Curcumin-loaded Poly Research Articles

Inhalation treatment of idiopathic pulmonary fibrosis with curcumin large porous microparticles

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with high mortality and poor prognosis. Curcumin shows anti-inflammatory effect by suppressing pro-inflammatory cytokines and inhibiting NF-κB mediated inflammation. Here, we developed inhalable curcumin-loaded poly(lactic-co-glycolic)acid (PLGA) large porous microparticles (LPMPs) for the treatment of IPF. Curcumin LPMPs were rough and loose particles with many pores on the surfaces and channels in the inner spaces. The mean geometric diameter of them was larger than 10 µm while the aerodynamic diameter was only 3.12 µm due to their porous structures. They showed a fine particle fraction (FPF) <4.46 μm of 13.41%, 71% cumulative release after 9 h, and more importantly, they avoided uptake by alveolar macrophages. Therefore, most of released curcumin had opportunities to enter lung tissues. Rat pulmonary fibrosis models were established via once intratracheal administration of bleomycin. Curcumin powders and curcumin LPMPs were administered on Days 2, 7, 14, and 21. Curcumin LPMPs remarkably attenuated lung injuries, decreased hydroxyproline contents, reduced the synthesis of collagen I, and inhibited the expressions of TNF-α, TGF-β1, NF-κB p65 and MMP9. Moreover, curcumin LPMPs showed higher antifibrotic activity than curcumin powders. Curcumin LPMPs are a promising inhalable medication for the treatment of IPF.

Evaluation of curcumin loaded chitosan/PEG blended PLGA nanoparticles for effective treatment of pancreatic cancer

Pancreatic cancer is considered as one of the most lethal type of cancer with a poor 5-year survival rate. Cancer metastasis represents one of the primary cause which limits therapy against this disease. Current chemotherapeutic approaches are largely ineffective, thus calling for the development of alternative strategies to combat this disease. In this regard, numerous studies have reported the anticancer effect of curcumin in different types of cancer including pancreatic cancer. However, low aqueous solubility, poor stability and decreased bioavailability associated with native curcumin holds back its use in clinical settings. In order to enhance its therapeutic value, polymeric nanoparticles (NPs) represent an ideal delivery system. Further, surface modification of NPs with various macromolecules, such as chitosan and polyethylene glycol (PEG) holds tremendous potential for improving the bioavailability and circulation time of native drug in the blood. In the present study, we have explored the above approach to formulate curcumin-loaded Poly d,l-lactide-co-glycolide (PLGA) NPs and further surface coated it with chitosan and PEG (CNPs) with anticipation to reduce the limitations associated with native curcumin delivery for achieving an optimum therapeutic effect. Results revealed that NPs are of nanometre range having smooth and spherical surface morphology and with an efficient loading of curcumin. In vitro, cellular studies revealed superior cytotoxicity, enhanced anti-migratory, anti-invasive and apoptosis-inducing ability of CNPs in metastatic pancreatic cancer in comparison to a native counterpart. Thus, we anticipate that the results from these studies can open up novel options for the treatment of pancreatic cancer.

“Curcumin-loaded Poly (d, l-lactide-co-glycolide) nanovesicles induce antinociceptive effects and reduce pronociceptive cytokine and BDNF release in spinal cord after acute administration in mice”

Given the poor bioavailability of curcumin, its antinociceptive effects are produced after chronic intravenous administration of high doses, while poly (d,l-lactide-co-glycolide)-loaded vesicles (PLGA) can improve drug delivery. This paper investigates the antinociceptive effects of curcumin-loaded PLGA nanovesicles (PLGA-CUR) administered via intravenous (i.v.) or intrathecal (i.t.) routes at low and high doses. The following models of pain were used: formalin test, zymosan-induced hyperalgesia and sciatic nerve ligation inducing neuropathic allodynia and hyperalgesia. PLGA-CUR administered intravenously was able to reduce the response to nociceptive stimuli in the formalin test and hyperalgesia induced by zymosan. Curcumin, instead, was inactive. Low-dose i.t. administration of PLGA-CUR significantly reduced allodynia produced by sciatic nerve ligation, whereas low doses of curcumin did not change the response to nociceptive stimuli. Long-lasting antinociceptive effects were observed when high doses of PLGA-CUR were administered intrathecally. At high doses, i.t. administration of curcumin only exerted rapid and transient antinociceptive effects. Measurement of cytokine and BDNF in the spinal cord of neuropathic mice demonstrate that the antinociceptive effects of PLGA-CUR depend on the reduction in cytokine release and BDNF in the spinal cord. The results demonstrate the effectiveness of PLGA-CUR and suggest that PLGA-CUR nanoformulation might be a new potential drug in the treatment of pain.

