Free Curcumin Research Articles

Immobilization of gold nanoparticles on folate-conjugated dendritic mesoporous silica-coated reduced graphene oxide nanosheets: a new nanoplatform for curcumin pH-controlled and targeted delivery.

In the present study, a new sandwich-like nanocomposite as a multifunctional smart nanocarrier for curcumin (Cur) targeted delivery and cell imaging was prepared by immobilization of gold nanoparticles on folic acid-modified dendritic mesoporous silica-coated reduced graphene oxide nanosheets (AuNPs@GFMS). The physical and chemical properties of the nanocomposite were investigated by atomic force microscopy (AFM), transmission electron microscopy (TEM), X-ray diffraction (XRD), UV-Vis, field-emission scanning electron microscopy (FE-SEM), Fourier transformation infrared (FT-IR), and Brunauer-Emmett-Teller (BET) surface area analysis. The nanocarrier exhibits a number of interesting properties, including good biocompatibility, biodegradability, and suitable surface area, which results in high drug loading capacity. In addition, this new drug delivery system showed sustained-release and pH-responsive properties. The in vitro cytotoxicity test of the free curcumin, free nanocarrier (AuNPs@GFMS), curcumin-loaded folate-conjugated nanocarriers (Cur-AuNPs@GFMS), and curcumin-loaded nanocarriers without folate-conjugation (Cur-AuNPs@GAMS) against two human cancer cell lines, including MCF-7 (human breast carcinoma cell lines) and A549 (human lung carcinoma cell lines) demonstrated that the therapeutic efficacy of Cur-AuNPs@GFMS is significantly greater than those of other compounds because the cancerous cells can uptake the folate-conjugated drug nanocarrier via a receptor-mediated mechanism. Fluorescence microscopic images and different staining techniques were also used to visualize the cellular uptake, anticancer activity, specific targeting ability, and photothermal potency of Cur-AuNPs@GFMS toward the MCF-7 cancer cells. The obtained results proved that the proposed system, Cur-AuNPs@GFMS, can be used as a potent anticancer agent in targeted cancer therapies for breast cancer.

PEG-coumarin nanoaggregates as π–π stacking derived small molecule lipophile containing self-assemblies for anti-tumour drug delivery

Polymeric self-assemblies formed by non-covalent interactions such as hydrophobic interactions, hydrogen bonding, π–π stacking, host-guest and electrostatic interactions have been utilised widely and exhibit controlled release of encapsulated drug. Beside carrier-carrier interactions, small molecule amphiphiles exhibiting carrier-drug interactions have recently been an area of interest for cancer drug delivery, as most of the hydrophobic anti-tumour drugs are aromatic and exhibit π–π conjugated structure. In the present study PEG-coumarin (PC) conjugates forming self-assembled nanoaggregates were synthesised with PEG (polyethylene glycol) as hydrophilic block and coumarin as small molecule lipophilic segment. Curcumin (CUR) as model conjugated aromatic drug was loaded in to the nanoaggregates via dual hydrophobic and π–π stacking interactions. The interactions between the conjugates and CUR, drug release profile and in vitro anti-tumour efficacy were investigated in detail. CUR-loaded nanoaggregate self-assembly was driven by π–π interactions and a maximum loading level of about 18 wt.% (~60 % encapsulation efficiency) was achieved. The average hydrodynamic diameter (Dav) was in the range of 120–160 nm and a spherical morphology was observed by transmission electron microscopy (TEM). A sustained release of CUR was observed for 90 h. Cytotoxicity evaluation of CUR-loaded nanoaggregates on pancreatic cancer cell lines indicated higher efficacy, IC50 ~11 and ~15 μM as compared to free CUR, IC50 ~14 and ~20 μM on human pancreatic carcinoma (MIA PaCa-2) and human pancreatic duct epithelioid carcinoma (PANC-1) cell lines respectively. PC conjugates provided a new strategy of fabricating nanoparticles for drug delivery and may form the basis for the development of advanced biomaterials in near future.

