Liposome-encapsulated Curcumin Research Articles

Temperature- and pH-responsive injectable chitosan hydrogels loaded with doxorubicin and curcumin as long-lasting release platforms for the treatment of solid tumors.

The efficacy of treating solid tumors with chemotherapy is primarily hindered by dose-limiting toxicity due to off-target effects and the heterogeneous drug distribution caused by the dense extracellular matrix. The enhanced permeability and retention (EPR) effect within tumors restricts the circulation and diffusion of drugs. To overcome these obstacles, hydrogels formed in situ at the tumor site have been proposed to promote drug accumulation, retention, and long-lasting release. We developed a thiolated chitosan (CSSH) hydrogel with a gelation point of 37°C. Due to the pH-sensitive characteristics of disulfides, the prepared hydrogel facilitated drug release in the acidic tumor environment. A drug release system composed of hydrophilic doxorubicin (Dox) and hydrophobic liposome-encapsulated curcumin (Cur-Lip) was designed to enhance the long-lasting therapeutic impacts and reduce adverse side effects. These composite gels possess a suitable gelation time of approximately 8-12min under physiological conditions. The cumulative release ratio was higher at pH = 5.5 than at pH = 7.4 over the first 24h, during which approximately 10% of the Dox was released, and Cur was released slowly over the following 24-120h. Cell assays indicated that the Cur-Lip/Dox/CSSH gels effectively inhibited the growth of cancer cells. These in situ-formed Cur-Lip/Dox gels with long-term drug release capabilities have potential applications for tumor suppression and tissue regeneration after surgical tumor resection.

Liposome-encapsulated curcumin attenuates HMGB1-mediated hepatic inflammation and fibrosis in a murine model of Wilson's disease.

Wilson's disease (WD) is an inherited disorder of copper metabolism with predominant hepatic manifestations. Left untreated, it can be fatal. Current therapies focus on treating copper overload rather than targeting the pathophysiology of copper-induced liver injuries. We sought to investigate whether liposome-encapsulated curcumin (LEC) could attenuate the underlying pathophysiology of WD in a mouse model of WD. Subcutaneous administration in a WD mouse model with ATP7B knockout (Atp7b-/-) resulted in robust delivery of LEC to the liver as determined by in-vitro and in-vivo imaging. Treatment with LEC attenuated hepatic injuries, restored lipid metabolism and decreased hepatic inflammation and fibrosis, and thus hepatosplenomegaly in Atp7b-/- mice. Mechanistically, LEC decreased hepatic immune cell and macrophage infiltration and attenuated the hepatic up-regulation of p65 by preventing cellular translocation of high-mobility group box-1 (HMGB-1). Moreover, decreased translocation of HMGB1 was associated with reduced splenic CD11b+/CD43+/Ly6CHi inflammatory monocyte expansion and circulating level of proinflammatory cytokines. Nevertheless there was no change in expression of oxidative stress-related genes or significant copper chelation effect of LEC in Atp7b-/- mice. Our results indicate that treatment with subcutaneous LEC can attenuate copper-induced liver injury in an animal model of WD via suppression of HMGB1-mediated hepatic and systemic inflammation. These findings provide important proof-of-principle data to develop LEC as a novel therapy for WD as well as other inflammatory liver diseases.

Pluronic F127-liposome-encapsulated curcumin activates Nrf2/Keap1 signaling pathway to promote cell migration of HaCaT cells.

