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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Prostaglandin D-2-loaded microspheres effectively activate macrophage effector functions

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Author(s):
Tartari Pereira, Priscilla Aparecida [1] ; Bitencourt, Claudia da Silva [1] ; dos Santos, Daiane Fernanda [1] ; Nicolete, Roberto [2] ; Gelfuso, Guilherme Martins [3] ; Faccioli, Lucia Helena [1]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Analises Clin Toxicol & Bromatol, BR-14040903 Sao Paulo - Brazil
[2] Fundacao Oswaldo Cruz Fiocruz Rondonia, BR-76812245 Porto Velho - Brazil
[3] Univ Brasilia, Fac Ciencias Saude, LTMAC, BR-70910900 Brasilia, DF - Brazil
Total Affiliations: 3
Document type: Journal article
Source: European Journal of Pharmaceutical Sciences; v. 78, p. 132-139, OCT 12 2015.
Web of Science Citations: 7
Abstract

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 D-2 (PGD(2)), have low water solubility and are unstable. The present study aimed to develop and characterize MS loaded with PGD(2) (PGD(2)-MS) to obtain an innovative tool to activate macrophages. PGD(2)-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-kappa B activation, as well as nitric oxide and cytokine production by alveolar macrophages (AMs) in response to PGD(2)-MS. PGD(2)-MS were spherical with a diameter of 5.0 +/- 3.3 mu m and regular surface, zeta potential of -13.4 +/- 5.6 mV, and 36% of encapsulation efficiency, with 16-26% release of entrapped PGD(2) at 4 and 48 h, respectively. PGD(2)-MS were more efficiently internalized by AMs than unloaded-MS, and activated NB-kappa B more than free PGD(2). Moreover, PGD(2)-MS stimulated the production of nitric oxide, TNF-alpha, IL-1 beta, and TGF-beta, more than free PGD(2), indicating that microencapsulation increased the activating effect of PGD(2) on cells. In LPS-pre-treated AMs, PGD(2)-MS decreased the release of IL-6 but increased the production of nitric oxide and IL-1 beta. These results show that the morphological characteristics of PGD(2)-MS facilitated interaction with, and activation of phagocytic cells; moreover, PGD(2)-MS retained the biological activities of PGD(2) to trigger effector mechanisms in AMs. It is suggested that PGD(2)-MS represent a strategy for therapeutic intervention in the lungs of immunocompromised subjects. (C) 2015 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 09/05106-6 - Evaluation of the role of the PGD2 and PGE2 in the efectors mechanisms of in vitro infection alveolar macrophages with Histoplasma capsulatum and in the immune response during in vivo experimental infection.
Grantee:Priscilla Aparecida Tartari Pereira
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 09/07169-5 - Lipid mediators as regulators of immune response
Grantee:Lúcia Helena Faccioli
Support Opportunities: Research Projects - Thematic Grants