Preparation and evaluation of curcumin-loaded self-assembled micelles

Objective: Curcumin being used to treat various chronic diseases while its poor bioavailability issue limited its wide clinical application as a therapeutic agent. The aim of this work was to prepare curcumin-loaded self-assembled micelles using soluplus and solutol®HS15 (SSCMs) to enhance curcumin’s solubility and thus oral bioavailability.Methods: Optimum formulation was investigated and the optimized ratio of drugs and excipients was obtained and the SSCMs were prepared via ethanol solvent evaporation method. The optimal SSCMs were characterized by transmission electron microscopy, drug content analysis including loading efficiency (LE%) and entrapment efficiency (EE%), and the cumulative amount of curcumin released from the micelles were all calculated using HPLC method. The in vitro cytotoxicity and the permeability of SSCMs were measured by Caco-2 cell monolayers and the oral bioavailability was evaluated by SD rats.Key findings: The solubility of curcumin in self-assembled micelles was dramatically increased by 4200 times as compared to free curcumin. Caco-2 cells transport experiment exhibited that while soluplus and solutol®HS15 were self-assembled into micelles, it could not only promote the permeability of curcumin across membrane for better absorption, but also could restrain the curcumin pumped outside due to the role of P-gp efflux mechanism of soluplus and solutol®HS15. Furthermore, the prepared SSCMs formulation was almost nontoxic and had safety performance on Caco-2 cells model. Moreover, curcumin’s oral bioavailability of SSCMs formulation in SD rats had doubled than that of free curcumin.Conclusions: The prepared SSCMs were characterized by PS, PDI, LE%, EE% data analysis. After the soluplus and solutol®HS15 were self assembled into micelles, both the solubility and membrane permeability of curcumin were evaluated to have been enhanced, as well as the effect of efflux pump of curcumin was inhibited, hence to promote oral absorption and generate an increased bioavailability.

NIR triggered liposome gold nanoparticles entrapping curcumin as in situ adjuvant for photothermal treatment of skin cancer

We report the synthesis of a biodegradable liposome gold nanoparticles for curcumin (Au-Lipos Cur NPs) delivery. This entrapped curcumin served as an in situ adjuvant for photothermal therapy. Curcumin was loaded in Au-Lipos NPs with an encapsulation efficiency of ∼70%. The gold coating enabled the NPs to specifically absorb NIR light (780nm) by virtue of Surface Plasmon Resonance (SPR) and this light energy was converted to heat. The generated heat destabilized the liposomal core enhancing the release of encapsulated curcumin. Photothermal transduction efficacy of Au-Lipos NPs (loaded with curcumin) showed a significant temperature rise upon laser irradiation causing irreversible cellular damage. In vitro photothermal effect and intracellular uptake was evaluated in B16 F10 (melanoma) cell line. Au-Lipos Cur NPs showed significantly enhanced uptake when compared with free curcumin. Enhancement in cancer cell cytotoxicity was observed in Au-Lipos Cur NPs treated group upon laser irradiation owing to curcumin. Our findings indicate that curcumin could serve as a potential in situ adjuvant for photothermal therapy of melanoma.

Macrophage repolarization using CD44-targeting hyaluronic acid–polylactide nanoparticles containing curcumin

The aim of this study was to evaluate the efficiency of using a natural substance, curcumin, encapsulated in CD44-targeting hyaluronate–polylactide (HA-PLA) nanoparticles (NPs) for the modulation of macrophage polarity from the pro-inflammatory M1 to anti-inflammatory M2 phenotype. For this purpose, the characterization of the NPs was monitored using 1HNMR, FTIR, DLS and FE-SEM. The effects of curcumin-encapsulated HA-PLA NPs on the viability of LPS/IFN-γ stimulated peritoneal macrophages were determined using MTT assay. The cellular uptake of free curcumin and nano-formulated curcumin was assessed using confocal microscopy. Also, the expression levels of iNOS-2 (M1 marker), Arg-1 (M2 marker) and also pro-inflammatory cytokines were measured by real-time PCR. Data showed that the nano-formulated curcumin with spherical shape, an average diameter of 102.5 nm and high cellular uptake was significantly less toxic to peritoneal macrophages. Furthermore, the nano-formulated curcumin effectively indicated a reduction in iNOS-2 and an increase in Arg-1 levels than free curcumin. The change in macrophage phenotype by curcumin-encapsulated HA-PLA NPs could suppress the inflammation in LPS/IFN-γ stimulated macrophages as evidenced by a major reduction in pro-inflammatory cytokines. Conclusively, the results suggested that the curcumin formulation with CD44-targeting HA-PLA NPs might be a promising platform for the treatment of inflammatory diseases.

