Preparation and characterization of dextran-zein-curcumin nanoconjugate for enhancement of curcumin bioactivity.

Curcumin is one of the most important polyphenolic nutrients in pharmaceutical industries. Unfortunately, its poor solubility and bioavailability have hampered its clinical application. To improve curcumin solubility and bioavailability, a natural nanocarrier made from protein-polysaccharide conjugate has been developed. Following antisolvent precipitation method, zein (Z) nanoparticles coated with dextran sulphate (DS) have been fabricated as curcumin (C) nanocarrier (DSZCNPs). The physicochemical properties of the nanoconjugate were measured using different techniques. Morphologically, DSZCNPs appeared spherical and monodispersed in scanning electron microscope (SEM) and transmission electron microscope (TEM) images. Curcumin encapsulation efficiency was ≈ 96%. DSZCNPs size was 180 nm and the polydispersity index value (PDI) 0.28. Zeta potential for DSZCNPs was -28.5 mV. DSZCNPs showed stability either for shelf storage (100 days) or at different pHs. Furthermore, DSZCNPs protected zein nanoparticles degradation in gastric environment and achieved controlled curcumin release in intestinal environment. DSZCNPs greatly enhanced the antioxidant activity of curcumin as demonstrated by DPPH assay. DSZCNPs had significant results in the reduction of colony forming unit (CFU%) against the tested microbes when compared with free curcumin. Also, the anticancer activity of DSZCNPs and free curcumin against hepatocellular carcinoma cells (HepG2) were assessed by MTT assay. IC50 for DSZCNPs was 13 µg/ml compared to 50 µg/ml for free curcumin indicating the therapeutic impact of DSZCNPs over free curcumin.Based on the above results, the developed zein-dextran nanocomplex exhibited high stability and improved the efficacy and bioactivity of curcumin suggesting its potential utility as nanovehicle for the hydrophobic drug curcumin.

Bioinspired synthesis of protein/polysaccharide-decorated folate as a nanocarrier of curcumin to potentiate cancer therapy.

Curcumin is a promising anticancer agent, but its clinical utilization has been hindered by its low solubility and bioaccessibility. To overcome these obstacles, we developed a natural protein-polysaccharide nanocomplex made from casein nanoparticles coated with a double layer of alginate and chitosan and decorated with folic acid (fCs-Alg@CCasNPs) for use as a nanocarrier for curcumin. The developed nanoformulation showed a drug encapsulation efficiency = 75%. The measured size distribution of fCs-Alg@CCasNPs was 333.8 ± 62.35 nm with a polydispersity index (PDI) value of 0.179. The recorded zeta potential value of fCs-Alg@CCasNPs was 28.5 mV. Morphologically, fCs-Alg@CCasNPs appeared spherical, as shown by transmission electron microscopy (TEM). The successful preparation of fCs-Alg@CCasNPs was confirmed by Fourier transform infrared (FTIR) spectroscopy of all the constituents forming the nanoformulation. Further in vitro investigations indicated the stability of fCs-Alg@CCasNPs as well as their controlled and sustained release of curcumin in the tumor microenvironment. Compared with free curcumin, fCs-Alg@CCasNPs induced a higher cytotoxic effect against a pancreatic cancer cell line. The in vivo pharmacokinetics of fCs-Alg@CCasNPs showed a significant AUC0-24 = 2307 ng.h/ml compared to 461 ng.h/ml of free curcumin; these results indicated high curcumin bioavailability in plasma. The in vivo results of tumor weight, the amount of DNA damage measured by comet assay and histopathological examination revealed that treating mice with fCs-Alg@CCasNPs (either intratumorally or intraperitonially) prompted higher therapeutic efficacy against Ehrlich carcinoma than treatment with free curcumin. Therefore, the incorporation of curcumin with protein/polysaccharide/folate is an innovative approach that can synergistically enhance curcumin bioavailability and potentiate cancer therapy with considerable biosafety.

Incorporating silver nanoshell-coated mesoporous silica nanoparticles improves physicochemical and antimicrobial properties of chitosan films.

Tailoring nanomaterials with tunable properties is of great importance to develop multifunctional candidates in the biomedical field. In the present study, we aimed to develop a promising nano-hybrid system composed of chitosan (CS) and mesoporous silica nanoparticles with a silver nanoshell coat (CS-AgMSNs). The physicochemical properties of CS-AgMSNs films were characterized using various techniques. Further, the mechanical properties of CS-AgMSNs were evaluated and compared with those of undoped CS film. Moreover, the antimicrobial activities of CS-AgMSNs (with different concentrations) were assessed against E-coli, S. aureus, C. albicans, and A. niger. Our results demonstrated that increasing the concentrations of doped AgMSNs (10 to 40 mg) in CS films lowered their transparency and blocked light transmission effectively. The measured elastic modulus of CS-AgMSNs films (20 and 30 mg) showed a decrease in the stiffness of CS films. Also, the elongation at break for CS-AgMSNs (40 mg) indicated a better flexibility. CS-AgMSNs films (10-40 mg) showed an enhanced antimicrobial activity in a concentration-dependent manner compared to undoped CS films. Collectively, the results suggest that our nano-hybrid CS-AgMSNs matrix has unique and promising properties, and holds potential for use in the biomedical field, food packaging, and textile industry.

