Chuda Chittasupho

Targeted delivery of doxorubicin to A549 lung cancer cells by CXCR4 antagonist conjugated PLGA nanoparticles.

Doxorubicin is used to treat a variety of cancers, but dose limiting toxicity or intrinsic and acquired resistance limits its application in many types of cancer. CXCR4 is a chemokine receptor which implicates in metastasis of cancers including lung cancer. LFC131, a peptide inhibitor of CXCR4-ligand binding, is a linear type of low molecular weight CXCR4 antagonist. In this study, we investigated the possibility of using LFC131 conjugated nanoparticles for targeted delivering doxorubicin to CXCR4 expressing lung cancer cells. The LFC131 peptide was conjugated to sodium carboxylmethyl cellulose coated poly(dl-lactic-co-glycolic acid) (PLGA) nanoparticles. Binding and cellular uptake of doxorubicin-loaded LFC131 conjugated nanoparticles (LFC131-DOX NP) in adenocarcinomic human alveolar basal epithelial cells called A549 cells were higher and faster than that of untargeted nanoparticles. The specificity of CXCR4-mediated internalization of LFC131-DOX NPs was confirmed by using free LFC131 peptide or anti-CXCR4 monoclonal antibody. Cell studies suggested that sustained release of doxorubicin afforded by PLGA nanoparticles may enable LFC131-DOX NP as a targeted and controlled release drug delivery system.

Pectin nanoparticle enhances cytotoxicity of methotrexate against hepG2 cells

Objective: This work has aimed to develop methotrexate-conjugated pectin nanoparticle for delivering a cytotoxic drug to hepatic cancer cell. Methods: Methotrexate was conjugated to pectin by carbodiimide chemistry. Nanoparticles of pectin conjugated with methotrexate (MTX) were then fabricated by using ionotropic gelation. The size, shape and surface charge were characterized by dynamic light scattering and microscopic method. Cytotoxicity of MTX-pectin nanoparticle was monitored by MTT assay. Results: Methotrexate-pectin nanoparticle was successfully formulated. Drug release study indicated that MTX-NP exhibited sustained drug release at pH 7.4. Sustained release of methotrexate may enable methotrexate-pectin nanoparticle as a controlled drug delivery system. Cytotoxicity study confirmed the activity of the drug incorporated in nanoparticles. In addition, the cytotoxicity of methotrexate was increased when conjugated to pectin nanoparticles, compared to free methotrexate. Conclusions: This study verified that pectin can deliver methotrexate to hepatic cancer cell and provide sustained drug delivery. The cytotoxicity of methotrexate was enhanced when methotrexate was conjugated to pectin indicating the improved drug delivery to cancer cell.

Productivity and quality of volatile oil extracted from Mentha spicata and M. arvensis var. piperascens grown by a hydroponic system using the deep flow technique

The purpose of this study was to determine the differences between spearmint (Mentha spicata L.) and Japanese mint (M. arvensis L. var. piperascens Malinv.) cultivated in either soil or nutrient solution using the deep flow technique (DFT). The differences were measured in terms of harvest period (full bloom period) and quantity and chemical components of volatile oils. The spearmint and Japanese mint were cultivated in four different nutrient formulas: plant standard nutrient, plant standard nutrient with an amino acid mixture, plant standard nutrient with a sulphur compound, and a combination of plant standard nutrient with an amino acid mixture and a sulphur compound. We observed that cultivation of spearmint and Japanese mint in nutrient solution using DFT is an effective method to provide high production of volatile oil, since it results in an earlier harvest period and higher quantity of volatile oil. We determined that for spearmint an amino acid mixture is an appropriate nutrient supplement to enhance production of volatile oil with optimum carvone content. Finally, we observed high menthol content in Japanese mint grown in all four nutrient formulas; however, supplementation with a combination of sulphur fertilisation and amino acid mixture yields the highest quantity of volatile oil.