Novel nano-cocoon like structures of polyethylene glycol–multiwalled carbon nanotubes for biomedical applications

In this article, we report the synthesis and use of a novel drug delivery particle, based on bio-compatible polymer polyethylene glycol (PEG-400) and multi-walled carbon nanotubes (MWCNTs). MWCNTs in PEG-400 were broken into small tubes by vortex mixing with tungsten-carbide balls for about 15 h. Length separation of MWCNTs was then done using differential centrifugation with various concentrations of PEG-400. The separated MWCNTs in PEG solution were further pelletized using high speed centrifugation and re-dispersed in water. Novel cocoon like oval nanoparticles of about 100–200 nm size was observed in one of the centrifuged fractions. TEM shows that the cocoons primarily have PEG enclosing few MWCNTs. However, similar structures were not found when differential centrifugation was done without MWCNTs. These nano-cocoons are hemo-compatible, non-toxic to mice fibroblast cell lines (L929), have great potential to be used as nano biomaterials and they could be loaded with naturally anti-cancerous drug curcumin. The cocoon–curcumin complex is dispersible in saline and could be internalized by brain cancer cells (C6 glioma) while free curcumin dispersed in saline could not enter C6 glioma cells.

Elaboration of curcumin-loaded rice bran albumin nanoparticles formulation with increased in vitro bioactivity and in vivo bioavailability

Curcumin, a yellow pigment present in the spice turmeric (Curcuma longa), has been linked with various bioactivities, but its optimum potential is limited by its lack of dispersibility in aqueous solvents and poor oral bioavailability. Here, we employed a protein-based nanoparticle approach to improve bioactivity and bioavailability. Curcumin was encapsulated with 95.94% efficiency in biodegradable nanoparticulate formulation based on rice bran albumin (RBA). The mean particle diameter and ζ-potential of curcumin-loaded RBA nanoparticles (Cur-RBA-NPs) were 120 nm and −36.3 mV, respectively. The in vitro bioactivity and in vivo bioavailability of Cur-RBA-NPs were evaluated. The results indicated that the in vitro bioactivities (antioxidant activity, anti-inflammatory activity, and anti-proliferative activity on tumor cells) of Cur-RBA-NPs were superior to those of free curcumin, respectively. Moreover, Cur-RBA-NPs significantly enhanced the bioavailability of curcumin in rats as compared with free curcumin. Besides, the results clearly indicated the promise of RBA-based nanoparticles for oral delivery of poorly bioavailable molecules like curcumin.

Encapsulation of curcumin in polymeric nanoparticles for antimicrobial Photodynamic Therapy.

