Conjugation of curcumin with PVP capped gold nanoparticles for improving bioavailability

Curcumin, a natural polyphenolic compound, has astounding therapeutic applications but lacks in bioavailability mainly due to its poor solubility in water. Polyvinyl pyrrolidone (PVP) which is a proven drug carrier has been used to facilitate the conjugation of curcumin with gold nanoparticles and to improve the solubility of curcumin in water. In this conjugate diaryl heptanoid chromophore group of curcumin which is a much needed group in biomedical applications remains intact as observed from FTIR and UV–vis spectroscopy analysis. The work shows good promise for such conjugates as therapeutic-cum-imaging materials in biomedical field.     

Preparation and characterization of lyophilised egg PC liposomes incorporating curcumin and evaluation of its activity against colorectal cancer cell lines

Curcumin has been associated with the treatment of various diseases in traditional medicine, among them cancer. The major problems that prevent its approval as therapeutic agent are its low water solubility and its relatively low in vivo bioavailability. Liposomes are considered as effective drug carriers because of their ability to solubilize hydrophobic compounds and to alter their pharmacokinetic properties. The purpose of this study was the development of lyophilised liposomal curcumin fully characterized in terms of its physical properties [(zeta-potential, size, size distribution and Polydispercity index (PI)], and to evaluate its in vitro cytotoxic against colorectal cancer cell lines in a short-term and in a long-term (clonogenic) assay. Curcumin was incorporated in egg-phosphatidylcholine (EPC) liposomes at a drug to lipid molar ratio 1:14 achieving high incorporation efficiency close to 85%. The liposomal curcumin was lyophilized preserving thus its stability. The reconstitution of the formulation resulted in the original liposomal suspension. The release in FBS showed a plateau near 14% at 96 hours of incubation. The in vitro studies against colorectal cancer cell lines have shown that liposomes improve the activity of curcumin especially in the long-term assay and the liposomal formulation found to be more potent against HCT116 and HCT15, cell lines which express the MDR phenotype. EPC liposomal curcumin in a molar ratio of curcumin/EPC 1:14 has shown improved cytotoxic activity versus free curcumin against colorectal cancer cell lines. In vivo studies based on the recent findings are in progress in our laboratory.     

Synthesis of hydrophilic superparamagnetic magnetite nanoparticles via thermal decomposition of Fe(acac), in 80 vol% TREG + 20 vol% TREM

In this paper, we report single step synthesis of hydrophilic superparamagnetic magnetite nanoparticles by thermolysis of Fe(acac)3 and their characterization of the properties relevant to biomedical applications like hyperthermia and magnetic resonance imaging (MRI). Size and morphology of the particles were determined by Transmission electron microscopy (TEM) while phase purity and structure of the particles were identified by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Magnetic properties were evaluated using vibrating sample magnetometer (VSM) and superconducting quantum interference device (SQUID) measurements. The as prepared nanoparticles were found to be superparamagnetic with the blocking temperature of 136 K and were easily suspendable in water. Cytotoxicity studies on human cervical (SiHa), mouse melanoma (B16F10) and mouse primary fibroblast cells demonstrated that up to a dose of 0.1 mg/ml, the magnetite nanoparticles were nontoxic to the cells. To evaluate the feasibility of their uses in hyperthermia and MRI applications, specific absorption rate (SAR) and spin-spin relaxation time (T2) were measured respectively. SAR has been calculated to be above 80 Watt/g for samples with the iron concentration of 5-20 mg/ml at 10 kA/m AC magnetic field and 425 kHz frequency. r2 relaxivity value was measured as 358.4 mM(-1)S(-1) which is almost double as compared to that of the Resovist, a commercially available MRI contrast agent. Thus the as-prepared magnetite nanoparticles may be used for hyperthermia and MRI applications due to their promising SAR and r2 values.     

