) and were utilized as a new structure for photo dynamic therapy (PDT). Drug loading and release study of CUR were performed and it was observed that nanocarriers showed a pH dependent drug release behavior. MTT assay, Hemolysis assay and lethal dose test were applied to determine the cytotoxicity of nanocarriers. These tests indicated that synthesized nanocarriers can be considered as nontoxic. Also, the photodynamic therapy experiments were performed by two groups: one group of cells were treated by different concentrations of nanocarriers without light and the other group were exposed to light. Then, the efficacy of PDT was determined by MTT and it was revealed that whenever nanocarriers were exposed to light the cytotoxicity was significantly high. Therefore, it was revealed that these nanocarriers are suitable to be utilized as a drug delivery systems and photo dynamic therapy agent.

Preparation and characterization of phosphate-stabilized amorphous calcium carbonate nanoparticles and their application in curcumin delivery

Nano-sized amorphous calcium carbonate (ACC) have a great potential for drug transport and drug delivery because of their high drug loading capacity, excellent biocompatibility and biodegradability. However, ACC is the thermodynamically least stable phase of calcium carbonate, and such thermal metastability often transforms it into more stable vaterite or calcite phases, so the inhibition of the phase transformation of ACC is of great significance for its application in drug delivery systems. Herein, phosphate as a morphology controlling additive was introduced to stabilize the metastable ACC. The results showed that the composite nanoparticles (named here the ACCP) with narrow size distribution located at approximately 128 nm (measured by dynamic light scattering) were obtained, when Ca2+ concentration and C/P were 10 mM and 7/3 respectively, prepared at 30 °C for 10 min. The powdered X-ray diffraction (XRD) results showed that phosphate has an excellent ability to stabilize ACC, and even after storage for 60 days at room temperature, the structure of ACCP remains amorphous. The in vitro drug release tests showed that ACCP nanoparticles had a high curcumin (Cur) loading capacity and a sustained drug release property. Moreover, the 1, 1-diphenyl-2-picrylhydrazyl radical (DPPH) radical scavenging activity assay showed that ACCP-encapsulating strategy could effectively prevent the decomposition of Cur. In vitro cytotoxicity tests demonstrated that the resultants have excellent biocompatibility. Therefore, the as-prepared ACCP nanoparticles are promising for drug delivery applications.

Synthesis of Superparamagnetic Iron Oxide Nanoparticle (SPIONs) for Drug Delivery and X-ray Imaging

Precursor iron molecular solution for the synthesis of SPIONs was optimized for the production of superparamagnetic iron oxide nanoparticles (SPIONs). Thus produced SPIONs were subjected for core-shell – SPIONs synthesis for drug delivery, which had the following four major stages (1) synthesis of SPIONs, (2) functionalization of SPIONs, (3) curcumin loading, and (4) biopolymer coating (Chitosan). Every stage of the synthesis was analyzed using various microscopic (TEM, SEM, AFM) and spectroscopic (UV Vis, FTIR, Zeta Analyzer, Raman Spectroscopy, GIXRD, PXRD, XPS, SQUID, VSM) analysis. Through spectroscopic techniques, mainly the elemental nature and the energy states of elements present all through the core-shell production were studied. The core-shells were subjected to drug delivery studies against HCT 116 and HeLa cells. Core-shell SPIONs were showing IC50 at 30μg and 80μg concentration against HeLa and HCT 116 cell lines, respectively. IC50 concentration was subjected for further anticancer studies through nuclear staining, flow cytometry, and expression of caspase 3 at four-time duration: 2 hours, 6 hours, 12 hours, and 24 hours. The core-shell SPIONs were found to induce cancer apoptosis, which was analyzed using quadrant and histogram statistics obtained as per flow-cytometer. Caspase 3 expression was analyzed using a caspase expression assay. Further, they were evaluated by histogram statistics. SPIONs were utilized as a contrasting agent for X-ray imaging, where it was showing the egg visibility. The response of SPIONs to X-ray was studied with and without the applied magnetic field. Later, the SPIONs were subjected to toxicity study against earthworm.