Curcumin (CUR) has been used as photosensitizer in antimicrobial Photodynamic Therapy (aPDT). However its poor water solubility, instability, and scarce bioavalibility hinder its in vivo application. The aim of this study was to synthesize curcumin in polymeric nanoparticles (NP) and to evaluate their antimicrobial photodynamic effect and cytoxicity. CUR in anionic and cationic NP was synthesized using polylactic acid and dextran sulfate by the nanoprecipitation method. For cationic NP, cetyltrimethylammonium bromide was added. CUR-NP were characterized by physicochemical properties, photodegradation, encapsulation efficiency and release of curcumin from nanoparticles. CUR-NP was compared with free CUR in 10% dimethyl sulfoxide (DMSO) as a photosensitizer for aPDT against planktonic and biofilms (mono-, dual- and triple-species) cultures of Streptococcus mutans, Candida albicans and Methicillin-Resistant Staphylococcus aureus. The cytotoxicity effect of formulations was evaluated on keratinocytes. Data were analysed by parametric (ANOVA) and non-parametric (Kruskal-Wallis) tests (α = 0.05). CUR-NP showed alteration in the physicochemical properties along time, photodegradation similar to free curcumin, encapsulation efficiency up to 67%, and 96% of release after 48h. After aPDT planktonic cultures showed reductions from 0.78 log10 to complete eradication, while biofilms showed no antimicrobial effect or reductions up to 4.44 log10. Anionic CUR-NP showed reduced photoinactivation of biofilms. Cationic CUR-NP showed microbicidal effect even in absence of light. Anionic formulations showed no cytotoxic effect compared with free CUR and cationic CUR-NP and NP. The synthesized formulations improved the water solubility of CUR, showed higher antimicrobial photodynamic effect for planktonic cultures than for biofilms, and the encapsulation of CUR in anionic NP reduced the cytotoxicity of 10% DMSO used for free CUR.

Induction of apoptosis in HeLa cancer cells by an ultrasonic-mediated synthesis of curcumin-loaded chitosan-alginate-STPP nanoparticles.

Natural herbal compounds have been widely introduced as an alternative therapeutic approach in cancer therapy. Despite potent anticancer activity of curcumin, its clinical application has been limited because of low water solubility and resulting poor bioavailability. In this study, we designed a novel ultrasonic-assisted method for the synthesis of curcumin-loaded chitosan–alginate–sodium tripolyphosphate nanoparticles (CS-ALG-STPP NPs). Furthermore, antitumor effect of curcumin-loaded NPs was evaluated in vitro. Field emission scanning electron microscopy (FE-SEM) and atomic force microscopy (AFM) were used to characterize the properties of NPs. Antitumor activity of curcumin-loaded NPs was assessed by using MTT and quantitative real-time polymerase chain reaction (qRT-PCR). FE-SEM and AFM data revealed the spherical morphology, and the average size of NPs was <50 nm. In vitro cytotoxicity assay suggested that curcumin-loaded CS-ALG-STPP NPs displayed significant antitumor activity compared with the free curcumin. Gene expression level analyses showed that curcumin NPs significantly increased the apoptotic gene expression. Collectively, our results suggest that curcumin-loaded NPs significantly suppressed proliferation and promoted the induction of apoptosis in human cervical epithelioid carcinoma cancer cells, which might be regarded as an effective alternative strategy for cancer therapy.

A Comparative Pharmacokinetic Assessment of a Novel Highly Bioavailable Curcumin Formulation with 95% Curcumin: A Randomized, Double-Blind, Crossover Study

ABSTRACTObjective: Curcumin exhibits many beneficial health-promoting characteristics. However, its poor oral absorption precludes its general use. This study assessed the bioavailability of a novel curcumin formulation compared to 95% curcumin and published results for various other curcumin formulations.Methods: A randomized, crossover, double-blind, comparator-controlled pharmacokinetic study was performed in 12 healthy adult subjects to determine the appearance of free curcumin and its metabolites curcumin sulfate and curcumin glucuronide in plasma after a single dose of a novel proprietary curcumin liquid droplet micromicellar formulation (CLDM) and unformulated 95% curcumin powder in capsule form. An equivalent 400-mg dose of each product was administered. The 95% curcumin contained 323 mg curcumin, and the CLDM contained 64.6 mg curcumin. Blood samples were drawn and plasma was analyzed for curcumin and its 2 conjugates without enzymatic hydrolysis by liquid chromatography–tandem mass spectroscopy.Results: Plasma levels of curcumin sulfate and curcumin glucuronide after 1.5 hours from CLDM were approximately 20 and 300 ng/mL, respectively, whereas the levels for 95% curcumin were near baseline. Free curcumin reached a maximum level of 2 ng/mL for CLDM and 0.3 ng/mL for 95% curcumin at 1.5 hours. For the CLDM, a small secondary free curcumin peak occurred at 12 hours and a tertiary 1.5-ng/mL peak occurred at 24 hours. The total curcumin absorbed as represented by the area under the curve (AUC)/mg administered curcumin for CLDM was 522 times greater than for the 95% curcumin.Conclusions: The novel CLDM formulation facilitates absorption and produces exceedingly high plasma levels of both conjugated and total curcumin compared to 95% curcumin. A comparison of the Cmax/mg curcumin and AUC/mg of administered curcumin for CLDM with data from pharmacokinetic studies of various enhanced absorption formulations indicate that the greatest absorption and bioavailability are produced with the novel CLDM formulation.