Melt electrospinning vs. solution electrospinning: A comparative study of drug-loaded poly (ε-caprolactone) fibres

Curcumin-loaded poly (ε-caprolactone) (PCL) fibres prepared by melt and solution electrospinning methods were both fabricated to investigate their difference in characterization and drug release behaviour. The increasing curcumin content did not influence the morphologies of melt electrospun fibre, but enhanced the range of diameter distribution of solution electrospun fibre owing to the curcumin aggregates in the spinning solution which disturbed the stability of jet. Moreover, a large amount of curcumin with amorphous state could be loaded in the melt electrospun fibre. Whereas the limited solubility of curcumin in the solvent led to the drug aggregates dispersing within the solution electrospun fibre. In addition, the melt electrospun fibres had low drug release rate without burst release on the profiles due to the high crystallinity in the fibre, but high drug release rate and burst release occurred on the release profiles of the solution electrospun fibres because of their low crystallinity, porous structure and roughness surface.

Curcumin Encapsulated into Methoxy Poly(Ethylene Glycol) Poly(ε-Caprolactone) Nanoparticles Increases Cellular Uptake and Neuroprotective Effect in Glioma Cells.

Curcumin is a natural polyphenolic compound isolated from turmeric (Curcuma longa) with well-demonstrated neuroprotective and anticancer activities. Although curcumin is safe even at high doses in humans, it exhibits poor bioavailability, mainly due to poor absorption, fast metabolism, and rapid systemic elimination. To overcome these issues, several approaches, such as nanoparticle-mediated targeted delivery, have been undertaken with different degrees of success. The present study was conducted to compare the neuroprotective effect of curcumin encapsulated in poly(ε-caprolactone) and methoxy poly(ethylene glycol) poly(ε-caprolactone) nanoparticles in U251 glioblastoma cells. Prepared nanoparticles were physically characterized by laser doppler anemometry, transmission electron microscopy, and X-ray diffraction. The results from laser doppler anemometry confirmed that the size of poly(ε-caprolactone) and poly(ethylene glycol) poly(ε-caprolactone) nanoparticles ranged between 200-240 nm for poly(ε-caprolactone) nanoparticles and 30-70 nm for poly(ethylene glycol) poly(ε-caprolactone) nanoparticles, and transmission electron microscopy images revealed their spherical shape. Treatment of U251 glioma cells and zebrafish embryos with poly(ε-caprolactone) and poly(ethylene glycol) poly(ε-caprolactone) nanoparticles loaded with curcumin revealed efficient cellular uptake. The cellular uptake of poly(ethylene glycol) poly(ε-caprolactone) nanoparticles was higher in comparison to poly(ε-caprolactone) nanoparticles. Moreover, poly(ethylene glycol) poly(ε-caprolactone) di-block copolymer-loaded curcumin nanoparticles were able to protect the glioma cells against tBHP induced-oxidative damage better than free curcumin. Together, our results show that curcumin-loaded poly(ethylene glycol) poly(ε-caprolactone) di-block copolymer nanoparticles possess significantly stronger neuroprotective effect in U251 human glioma cells compared to free curcumin and curcumin-loaded poly(ε-caprolactone) nanoparticles.