Gelatin Encapsulated Curcumin Nanoparticles Moderate Behavior of Human Primary Gingival Fibroblasts In Vitro

Objective.Currently, there is no study evaluating the effect of nano-curcumin on human oral cells in vitro. In this study, we developed gelatin encapsulated curcumin nanoparticles (GelCur) and cultured the primary human gingival fibroblasts (hGFs) to verify the effect of GelCur on the cellular events related to oral wound healing capacities, such as cell migration and proliferation of gingival fibroblasts.Materials and Methods.GelCur was produced by the sonoprecipitation method. Particle size, zeta potential, SEM morphological observation, entrapment efficiency, and drug loading were used to characterize new GelCur. Primary hGFs were cultured from the attached gingival tissue of healthy third molar teeth. The effect of different concentrations of GelCur on hGFs was investigated by cell toxicity assay (MTT), cell proliferation assay, and cell migration assays by scratch test and transwell migration assay.Results.The average particle size of GelCur was around 356 nm with a moderate zeta potential of 26.5 mV. The mean PdI value of GelCur was 0.2, while the entrapment efficiency and drug loading of curcumin in this study were around 57% and 2.4%, respectively. IC30of GelCur on hGFs was 3.96 mg/ml, while IC50was 12,37 mg/ml. More than 70% of cells were viable after 24 hours incubated with 1, 2, and 3 mg/ml GelCur. At the concentration of 2 mg/ml GelCur virtually limited cell proliferation and migration.Conclusions.GelCur remained physically stable and did not alter cell proliferation and migration. The concentration of GelCur <3.96 mg/ml did not cause hGF cytotoxicity. Our study showed that within appropriate doses, GelCur can be used safely for hGFs.

Cytotoxicity evaluation of curcumin-loaded affibody-decorated liposomes against breast cancerous cell lines

Curcumin is known as an effective anticancer herbal medicine but unfortunately, its bioavailability is poor which necessitate efforts for developing more efficient and specific delivery systems. Human epidermal growth factor receptor 2 (HER 2) due to its overexpression in various types of cancers, is demonstrated to be a good candidate as a target for anticancer therapy. In this study, cytotoxicity of curcumin encapsulated in ZHER2:342 Affibody-decorated liposome was investigated against SKBR3 and MCF-7 cancerous cell lines. Curcumin-containing liposomes were prepared from soybeans lecetin and cholesterol by thin-film hydration method. Affibody ZHER2:342 molecules via C-terminal cysteine residue were conjugated covalently to the prepared liposomes. Particle size analysis was performed using atomic force microscopy (AFM) and dynamic light scattering (DLS). Curcumin loading was measured using UV-Vis spectrophotometry and cytotoxic activity of curcumin formulations against cancerous cell lines was investigated by MTT assay. Induction of apoptosis was investigated using flow cytometry through Annexin V staining. Particle analysis showed the formation of spherical liposomes with a mean diameter of about 150 nm. Cytotoxic activity of curcumin was improved by its encapsulation in both liposomes and affibody-decorated liposomes. The Annexin V staining indicated the induction of apoptosis by affibody-decorated liposomes in both MCF-7 and SKBR3 cells. Decoration of curcumin-loaded liposomes with affibody ZHER2:342 may improve curcumin apoptotic function independently of HER2 expression level.

Anticancer Drug Delivery Systems Based on Curcumin Nanostructures: A Review

In recent years, the application of nanostructures in biomedical and pharmaceutical fields has increased. The special designs and compositions make nanocomposites very useful alternatives to conventional materials. Curcumin is a promising anti-cancer agent that has a positive and significant effect on chemotherapeutic achievements. The anticancer properties of curcumin have been widely investigated in different forms such as nanoparticles and nanocomposite structures. Chitosan-based nanocomposites, magnetic nanoparticles, polymer nanocomposites and blends, and montmorillonite- and alginate-based nanocomposites have been used in loading curcumin for various purposes. The anticancer preparations of curcumin nanoparticles and drug release systems employing curcumin-loaded nanoparticles, electrospun nanofibers, and hydrogel nanocomposites have been investigated. This review provides a summary of the applications of nanostructures containing curcumin, especially in controlled drug release systems. The curcumin nanoparticles and nanocomposites are suitable candidates for anticancer applications. On the nano-scale, curcumin has better aqueous solubility and, if used in a nanocomposite, there is a good ability for manipulating the drug delivery system properties.