Exosomes for the Enhanced Tissue Bioavailability and Efficacy of Curcumin.

Exosomes are extracellular microvesicles with a particle size of 30-100nm and carry a cargo of proteins, lipids, RNA, and DNA. Their properties of shuttling in-and-out of the cells suggest that these particles can be exploited as a nano drug carrier. In this manuscript, we show that curcumin can be delivered effectively using milk-derived exosomes. Curcumin when mixed with exosomes in the presence of 10% ethanol:acetonitrile (1:1) provided a drug load of 18-24%, and the formulation stored at - 80°C was stable for 6months as determined by particle size analysis, drug load, and antiproliferative activity. The uptake of exosomes by cancer cells involved caveolae/clathrin-mediated endocytosis. Oral administration of exosomal curcumin (ExoCUR) in Sprague-Dawley rats demonstrated 3-5 times higher levels in various organs versus free agent. ExoCUR showed enhanced antiproliferative activity against multiple cancer cell lines including, breast, lung, and cervical cancer compared with the free curcumin. ExoCUR showed significantly higher anti-inflammatory activity measured as NF-κB activation in human lung and breast cancer cells. To determine in vivo antitumor activity, nude mice bearing the cervical CaSki tumor xenograft were treated with ExoCUR by oral gavage, curcumin diet, exosomes alone, and PBS as controls. While curcumin via dietary route failed to elicit any effect, exosomes had a modest (25-30%) tumor growth inhibition. However, ExoCUR showed significant inhibition (61%; p<0.01) of the cervical tumor xenograft. No gross or systemic toxicity was observed in the rats administered with the exosomes or ExoCUR. These results suggest that exosomes can be developed as potential nano carriers for delivering curcumin which otherwise has encountered significant tissue bioavailability issues in the past.

Curcumin encapsulated zeolitic imidazolate frameworks as stimuli responsive drug delivery system and their interaction with biomimetic environment

Metal organic frameworks (MOFs) exhibit unique features of finely tunable pore structures, excellent chemical stability and flexible surface structural functionality, making them advantageous for a wide range of applications including energy storage, compound separation, catalysis, and drug delivery. The present work enlightens a novel approach of single step fabrication of CCM-ZIF-8 as a drug carrier and its application as stimuli responsive drug delivery systems via external stimuli involving change in pH and in presence of biomimetic cell membrane like environment using liposomes and SDS micelles. The methodology is devoid of any post synthesis drug loading steps. The synthesized curcumin encapsulated ZIF-8 frameworks demonstrate ultrahigh drug encapsulation efficiency (ca. 83.33%) and good chemical stability. In vitro drug release of curcumin was three times higher in acidic medium than in physiological pH. Cytotoxicity results demonstrated enhanced therapeutic effect of CCM-ZIF-8 than free curcumin. Confocal microscopy results confirmed the easy cellular internalization of CCM-ZIF-8 in HeLa cells. Intracellular distribution studies at various incubation times confirmed the clathrin-mediated endocytosis to lysosomal pathway of CCM-ZIF-8, but without mitochondria being an intracellular fate. The results signify that CCM-ZIF-8 is an efficient drug carrier for passive tumor therapy in future for cancer treatments.

The Effects of Nanoencapsulated Curcumin-Fe3O4 on Proliferation and hTERT Gene Expression in Lung Cancer Cells.

