Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions

[Display omitted] 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...

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Published inEuropean journal of pharmaceutical sciences Vol. 78; pp. 132 - 139
Main Authors Pereira, Priscilla Aparecida Tartari, da Silva Bitencourt, Claudia, dos Santos, Daiane Fernanda, Nicolete, Roberto, Gelfuso, Guilherme Martins, Faccioli, Lúcia Helena
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 12.10.2015
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ISSN0928-0987
1879-0720
1879-0720
DOI10.1016/j.ejps.2015.07.001

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Summary:[Display omitted] 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±3.3μm and regular surface, zeta potential of −13.4±5.6mV, and 36% of encapsulation efficiency, with 16–26% release of entrapped PGD2 at 4 and 48h, 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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ISSN:0928-0987
1879-0720
1879-0720
DOI:10.1016/j.ejps.2015.07.001