Curcumin (CUR) is an extract of Curcuma longa Linn., which has various pharmacological activities. The instability, low water solubility and bioavailability of CUR greatly limit its clinical application. This work prepared Pluronic F127-liposome-encapsulated curcumin (CUR-LIP-F127) and explored its functional role in wound healing. Liposome-encapsulated curcumin (CUR-LIP) and CUR-LIP-F127 were prepared. Human keratinocyte cell line (HaCaT) was treated with CUR, Pluronic F127-liposome (LIP-F127) and CUR-LIP-F127, or combined with ML385 (Nrf2 inhibitor). The expression of mRNAs and proteins was detected by quantitative real-time PCR and western blotting. MTT and wound healing assays were performed to detect cell viability and migration. CUR, LIP-F127 and CUR-LIP-F127 all had no influence on cell viability of HaCaT cells. CUR-LIP-F127 treatment significantly accelerated cell migration and enhanced the expression of nuclear factor erythroid-related factor 2 (Nrf2) and kelch-like erythroid cell-derived protein 1 (Keap1) in HaCaT cells with respect to CUR or LIP-F127 treatment. ML385 treatment impaired CUR-LIP-F127-mediated promotion of migration and up-regulation of Nrf2 and Keap1 in HaCaT cells. This work demonstrated that CUR-LIP-F127 activated Nrf2/Keap1 signaling pathway to promote migration of HaCaT cells, suggesting that CUR-LIP-F127 may contribute to wound healing.

Curcumin-Loaded Liposome Preparation in Ultrasound Environment under Pressurized Carbon Dioxide.

Curcumin-loaded liposomes were prepared using a supercritical carbon dioxide (SCCO2)–ultrasound environment system. The experiments were performed at temperatures of 40–70 °C and pressures of 10–25 MPa in a batch system with ultrasonication for 60 min. Transmission electron microscopy (TEM) images revealed liposome products with spherical morphologies and diameters of <100 nm. Dynamic light scattering (DLS) analysis indicated that the curcumin-loaded liposome nanosuspension exhibited good stability. Changing the operating conditions influenced the amount of liposome-encapsulated curcumin; as the operating temperature or pressure increased, the diameter of the liposome products and the amount of liposome-encapsulated curcumin increased and decreased, respectively. Herein, we described an innovative and practical organic-solvent-free method for generating liposomes from phospholipids.

Engineering of Portable Smartphone Integrated with Liposome-Encapsulated Curcumin for Onsite Visual Ratiometric Fluorescence Imaging of Hypochlorite.

Precisely onsite monitoring of hypochlorite (ClO- ) is of great significance to guide its rational use, reducing/avoiding its potential threat toward food safety and human health. Considering ClO- could quench fluorescence of curcumin (CCM) by oxidizing the o-methoxyphenol of CCM into benzoquinone, a portable ratiometric fluorescence sensor integrated with smartphone was designed for realizing the visual point-of-care testing (POCT) of ClO- . The amphiphilic phospholipid polymer was used as carrier to wrap curcumin, forming a novel liposome-encapsulated CCM, which provided a scaffold to bind with [Ru(bpy)3 ]2+ through electrostatic interaction, thus assembling [Ru(bpy)3 ]2+ -functionalized liposome-encapsulated CCM ([Ru(bpy)3 ]2+ @CCM-NPs). Further integrated with smartphone, visual imaging of [Ru(bpy)3 ]2+ @CCM-NPs could be achieved and the accurate onsite detection of ClO- could be realized with a detection limit of 66.31 nM and a linear range of 0.2210 to 80.0 μM. In addition, the sensor could monitor ClO- in real samples with an onsite detection time of ∼154.0 s.

In vitro and in vivo activity of liposome-encapsulated curcumin for naturally occurring canine cancers.

Curcumin has well-established anti-cancer properties in vitro, however, its therapeutic potential has been hindered by its poor bioavailability. Lipocurc is a proprietary liposome-encapsulated curcumin formulation that enables intravenous delivery and has been shown to reach its highest concentration within lung tissue. The goal of this study was to characterize the anti-cancer and anti-angiogenic activity of Lipocurc in vitro, in addition to evaluating Lipocurc infusions in dogs with naturally occurring cancer. We therefore evaluated the effect of Lipocurc, relative to free curcumin, on the viability of canine osteosarcoma, melanoma and mammary carcinoma cell lines, as well as the ability of Lipocurc to inhibit endothelial cell viability, migration and tube formation. We also undertook a pilot clinical trial consisting of four weekly 8-hour Lipocurc infusions in 10 cancer-bearing dogs. Tumour cell proliferation was inhibited by curcumin at concentrations exceeding those achievable in the lung tissue of dogs. Similarly, equivalent high concentrations of Lipocurc and curcumin also inhibited endothelial cell viability, migration and tube formation. Four out of six dogs completing planned infusions of Lipocurc experienced stable disease; however, no radiographic responses were detected.