The aim of the study wasto fabricate curcumin-loaded PLGA-PEG-Fe3O4 nanoparticles and comprise the effects of pure curcumin and curcumin-nanomagnetic encapsulated in PLGA-PEG on cell cytotoxicity and hTERT gene expression in A549 lung cancer cell line. Lung cancer is the most common cancer in men and one of the four main cancers that occurs in women. Telomerase is active in more than 85% of various cancerous cells such as lung cancer while its activity is very low in normal cells. Strong evidences of antitumor effects of curcumin; such as the activation of apoptosis, inhibition of angiogenesis and prevention of metastasis, have been confirmed. However, extensive clinical application of this relatively efficacious agent in cancer therapy has been limited because of poor aqueous solubility, and consequently, minimal systemic bioavailability. Nanoparticle-based targeted drug delivery approach has the potential for rendering curcumin specifically at the favorite site using an external magnetic field. It can also improve availability and circumvent the pitfalls of poor solubility. Curcumin and Fe3O4 were encapsulated inside the PLGA-PEG co-polymer. Then, the curcumin loaded PLGA-PEG-Fe3O4 nanoparticles were characterized using SEM, FTIR and VSM. In the next step, the cytotoxic effect of different concentrations (0-120 µM) of free curcumin and equivalent doses of curcumin-loaded PLGA-PEG-Fe3O4 was assessed using MTT assay at 24-72 hours. Also, gene expression levels of hTERT were measured through Realtime PCR. By encapsulation of curcumin-Fe3O4, cytotoxicity of the drug substantially increased for all concentrations. IC50 of pure curcumin and nano-encapsulated curcumin during 24, 48 and 72 hours was obtained as 50.5, 49.1 and 48.3 µM and 23.7, 13.6 and 7.3 µM, respectively. Moreover, nano-encapsulated curcumin showed time-dependent cytotoxic effect on A549 cell line during 24, 48, 72 hours in comparison to pure curcumin. In addition, the expression level of the hTERT was reduced with increasing concentrations in both pure and nano-encapsulated curcumin. Compared to pure form, nano-encapsulated curcumin caused further decline in the expression levels of the gene. Curcumin incorporating with Fe3O4 loaded into PLGA-PEG co-polymer, as an effective targeted carrier, can make a promising horizon in targeted lung cancer therapy.

Curcumin-encapsulated polymeric nanoparticles for metastatic osteosarcoma cells treatment

Osteosarcoma is a high-class malignant bone cancer with a less than 20% five-year survival rate due to its early metastasis potential. There is an urgent need to develop a versatile and innoxious drug to treat metastatic osteosarcoma. Curcumin (Cur) has shown its potential for the treatment of many cancers; however, the clinical implication of native curcumin is severely hindered by its intrinsic property. In this study, a mixed system of monomethoxy (polyethylene glycol)-poly(d, l-lactide-co-glycolide)/poly(e-caprolactone) (mPEG-PLGA/PCL) was used to build a formulation of curcumin-encapsulated nanoparticles (Cur-NPs), which significantly improved the solubility, stability and cellular uptake of curcumin. Moreover, the Cur-NPs were superior to free curcumin in the matter of inhibition on the proliferation, migration and invasion of osteosarcoma 143B cells. It was found that both free curcumin and Cur-NPs could decrease the expressions of c-Myc and MMP7 in the level of mRNA and protein, which explained why free curcumin and Cur-NPs could inhibit the proliferation and invasion of metastatic osteosarcoma 143B cells. The Cur-NPs provided a promising strategy for metastatic osteosarcoma treatment.

Encapsulation in lysozyme/A. Sphaerocephala Krasch polysaccharide nanoparticles increases stability and bioefficacy of curcumin

A facile approach to fabricate nanoparticles (NPs) via self-assembly of lysozyme (Ly) and purified Artemisia sphaerocephala Krasch seed polysaccharide (ASKP-3) was developed for the first time to encapsulate and protect curcumin. The nanoparticle size and morphology were characterized. The results showed that Ly/ASKP-3 NPs were spherical with narrow particle size distribution. Curcumin-loaded NPs greatly increased curcumin stability in phosphate buffer at physiological pH. The cancer cell viability assay indicated that encapsulated curcumin exhibited higher antitumor potential than free curcumin. Curcumin-loaded NPs was effectively endocytosed by HepG2 cells, resulting in enhanced apoptosis in cancer cells as compared to free curcumin. Furthermore, the curcumin-loaded NPs significantly increased the serum level of curcumin in mice after oral administration. Overall, our results demonstrated that nanosized proteins/polysaccharides complex could be used to protect labile lipophilic compounds such as curcumin to enhance their bioavailability in vivo, supporting potential application of curcumin-loaded proteins/polysaccharides complex in functional foods.

