Forster Resonance Energy Transfer-Based Stability Assessment of PLGA Nanoparticles in Vitro and in Vivo

The knowledge of in vitro and in vivo stability of polymeric nanoparticles is vital for the development of clinical formulations for drug delivery and cell labeling applications. Forster resonance energy transfer (FRET)-based fluorescence labeling approaches are promising tools to study nanoparticle stability under different physiological conditions. Here, we present the FRET-based stability assessment of poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating BODIPY-FL12 and Nile Red as the donor and acceptor, respectively. The stability of PLGA nanoparticles is studied via monitoring the variations of fluorescence emission characteristics along with colloidal characterization. Accordingly, PLGA nanoparticles are colloidally stable for more than 2 weeks when incubated in aqueous buffers in situ, whereas in vitro particle degradation starts in between 24 and 48 h, reaching a complete loss of FRET at 72 h as shown with fluorescence microscopy imaging and flow cytometry analysis. PLGA nanoparticles systemically administered to mice predominantly accumulate in the liver, in which FRET no longer takes place at time points as early as 24 h postadministration as determined by ex vivo organ imaging and flow cytometry analysis. The results of this study expand our knowledge on drug release and degradation behavior of PLGA nanoparticles under different physiological conditions, which will prove useful for the rational design of PLGA-based formulations for various applications that can be translated into clinical practice

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Synthesis, crystal structure and photoluminescence study of green light emitting bis(1[(4-butylphenyl)imino]methyl naphthalen-2-ol) Ni(II) complex

Synthetically feasible and cost effective Ni(II) complex phosphor (4) as green organic light emitting diode (OLED) was prepared by using Schiff base 1-[(4-butylphenyl)imino]methyl naphthalen-2-ol (3). The single crystals of Ni(II) complex were grown from chloroform and hexane (1:1 v/v) solution. The green crystals of the complex were characterized by using single crystal XRD studies and were evaluated for their photophysical properties. From the Diffused Reflectance Spectrum of the complex, the measured band gap energy was found to be 1.83 eV and the PL spectrum of the complex showed emission peak at 519 nm. The excitation peaks at 519 nm were appeared at 394 nm and 465 nm. The Commission Internationale De L'Eclairage (CIE) chromaticity diagram indicated that, the complex exhibit green color. Hence, Ni(II) complex (4) could be a promising green OLED for developing strong electroluminescent materials for flat panel display applications

A novel sarsasapogenin glycoside from Asparagus racemosus elicits protective immune responses against HBsAg

The aim of the present investigation was to evaluate the adjuvant potential of a novel sarsasapogenin glycoside (immunoside) isolated from Asparagus racemosus in combination with hepatitis B surface antigen(HBsAg). Various in vitro and animal derived protocols were used to determine the response of immunoside adjuvanted with HBsAg and the results were compared with alum adjuvanted with HBsAg.Several biomarkers such as antibody titre (IgG, IgG1/IgG2a) were measured in mice sera. Cell proliferation, cytokines (IL-2, IFN-� and IL-4), and lymphocyte sub-populations (CD4/CD8, CD3 and CD19)were determined in splenocytes from mice administered subcutaneously with test substances. In these cells CD4/CD8 derived IFN-� release was also determined. Macrophage preparations were used for the determination of IL-12, IFN-� and nitrite content. Seroconversion potential was compared with a standard vaccine. Acute safety evaluation of immunoside was done in mice. Effect of immunoside on red blood cell haemolysis was determined. The results have suggested that immunoside potentially enhanced anti-HBsAg immune response via augmenting Th1/Th2 response in a dose dependent manner

Clinically-Applicable Perfluorocarbon-Loaded Nanoparticles For In vivo Photoacoustic, (19)F Magnetic Resonance And Fluorescent Imaging

Contains fulltext : 193511.pdf (publisher's version ) (Open Access)Photoacoustic imaging (PAI) is an emerging biomedical imaging technique that is now coming to the clinic. It has a penetration depth of a few centimeters and generates useful endogenous contrast, particularly from melanin and oxy-/deoxyhemoglobin. Indocyanine green (ICG) is a Food and Drug Administration-approved contrast agents for human applications, which can be also used in PAI. It is a small molecule dye with limited applications due to its fast clearance, rapid protein binding, and bleaching effect. Methods: Here, we entrap ICG in a poly(lactic-co-glycolic acid) nanoparticles together with a perfluorocarbon (PFC) using single emulsion method. These nanoparticles and nanoparticle-loaded dendritic cells were imaged with PA, (19)F MR, and fluorescence imaging in vitro and in vivo. Results: We formulated particles with an average diameter of 200 nm. The encapsulation of ICG within nanoparticles decreased its photobleaching and increased the retention of the signal within cells, making it available for applications such as cell imaging. As little as 0.1x10(6) cells could be detected in vivo with PAI using automated spectral unmixing. Furthermore, we observed the accumulation of ICG signal in the lymph node after subcutaneous injection of nanoparticles. Conclusion: We show that we can label primary human dendritic cells with the nanoparticles and image them in vitro and in vivo, in a multimodal manner. This work demonstrates the potential of combining PAI and (19)F MRI for cell imaging and lymph node detection using nanoparticles that are currently produced at GMP-grade for clinical use

RLJ-NE-299A: A new plant based vaccine adjuvant

Alum has been in use since long as an adjuvant for vaccines. However, its use as a vaccine adjuvant offers limitation in supporting cell mediated response. Therefore, a new plant based product RLJ-NE-299A from Picrorhiza kurroa reported for its immunostimulatory activity, has been explored for its potential as an alternative adjuvant. In order to compare the adjuvant activity with alum, antigen-specific immune responses were evaluated following immunization with a formulation containing hepatitis B surface antigen (HBsAg) adjuvanted with RLJNE- 299A and alum in mice. The adjuvant RLJ-NE-299A up-regulated remarkably the expression of Th1 cytokines IL-2, IL-12, IFN-�,TNF � and Th2 cytokine IL-4 in lymph node cell cultures after 2 weeks of primary immunization with HBsAg. Further, the levels of both immunoglobulins IgG2a (Th1) and IgG1 (Th2) subtypes increased profoundly in blood sera of mice immunized with HBsAg/RLJ-NE-299A. The results indicated that RLJ-NE-299A has strong potential to increase both cell mediated and humoral immune responses and is capable of sustaining the total antigen-specific antibody response. Besides, the RLJ-NE-299A provides a signal to gear up both CD4 helper cells (Th1 and Th2) and CD8 cells populations, which may have important implications for vaccination against hepatitis B virus. Variable doses of RLJ-NE-299A (0.312 1340 �g) containing vaccine antigen (HBsAg) were well tolerated with optimum T cell response at 2.5 �g/ml. Not only this, the adjuvant was also able to induce cellular immune responses to HBsAg as evidenced by Th1 and Th2 cytokines upregulation, which enabled mice to overcome the unresponsiveness to antigen HBsAg encountered with alum-adjuvanted vaccine in otherwise non-responding mice population. The study presents evidence that the HPLC standardized fraction RLJ-NE-299A, is an adjuvant of choice over alum in improving and maintaining the improved immune status against HBsAg, and may also prove useful adjuvant candidate with other vaccine antigens, too

Nanoparticles for "two color" F-19 magnetic resonance imaging: Towards e combined imaging of biodistribution and degradation

Contains fulltext : 217381.pdf (publisher's version ) (Open Access