Alginate-coated caseinate nanoparticles for doxorubicin delivery: Preparation, characterisation, and in vivo assessment.

Natural protein-based nanoparticles are promising nano-vehicles for the delivery of chemotherapeutic drugs. Caseinate nanoparticles loaded with doxorubicin (CasNPs-DOX) have been surface-modified with the natural polysaccharide alginate to generate the novel nanocarrier Alg-CasNPs-DOX. The fabricated nanoparticles have been characterised by transmission electron microscopy, Fourier-transform infrared spectroscopy, dynamic light scattering, fluorescence spectroscopy, and zeta potential measurement. Drug encapsulation and release profiles were also investigated. In vivo studies were conducted to evaluate the therapeutic efficacy of this novel drug delivery system in tumour-bearing mice. The biodistribution and toxicity of the nano-formulation were also assessed. The results showed that encapsulation of DOX in Alg-CasNPs-DOX not only led to controlled and sustained drug release but also significantly enhanced the effectiveness of DOX against Ehrlich carcinoma. Moreover, no significant changes were observed in liver and kidney enzymes, indicating the selective delivery of DOX to the tumour site, thus minimising DOX toxicity to certain vital organs. Accordingly, Alg-CasNPs-DOX was shown as a promising DOX nanocarrier for improving the therapeutic efficacy of DOX against cancer compared to that of free DOX.

Long-term biodistribution and toxicity of curcumin capped iron oxide nanoparticles after single-dose administration in mice.

AIM: In this study, in vivo biodistribution, clearness and toxicity of curcumin capped iron oxide nanoparticles (Cur-IONPs) were addressed in different body organs. MATERIALS AND METHODS: The physicochemical properties of the prepared Cur-IONPs were investigated. Long term (3 weeks) biodistribution, clearness and toxicity were assessed for a single-dose administration of Cur-IONPs (5 mg/kg). The iron content in liver, kidney, spleen and brain was quantified using atomic absorption spectroscopy. Serum biochemical parameters were also measured. KEY FINDINGS: The integrated in vivo results demonstrated that Cur-IONPs was mostly taken up in the liver and spleen reaching its highest levels on days 1 and 2, respectively. In the brain, the results showed significant accumulation of Cur-IONPs between 1 h to 1-day post injection. This represented the successful penetration Cur-IONPs across the blood-brain barrier. Serum biochemical analysis demonstrated a temporal disturbance in the performance of body organs. Also, the body weights showed no alteration throughout the experiment. SIGNIFICANCE: It has been deduced that the promising green synthesized Cur-IONPs as an "All in One" nanoplatform is safe enough to be used in diagnostic and therapeutic purposes.

Multifunctional magnetic-gold nanoparticles for efficient combined targeted drug delivery and interstitial photothermal therapy.

Abundant efforts have recently been made to design potent theranostic nanoparticles, which combine diagnostic and therapeutic agents, for the effective treatment of cancer. In this study, we developed multifunctional magnetic gold nanoparticles (MGNPs) that are able to (i) selectively deliver the drug to the tumor site in a controlled-release manner, either passively or by using magnetic targeting; (ii) induce photothermal therapy by producing heat by near-infrared (NIR) laser absorption; and (iii) serve as contrast agents for magnetic resonance imaging (MRI) (imaging-guided therapy). The prepared MGNPs were characterized by different physical techniques. They were then coated and conjugated with polyethylene glycol (PEG) and doxorubicin (DOX) to form MGNP-DOX conjugates. The high efficacy of MGNP-DOX for combined chemo-photothermal therapy was observed both in vitro and in vivo. The effectiveness of MGNP-DOX as theranostic nanoparticles was confirmed by histopathological examination and immunohistochemical studies. Moreover, MGNP-DOX showed good potential as MRI contrast agents for guided chemo-photothermal synergistic therapy.

Ehrlich tumor inhibition using doxorubicin containing liposomes.