Antiplasmodial Activity and Toxicological Assessment of Curcumin PLGA-Encapsulated Nanoparticles.

Curcumin is a polyphenolic pigment isolated from the rhizomes of Curcuma longa (turmeric), a medicinal plant widely used in the ancient Indian and Chinese medicine. The antiplasmodial activity of curcumin is often hampered by its fast metabolism and poor water solubility, thus its incorporation into a delivery system could circumvent this problem. This study aimed to evaluate the in vivo antiplasmodial activity and the toxicity assessment of curcumin incorporated into poly (lactic-co-glycolic) acid (PLGA) nanoparticles. Curcumin was loaded with poly (D,L-lactic-co-glycolic acid) (PLGA) using solvent evaporation from oil-in-water single emulsion method. The nanoparticles were characterized and evaluated in vivo for antimalarial activities using Peter’s 4-day suppressive protocol in mice model. Hematological and hepatic toxicity assays were performed on whole blood and plasma, respectively. In vivo anti-parasitic test and toxicity assays for free and encapsulated drug were performed at 5 and 10 mg/kg. In vitro cytotoxicity of free and PLGA encapsulated curcumin (Cur-PLGA) to RAW 264.7 cell line was also determined at varying concentrations (1000–7.8 μg/mL). The size and entrapment efficiency of the nanoparticulate drug formulated was 291.2 ± 82.1 nm and 21.8 ± 0.4 respectively. The percentage parasite suppression (56.8%) at 5 mg/kg was significantly higher than in free drug (40.5%) of similar concentration (p < 0.05) but not at 10 mg/kg (49.5%) at 4-day post-treatment. There were no significant differences in most of the recorded blood parameters in free curcumin and PLGA encapsulated nanoparticulate form (p > 0.05) except in lymphocytes which were significantly higher in Cur-PLGA compared to the free drug (p < 0.05). There were no significant differences in hepatotoxic biomarkers; aspartate aminotransferase and alanine aminotransferase concentrations in various treatment groups (p > 0.05). At higher concentrations (1000 and 500 μg/mL), Cur-PLGA entrapped nanoparticle showed higher toxicity compared with the free drug (p < 0.05) in exposed RAW 264.7 cell line. The cell viability was, however, higher in Cur-PLGA nanoparticles than in free curcumin at lower concentrations (p > 0.05). The antiplasmodial activity and safety of Cur-PLGA was better at lower concentration.

Improving anti-melanoma effect of curcumin by biodegradable nanoparticles.

Melanoma is known as the most common malignant cutaneous cancer. Curcumin, a natural component, has been shown to have various activities such as anti-oxidant, anti-septic, anti-inflammatory, anti-biotic, anti-amyloid and anti-thrombosis. However, there is a greatest obstacle in the administration of curcumin due to its hydrophobicity and low oral bioavailability. In this study, we formulated curcumin-loaded MPEG-PLA (Curcumin/MPEG-PLA) micelles aiming to improve its solubility in aqueous solution and investigated anti-tumor effect on melanoma in vitro and in vivo. The spherical curcumin/MPEG-PLA micelles were completely dispersed in normal saline and could release curcumin in a sustained manner in vitro. In addition, we demonstrated that curcumin/MPEG-PLA micelles had stronger cytotoxicity and induced a higher percentage of apoptosis in B16 and A375 cancer cells than free curcumin in vitro. The immunohistochemical study revealed that curcumin/MPEG-PLA micelles induced more melanoma cell apoptosis than free curcumin and inhibited neovascularization in tumor tissues. In conclusion, the curcumin/MPEG-PLA micelles have potential clinical application for melanoma.