Comparative enhancement of curcumin cytotoxic photodynamic activity by nanoliposomes and gold nanoparticles with pharmacological appraisal in HepG2 cancer cells and Erlich solid tumor model

Curcumin is a natural pigment that generates singlet oxygen upon light excitation, hence it can be used as a photosensitizer in photodynamic therapy. The extremely low water solubility and poor systemic bioavailability make curcumin a challenging molecule to be used clinically. In this study, two nanocarrier systems for curcumin were prepared and characterized; nanoliposomes and polyvinyl pyrrolidone-capped gold nanoparticles. The dark and photocytotoxicity were investigated as a function of light fluence rate (100 and 200?mW/cm²) on HepG2 cancer cells. In vivo Erlich tumor model was developed and comparison of the tumor volume, survival rate, and histopathological alterations was made for the two nanocarriers. Results showed that both curcumin nanocarriers were successfully prepared and characterized. Light irradiation was able to augment the cytotoxicity of both curcumin liposomes and gold nanoparticles, with the former being superior in cytotoxicity compared to the latter. The tumor size was almost diminished 1 month post-photodynamic treatment for both systems with regression in the number of tumor cells upon histopathological evaluation, with curcumin liposomes producing better tumor regression than gold nanoparticles with comparable survival rate. Liposomes were confirmed to be superior to gold nanoparticles as a photodynamic treatment modality for cancer.     

超顺磁单分散性Fe3O4磁纳米粒的制备及性能表征

具有超顺磁单分散性的Fe₃O₄磁纳米粒在生物医学材料领域有着广泛的用途. 本研究在水、乙醇和甲苯混合体系74℃回流的条件下制备了具有超顺磁性的表面含油酸的Fe₃O₄磁纳米粒,研究了制备过程中OH^-浓度的变化对磁纳米粒的表面性能、粒径、分散性及磁性能的影响, 并对其机理进行了初步探讨. 采用XRD、FTIR、DLS、TEM和VSM等手段对制备的磁纳米粒进行表征. 结果表明, 当NaOH/Fe(Ⅱ)摩尔比＜8时, Fe₃O₄磁纳米粒表面含油酸可良好地分散于非极性溶剂中, NaOH的加入对磁纳米粒的粒径和饱和磁化强度等性能无明显影响;而当NaOH/Fe(Ⅱ)摩尔比≥8时, Fe₃O₄磁纳米粒仅能分散于水等极性溶剂中, 饱和磁化强度虽可增至40A·m²/kg, 但为多分散且易团聚.     

Stabilizing effect of the cyclodextrins additive to spray-dried particles of curcumin/polyvinylpyrrolidone on the supersaturated state of curcumin

Although curcumin is considered to have various therapeutic effects, its use as a functional food or supplement is restricted owing to its low water solubility and bioavailability. To increase the solubility of curcumin in water, the use of polyvinylpyrrolidone (PVP) and vinylpyrrolidone-vinyl acetate copolymers with a pyrrolidone skeleton was noted to be promising. In particular, the bi-component formulations of curcumin/PVP prepared through spray drying exhibited an amorphous state in powder X-ray diffraction observations and temporally increased the apparent solubility of curcumin to over 5000 times that of untreated curcumin; nevertheless, after 24 h, the solubility decreased owing to the unstable supersaturated state of curcumin. The addition of α-cyclodextrin (α-CyD) in the bi-component curcumin/PVP formulation helped maintain the supersaturated state of curcumin, whereas the addition of β- and γ-CyD led to the collapse of the supersaturated state. The addition of α-CyD can likely help inhibit the nucleation and crystal growth of curcumin, through the interaction among the solubilized units of curcumin/PVP and α-CyD.     

Solubility of core materials in aqueous polymeric solution effect on microencapsulation of curcumin

