Biodegradable microspheres containing leukotriene B4 and cell-free antigens from Histoplasma capsulatum activate murine bone marrow-derived macrophages

Santos, Daniela Soares; Bitencourt, Claudia S.; Gelfuso, Guilherme M.; Pereira, Priscilla Aparecida Tártari; Souza, Patrícia Jorge Soalheiro de; Sorgi, Carlos Artério; Nicolete, Roberto; Faccioli, Lúcia Helena

doi:10.1016/j.ejps.2011.10.005

Cited by 21 publications

(19 citation statements)

References 64 publications

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“…The efficiency of PGD 2 encapsulation and its release kinetics reinforce the hypothesis that these MS are suitable for the activation of cells. The results reported here are similar to those previously reported by our group for the arachidonic acid-derived lipid mediators LTB 4 and PGE 2 , showing that lipid mediators could be efficiently encapsulated (Dos Santos et al, 2011;Nicolete et al, 2007).…”

Section: Discussionsupporting

confidence: 94%

“…PGD 2 -MS and unloaded-MS were prepared under sterile conditions, i.e., all flasks and equipment used in their preparation were previously autoclaved and manipulation always occurred under laminar flow, to avoid microbiological contamination of the samples. Even thought, a Limulus amoebocyte (LAL) test was performed after each batch of MS was prepared to detect free LPS in samples (Dos Santos et al, 2011;Trombone et al, 2007). The maximum level of endotoxin that is considered safe according to the European Pharmacopoeia is 5 EU/kg/h.…”

Section: Preparation Of Pgd 2 -Msmentioning

confidence: 99%

“…Furthermore, they possess adequate stability in a biological environment (Lima and Rodrigues Junior, 1999) and, upon degradation, release lactic and glycolic acids, which are biocompatible (Bazile et al, 1992;Lima and Rodrigues Junior, 1999). These polymers have been shown to be efficient carriers for biomolecules and to enable sustained release of the encapsulated lipid mediators (Dos Santos et al, 2011;Eldridge et al, 1991;Lima et al, 2003;Nicolete et al, 2007Nicolete et al, , 2008aNicolete et al, , 2008cNicolete et al, , 2009). Moreover, microencapsulation in PLGA microspheres yields polymeric particles of an appropriate size (<10 lm) for efficient interaction with phagocytes (Nicolete et al, 2007(Nicolete et al, , 2008c, as well as for efficient intranasal, intratracheal, intramuscular, and intravenous administration (Eldridge et al, 1991;O'Hagan et al, 1993).…”

Section: Introductionmentioning

confidence: 98%

“…Leukotriene B4 (LTB 4 ) and PGE 2 have already been efficiently encapsulated in poly (lactic-co-glycolic acid) microspheres (PLGA-MS) with preservation of their biological activity (Dos Santos et al, 2011;Nicolete et al, 2007Nicolete et al, , 2008aNicolete et al, , 2008cNicolete et al, , 2009. Lactic/glycolic acid polymers produce drug delivery systems with potentially high encapsulation efficiencies, determined by the chemical characteristics of the target molecules (Cohen et al, 1994;Wu, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions

Pereira

Bitencourt

Santos

et al. 2015

European Journal of Pharmaceutical Sciences

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Biodegradable lactic-co-glycolic acid (PLGA) microspheres (MS) improve the stability of biomolecules stability and allow enable their sustained release. Lipid mediators represent a strategy for improving host defense; however, most of these mediators, such as prostaglandin D2 (PGD2), have low water solubility and are unstable. The present study aimed to develop and characterize MS loaded with PGD2 (PGD2-MS) to obtain an innovative tool to activate macrophages. PGD2-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process, and the size, zeta potential, surface morphology and encapsulation efficiency were determined. It was also evaluated in vitro the phagocytic index, NF-κB activation, as well as nitric oxide and cytokine production by alveolar macrophages (AMs) in response to PGD2-MS. PGD2-MS were spherical with a diameter of 5.0±3.3 μm and regular surface, zeta potential of -13.4±5.6 mV, and 36% of encapsulation efficiency, with 16-26% release of entrapped PGD2 at 4 and 48 h, respectively. PGD2-MS were more efficiently internalized by AMs than unloaded-MS, and activated NF-κB more than free PGD2. Moreover, PGD2-MS stimulated the production of nitric oxide, TNF-α, IL-1β, and TGF-β, more than free PGD2, indicating that microencapsulation increased the activating effect of PGD2 on cells. In LPS-pre-treated AMs, PGD2-MS decreased the release of IL-6 but increased the production of nitric oxide and IL-1β. These results show that the morphological characteristics of PGD2-MS facilitated interaction with, and activation of phagocytic cells; moreover, PGD2-MS retained the biological activities of PGD2 to trigger effector mechanisms in AMs. It is suggested that PGD2-MS represent a strategy for therapeutic intervention in the lungs of immunocompromised subjects.

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Section: Discussionsupporting

confidence: 94%

Section: Preparation Of Pgd 2 -Msmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions

Pereira

Bitencourt

Santos

et al. 2015

European Journal of Pharmaceutical Sciences

Self Cite

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“…Therefore, the aim of this study was to investigate the role of leukotriene B4 in the differentiation of cells from the monocytic lineage (J774A.1) into osteoclasts, after stimulation with leukotriene B4 encapsulated in microspheres. This therapeutic strategy, based on the use of polylactic-co-glycolic acid microspheres (PLGA), promote a sustained delivery of lipid mediator over time since lipid mediators are extremely labile (Nicolete et al, 2009;Santos et al, 2011;Pereira et al, 2015;Reis et al, 2017;Lorencetti-Silva et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Osteoclast Differentiation and Activation by Leukotriene B4 Loaded in Microspheres

Lorencetti-Silva

Arnez

Thomé

et al. 2020

Preprint

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Aim: Leukotriene B 4 (LTB 4 ) is a labile inflammatory lipid mediator important for host defense. We hypothesised that sustained delivery of LTB 4 would be a therapeutic strategy to prevent osteoclast cell differentiation in bone resorption in inflammatory diseases. Therefore, the aim of this study was to investigate the role of LTB 4 in differentiation of monocytic lineage cells into osteoclasts after stimulation with LTB 4 loaded in microspheres (MS). Design: LTB 4 -MS were prepared using an oilin-water emulsion solvent extraction-evaporation process. Sterility, LPS contamination, characterization and efficiency of LTB 4 encapsulation were investigated. J774A.1 cells were cultured in the presence of monocyte colony stimulating factor (M-CSF) and ligand for receptor activator of nuclear factor kappa B (RANKL) and then stimulated with LTB 4 -MS. Cytotoxicity was determined by lactate dehydrogenase assay, osteoclast formation by means of the activity of tartrate-resistant acid phosphatase enzyme and gene expression was measured by quantitative reverse transcription polymerase chain reaction to investigate regulation of Alox5, Alox5ap, Acp5, Mmp9, Calcr and Ctsk. Results: We found that 5-lipoxygenase pathway is involved in the osteoclastic differentiation hematopoietic lineage cells and that exogenous addition of LTB 4 -MS inhibited osteoclastogenesis induced by M-CSF and RANKL. The mechanism of LTB 4 -MS involved induction of Mmp9 gene expression and inhibition of Calcr and Ctsk, without changing Acp5. Conclusion: LTB 4 -MS inhibited differentiation of macrophages into an osteoclastic phenotype and cell activation under M-CSF and RANKL stimulus shedding light on a potential therapeutic strategy to prevent osteoclast differentiation.

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Scaffolds with drug delivery capability

Mouriño

2022

Tissue Engineering Using Ceramics and Polymers

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Biodegradable microspheres containing leukotriene B4 and cell-free antigens from Histoplasma capsulatum activate murine bone marrow-derived macrophages

Cited by 21 publications

References 64 publications

Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions

Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions

Inhibition of Osteoclast Differentiation and Activation by Leukotriene B4 Loaded in Microspheres

Scaffolds with drug delivery capability

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