Facile preparation of pH-sensitive chitosan microspheres for delivery of curcumin; characterization, drug release kinetics and evaluation of anticancer activity

Curcumin (CUR) is a lowly water-soluble natural polyphenol with chemopreventive and chemotherapeutic activities. Hence, to achieve the system with good CUR loading ability, porous MIL-88 (Fe) was prepared in the presence of the presynthesized graphene quantum dots (GQDs) (GQDs@MIL-88 (Fe)). In the following, CUR loaded in the fabricated GQDs@MIL-88 (Fe) nanohybrid. The characterization techniques; Fourier transform infrared (FT-IR), X-ray powder diffraction (XRD), scanning electron microscope (SEM), photoluminescence (PL), and Brunauer–Emmett–Teller (BET) analysis showed success in the synthesis of GQDs@MIL-88 (Fe). Moreover, the FT-IR analysis displayed the loading of CUR and the formation of CUR@GQDs@MIL-88(Fe). Chitosan (CS) was used as a green coating to enhance the biocompatibility of the prepared system (CS/CUR@GQDs@MIL-88(Fe). The fabricated microspheres showed pH-sensitive swelling behavior and released 38.3% of CUR in pH 5.0 which is better fitted with the First-order kinetic model (R2 = 0.9726). In comparison with CUR@GQDs@MIL-88(Fe), the MTT and DAPI assay exhibited less toxic effect for CS/CUR@GQDs@MIL-88(Fe) against MDA-MB 231 cells. Moreover, the safety of the CS/CUR@GQDs@MIL-88(Fe) confirmed after incubation against MCF 10A as a model of the normal cell line. The results conveyed a new concept that the CS/CUR@GQDs@MIL-88(Fe) is a potential candidate for using as a biocompatible carrier with controlled drug delivery ability.

The influence of NLC composition on curcumin loading under a physicochemical perspective and in vitro evaluation

The use of (nanostructured lipid carries) NLC to disperse curcumin in aqueous media is widely found in literature. However, few studies systematically analyze the influence of the lipid matrix composition and the presence of curcumin on the physicochemical characteristics of NLC. Thus, the present work aimed to verify the influence of the NLC composition on its structure. Different solid lipid (SL) to liquid lipid (LL) ratios were evaluated, yielding NLC < 600 nm and <400 nm with the use of MCT and castor oil, respectively. The addition of Tween 80 favored the formation of smaller structures. Thermal analysis data confirmed the formation of different structures due to their different composition and also after the incorporation of curcumin. The present study also describes a correlation between the rheology of the NLC dispersion and the degree of structural organization of the NLC, indicating the formation of structures with a differentiated degree of organization. Photomicrographs showed the formation of two different structures, multiple types and amorphous, with drug concentrated in nucleus. in vitro studies have not shown significant IC50 differences between the systems developed with curcumin; however, the time and effectiveness of internalization were different for the two developed systems. The interaction between SL and LL demonstrated to be an important parameter that should be considered before the development of NLC, also the molecular characteristics of each component must be verified in order to develop NLC on a desirable type.

Utilization of undesirable heat-induced precipitates/sediments in soy sauce production to fabricate nanoparticles for curcumin delivery

This study aimed to utilize an unwanted by-product of soy sauce production, the heat-induced precipitates/sediments (HPSS), to fabricate HPSS nanoparticles using a pH-driven method for their use as nano-carriers of unstable curcumin. The results showed that curcumin could successfully complex with HPSS at pH 6.0, 7.0 and 8.0, via hydrogen bonding, electrostatic interactions and hydrophobic interactions, with high encapsulation efficiency (>96%), stability and DPPH radical scavenging activity. Comparable properties were found among the HPSS nanoparticles and derived HPSS-curcumin nanocomplexes obtained at the three pHs, although the HPSS nanoparticles had the highest curcumin loading amount (10.14 μg/mg) and greatest DPPH radical scavenging power (SC50 0.89 μg/mL) at pH 7.0, and the nanocomplexed curcumin was most stable at pH 6.0. Thus, HPSS can be utilized as delivery vehicles for hydrophobic substances in food and medicinal applications, and pH is a critical variable governing the outcomes.