Curcumin, the main active constituent of turmeric herb (Curcuma longa L.) have been reported to possess many medicinal values. The application of curcumin in dermatological preparations is limited by their intense yellow color property, which stains the fabric and skin. The objectives of this study were to reduce the color staining effect and enhance the stability of curcumin via microencapsulation using gelatin simple coacervation method. As for curcumin, ethanol and acetone were used as coacervating solvents. Curcumin was dispersed in ethanol while dissolved in acetone. Irrespective of the types of coacervating solvents used, microencapsulation resolved the color-staining problem and enhanced the flow properties and photo-stability of curcumin. Nevertheless, it was found that more spherical curcumin microcapsules with higher yield, higher curcumin loading, and higher entrapment efficiency were obtained with acetone than ethanol. The in vitro release of curcumin after microencapsulation was slightly prolonged. Further evaluation of the effects of solubility of core materials in coacervating solvent or polymeric aqueous solution using six different drug compounds, namely, ketoconazole, ketoprofen, magnesium stearate, pseudoephedrine HCl, diclofenac sodium, and paracetamol, suggested that the solubility of core materials in aqueous polymeric solution determined the successful formation of microcapsules. Microcapsules could only be formed if the core materials were not dissolved in the aqueous polymeric solution while the core materials could either be dissolved or dispersed in the coacervating solvent. In summary, microencapsulation not only circumvents the color-staining problem but also improved the stability and flowability of curcumin. The solubility of core material in aqueous polymeric solution plays a pivotal role in determining the successful formation of microcapsules.     

Synthesis of biomimetic poly[2-(methacryloyloxy)ethyl phosphorycholine]-coated magnetite nanoparticles via surface-initiated atom transfer radical polymerization

Modification of magnetite nanoparticles with biomimetic poly[2-(methacryloyloxy)ethyl phosphorycholine] (poly(MPC)) via surface-initiated atom transfer radical polymerization (ATRP) was carried out. Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analyses (TGA) and zeta potential studies indicated that well defined poly (MPC) was successfully grafted on the surface of magnetite nanoparticles. X-ray diffraction results showed the structure of magnetite nanoparticles after surface modification was not changed. The poly (MPC)-coated magnetite nanoparticles had a mean transmission electron microscopy (TEM) diameter of 11 +/- 1.5 nm. The resulting nanomaterials were superparamagnetic at room temperature, exhibited good colloidal stability in aqueous media and good responsibility to magnetic field. Such magnetite nanoparticles with biomimetic surface have potential application in prolonging circulation time in vivo.     

Solubility of Core Materials in Aqueous Polymeric Solution Effect on Microencapsulation of Curcumin

Curcumin, the main active constituent of turmeric herb (Curcuma longa L.) have been reported to possess many medicinal values. The application of curcumin in dermatological preparations is limited by their intense yellow color property, which stains the fabric and skin. The objectives of this study were to reduce the color staining effect and enhance the stability of curcumin via microencapsulation using gelatin simple coacervation method. As for curcumin, ethanol and acetone were used as coacervating solvents. Curcumin was dispersed in ethanol while dissolved in acetone. Irrespective of the types of coacervating solvents used, microencapsulation resolved the color-staining problem and enhanced the flow properties and photo-stability of curcumin. Nevertheless, it was found that more spherical curcumin microcapsules with higher yield, higher curcumin loading, and higher entrapment efficiency were obtained with acetone than ethanol. The in vitro release of curcumin after microencapsulation was slightly prolonged. Further evaluation of the effects of solubility of core materials in coacervating solvent or polymeric aqueous solution using six different drug compounds, namely, ketoconazole, ketoprofen, magnesium stearate, pseudoephedrine HCl, diclofenac sodium, and paracetamol, suggested that the solubility of core materials in aqueous polymeric solution determined the successful formation of microcapsules. Microcapsules could only be formed if the core materials were not dissolved in the aqueous polymeric solution while the core materials could either be dissolved or dispersed in the coacervating solvent. In summary, microencapsulation not only circumvents the color-staining problem but also improved the stability and flowability of curcumin. The solubility of core material in aqueous polymeric solution plays a pivotal role in determining the successful formation of microcapsules.     

