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Thiruvananthapuram, India

Vini R.,Cancer Research Programme | Sreeja S.,Cancer Research Programme
BioFactors | Year: 2015

Punica granatum has a recorded history of pharmacological properties which can be attributed to its rich reservoir of phytochemicals. Investigations in recent years have established its tremendous potential as an antitumorogenic agent against various cancers including breast cancer, which is the second leading cause of cancer-related deaths in women. The plausible role of Punica as a therapeutic agent, as an adjuvant in chemotherapy, and its dietary implications as chemopreventive agent in breast cancer have been explored. Mechanistic studies have revealed that Punica extracts and its components, individually or in combination, can modulate and target key proteins and genes involved in breast cancer. Our earlier finding also demonstrated the role of methanolic extract of pomegranate pericarp in reducing proliferation in breast cancer by binding to estrogen receptor at the same time not affecting uterine weight unlike estradiol or tamoxifen. This review analyses other plausible mechanisms of Punica in preventing the progression of breast cancer and how it can possibly be a therapeutic agent by acting at various steps of carcinogenesis including proliferation, invasion, migration, metastasis, angiogenesis, and inflammation via various molecular mechanisms. © 2015 BioFactors. Source


Ashwanikumar N.,Rajiv Gandhi Center for Biotechnology | Kumar N.A.,Cancer Research Programme | Asha Nair S.,Cancer Research Programme | Vinod Kumar G.S.,Rajiv Gandhi Center for Biotechnology
Acta Biomaterialia | Year: 2014

The encapsulation of 5-fluorouracil (5-FU) in hydrophobic polymeric materials is made feasible by a lipid-based prodrug approach. A lipid-5-FU conjugate of 5-FU with palmitic acid was synthesized in two-step process. A synthesized dipalmitoyl derivative (5-FUDIPAL) was characterized using Fourier transform infrared spectroscopy and 1H-nuclear magnetic resonance. The 5-FUDIPAL was encapsulated in polyester-based polymers by the double emulsion-solvent evaporation method. The nanoparticles were characterized by scanning electron microscopy, transmission electron microscopy and dynamic light scattering. The thermal stability was assessed by differential scanning calorimetry data. In vitro release kinetics measurements of the drug from nanoparticles showed the controlled release pattern over a period of time. Cytotoxicity measurements by MTT assay confirmed that dipalmitoyl derivative in nano formulation successfully inhibited the cell growth. Thus the combined physical and biological evaluation of the different polyester-based nanoparticle containing the modified drug showed a facile approach to delivering 5-FU to the tumour site with enhanced efficacy. © 2014 Acta Materialia Inc. Source


Ashwanikumar N.,Rajiv Gandhi Center for Biotechnology Poojappura | Kumar N.A.,Cancer Research Programme | Nair S.A.,Cancer Research Programme | Vinod Kumar G.S.,Rajiv Gandhi Center for Biotechnology Poojappura
RSC Advances | Year: 2014

In the present study, we report a phenylalanine (Phe)-containing self-assembling peptide nanofibrous material (RATEA-F8) for the delivery of the drug 5-fluorouracil (5-FU) and leucovorin (LV), which exhibit synergistic actions against colon cancer. Solid phase peptide synthesis, followed by morphological characterisation of the material, depicts a facile formation of nanofiber in a time-dependent manner. Structural analysis and physical characterisation of the material were performed by transmission electron microscopy (TEM), circular dichriosm, spectrofluorimetry and oscillatory rheology. The in vitro release was also studied for 5-FU, LV and a model molecule namely Phe. The facile cellular uptake (monitored using confocal microscopy) and significant amount of cytotoxicity displayed by the drug entrapped peptide nano material further confirms the efficacy of the developed system for the drug delivery purpose. © 2014 The Royal Society of Chemistry. Source


Besses C.,Cancer Research Programme | Zeller W.,Ballindamm 3 | Alvarez-Larran A.,Cancer Research Programme | Coll R.,Clinical Research | And 4 more authors.
International Journal of Clinical Pharmacology and Therapeutics | Year: 2012