Enhancement of loading and oral bioavailability of curcumin loaded self-microemulsifying lipid carriers using Curcuma oleoresins

The therapeutic applications of curcumin, a phenolic compound extracted from Curcuma species, is limited due to poor bioavailability. To enhance the bioavailability, self-microemulsifying drug delivery systems (SMEDDS) with curcumin were prepared. Ethyl oleate, Tween 80, and Transcutol® P with surfactant: co-surfactant ratio of 2:1 w/w was selected based on the solubility and pseudo-ternary phase diagrams. The optimized formulation (S-Eo3) was evaluated for use of spice oleoresins as curcumin bioenhancers. The oleophilic phase of curcumin containing SMEDDS formulations was then successfully modified by using bioactive oleoresins extracted from two Curcuma species, viz. C. longa (S-CL1) and C. aromatica (S-CA1). The curcumin content in S-Eo3, S-CL1, and S-CA1 were 69.6 ± 0.23, 82.4 ± 0.62, and 88.8 ± 0.46 mg/g, respectively. Thus, by the partial modification of oleophilic phase of SMEDDS with spice oleoresin (acting as bioenhancer) resulted in ∼88 k improvement of curcumin aqueous solubility. The pharmacokinetic study in male Wistar rats showed that the relative bioavailability of curcumin in S-CL1 and S-CA1 were 26- and 29-fold vis-à-vis 22-fold in S-Eo3 compared to curcumin suspension. All the SMEDDS formulations were stable for three months as established by ICH guidelines.

Layer-by-Layer Decorated Nanoscale ZIF-8 with High Curcumin Loading Effectively Inactivates Gram-Negative and Gram-Positive Bacteria.

Bacteria-mediated infectious diseases have become a health-care challenge globally since the development of antibiotic resistance. Reactive oxygen species produced by photosensitizers have great potential in fighting bacterial infections, especially against Gram-negative bacteria that are hard to kill by regular methods owing to their formidable defensive membrane structures under the premise of avoiding overuse of antibiotics. In this work, a small molecular photosensitizer, curcumin (CCM), was used as a model and encapsulated into zeolitic imidazolate framework-8 (ZIF-8). Then the ZIF-8 loaded with CCM (CCM@ZIF-8) was decorated with biocompatible polymers hyaluronic acid (HA) and chitosan (CS) by the layer-by-layer self-assembly technique to yeild in an antibacterial CCM@ZIF-8@HA@CS nanoparticle with a high local positive charge density and is capable of binding the surface of bacteria by electrostatic interactions. The CCM drug loading capability of the nanoparticle was found to be as high as 10.89%. Upon exposure to blue light (72 J/cm2) for 10 min, the minimum inhibitory concentration and minimum bactericidal concentration of CCM@ZIF-8@HA@CS against Gram-positive bacteria (G(+)) Staphylococcus aureus (S. aureus) and Gram-negative bacteria (G(-)) Escherichia coli (E. coli) were the same, which were as low as 0.625 and 2.5 μg/mL, respectively, showing highly effective antibacterial activities. After treatment with CCM@ZIF-8@HA@CS under blue-light irradiation, the membranes of S. aureus and E. coli folded and cracked. Importantly, the antibacterial agent showed good biocompatibility in the cytotoxicity test using L929 cells and hemolysis test using rabbit blood cells under blue-light irradiation. Therefore, this CCM@ZIF-8@HA@CS nanocomposite is expected to find application in the treatment of superficial traumatic and refractory chronic infections caused by G(+) and G(-).

Co-delivery of Doxorubicin and Curcumin with Polypeptide Nanocarrier for Synergistic Lymphoma Therapy