Preparation and characterization of Ni-nitrilotriacetic acid bearing poly(methacrylic acid) coated superparamagnetic magnetite nanoparticles

Stable superparamagnetic magnetite (Fe3O4) nanoparticles were synthesized via co-precipitation in the presence of poly(methacrylic acid) (PMAA) in aqueous solution. The polymer coated Fe3O4 nanoparticles were characterized using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, thermal analysis, and vibrating sample magnetometry (VSM) techniques. These measurements reveal the presence of magnetite nanoparticles with a size of approximately 8 nm inside the PMAA matrix. The magnetization value of these superparamagnetic nanoparticles at room temperarure and 7 T was measured as about 40 emu/g. PMAA-coated Fe3O4 nanoparticles were further assembled with Ni-chelate through a reaction between a primary amine-bearing NTA (nitrilotriacetic acid) ligand and carboxy-functional groups of PMAA. NTA-PMAA-coated magnetite nanoparticles were then loaded with nickel ions and characterized using FTIR. The average amount of binded Ni on the surface of the NTA-modified PMAA coated Fe3O4 was calculated as 1.65 +/- 0.3 x 10(-6) mol nickel(II) ions per g of the magnetic particles from the inductively coupled plasma optical emission spectroscopy (ICP-OES) measurements.     

Synthesis of magnetite/amphiphilic polymer composite nanoparticles as potential theragnostic agents

This study describes the synthesis of magnetite/amphiphilic polymer composite nanoparticles that can be potentially used simultaneously for cancer diagnosis and therapy. The synthesis method was a one-shot process wherein magnetite nanoparticles were mixed with core-crosslinked amphiphilic polymer (CCAP) nanoparticles, prepared using a copolymer of a urethane acrylate nonionomer (UAN) and a urethane acrylate anionomer (UAA). The CCAP nanoparticles had a hydrophobic core and a hydrophilic exterior with both PEG segments and carboxylic acid groups, wherein the magnetite nanoparticles were coordinated and stabilized. According to DLS data, the ratio of UAN to UAA and the ratio of magnetite to polymer are keys to controlling the size and thus, the stability of the composite nanoparticles. The magnetic measurement indicated that the composite nanoparticles had superparamagnetic properties and high saturation magnetization. The preliminary magnetic resonance imaging showed that the particles produced an enhanced image even when their concentration was as low as 80 microg/ml.     

In vitro biological activities of anionic gamma-Fe2O3 nanoparticles on human melanoma cells

Three magnetic fluid (MF) samples containing gamma-Fe2O3 (maghemite) nanoparticles surface-coated with either meso-2,3-dimercaptosuccinic acid (DMSA), citric acid or lauric acid were prepared, characterized, and assessed for their cytotoxic potential on the human SK-MEL-37 melanoma cell line. Ultra-structural analysis was also performed using transmission electron microscopy (TEM). In vitro cytotoxicity was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The inhibitory concentration (IC50) derived from the sigmoidal dose response curve was 254 microg-iron/mL (95% confidence interval 239-270 microg-iron/mL) for lauric acid-coated nanoparticles. DMSA-coated nanoparticles did not exhibit a clear trend toward toxicity (IC50 value is more than 2260 +/- 50 microg-iron/mL) and the IC50 value was about 433 +/- 14 microg-iron/mL for citric-acid coated nanoparticles. The cytotoxic response correlated with both the hydrodynamic diameter and the zeta potential suggests that the chain length of the carboxylic acid of the coating species may influence metabolic cellular process. Also the assayed nanoparticles can be considered non-cytotoxic to human melanoma cells since IC50 values are higher than plasma concentration usually observed in clinical use of contrast agents. Using TEM we verified that all assayed nanoparticles were internalized by cells through endocytic vesicles. Additionally, cells treated with lauric acid-coated nanoparticles at high concentration (588 or 840 microg-iron/mL) displayed morphological features of apoptosis (surface blebbing, intense vacuolization and chromatin condensation) or a typical DNA ladder pattern when analyzed by TEM or agarose gel electrophoresis, respectively. Apoptotic events may be operative, suggesting a promising therapeutic application for the lauric acid-coated nanoparticle in the treatment of cancer cells.     