In vitro delivery of curcumin with cholesterol-based cationic liposomes

A new cholesterol-based cationic lipid was synthesized; liposomes prepared on its basis were evaluated as drug delivery vehicles for curcumin. Free and liposome-encapsulated curcumin cytotoxicity against HeLa, A549, HepG2, K562 and 1301 cell lines was assessed. Liposomal curcumin with ED50 values ranging from 2.5-10 microM exhibited 2-8 times higher cytotoxicity than free curcumin. The synthetic cholesterol-based cationic lipid also enhanced cellular uptake of curcumin into tested cells. Cationic liposome alone showed low cytotoxicity at high doses with ED50 values of 90-210 microM.

RETRACTED: Liposome-encapsulated curcumin suppresses neuroblastoma growth through nuclear factor-kappa B inhibition

Nuclear factor-κB (NF-κB) has been implicated in tumor cell proliferation and survival and in tumor angiogenesis. We sought to evaluate the effects of curcumin, an inhibitor of NF-κB, on a xenograft model of disseminated neuroblastoma. For invitro studies, neuroblastoma cell lines NB1691, CHLA-20, and SK-N-AS were treated with various doses of liposomal curcumin. Disseminated neuroblastoma was established invivo by tail vein injection of NB1691-luc cells into SCID mice, which were then treated with 50 mg/kg/day of liposomal curcumin 5 days/week intraperitoneally. Curcumin suppressed NF-κB activation and proliferation of all neuroblastoma cell lines invitro. Invivo, curcumin treatment resulted in a significant decrease in disseminated tumor burden. Curcumin-treated tumors had decreased NF-κB activity and an associated significant decrease in tumor cell proliferation and an increase in tumor cell apoptosis, as well as a decrease in tumor vascular endothelial growth factor levels and microvessel density. Liposomal curcumin suppressed neuroblastoma growth, with treated tumors showing a decrease in NF-κB activity. Our results suggest that liposomal curcumin may be a viable option for the treatment of neuroblastoma that works via inhibiting the NF-κB pathway.

Evaluation of an Oral Carrier System in Rats: Bioavailability and Antioxidant Properties of Liposome-Encapsulated Curcumin

To enhance the curcumin absorption by oral administration, liposome-encapsulated curcumin (LEC) was prepared from commercially available lecithins (SLP-WHITE and SLP-PC70) and examined for its interfacial and biochemical properties. A LEC prepared from 5 wt % of SLP-PC70 and 2.5 wt % of curcumin gave a good dispersibility with 68.0% encapsulation efficiency for curcumin, while those from SLP-WHITE did not. Moreover, the resulting LEC using SLP-PC70 was confirmed to be composed of small unilamellar vesicles with a diameter of approximately 263 nm. The resulting LEC was then examined for its effect on bioavailability in Sprague-Dawley (SD) rats. Three forms of curcumin [curcumin, a mixture of curcumin and SLP-PC70 (lecithin), and LEC] were then administered orally to SD rats at a dose of 100 mg curcumin/kg body weight. The pharmacokinetic parameters following curcumin administration were determined in each form. Pharmacokinetic parameters after oral administration of LEC were compared to those of curcumin and a mixture of curcumin and lecithin. High bioavailability of curcumin was evident in the case of oral LEC; a faster rate and better absorption of curcumin were observed as compared to the other forms. Oral LEC gave higher C(max) and shorter T(max) values, as well as a higher value for the area under the blood concentration-time curve, at all time points. These results indicated that curcumin enhanced the gastrointestinal absorption by liposomes encapsulation. Interestingly, the plasma antioxidant activity following oral LEC was significantly higher than that of the other treatments. In addition, the plasma curcumin concentration was significantly correlated to plasma antioxidant activities, and enhanced curcumin plasma concentrations might exert a stronger influence on food functionality of curcumin. The available information strongly suggests that liposome encapsulation of ingredients such as curcumin may be used as a novel nutrient delivery system.