The traditional chemotherapy, including Adriamycin (Doxorubicin, DOX), is widely used and is part of the first-line chemotherapy of invasive B cell lymphoma. DOX is nonselective cytotoxic drug and has many adverse effects, which limit its clinical application in combination with other anti-cancer drugs. Optimization of the delivery system targeting tumor microenvironment could be a feasible approach that may have significant clinical significance. Further, combination of DOX with other anticancer drugs, such as curcumin, can enhance the synergistic effects, possibly through epigenetic mechanisms. Hence, we evaluated the efficacy and toxicity of novel nanoparticles that enable the co-delivery of DOX and curcumin in the treatment of invasive B cell lymphoma both in vivo and vitro. The polymer nano materials [mPEG-b-P(Glu-co-Phe)] was used to co-load DOX and curcumin (CUR): L-DOX + CUR. DOX signal was measured to determine the ability of the drugs entering the cells by flow cytometry, and the different enrichment areas in the cells were directly observed by confocal microscope. The toxicity of LDOX + CUR was tested by CCK-8 assay in different cells, and the synergistic coefficients were calculated. The cell apoptosis and the possible mechanisms of apoptosis pathways regulation by L-DOX + CUR were examined using flow cytometry and Western Blot. The MTD (maximum tolerable dose) test was performed in mice. Tumor-bearing SCID mice (i.e., BJAB cell) were used to evaluate the in vivo efficacy of L-DOX + CUR. L-DOX + CUR, was prepared successfully, and the mole ratio of DOX and CUR fixed in 1.0:1.2. (DOX loading rate 9.7%, CUR loading rate 8.1%). L-DOX + CUR exhibited increased intracellular delivery and the main enrichment area of DOX was nucleus. L-DOX + CUR increased cytotoxicity, induced higher rates of apoptosis, and had synergistic effect, especially in BJAB cells (min CI 0.019). It even had epigenetic effect and affected miRNA levels favorably by down-regulating miR-21, miR-199a and up-regulating miR-98 and miR-200c. Additionally, L-DOX + CUR increased MTD in Kunming mice (i.e., 25 mg/kg), compared to DOX (10 mg/kg) and L-DOX (20 mg/kg). In BJAB cell bearing SCID mice, L-DOX + CUR treatment suppressed tumor growth compared to DOX or L-DOX alone, and exhibited less weight loss in mice. We developed new polymer nanoparticles-mPEG-b-P (Glu-co-Phe) co-loaded with DOX and DUR. L-DOX + CUR exhibited synergistic cytotoxic and apoptotic effects on invasive B cell lymphoma. Treatment of L-DOX + CUR potentiated tumor killing in xenografts and reduced toxicity in vivo.

Evaluation radioprotective effect of curcumin conjugated albumin nanoparticles.

In this research, curcumin (CUR) conjugated albumin based nanoparticles (BSA-CUR) were designed for improvement and evaluation radioprotective effect of CUR. In this way, we have prepared BSA-CUR by covalently binding the CUR with BSA. Next, this synthesized prodrug was evaluated for physical and chemical properties by Fourier-transform infrared (FTIR), Dynamic light scattering (DLS), Transmission electron microscopy (TEM), Ultraviolet-visible (UV/Vis), and Differential scanning calorimetry (DSC) analysis. Furthermore, the chemical stability of designed prodrug was appraised. The result shows that the size of nanoparticles is 174.4nm with a polydispersity index (PdI) of 0.191. The nanoparticles have a high loading capacity and show sustained release behavior. Loading of CUR to BSA not only could increase the chemical stability of CUR, but also could improve radioprotection efficacy of it's against X-Ray irradiation. The HHF-2 cells show 107% viability in the presence of BSA-CUR at a concentration of 50µg/mL, whereas non-treated cells show 46% viability, under X-Ray irradiation. Also in vivo study results show that, four out of five mice have died when the mice irradiated by X-Ray and no received any treatment. Although, for a group that treated with BSA-CUR and also irradiated by X-Ray, median survival and survival rate was higher than CUR treated and control mice, and only two out of five mice have died. The result of this study proved that BSA-CUR can be used as a proficient vehicle for improving the potential radioprotective effect of CUR.

Synthesis and Characterization of Pectin Membrane as a Matrix for Curcumin Sustained-Release

This study aims to synthesize pectin membranes, characterization of pectin membranes use FTIR, XRD, SEM, and to see the loading of curcumin in pectin membranes as a drug delivery system by contact time variations. Pectin membrane synthesize by dissolved 0.5 gram of pectin powder in 25 ml of 2% acetic acid solution then stirred for 1 hour. The solution is molded in membrane mold then oven for 24 hours at 50°C. Pectin membranes were characterized by FTIR to determine functional groups, XRD test to determine crystallinity, and SEM test to determine the surface morphology. The loading of curcumin in pectin membrane are carried out by contacting the pectin membrane into 100 ppm curcumin at various times of 5 to 120 minutes. Determination of curcumin concentration contained in pectin membrane use UV-Vis spectrophotometer at λ 426 nm. The results showed that the produced of pectin membrane was thin, pellucid, and homogeneous sheets. The results of FTIR characterization showed OH group at wave number 3448.72 cm−1 and carbonyl group at wave number 1604.77 cm−1. XRD characterization result showed that the pectin membrane was amorf. SEM characterization results showed smooth and flat surface morphology. The optimum contact time in loading curcumin proses in pectin membrane was 60 minutes with a loading percentage of 10%.