Encapsulation of curcumin within poly(amidoamine) dendrimers for delivery to cancer cells

Curcumin has anti-proliferative and pro-apototic properties against a variety of cancer cells in vitro. Unfortunately, the water-insolubility and instability leads to its low bioavailability in vivo tests. Here, we report a general approach to using poly(amidoamine) dendrimer with acetyl terminal groups to encapsulate curcumin(G₅-Ac/Cur) for drug delivery to cancer cells. The solubility, release kinetics, anticancer activity, and apoptotic-related protein expression (Bax and Bcl-2) were investigated in detail. Comparing with curcumin, the water-solubility value of G₅-Ac/Cur increased 200-fold, and the release of curcumin from the complexes was in a sustained manner. G₅-Ac/Cur showed higher anti-proliferative activity against A549 cell lines and had the better effect on the generation of intracellular reactive oxygen species, the mitochondrial membrane potential and cell apoptosis. Furthermore, the ratio of Bax/Bcl-2 was higher in samples treated with G₅-Ac/Cur. The results indicated that the G₅-Ac drug delivery system could improve the solubility and anti-cancer effect of curcumin.     

Bi-layered polymer–magnetite core/shell particles: synthesis and characterization

Polymer magnetic core particles receive growing attention due to these materials owing magnetic properties which are widely used in different applications. The prepared composite particles are characterized with different properties namely: a magnetic core, a hydrophobic first shell, and finally an external second hydrophilic shell. The present study describes a method for the preparation of bi-layered polymer magnetic core particles (diameter range is 50–150 nm). This method comprises several steps including the precipitation of the magnetic iron oxide, coating the magnetite with oleic acid, attaching the first polymer shell by miniemulsion polymerization and finally introducing hydrophilic surface properties by condensation polymerization. The first step is the formation of magnetite nanoparticles within a co-precipitation process using oleic acid as the stabilizing agent for magnetite. The second step is the encapsulation of magnetite into polyvinylbenzyl chloride particles by miniemulsion polymerization to form a magnetic core with a hydrophobic polymer shell. The hydrophobic shell is desired to protect magnetite nanoparticles against chemical attack. The third step is the coating of magnetic core hydrophobic polymer shell composites with a hydrophilic layer of polyethylene glycol by condensation polymerization. Regarding the miniemulsion polymerization the influence of the amount of water, the mixing intensity and the surfactant concentration were studied with respect to the formation of particles which can be further used in chemical engineering applications. The resulting magnetic polymer nanoparticles were characterized by particle size measurement, chemical stability, iron content, TEM, SEM, and IR.     

Magnetic properties of magnetite nanoparticles coated with mesoporous silica by sonochemical method

In this paper we present the magnetic properties of mesoporous silica-coated Fe₃O₄ nanoparticles. The coating of magnetite nanoparticles with mesoporous silica shell was performed under ultrasonic irradiation. The obtained mesoporous silica-coated magnetite nanoparticles were characterized by powder X-ray diffraction, focused ion beam-scanning electron microscopy, nitrogen adsorption-desorption isotherms and vibrating sample magnetometer. The hysteretic behavior was studied using first-order reversal curves diagrams. The X-ray diffraction result indicates that the extreme chemical and physical conditions created by acoustic cavitations have an insignificant effect on crystallographic structural characteristic of magnetite nanoparticles. Changes in the coercivity distributions of the magnetite nanoparticles were observed on the first-order reversal curves diagrams for the samples with coated particles compared with the samples containing uncoated particles of magnetite. The coated particles show an increased most probable coercivity of about 20% compared with the uncoated particles which can be associated with an increased anisotropy due to coating even if the interaction field distribution measured on the diagrams are virtually identical for coated/uncoated samples.     

Oriented growth of magnetite along the carbon nanotubes via covalently bonded method in a simple solvothermal system

A new type of CNTs/magnetite hybrid material was prepared via covalently bonded method in a simple solvothermal system using FeCl₃ as iron source, ethylene glycol as the reducing agent, and 4-aminophenoxyphthalonitrile-grafted CNTs as templates. The magnetite nanoparticles, with the diameters of 70-80 nm, were self-assembled along the CNTs. The FTIR, UV-vis and DSC revealed that a stable covalent bond between nitriles group and iron ion promoted the oriented growth of magnetite nanoparticles along the CNTs, resulting in good dispersibility and solution storage stability. The magnetic properties measurements indicated that a higher saturated magnetization (70.7 emu g⁻¹) existed in the CNTs/magnetite hybrid material, which further enhanced the electromagnetic properties. The magnetic loss was caused mainly by natural resonance, which is in good agreement with the Kittel equation results. The novel electromagnetic hybrid material is believed to have potential applications in the microwave absorbing performances.     

