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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmaceutical Sciences; v. 78, p. 132-139, OCT 12 2015.
• Citações Web of Science: 7

Resumo

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)

• Processo FAPESP: 09/07169-5 - Mediadores lipídicos como reguladores da resposta imune
• Beneficiário: Lúcia Helena Faccioli
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/05106-6 - Avaliação do papel da PGD2 e da PGE2 nos mecanismos efetores de macrófagos alveolares infectados in vitro com Histoplasma capsulatum e na resposta imune durante infecção experimental in vivo
• Beneficiário: Priscilla Aparecida Tartari Pereira
• Linha de fomento: Bolsas no Brasil - Doutorado