Dual drug delivery of curcumin and niclosamide using PLGA nanoparticles for improved therapeutic effect on breast cancer cells

A number of potent chemopreventives like curcumin and niclosamide have shown promising activities in cancer, although having the drawback of poor bioavailability. To improve the utility of these drugs in cancer therapy, we have encapsulated curcumin and niclosamide in poly(lactic-co-glycolide) (PLGA) nanoparticles, in the presence of poly(vinyl alcohol), using the nanoprecipitation method. We successfully synthesised spherical PLGA nanoparticles, either with each of the single drug individually or with both drugs together, for dual drug loaded samples. FTIR spectroscopy confirmed the successful loading of curcumin and niclosamide in PLGA nanoparticles. The encapsulation efficiency was 48.15% and 70.27% for curcumin and niclosamide, respectively, when loaded individually; which increased to 58.09% for curcumin and 85.36% for niclosamide, with simultaneous dual drug encapsulation. In vitro drug release showed that, as required, a much higher amount of drug released at the acidic pH 6.0 of cancer cells (86.01%, 95.04%, for curcumin and niclosamide, respectively), compared to normal, healthy cell’s pH of 7.4 (25.70% and 60.92% for these two same drugs). MTT assay revealed that dual-drug loaded PLGA nanoparticles exhibited a higher anticancer effect, compared to a bare mixture of two drugs in DMSO (having no PLGA). Therefore, PLGA nanoparticles can be used as an effective carrier to deliver the two hydrophobic drugs to MDA-MB-231 breast cancer cells, for a superior anticancer effect.

Preparation of Curcumin Nanoemulsion in Soybean Oil – Tween 80 System by Wet Ball Milling Method

Curcumin nanoemulsion which has a particle size of 20-200 nm, is one of the curcumin drug delivery system that can increase curcumin solubility and bioavailability. The previous method of curcumin nanoemulsion formulation is modified thin-film hydration followed by sonication that has a long process and using organic solvent. This study aims to make curcumin nanoemulsion by wet ball milling method in soybean oil – Tween 80 system. Nanoemulsion is expected to have smallest particle size, high curcumin loading capacity and good stability during storage. Preparation of curcumin nanoemulsion is done by wet milling method which consists of curcumin as drug, soybean oil as curcumin solvent, tween 80 as stabilizer, water as dispersed medium and milling beads as milling media on the vial with various milling time. Particle size and polydispersity index are monitored using dynamic light scattering while nanoemulsion morphology is observed using digital imaging microscope. Results show that optimum milling times is 24 h and the highest curcumin added which produces less than 500 nm particles is 300 mg which is stable during 60 days of storage. Particle size of the nanoemulsion is ranging from 127 – 338 nm. In addition, wet ball milling methods is relatively simple and easy to apply.

Curcumin-loaded electrospun nonwoven as a colorimetric indicator for volatile amines

Colorimetric indicators are useful in intelligent food packaging applications. As a natural food colorant, curcumin is a promising colorimetric indicator for the detection of alkaline compounds produced during food spoilage. In this study, curcumin-loaded electrospun nonwovens were developed for the detection of amines, which are principal spoilage volatiles of fish and aquatic products. The spin dope solution for electrospinning was prepared by dispersing curcumin (0.32% w/w) in 14% (w/w) polyvinylpyrrolidone (PVP) or 9% (w/w) ethylcellulose (EC)/0.2% (w/w) poly(ethylene oxide) (PEO) solution in anhydrous ethanol. Curcumin-loaded nonwovens were obtained by free surface electrospinning and subsequently characterized for amine detection. When exposed to amine volatiles, the nonwoven indicators exhibited striking yellow-to-orange/red color transition, along with a reduction in curcumin's fluorescence intensity. Both EC/PEO- and PVP-based nonwovens were capable of discriminating six different volatile amines (trimethylamine, ammonia, dimethylamine, triethylamine, piperidine and hydrazine) at 0.2 mmol level. Comparing the two nonwoven carriers, EC/PEO resulted in smaller fiber diameter (1.06 μm) and higher curcumin loading efficiency (91%) than those derived from PVP (83% loading efficiency and 1.52 μm diameter). The limit of detection (LOD) and limit of quantitation (LOQ) of using EC/PEO-based fiber for amine detection were lower than PVP-based fiber, except for TMA.