Objective: To ascertain the role of patient age as an influencing factor in the pharmacokinetics of anagrelide and to clarify whether different dosing is required in young (18-50 years) vs. elderly (≥ 65 years) patients with essential thrombocythemia (ET). Method: This Phase II, multicenter, open-label study compared the pharmacokinetics, pharmacodynamics and tolerability of anagrelide and its active metabolite, 3-hydroxy-anagrelide, in young and elderly patients with ET. Three days prior to pharmacokinetic assessment, patients divided their normal daily anagrelide into a structured twice-daily dosing (BID) schedule. Serial blood samples were obtained for pharmacokinetic and pharmacodynamic analysis over a 12-h dosing interval. Anagrelide and 3-hydroxy-anagrelide plasma concentrations were normalized to a common dose (1 mg BID) to control for dosing differences between patients. Patients were monitored routinely for adverse events (AEs) and vital signs. Results: A total of 24 patients (12 young; 12 elderly) completed the study. The dose-normalized anagrelide maximum observed plasma concentration (Cmax) and area under the plasma concentration vs. time curve over one dosing interval (AUC τ), were higher in elderly patients compared with young patients (Cmax: 3.63 vs. 2.66 ng/ml; p = 0.09, AUCτ: 10.3 vs. 6.4 ngxh/ml; p = 0.01). In contrast, the dose-normalized 3-hydroxy-anagrelide Cmax and AUCτ were lower in the elderly patients when compared with young patients (Cmax: 4.19 vs. 7.26 ng/ml; p = 0.02, AUCτ: 17.4 vs. 27.6 ngxh/ml; p = 0.03). No significant difference was observed in the geometric mean terminal half-life (t1/2) of anagrelide in elderly and young patients (1.4 vs. 1.3 h, respectively; p = 0.38), whereas the geometric mean t1/2 of 3-hydroxy-anagrelide was significantly longer in the elderly patients compared with the young patients (3.5 vs. 2.7 h, respectively; p = 0.01). There were no significant differences in platelet count or vital signs between the age groups. Anagrelide was well tolerated; there were no serious AEs or AEs that led to withdrawal from the study. Conclusions: To conclude, the differences observed in anagrelide and 3-hydroxy-anagrelide pharmacokinetics do not justify using a different dosing regimen in young vs. elderly patients with ET. ©2012 Dustri-Verlag Dr. K. Feistle. Source


Ashwanikumar N.,Rajiv Gandhi Center for Biotechnology | Kumar N.A.,Cancer Research Programme | Nair S.A.,Cancer Research Programme | Kumar G.S.V.,Rajiv Gandhi Center for Biotechnology
Colloids and Surfaces B: Biointerfaces | Year: 2014

We now report the synthesis of a random copolymer of poly-lactic-co-glycolic acid (PLGA) grafted branched polyethylenimine (BPEI) and the use of it as a multi drug delivery system (DDS). The methotrexate (MTX) was conjugated to BPEI through DCC/NHS chemistry. The copolymer-drug conjugate (PBP-MTX) was characterised by FT-IR and 1H NMR spectroscopy. The PBP-MTX was converted into nanomicelles with entrapped 5-fluorouracil (5-FU) through nanoprecipitation technique. The size, shape, morphology and surface charge of the nanomicelles were confirmed using different techniques. The thermal behaviour and distribution of both conjugated and entrapped drug through the polymeric matrix were assessed by differential scanning calorimetry (DSC) and powder X-ray diffraction analysis (PXRD). In vitro drug release pattern of the nanomicelles was examined to ascertain the release pattern of two drugs namely 5-FU and MTX. The cellular uptake studies demonstrated higher uptake of the nanomicelles in colon cancer cell line HCT 116. Further the cytotoxicity evaluation of nanomicelles illustrated promising action which confirms the use of the system as a potential DDS to colon cancer. © 2014 Elsevier B.V. Source

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