Liposome-Encapsulated Curcumin Suppresses Growth of Head and Neck Squamous Cell CarcinomaIn vitroand in Xenografts through the Inhibition of Nuclear Factor κB by an AKT-Independent Pathway

The purpose of this study was to determine whether a liposomal formulation of curcumin would suppress the growth of head and neck squamous cell carcinoma (HNSCC) cell lines CAL27 and UM-SCC1 in vitro and in vivo. HNSCC cell lines were treated with liposomal curcumin at different doses and assayed for in vitro growth suppression using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. A reporter gene assay was done on cell lines to study the effect of liposomal curcumin on nuclear factor kappaB (NFkappaB) activation. Western blot analysis was done to determine the effect of curcumin on the expression of NFkappaB, phospho-IkappaBalpha, phospho-AKT (pAKT), phospho-S6 kinase, cyclin D1, cyclooxygenase-2, matrix metalloproteinase-9, Bcl-2, Bcl-xL, Mcl-1L, and Mcl-1S. Xenograft mouse tumors were grown and treated with intravenous liposomal curcumin. After 5 weeks, tumors were harvested and weighed. Immunohistochemistry and Western blot analyses were used to study the effect of liposomal curcumin on the expression of NFkappaB and pAKT. The addition of liposomal curcumin resulted in a dose-dependent growth suppression of both cell lines. Liposomal curcumin treatment suppressed the activation of NFkappaB without affecting the expression of pAKT or its downstream target phospho-S6 kinase. Expression of cyclin D1, cyclooxygenase-2, matrix metalloproteinase-9, Bcl-2, Bcl-xL, Mcl-1L, and Mcl-1S were reduced, indicating the effect of curcumin on the NFkappaB pathway. Nude mice xenograft tumors were suppressed after 3.5 weeks of treatment with i.v. liposomal curcumin, and there was no demonstrable toxicity of liposomal curcumin upon autopsy. Immunohistochemistry and Western blot analysis on xenograft tumors showed the inhibition of NFkappaB without affecting the expression of pAKT. Liposomal curcumin suppresses HNSCC growth in vitro and in vivo. The results suggest that liposomal curcumin is a viable nontoxic therapeutic agent for HNSCC that may work via an AKT-independent pathway.

R424 – Suppression of HNSCC with Liposomal Curcumin and Cisplatin

Problem To investigate whether curcumin, previously shown to inhibit growth of head and neck squamous cell carcinoma (HNSCC), can potentiate the anti-tumor effects of cisplatin in vitro and in vivo. Methods HNSCC cells were treated with curcumin and cisplatin, individually and together, and assayed for growth using MTT, western blotting, and immunofluorescence. Five-week old female athymic nude mice were utilized for in vivo experiments. HNSCC cells were injected to form xenograft tumors. Liposomal curcumin (50 ug/kg, maximum volume of 100ul) was administered intravenously three times per week for four weeks via tail vein injection. Mice were divided into three groups: no injection, liposomes alone, or liposomal cur-cumin. At the end of the fourth week, a single dose of intraperitoneal cisplatin was given to all groups. At the end of five weeks, the mice were euthanized and tumors were dissected and weighed. Results Addition of curcumin or cisplatin alone or in combination resulted in cell death. Introduction of suboptimal levels of both agents in vitro demonstrated a synergistic suppression of HNSCC cell line growth compared to individual agents. Xenograft tumors in nude mice treated with combination curcumin and cisplatin showed superior tumor growth suppression compared to control mice and mice treated with liposome alone. Average tumor size for mice treated with combination therapy was 30% smaller than controls. Conclusion Curcumin potentiates the anti-tumor activity of Cisplatin in vivo. Our data supports further investigation into the potential use of curcumin in combination with cisplatin in the treatment of HNSCC. Significance Current treatment modalities for HNSCC carry significant morbidity, which has led to the investigation of less toxic therapies. Previous studies by our group have demonstrated that liposome-encapsulated curcumin can suppresses growth of HNSCC. In this study, we assess the potential of combining liposomal curcumin with cisplatin in the treatment of HNSCC.