Formulation optimization, characterization, and evaluation of in vitro cytotoxic potential of curcumin loaded solid lipid nanoparticles for improved anticancer activity

The aim of the present research was to develop a novel, biocompatible, amenable to industrial scale up and affordable solid lipid nanoparticles (SLN) preparation of curcumin and evaluate the therapeutic efficacy in vitro using cancer cells. We have incorporated cholesterol as the lipid to prepare SLN along with the Poloxamer-188 as stabilizer. High shear homogenization was used to prepare the SLN and formulation was optimized using Quality by Design The optimized Chol CUR SLN exhibited a narrow size distribution with a particle size of 166.4±3.5nm. Percentage encapsulation (%EE) was found to be 76.9±1.9%. The SLN were further characterized by DSC, FTIR, XRD and drug release. In vitro cell studies in MDA-MB-231 (Human Breast cancer) cell line revealed that the Chol CUR SLN showed superior cytotoxicity and uptake in comparison to the free curcumin. Furthermore, Chol CUR SLN induced a significantly higher apoptosis compared to free CUR treatment. These results indicated that the curcumin encapsulated in Chol SLN was able to significantly improve the cytotoxic potential and induction of apoptosis in MDA-MB-231 cells. The promising result from our study could lead a further exploration of this nanoparticle formulation to be utilized clinically for cancer treatment.

Nanoparticles prepared by proso millet protein as novel curcumin delivery system

Encapsulation of lipophilic bioactive compounds using plant-derived proteins as delivery systems has received increasing interest. In this study, proso millet protein was extracted by either wet milling or 60% (v/v) aqueous ethanol and then used as the wall material to encapsulate curcumin. Millet protein was composed of prolamines that showed a significant difference in surface hydrophobicity depending on extraction procedure. The millet protein-curcumin nanoparticles were spherical with diameter around 250–350nm. The entrapment efficiency ranged from 11.2% to 78.9%, with millet protein extracted by ethanol showing better performance than that by wet milling process. The encapsulated curcumin exhibited a lower degradation rate than free curcumin at 60°C. The encapsulation showed no negative effect on the antioxidant activity of curcumin as assessed by the DPPH and ABTS assays. These results suggested that MP could be a promising encapsulant for the delivery of lipophilic compounds.

Co-delivery of hydrophilic and hydrophobic drugs by micelles: a new approach using drug conjugated PEG–PCLNanoparticles

Co-delivery strategy has been proposed to minimize the amount of each drug and to achieve the synergistic effect for cancer therapies. A conjugate of the antitumor drug, doxorubicin, with diblock methoxy poly (ethylene glycol)-poly caprolactone (mPEG-PCL) copolymer was synthesized by the reaction of mPEG–PCL copolymer with doxorubicin in the presence of p-nitrophenylchloroformate. The conjugated copolymer was characterized in vitro by 1H-NMR, FTIR, DSC and GPC techniques. Then, the doxorubicin conjugated mPEG–PCL(DOX–mPEG-PCL) was self-assembled into micelles in the presence of curcumin in aqueous solution. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM).The encapsulation efficiency of doxorubicin and curcumin were 82.31 ± 3.32 and 78.15 ± 3.14%, respectively. The results revealed that the micelles formed by the DOX–mPEG-PCL with and without curcumin have spherical structure with average size of 116 and 134 nm respectively. The release behavior of curcumin and doxorubicin loaded to micelles were investigated in a different media. The release rate of micelles consisted of the conjugated copolymer was pH dependent as it was higher at lower pH than in neutral condition. Another feature of the conjugated micelles was a sustained release profile. The cytotoxicity of micelles were evaluated by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, atetrazole) assay on lung cancer A549 cell lines. In vitro cytotoxicity assay showed that the mPEG–PCL copolymer did not affect the growth of A549 cells. The cytotoxic activity of the micelles against A549 cells was greater than free doxorubicin and free curcumin.