Evaluation of protein corona formation and anticancer efficiency of curcumin-loaded zwitterionic silica nanoparticles

Objective(s): Study and development of antifouling nanosystem for conjugation of drugs were attracting great attention in recent years. The present study aimed to develop novel curcumin-loaded silica nanoparticles containing zwitterionic coating as an antifouling system to provide protein corona free nanoformulations for curcumin. Materials and Methods: Silica nanoparticles were prepared using the Stober method, and mono- and bi-functionalized nanoparticles were obtained by modifying the surface of the bare silica nanoparticles with (3-aminopropyl)triethoxysilane (APTES), polyethylene glycol amine, APTES with sulfobetaine, and polyethylene glycol amine with sulfobetaine. Nanoparticle characterization, curcumin release, and measurement of protein corona inhibition were performed after incubation in the human plasma and MTT assay to confirm the stability and efficiency of the nanoparticles. Results: The presence of the sulfobetaine group could influence the curcumin loading capacity of the silica nanoparticles. The results of sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated no significant protein adsorption on the curcumin-loaded, zwitterionic-coated nanoparticles compared to the other nanoparticles. In addition, the MTT assay confirmed the cytotoxicity of the curcumin-loaded sulfobetaine-APTES-silica nanoparticles on MCF-7 cancer cells.Conclusion: Our findings confirmed the effects of the zwitterionic coating on the physicochemical properties of the nanoparticles. These findings play a key role in the development of novel nanoparticles for drug delivery applications.

99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation.

BackgroundEmerging cancer therapy requires highly sensitive diagnosis in combination with cancer-targeting therapy. In this study, a self-assembled pH-sensitive curcumin (Cur)-loaded nanoparticle of 99mTc radiolabeled hyaluronan-cholesteryl hemisuccinate conjugates (HA-CHEMS) and D-a-tocopheryl polyethylene glycol succinate (TPGS) was prepared for breast cancer synergistic theranostics.Materials and MethodsThe synthesized amphiphilic HA-CHEMS conjugates and TPGS self-assembled into Cur-loaded nanoparticles (HA-CHEMS-Cur-TPGS NPs) in an aqueous environment. The physicochemical properties of HA-CHEMS-Cur-TPGS NPs were characterized by transmission electron microscopy (TEM) and dynamic lighter scattering (DLS). The in vitro cytotoxicity of HA-CHEMS-Cur-TPGS NPs against breast cancer cells was evaluated by using the methyl thiazolyl tetrazolium (MTT) assay. Moreover, the in vivo animal experiments of HA-CHEMS-Cur-TPGS NPs including SPECT/CT imaging biodistribution and antitumor efficiency were investigated in 4T1 tumor-bearing BALB/c mice; furthermore, pharmacokinetics were investigated in healthy mice.ResultsHA-CHEMS-Cur-TPGS NPs exhibited high curcumin loading, uniform particle size distribution, and excellent stability in vitro. In the cytotoxicity assay, HA-CHEMS-Cur-TPGS NPs showed remarkably higher cytotoxicity to 4T1 cells with an IC50 value at 38 μg/mL, compared with free curcumin (77 μg/mL). Moreover, HA-CHEMS-Cur-TPGS NPs could be effectively and stably radiolabeled with 99mTc. The SPECT images showed that 99mTc-HA-CHEMS-Cur-TPGS NPs could target the 4T1 tumor up to 4.85±0.24%ID/g at 4 h post-injection in BALB/c mice. More importantly, the in vivo antitumor efficacy studies showed that HA-CHEMS-Cur-TPGS NPs greatly inhibited the tumor growth without resulting in obvious toxicities to major organs.ConclusionThe results indicated that HA-CHEMS-Cur-TPGS NPs with stable 99mTc labeling and high curcumin-loading capacity hold great potential for breast cancer synergistic theranostics.