Antibacterial performance and in vivo diabetic wound healing of curcumin loaded gum tragacanth/poly(ε-caprolactone) electrospun nanofibers

In this study we describe the potential of electrospun curcumin-loaded poly(ε-caprolactone) (PCL)/gum tragacanth (GT) (PCL/GT/Cur) nanofibers for wound healing in diabetic rats. These scaffolds with antibacterial property against methicillin resistant Staphylococcus aureus as gram positive bacteria and extended spectrum β lactamase as gram negative bacteria were applied in two forms of acellular and cell-seeded for assessing their capability in healing full thickness wound on the dorsum of rats. After 15days, pathological study showed that the application of GT/PCL/Cur nanofibers caused markedly fast wound closure with well-formed granulation tissue dominated by fibroblast proliferation, collagen deposition, complete early regenerated epithelial layer and formation of sweat glands and hair follicles. No such appendage formation was observed in the untreated controls during this duration. Masson's trichrome staining confirmed the increased presence of collagen in the dermis of the nanofiber treated wounds on day 5 and 15, while the control wounds were largely devoid of collagen on day 5 and exhibited less collagen amount on day 15. Quantification analysis of scaffolds on day 5 confirmed that, tissue engineered scaffolds with increased amount of angiogenesis number, granulation tissue area (μ2), fibroblast number, and decreased epithelial gap (μ) can be more effective compared to GT/PCL/Cur nanofibers.

Concanavaline A conjugated bacterial polyester-based PHBHHx nanoparticles loaded with curcumin for breast cancer therapy

The aim of this study was to evaluate therapeutic potential of curcumin-loaded poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin-loaded NPs (ConA-CUR-NPs) for breast cancer treatment. The size and zeta potential of prepared NPs were about 228 ± 5 nm and −23.3 mV, respectively. The entrapment efficiencies of polymer/drug weight ratios, 1.25CUR-NPs, 2.5CUR-NPs, 5CUR-NPs, ConA-1.25CUR-NPs, ConA-2.5CUR-NPs and ConA-5CUR-NPs were found to be ≈68, 55, 45, 70, 60 and 51%, respectively. Optimized NPs formulations in the freeze-dried form were assessed with their short-term stability for 30 days of storage at 4 °C and 25 °C. Anticancer activity of ConA-CUR-NPs was proved by MTT assay and reconfirmed by double staining and flow cytometry results. The anticancer activity of ConA-CUR-NPs was measured in human breast cancer cells (MDA-MB 231) in vitro, and the results revealed that the ConA-CUR-NPs had better tumor cells decline activity.

Protective action of curcumin and nano-curcumin against arsenic-induced genotoxicity in rats in vivo.

We explored whether nanoformulation of curcumin can cause better protective effect than free curcumin against arsenic-induced genotoxicity. Curcumin-loaded Poly(lactic-co-glycolic acid) nanoparticles (CUR-NP) were prepared by emulsion technique. The CUR-NP were water soluble and showed biphasic release pattern. Rats were divided into 5 groups of 6 each. Group I served as the control. Group II rats were exposed to sodium arsenite (25ppm) daily through drinking water for 42days. Groups III, IV and V were maintained as in Group II, however, they were also administered empty nanoparticle, curcumin (100mg/kgbw) and CUR-NP (100mg/kgbw), respectively, by oral gavage during the last 14days of arsenic exposure. On the 43rdday, genotoxic effects were evaluated in bone marrow cells. Arsenic increased chromosomal aberrations, micronuclei formation and DNA damage. Both free curcumin and CUR-NP attenuated these arsenic-mediated genotoxic effects. However, the result suggests that nanoformulation have better protective effect than free curcumin at the same dose level.

Preparation of curcumin-loaded poly(ester amine) nanoparticles for the treatment of anti-angiogenesis.

The aim of this study was to prepare curcumin loaded poly(ester amine) nanoparticles and enhance their hydrophilicity and treatment efficacy on anti-angiogenesis zebra fish model. Poly(ester amine) (PEA) copolymer was synthesized in this study. The curcumin-loaded PEA nanoparticles were prepared through double emulsion-solvent evaporation technique. The average particle size of obtained nanoparticles was about 100 nm. The zeta potential of prepared nanoparticles was about 35.8+/-2.4 mV. Transmission electron microscopy demonstrated a narrow size distribution with in vitro release profile demonstrating in vitro slow release of curcumin from the PEA nanoparticles. The in vitro cytotoxicity of the curcumin encapsulated PEA nanoparticles nearly had the same tendency of cytotoxic activity in vitro with free curcumin on tumor cells. In vitro cellular uptake of the curcumin-loaded nanoparticles demonstrated in Hela cells demonstrated that this kind of nanoparticles can be a promising candidate as a drug delivery system to cancer cells. The Cur/PEA nanoparticles more efficiently inhibited angiogenesis (in vivo) in transgenic zebra fish model and Alginate-encapsulated tumor cells than free curcumin. No mortality or significant lesions were observed from histopathological study of the major organs. From our results, we can conclude that the prepared PEA nanoparticles are an efficient curcumin drug delivery system for anti-angiogenesis therapy.

