Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier, PLGA

Nanoscaled devices have great potential for drug delivery applications due to their small size. In the present study, we report for the first time the preparation and evaluation of antitumor efficacy of 5-fluorouracil (5-FU)-entrapped poly (D, L-lactic-co-glycolic acid) (PLGA) nanoparticles with dependence on the lactide/glycolide combination of PLGA. 5-FU-loaded PLGA nanoparticles with two different monomer combinations, 50-50 and 90-10 were synthesized using a modified double emulsion method, and their biological evaluation was done in glioma (U87MG) and breast adenocarcinoma (MCF7) cell lines. 5-FU-entrapped PLGA 50-50 nanoparticles showed smaller size with a high encapsulation efficiency of 66%, which was equivalent to that of PLGA 90-10 nanoparticles. Physicochemical characterization of nanoparticles using differential scanning calorimetry and X-ray diffraction suggested the presence of 5-FU in molecular dispersion form. In vitro release studies showed the prolonged and sustained release of 5-FU from nanoparticles with both the PLGA combinations, where PLGA 50-50 nanoparticles showed faster release. Nanoparticles with PLGA 50-50 combination exhibited better cytotoxicity than free drug in a dose- and time-dependent manner against both the tumor cell lines. The enhanced efficiency of PLGA 50-50 nanoparticles to induce apoptosis was indicated by acridine orange/ethidium bromide staining. Cell cycle perturbations studied using flow cytometer showed better S-phase arrest by nanoparticles in comparison with free 5-FU. All the results indicate that PLGA 50-50 nanoparticles possess better antitumor efficacy than PLGA 90-10 nanoparticles and free 5-FU. Since, studies have shown that long-term exposure of ailing tissues to moderate drug concentrations is more favorable than regular administration of higher concentration of the drug; our results clearly indicate the potential of 5-FU-loaded PLGA nanoparticles with dependence on carrier combination as controlled release formulation to multiplex the therapeutic effect of cancer chemotherapy

A Rapid Protocol for Somatic Embryogenesis Mediated Regeneration in Banana (Musa Spp.) Cv. Nendran

A simple and rapid protocol for somatic embryogenesis in banana cv. Nendran (AAB) using immature male flowers (IMF) has been developed. The IMF produced palewhite to yellow, globular embryogenic callus on MS medium supplemented with BA (0.05 - 0.50mgL-1) and picloram (0.50 - 2.00mgL-1) with explant response of to 30 per cent. Addition of ascorbic acid (20mgL-1) and Gelrite© (0.45 per cent) to callus induction medium reduced interference from phenolic exudation. Embryogenesis was induced (33.3 to 60 per cent) on semisolid (0.30 per cent Gelrite©) MS medium supplemented with BA 2mgL-1 + IAA 0.5mgL-1. The somatic embryos showed 60-80 per cent germination on half- strength semisolid MS medium with BA 2mgL-1 + IAA 0.5mgL-1. Transfer of germinated embryos to semisolid MS medium supplemented with BA 2mgL-1 + NAA 1mgL-1under 14 h light /8h dark photoperiod resulted in hundred percent conversion to plantlets. This protocol takes merely 6 months for producing plantlets from immature flower buds through somatic embryogenesis, without any intermediate liquid cultures

Magnetoelectric coupling in strained strontium titanate and Metglas based magnetoelectric trilayer

Direct magneto electric coupling is observed with a magnetoelectric coupling coefficient (MECC) of 806 mV cm−1 Oe−1 at 750 Hz in strontium titanate (STO) - Metglas - strontium titanate (STO-Metglas-STO) trilayer thin films with a total thickness of 600 nm. The piezoelectricity in the strained STO layer, which is otherwise a paraelectric material, enabled the sandwiched magneto electric structure to exhibit a fair sub resonant magneto electric coupling. Theoretical models proposed by Bichurin et al. and Hasanyan et al. are employed to calculate the values of MECC at sub resonant condition for the system, which is noted as 853 mV cm−1 Oe−1. The frequency dependence of MECC coefficient is also calculated and the resonance frequency is estimated as 706 Hz.publishe

Folic acid conjugated δ-valerolactone-poly(ethylene glycol) based triblock copolymer as a promising carrier for targeted doxorubicin delivery.

The aim of this study is to test the hypothesis that the newly synthesized poly(δ-valerolactone)/poly(ethylene glycol)/poly(δ-valerolactone) (VEV) copolymer grafted with folic acid would impart targetability and further enhance the anti-tumor efficacy of doxorubicin (DOX). Here, folic acid conjugated VEV (VEV-FOL) was synthesized by a modified esterification method and characterized using IR and NMR. DOX loaded VEV-FOL micelles were synthesized using a novel solvent evaporation method and were obtained with a mean diameter of 97 nm with high encapsulation efficiency and sustained in vitro release profile. Comparative studies of polymer micelles with and without folate for cellular uptake and cytotoxicity were done on folate receptor-positive breast cancer cell line, MDAMB231. The intracellular uptake tests showed significant increase in folate micellar uptake when compared to non-folate-mediated micelles. MTT assay followed by apoptosis assays clearly indicated that folate decorated micelles showed significantly better cytotoxicity (IC50 = 0.014 µM) and efficiency to induce apoptosis than other treated groups. Moreover, a significant G2/M arrest was induced by DOX loaded VEV-FOL micelles at a concentration where free drug failed to show any activity. Thus, our results show that the folic acid-labeled VEV copolymer is a promising biomaterial with controlled and sustainable tumor targeting ability for anticancer drugs which can open new frontiers in the area of targeted chemotherapy

Multiple myeloma presenting as extensive limb gangrene

Cryoglobulinemic vasculitis is one of the rare manifestations of plasma cell dyscrasias. A 54-year-old diabetic housewife presented with pain and blackish discoloration of her right foot and medial four fingers of the right hand. She underwent transmetatarsal amputation of her right and left feet due to digital gangrene 1 year and 9 months back respectively. On diagnostic evaluation, she was found to have multiple myeloma with cryoglobulinemic vasculitis. This case report emphasizes the importance of considering the possibility of cryoglobulinemic vasculitis and underlying plasma cell dyscrasias in patients presenting with gangrene of extremity

Cell cycle analysis.

<p>Variation in cell cycle of MDAMB231 cells on treatment with different DOX formulations (0.01 µM) for 24 h analyzed using FACS.</p

Transmission Electron Microscope (TEM) image of doxorubicin loaded Folate conjugated VEV micelles (FVEVDMs).

<p>Transmission Electron Microscope (TEM) image of doxorubicin loaded Folate conjugated VEV micelles (FVEVDMs).</p

Cellular uptake showing comparison of intracellular fluorescence of doxorubicin: Incubation of MDAMB231 cells with different doxorubicin formulations (1 µM) for 2 h is shown by (a) Confocal microscopy images showing intracellular fluorescence of doxorubicin (b) Flow cytometry histograms showing intensity of uptake (c) Comparison of uptake efficiency by intensity of doxorubicin fluorescence.

<p>Bars marked with *p<0.05,***p<0.001 shows the level of significance of difference at the same concentration (n = 3).</p