Shaping of molecular weight distribution by iterative learning probability density function control strategies

A mathematical model is developed for the molecular weight distribution (MWD) of free-radical styrene polymerization in a simulated semi-batch reactor system. The generation function technique and moment method are employed to establish the MWD model in the form of Schultz-Zimmdistribution. Both static and dynamic models are described in detail. In order to achieve the closed-loop MWD shaping by output probability density function (PDF) control, the dynamic MWD model is further developed by a linear B-spline approximation. Based on the general form of the B-spline MWD model, iterative learning PDF control strategies have been investigated in order to improve the MWD control performance. Discussions on the simulation studies show the advantages and limitations of the methodology

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble Leishmania antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid A confers protection against experimental visceral leishmaniasis

Maritsa Margaroni,1,2 Maria Agallou,1 Evita Athanasiou,1 Olga Kammona,3 Costas Kiparissides,3,4 Catherine Gaitanaki,2 Evdokia Karagouni1 1Laboratory of Cellular Immunology, Department of Microbiology, Hellenic Pasteur Institute, 2Department of Animal and Human Physiology, School of Biology, National and Kapodistrian University of Athens, Athens, 3Chemical Process & Energy Resources Institute, Centre for Research and Technology Hellas, 4Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki, Greece Abstract: Visceral leishmaniasis (VL) persists as a major public health problem, and since the existing chemotherapy is far from satisfactory, development of an effective vaccine emerges as the most appropriate strategy for confronting VL. The development of an effective vaccine relies on the selection of the appropriate antigen and also the right adjuvant and/or delivery vehicle. In the present study, the protective efficacy of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), which were surface-modified with a TNFα-mimicking eight-amino-acid peptide (p8) and further functionalized by encapsulating soluble Leishmania infantum antigens (sLiAg) and monophosphoryl lipid A (MPLA), a TLR4 ligand, was evaluated against challenge with L. infantum parasites in BALB/c mice. Vaccination with these multifunctionalized PLGA nanoformulations conferred significant protection against parasite infection in vaccinated mice. In particular, vaccination with PLGA-sLiAg-MPLA or p8-PLGA-sLiAg NPs resulted in almost complete elimination of the parasite in the spleen for up to 4 months post-challenge. Parasite burden reduction was accompanied by antigen-specific humoral and cellular immune responses. Specifically, injection with PLGA-sLiAg-MPLA raised exclusively anti-sLiAg IgG1 antibodies post-vaccination, while in p8-PLGA-sLiAg-vaccinated mice, no antibody production was detected. However, 4 months post-challenge, in mice vaccinated with all the multifunctionalized NPs, antibody class switching towards IgG2a subtype was observed. The study of cellular immune responses revealed the increased proliferation capacity of spleen cells against sLiAg, consisting of IFNγ-producing CD4+ and CD8+ T cells. Importantly, the activation of CD8+ T cells was exclusively attributed to vaccination with PLGA NPs surface-modified with the p8 peptide. Moreover, characterization of cytokine production in vaccinated–infected mice revealed that protection was accompanied by significant increase of IFNγ and lower levels of IL-4 and IL-10 in protected mice when compared to control infected group. Conclusively, the above nanoformulations hold promise for future vaccination strategies against VL. Keywords: nanovaccine, soluble Leishmania antigen, visceral leishmaniasis, immune response, T cells, cytokines&nbsp

Transcriptome Analysis Identifies Immune Markers Related to Visceral Leishmaniasis Establishment in the Experimental Model of BALB/c Mice

Visceral leishmaniasis (VL) caused by Leishmania donovani and L. infantum is a potentially fatal disease. To date there are no registered vaccines for disease prevention despite the fact that several vaccines are in preclinical development. Thus, new strategies are needed to improve vaccine efficacy based on a better understanding of the mechanisms mediating protective immunity and mechanisms of host immune responses subversion by immunopathogenic components of Leishmania. We found that mice vaccinated with CPA162−189-loaded p8-PLGA nanoparticles, an experimental nanovaccine, induced the differentiation of antigen-specific CD8+ T cells in spleen compared to control mice, characterized by increased dynamics of proliferation and high amounts of IFN-γ production after ex vivo re-stimulation with CPA162−189 antigen. Vaccination with CPA162−189-loaded p8-PLGA nanoparticles resulted in about 80% lower parasite load in spleen and liver at 4 weeks after challenge with L. infantum promastigotes as compared to control mice. However, 16 weeks after infection the parasite load in spleen was comparable in both mouse groups. Decreased protection levels in vaccinated mice were followed by up-regulation of the anti-inflammatory IL-10 production although at lower levels in comparison to control mice. Microarray analysis in spleen tissue at 4 weeks post challenge revealed different immune-related profiles among the two groups. Specifically, vaccinated mice were characterized by similar profile to naïve mice. On the other hand, the transcriptome of the non-vaccinated mice was dominated by increased expression of genes related to interferon type I, granulocyte chemotaxis, and immune cells suppression. This profile was significantly enriched at 16 weeks post challenge, a time-point which is relative to disease establishment, and was common for both groups, further suggesting that type I signaling and granulocyte influx has a significant role in disease establishment, pathogenesis and eventually in decreased vaccine efficacy for stimulating long-term protection. Overall, we put a spotlight on host immune networks during active VL as potential targets to improve and design more effective vaccines against disease. © Copyright © 2019 Agallou, Athanasiou, Kammona, Tastsoglou, Hatzigeorgiou, Kiparissides and Karagouni

Uptake of BSA-FITC loaded PLGA nanoparticles by bone marrow-derived dendritic cells induces maturation but not IL-12 or IL-10 production