CXCR4 targeted dendrimer for anti-cancer drug delivery and breast cancer cell migration inhibition

Graphical abstract Figure. No Caption available. Abstract CXCR4 and its ligand CXCL12 play a critical role in the metastasis of various types of cancer including breast cancer. Breast tumors preferentially metastasize to the lung, bones and distant lymph nodes, secreting high levels of CXCL12. We hypothesized that targeted inhibition of CXCR4 in breast cancer cells should suppress CXCR4‐positive tumor cells toward secondary metastatic sites. In the present study, the efficacy of CXCR4 targeted dendrimers carrying DOX (LFC131‐DOX‐D4) on cellular binding, cytotoxicity, and migration of BT‐549‐Luc and T47D breast cancer cells was investigated. PAMAM dendrimers encapsulating DOX was surface functionalized with LFC131 peptide which recognized CXCR4 expressed on the surface of breast cancer cells. The LFC131‐DOX‐D4 bound to breast cancer cells resulting in significantly enhanced in vitro cellular toxicity as compared with non‐targeted dendrimers. The LFC131‐D4 exhibited remarkable reduced migration of BT‐549‐Luc breast cancer cells toward chemoattractant. This report demonstrated the potential utility of LFC131‐dendrimer conjugates for breast cancer therapy and metastasis.

Wound healing activity of Pluchea indica leaf extract in oral mucosal cell line and oral spray formulation containing nanoparticles of the extract

Abstract Context: Pluchea indica (L.) Less (Asteraceae) is an herb used as a traditional medicine for wound healing. The chemical compounds found in Pluchea indica leaves are phenolic acids, flavonoids, anthocyanins and carotenoids. Objective: This study investigates the effect of Pluchea indica leaf ethanol extract and its nanoparticles (NPs) on cytotoxicity, cell survival and migration of human oral squamous carcinoma cell line. Materials and methods: Cell viability was measured using MTT assay to assess the effect of Pluchea indica leaf extract and NPs (1–500u2009μg/mL) on cytotoxicity and cell survival. The effect of Pluchea indica leaf extract and NPs on cell migration was determined by scratch assay. The % relative migration was calculated after 24, 48 and 72u2009h of treatment. Results: The sizes of Pluchea indica leaf extract NPs were in a range of nanometers. NPs possessed negative charge with the polydispersity index (PDI) smaller than 0.3. After the treatment for 24, 48 and 72u2009h, Pluchea indica leaf extract had IC50 value of 443.2, 350.9 and 580.5u2009μg/mL, respectively, whereas the IC50 value of NPs after the treatment for 24, 48 and 72u2009h were 177.4, 149.2 and 185.1u2009μg/mL, respectively. The % relative migration of cells was significantly increased when the cells were treated with 62.5 and 125u2009μg/mL of the extract and 62.5u2009μg/mL of NPs. Discussion and Conclusions: NPs increased cytotoxicity of the Pluchea indica leaf extract, increased the migration of cells at low concentration and increased colloidal stability of the extract in an oral spray formulation.

Surface modification of poly(D,L-lactic-co-glycolic acid) nanoparticles using sodium carboxymethyl cellulose as colloidal stabilize.

Poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NPs) have been widely used as drug delivery systems for both small molecules and macromolecules. However, the colloidal stability problem remains unsolved. This study aims to investigate the possibility of using sodium carboxymethyl cellulose (SCMC) as a stabilizing agent of PLGA NPs. In this study, PLGA NPs were fabricated using various concentrations of SCMC (0.01, 0.1 and 0.5% w/v) by solvent displacement method. SCMC coated NPs were characterized using DLS, FTIR, DSC, colorimetric method. Particle size, polydispersity index, zeta potential values and SCMC adsorption increased with SCMC concentration. FTIR spectra, DSC thermograms and results of colorimetry suggested the interaction of SCMC and PLGA NPs. The stability of SCMC coated PLGA NPs was observed during the storage of three weeks in water. The stability of SCMC coated NPs in serum was also evaluated. Cell viability study revealed that there was no toxicity increased when SCMC was used as a stabilizing agent up to a concentration of 0.1% w/v. SCMC coated PLGA NPs bound A549 cells in a time dependent manner and with a greater extent than uncoated PLGA NPs. In conclusion, SCMC can be used to stabilize PLGA NPs by adsorbing on the surface of NPs.