Efficacy of lytic peptide-bound magnetite nanoparticles in destroying breast cancer cells

A 23-amino-acid synthetic lytic peptide (Hecate) was covalently linked to magnetite nanoparticles and the lytic peptide-bound nanoparticles were characterized by X-ray absorption near-edge structure spectroscopy, transmission electron microscopy, and electron diffraction. Investigation of magnetic properties with a superconducting quantum interference device (SQUID) magnetometer has shown a reduction in the saturation magnetization (Ms) of magnetite nanoparticles after binding with lytic peptide. An in vitro cell culture assay with breast cancer cell lines MDA-MB-435S revealed that the lytic peptide-bound magnetite nanoparticles were therapeutically active.     

An efficient method for decoration of the multiwalled carbon nanotubes with nearly monodispersed magnetite nanoparticles

A one-pot method has been developed to prepare magnetite nanoparticles decorated carbon nanotubes (CNTs) by thermal decomposition of iron chloride on CNTs templates in diethylene glycol. The morphological and structural characterizations indicate that magnetite nanoparticles are coated on the surfaces of the CNTs to form CNT-based nanocomposites. The density of magnetite nanoparticles on CNTs could be easily tuned by adjusting the weight ratio of iron chloride to CNTs. Magnetic measurements showed that the nanocomposites are superparamagnetic at room temperature and the magnetic properties of the samples can also be tuned by adjusting preparing conditions. The nanocomposites can be readily dispersed in water to form a stable solution and can be manipulated using an external magnetic field. As-synthesized nanocomposites may have potential applications in target–drug delivery, detection and separations, and in clinical diagnosis.     

Passively Targeted Curcumin‐Loaded PEGylated PLGA Nanocapsules for Colon Cancer Therapy In Vivo

Clinical applications of curcumin for the treatment of cancer and other chronic diseases have been mainly hindered by its short biological half‐life and poor water solubility. Nanotechnology‐based drug delivery systems have the potential to enhance the efficacy of poorly soluble drugs for systemic delivery. This study proposes the use of poly(lactic‐co‐glycolic acid) (PLGA)‐based polymeric oil‐cored nanocapsules (NCs) for curcumin loading and delivery to colon cancer in mice after systemic injection. Formulations of different oil compositions are prepared and characterized for their curcumin loading, physico‐chemical properties, and shelf‐life stability. The results indicate that castor oil‐cored PLGA‐based NC achieves high drug loading efficiency (≈18% w(drug)/w(polymer)%) compared to previously reported NCs. Curcumin‐loaded NCs internalize more efficiently in CT26 cells than the free drug, and exert therapeutic activity in vitro, leading to apoptosis and blocking the cell cycle. In addition, the formulated NC exhibits an extended blood circulation profile compared to the non‐PEGylated NC, and accumulates in the subcutaneous CT26‐tumors in mice, after systemic administration. The results are confirmed by optical and single photon emission computed tomography/computed tomography (SPECT/CT) imaging. In vivo growth delay studies are performed, and significantly smaller tumor volumes are achieved compared to empty NC injected animals. This study shows the great potential of the formulated NC for treating colon cancer.     

Seed-mediated synthesis of iron oxide and gold/iron oxide nanoparticles

In this study, we prepared magnetic iron oxide and gold/iron oxide nanoparticles (NPs) and characterized their morphologies and properties by XRD, TEM, EDX, VSM and UV-vis measurements. The magnetite iron oxide NPs of 10 nm were synthesized by coprecipitation of Fe2+ and Fe+3 in the solution of NH4OH and then they were used as seed particles for the subsequent growth to prepare the magnetite NPs of different particle sizes and also to prepare gold/iron oxide composite NPs. All those magnetite NPs are superparamagnetic and the gold/iron oxide composite NPs combine the optical and magnetic properties, which are contributed by gold and iron oxide components, respectively.