Nanoparticles prepared from biodegradable polymers, such as poly(lactide-co-glycolide) (PLGA), represent a new approach for vaccine delivery due to their ability to be taken up by phagocytes and activate immune responses. In this study, fluorescently labelled bovine serum albumin (BSA-FITC)-loaded PLGA nanoparticles, of an average size ∼300 nm were prepared and examined for their ability to be taken up by bone marrow-derived dendritic cells (BM-DCs) in vitro and thus to promote their maturation and activation. The synthesized nanoparticles did not exhibit any cytotoxic or hemolytic effect and were taken up by BM-DCs efficiently, in a time and dose dependent manner. The localization of BSA-FITC loaded PLGA nanoparticles both in the acidophilic cellular compartments and the cytoplasm resulted in the maturation of BM-DCs expressing higher levels of costimulatory and MHC class II molecules in comparison to empty PLGA nanoparticles. However, the absence of IL-12 or IL-10 production indicates partial activation of BM-DCs suggesting the necessity of an adjuvant addition in order to facilitate DCs functionalization. Copyright © 2013 American Scientific Publishers. All rights reserved

Vaccination with poly(D,L-lactide-co-glycolide) nanoparticles loaded with soluble leishmania antigens and modified with a TNFα-mimicking peptide or monophosphoryl lipid aconfers protection against experimental visceral leishmaniasis

Visceral leishmaniasis (VL) persists as a major public health problem, and since the existing chemotherapy is far from satisfactory, development of an effective vaccine emerges as the most appropriate strategy for confronting VL. The development of an effective vaccine relies on the selection of the appropriate antigen and also the right adjuvant and/or delivery vehicle. In the present study, the protective efficacy of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), which were surface-modified with a TNFα-mimicking eight-amino-acid peptide (p8) and further functionalized by encapsulating soluble Leishmania infantum antigens (sLiAg) and monophosphoryl lipid A (MPLA), a TLR4 ligand, was evaluated against challenge with L. infantum parasites in BALB/c mice. Vaccination with these multifunctionalized PLGA nanoformulations conferred significant protection against parasite infection in vaccinated mice. In particular, vaccination with PLGA-sLiAg-MPLA or p8-PLGA-sLiAg NPs resulted in almost complete elimination of the parasite in the spleen for up to 4 months post-challenge. Parasite burden reduction was accompanied by antigen-specific humoral and cellular immune responses. Specifically, injection with PLGA-sLiAg-MPLA raised exclusively anti-sLiAg IgG1 antibodies post-vaccination, while in p8-PLGA-sLiAg-vaccinated mice, no antibody production was detected. However, 4 months post-challenge, in mice vaccinated with all the multifunctionalized NPs, antibody class switching towards IgG2a subtype was observed. The study of cellular immune responses revealed the increased proliferation capacity of spleen cells against sLiAg, consisting of IFNγ-producing CD4+ and CD8+ T cells. Importantly, the activation of CD8+ T cells was exclusively attributed to vaccination with PLGA NPs surface-modified with the p8 peptide. Moreover, characterization of cytokine production in vaccinated–infected mice revealed that protection was accompanied by significant increase of IFNγ and lower levels of IL-4 and IL-10 in protected mice when compared to control infected group. Conclusively, the above nanoformulations hold promise for future vaccination strategies against VL. © 2017 Margaroni et al

Monitoramento in situ e em tempo real de variáveis morfológicas do poli(cloreto de vinila) usando espectroscopia NIR Monitoring in situ and in real time the morphological variables of pvc using NIR spectroscopy

Este trabalho ilustra o uso de espectroscopia do infravermelho próximo (NIRS) para fins de monitoramento da polimerização em suspensão de cloreto de vinila em tempo real. Resultados inéditos mostraram que é possível acompanhar a evolução de importantes propriedades morfológicas de resinas de PVC [poli(cloreto de vinila)], como por exemplo, BD (densidade aparente), CPA (absorção de plastificante a frio), DTP (distribuição de tamanho de partículas) e Dp (diâmetro de partícula). Mostrou-se também, pela primeira vez, que é possível analisar quantitativamente, com o auxílio da sonda NIRS in situ, a estrutura morfológica da partícula de PVC. Com a possibilidade de predizer a evolução dinâmica dos parâmetros morfológicos em tempo real, mostrou-se que é possível injetar dispersantes e variar a velocidade de agitação durante a reação para fins de controle das variáveis BD, CPA e DTP do PVC, até que o ponto de identificação da partícula seja atingido. Por meio do monitoramento e da estratégia de controle proposta, é possível antecipar fugas de temperatura no reator, aumentar a segurança do processo, diminuir o tempo de desenvolvimento de resinas com características morfológicas diferenciadas, evitando perdas de margem oriundas da venda de produtos fora de especificação, e otimizar os recursos para o desenvolvimento de novos produtos.<br>This work illustrates the use of near infrared spectroscopy (NIRS) for monitoring of the suspension polymerization of vinyl chloride in real time. Obtained results showed that it is possible to track in situ and in real time important morphological properties of PVC resins, such as BD (bulk density), CPA (cold plasticizer absorption), PSD (particle size distribution) and Dp (average particle diameter). It was also shown for the first time that it is possible to analyze quantitatively, with the help of in situ NIRS probe, the morphological structure of the PVC particles. As a consequence, it was shown that is possible to inject dispersants and vary the agitation speed during the reaction for proper control of BD, CPA and the PSD of PVC, before attainment of the particle identification point. Through the proposed monitoring and control strategies, it is possible to anticipate reactor disturbances (increasing the process safety) and to reduce the time needed for development of resins with different morphological characteristics (avoiding losses caused by off-specification), allowing for optimization of the product development process

Activation of the complement by PLGA nanoparticles.

Nanobiopharmaceutic

Activation of the complement by PLGA nanoparticles : an in vitro study.

Nanobiopharmaceutic