Ehrlich tumors were grown in female balb mice by subcutaneous injection of Ehrlich ascites carcinoma cells. Mice bearing Ehrlich tumor were injected with saline, DOX in solution or DOX encapsulated within liposomes prepared from DMPC/CHOL/DPPG/PEG-PE (100:100:60:4) in molar ratio. Cytotoxicity assay showed that the IC50 of liposomes containing DOX was greater than that DOX only. Tumor growth inhibition curves in terms of mean tumor size (cm(3)) were presented. All the DOX formulations were effective in preventing tumor growth compared to saline. Treatment with DOX loaded liposomes displayed a pronounced inhibition in tumor growth than treatment with DOX only. Histopathological examination of the entire tumor sections for the various groups revealed marked differences in cellular features accompanied by varying degrees in necrosis percentage ranging from 12% for saline treated mice to 70% for DOX loaded liposome treated mice. The proposed liposomal formulation can efficiently deliver the drug into the tumor cells by endocytosis (or passive diffusion) and lead to a high concentration of DOX in the tumor cells. The study showed that the formulation of liposomal doxorubicin improved the therapeutic index of DOX and had increased anti-tumor activity against Ehrlich tumor models.

Doxorubicin loaded magnetic gold nanoparticles for in vivo targeted drug delivery.

Treatment of approximately 50% of human cancers includes the use of chemotherapy. The major problem associated with chemotherapy is the inability to deliver pharmaceuticals to specific site of the body without inducing normal tissue toxicity. Latterly, magnetic targeted drug delivery (MTD) has been used to improve the therapeutic performance of the chemotherapeutic agents and reduce the severe side effects associated with the conventional chemotherapy for malignant tumors. In this study, we were focused on designing biocompatible magnetic nanoparticles that can be used as a nanocarrier's candidate for MTD regimen. Magnetic gold nanoparticles (MGNPs) were prepared and functionalized with thiol-terminated polyethylene glycol (PEG), then loaded with anti-cancer drug doxorubicin (DOX). The physical properties of the prepared NPs were characterized using different techniques. Transmission electron microscopy (TEM) revealed the spherical mono-dispersed nature of the prepared MGNPs with size about 22 nm. Energy dispersive X-ray spectroscopy (EDX) assured the existence of both iron and gold elements in the prepared nanoparticles. Fourier transform infrared (FTIR) spectroscopy assessment revealed that PEG and DOX molecules were successfully loaded on the MGNPs surfaces, and the amine group of DOX is the active attachment site to MGNPs. In vivo studies proved that magnetic targeted drug delivery can provide a higher accumulation of drug throughout tumor compared with that delivered by passive targeting. This clearly appeared in tumor growth inhibition assessment, biodistribution of DOX in different body organs in addition to the histopathological examinations of treated and untreated Ehrlich carcinoma. To assess the in vivo toxic effect of the prepared formulations, several biochemical parameters such as aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), urea, uric acid and creatinine were measured. MTD technology not only minimizes the random distribution of the chemotherapeutic agents, but also reduces their side effects to healthy tissues, which are the two primary concerns in conventional cancer therapies.

Preparation and characterization of magnetic gold nanoparticles to be used as doxorubicin nanocarriers.

Magnetic targeted drug delivery (MTD), using magnetic gold nanoparticles (Fe3O4@Au NPs) conjugated with an anti-cancer drug is a promise modality for cancer treatment. In this study, Fe3O4@Au NPs were prepared and functionalized with thiol-terminated polyethylene glycol (PEG), then loaded with anti-cancer drug doxorubicin (DOX). The physical properties of the prepared NPs were characterized using different techniques. Transmission electron microscopy (TEM) revealed the mono dispersed nature of Fe3O4@Au NPs with an average size of 20 nm which was confirmed using Dynamic light scattering (DLS) measurements. Zeta potential measurements along with UV-VIS spectroscopy demonstrated surface DOX loading on Fe3O4@Au NPs. Energy Dispersive X-ray Spectroscopy (EDX) assured the existence of both iron and gold elements in the prepared NPs. The paramagnetic properties of the prepared NPs were assessed by vibrating sample magnetometer (VSM). The maximum DOX-loading capacity was 100 µg DOX/mg of Fe3O4@Au NPs. It was found that DOX released more readily at acidic pH. In vitro studies on MCF-7 cell line elucidated that DOX loaded Fe3O4@Au NPs (Fe3O4@Au-PEG-DOX) have more potent therapeutic effect than free DOX. Knowledge gained in this study may open the door to pursue Fe3O4@Au NPs as a viable nanocarriers for different molecules delivery in many diagnostic and therapeutic applications.

Mesoporous silica coated gold nanorods loaded doxorubicin for combined chemo-photothermal therapy.