Doxorubicin-Loaded Micelle Targeting MUC1: A Potential Therapeutic for MUC1 Triple Negative Breast Cancer Treatment

BACKGROUNDnTriple negative breast cancer (TNBC) is an aggressive disease associated with poor prognosis and lack of validated targeted therapy. Thus chemotherapy is a main adjuvant treatment for TNBC patients, but it associates with severe toxicities. For a better treatment outcome, we developed an alternative therapeutic, doxorubicin (DOX)-loaded micelles targeting human mucin1 protein (MUC1) that is less toxic, more effective and targeted to TNBC.nnnMETHODSnFrom many candidate peptides, QNDRHPR-GGGSK (QND) and HSQLPQV-GGGSK (HSQ) were identified computationally, synthesized and purified using solid phase peptide synthesis and semipreparative HPLC. The peptides showed significant high binding to MUC1 expressing cells using a fluorescent microscope. The peptides were then conjugated on pegylated octadecyl lithocholate copolymer. DOX-encapsulated micelles were formed through self-assembly. MUC1-targeted micelles were characterized using dynamic light scattering (DLS) and Transmission Electron Microscopy (TEM). Drug entrapment efficiency was examined using a microplate reader. Cytotoxicity, binding, and uptake were also investigated.nnnRESULTSnTwo types of DOX-loaded micelles with different targeting peptides, QND or HSQ, were developed. DOX-loaded micelles were spherical in shape with average particle size around 300-320 nm. Drug entrapment efficiency of untargeted and targeted DOX micelles was about 71-93%. Targeted QND-DOX and HSQ-DOX micelles exhibited significantly higher cytotoxicity compared to free DOX and untargeted DOX micelles on BT549-Luc cells. In addition, significantly greater binding and uptake were observed for QND-DOX and HSQ-DOX micelles on BT549-Luc and T47D cells.nnnCONCLUSIONnTaken together, these results suggested that QND-DOX and HSQ-DOX micelles have a potential application in the treatment of TNBC-expressing MUC1.

CXCR4-targeted Nanoparticles Reduce Cell Viability, Induce Apoptosis and Inhibit SDF-1α Induced BT-549-Luc Cell Migration In Vitro

BACKGROUNDnCXCR4 possesses a critical role in several intracellular events such as chemotaxis, invasion and adhesion, which are associated with metastasis of cancer cell.nnnOBJECTIVEnIn this study, CXCR4 targeted polymeric nanoparticle was developed for delivering cytotoxic drug and blocking the chemokine induced migration of cells expressing CXCR4.nnnMETHODnA peptide which was a linear form of CXCR4 antagonist (LFC131) was attached to PLGA nanoparticles (LFC131-NPs) and PLGA nanoparticles encapsulating DOX (LFC131-DOX-NPs). The cellular binding and internalization of LFC131-DOX-NPs were investigated.nnnRESULTSnThe binding and internalization of LFC131-DOX-NPs were higher and more rapidly compared to unconjugated NPs. LFC131-NPs blocked SDF-1α induced migration of BT-549-Luc cells. MTT assays demonstrated that LFC131-NPs and LFC131-DOX-NPs decreased cell viability in a dose dependent manner in 24, 72 and 120 h incubation.nnnCONCLUSIONnA treatment concept of blocking breast cancer cell migration from interaction with SDF- 1α by using LFC131-NPs and then attacking breast cancer cells with doxorubicin might increase the efficacy of current breast cancer treatment.