Development of curcumin-loaded poly(hydroxybutyrate-co-hydroxyvalerate) nanoparticles as anti-inflammatory carriers to human-activated endothelial cells

Curcumin (Cm)-loaded poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanoparticles (CmPN) were obtained and characterized and their effect on human endothelial cells (HEC) was assessed. Different CmPN formulations have been prepared using the emulsion solvent evaporation technique, and characterized for size, structure, Zeta potential, Cm entrapment efficiency, and in vitro Cm release. CmPN cytotoxicity and cellular uptake have been followed using HEC. Also, the effect of CmPN treatment on the p38MAPK signaling pathway in endothelial cells was investigated. The results obtained by electron and atomic force microscopy revealed the spherical shape of the CmPN formulation. Based on size and encapsulation efficiency, the CmPN formulation with the average diameter of 186 nm and with the highest encapsulation efficiency (83 %) has been used in the further studies. The release of Cm from CmPN was ~18 % after 8 h of incubation at 37 °C, followed by a slow release until 144 h, when it reached 44 %, indicating a controlled release. CmPN are taken up by HEC and exhibited low cytotoxicity at concentrations up to 10 μM. The pre-treatment of HEC with CmPN before exposure to tumor necrosis factor-alpha (TNF-α) determined a decrease of p38MAPK phosphorylation. In conclusion, Cm encapsulated into PHBV nanoparticles, at concentration up to 10 μM, has low cytotoxicity and display anti-inflammatory activity on TNF-α-activated HEC by suppressing the phosphorylation of p38MAPK.

Characteristics of curcumin-loaded poly (lactic acid) nanofibers for wound healing

Curcumin (Cur) is a well-known extract of the root of Curcuma longa L. that has multi biological functions such as anti-oxidation, anti-inflammatory, anti-cancer, and wound healing properties. In the present study, poly (lactic acid) (PLA) nanofibers were used as a carrier for Cur because PLA nanofibers are biocompatible and have a high-specific surface area and high porosity, which can enhance the functional properties of Cur. The chemical and biological characteristics of Cur/PLA blended nanofibers containing varied amounts of Cur were examined. An increase from 0.125 to 6.250 wt% Cur in PLA caused a decrease in the diameters of the nanofibers from 971 ± 274 to 562 ± 177 nm. At Cur concentrations of <1.250 wt%, PLA and Cur showed good miscibility in the blended nanofibers, as shown by FTIR analysis and tensile tests. The inclusion of Cur in the blended nanofibers at concentration as low as 0.125 wt% promotes the attachment and proliferation of cells. The in vivo wound healing capability of Cur-loaded PLA nanofibers was assessed in a mouse model; treatment with Cur-loaded PLA nanofibers significantly increased the rate of wound closure (87 %) by day 7 compared with that of PLA nanofibers (58 %). The results of this study suggest that Cur-loaded nanofibers with appropriate Cur concentration are nontoxic and have potential as component of wound-healing patches.

Preparation of curcumin loaded poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) nanofibers and their in vitro antitumor activity against Glioma 9L cells

The purpose of this work was to develop implantable curcumin-loaded poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) nanofibers, which might have potential application in cancer therapy. Curcumin was incorporated into biodegradable PCEC nanofibers by electrospinning method. The surface morphology of the composite nanofibers was characterized on Scanning Electron Microscope (SEM). The average diameter of the nanofibers was 2.3-4.5μm. In vitro release behavior of curcumin from the fiber mats was also studied in detail. The in vitro cytotoxicity assay showed that the PCEC fibers themselves did not affect the growth of rat Glioma 9L cells. Antitumor activity of the curcumin-loaded fibers against the cells was kept over the whole experiment process, while the antitumor activity of pure curcumin disappeared within 48 h. These results strongly suggested that the curcumin/PCEC composite nanofibers might have potential application for postoperative chemotherapy of brain cancers.