The efficacy of the combined chemo-photothermal therapy, using a mesoporous silica-coated gold nanorods loaded DOX (pGNRs@mSiO2-DOX), was consistently tested both in vitro and in vivo. The prepared nanoparticles that were characterized using transmission electron microscopy (TEM), UV-vis absorption spectroscopy and zeta potential showed high doxorubicin loading capacity in addition to its pH-responsive release. The pGNRs@mSiO2-DOX photo-heat conversion characteristic found to be stable for several repeated NIR irradiated doses was tested in simulated body fluid. In vitro results showed that pGNRs@mSiO2-DOX causes a significant damage in breast cancer cell line MCF-7 compared to free DOX. Contrary to this, it showed low toxicity to human amnion wish cells compared to CTAB coated GNRs and free DOX. In vivo results showed that intravenous administration of pGNRs@mSiO2-DOX (1.7 mg/kg) markedly suppresses the growth of subcutaneous Ehrlich carcinoma in female Balb mice (p<0.0001). Consistently, histopathological examination revealed a complete loss of tumor cellular details for mice that received the combined treatment. Based on the obtained results, this passively targeted pGNRs@mSiO2-DOX could specifically deliver drug and excessive local heat to tumor sites achieving high combined therapeutic efficacy.

Enhancement of the ocular therapeutic effect of prednisolone acetate by liposomal entrapment.

Eye drops account for 90% of ophthalmic formulations despite of the rapid precorneal drug loss. Our aim is to test the effect of positive charge induction and the subsequent size reduction on the efficiency of liposomes as ocular drug delivery system for the lipophilic drug prednisolone acetate (PSA). Different formulations of PSA-loaded liposomes, positive multilamellar liposomes (pMLV), positive small (nano-sized) unilamellar liposomes (pSUV) and neutral multilamellar liposomes (nMLV), were prepared. These formulations were characterized by measuring surface charge, size distribution, entrapment efficiency, release rate, and ability to deliver PSA across the cornea. In vitro studies showed that positive charge induction reduces the transcorneal flux (about 1.9-fold lower than nMLV), while the subsequent size reduction results in higher flux (about 1.2-fold higher than nMLV). But in vivo results revealed that pSUV produced more concentrations of PSA in aqueous humor than nMLV (P < 0.05) suggesting greater chance for drug penetration, pSUV were more effective than nMLV in this regard (P < 0.05). As revealed by in vivo studies and ophthalmic examinations, positive charge induction and the subsequent size reduction increased the efficiency of liposomes as ocular drug delivery system for PSA.

Preparation and characterization of SiO2-Au nanoshells: in vivo study of its photo-heat conversion.

In the event of cancer treatment, photothermal therapy has met successful cancerous cells damage with highly reduced toxicity to normal cells. The prepared GNSs samples have been characterized using transmission electron microscope (TEM), dynamic light scattering, zeta potential and UV-VIS absorption spectroscopy. In-vivo photo-heat conversion of GNSs accumulated in Ehrlich tumor cells inoculated in female balb mice was monitored by measuring tumor tissue temperature as a function of NIR laser exposure time. Resultant heating and therapeutic efficacy were assessed by monitoring tumor growth/regression and tumor cells necrotic percentage. Histopathological examinations for treated and control tumors using light microscope and transmission electron microscopes (TEM) were performed to evaluate the treatment effects. Passively targeted pegylated gold nanoshells were found to have localized photo-heat conversion sufficient to selectively destruct tumor cells. This has been emphasized by the significant decrease in Ehrlich tumor volume for treated groups that administrated either intratumorly (IT) or intravenously (IV) with GNSs. Light microscope examinations revealed high necrotic percentages for both administration routes. TEM images showed degenerated cell membrane and nuclear envelop as well as the appearance of nucleus debris and other cell organelles. This non-invasive protocol showed great promise as a technique for selective cancer photo-thermal therapy.

Low power argon laser-induced thermal therapy for subcutaneous Ehrlich carcinoma in mice using spherical gold nanoparticles.

The present study examines the feasibility of a low power argon laser-induced thermal therapy to Ehrlich carcinoma, employing a direct administration of spherical gold nanoparticles (GNPs). This modality utilizes the advantage of strong surface plasmon resonance exhibited by spherical GNPs in the visible range. Ehrlich tumors were grown in female balb mice by subcutaneous injection of Ehrlich ascites carcinoma cells. GNPs with an average diameter 13 +/- 1.2 nm and optical density (ODlambda:518 nm = 3) were directly injected within the tumor interstitium. Tumors were then illuminated with a continuous-wave (CW) argon ion laser with irradiance 55 mW cm-2 for 45 min. All laser-GNPs treated tumors exhibited a significant suppression in tumor growth throughout 15 days. On the contrary, sham-treated group (laser treatment without GNPs injection) and control group (neither laser nor GNPs treatment) showed a progressive increase in tumor growth during the same period. Histopathological examination demonstrated extensive necrotic percentage in laser-GNPs treated group (90%) in comparison with sham (35%) or control group (3-7%). A wide-angle X-ray scattering also revealed detectable changes in tumor protein structure exposed to both laser and GNPs. It can be concluded from this study that the intense surface plasmon resonance exhibited by spherical GNPs in the visible range could be very useful as a noninvasive technique for photothermal therapy of skin or near-surface type tumors that need much less laser energy and lower concentrations of GNPs.