Development and characterization of anti-inflammatory activity of curcumin-loaded biodegradable microspheres with potential use in intestinal inflammatory disorders

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• 作者：E. Blanco-Garcí ; a^a ; F.J. Otero-Espinar^a ; J. Blanco-Mé ; ndez^a ; J.M. Leiro-Vidal^b ; A. Luzardo-Á ; lvarez^a ; ^{asteriam.luzardo@usc.es}
• 关键词：Ms ; microspheres ; ZN ; zein ; PVMMA ; poly (methyl vinyl ether)-co-(maleic anhydride) Gantrez® ; AN119 ; CRM ; curcumin ; EE ; encapsulation efficiency ; SEM ; scanning electron microcsopy ; FT-IR ; Fourier transformed Infrared ; PBS ; phosphate buffered saline ; DSC ; differential scanning calorimetry ; NO ; nitric oxide ; PGE2 ; prostaglandin E2 ; LPS ; lipopolysaccharide ; PI ; propidium iodide ; TNFα ; tumour necrosis factor alpha ; IL-1β ; interleukine-1beta ; NOS-2 ; nitric oxide synthase 2 ; COX-2 ; cyclooxygenase 2
• 刊名：International Journal of Pharmaceutics
• 出版年：2017
• 出版时间：25 February 2017
• 年：2017
• 卷：518
• 期：1-2
• 页码：86-104
• 全文大小：2391 K
• 卷排序：518

文摘

This research addresses the development and in vitro evaluation of a microparticulate system intended for intestine-targeted delivery of curcumin (CRM), a natural polyphenol with anti-inflammatory properties. Microspheres (Ms) based on zein (ZN) and Gantrez® AN119 (PVMMA) were prepared by spray-drying and coated with a pH-sensitive polymer (Eudragit® FS30D). An experimental design was performed to optimize the microparticulate formulation. A detailed characterization of systems was carried out by SEM, DSC, FTIR, particle size, ζ potential measurements and in vitro CRM release. The optimized formulation was evaluated in LPS-stimulated RAW 264.7 macrophages to investigate its anti-inflammatory activity. FTIR and DSC studies suggest a predominant presence of α-helix structure for ZN when formulated and also, a strong interaction between components. The stabilization of α-helix by PVMMA or CRM would take place by hydrogen bonds. Although the encapsulation efficiency was high (89%) for ZN/PVMMA Ms, the coating process with Eudragit® led to an EE decrease of 62%. Coating of Ms was found to retain a 20% of drug within 6 h of release, although a strong initial burst release was observed. Cells viability and apoptosis were not affected when cells were co-incubated with coated Ms with CRM. The exposure of unstimulated cells to Ms did not show any effect on NO and PGE2 production. However, a reduction in NO and PGE2 production was obtained when CRM-loaded Ms were co-incubated with stimulated macrophages. Further, this inhibition was significantly higher compared to the decrease obtained when Ms with pure CRM were used in culture, which suggested a synergistic effect of CRM and Ms. Finally, CRM-loaded Ms caused a significant inhibition of analysed pro-inflammatory cytokines (TNFα, IL-1β, NOS2, COX-2) in macrophages stimulated with LPS.All these results confirm the advantageous features of ZN/PVMMA microspheres as a serious alternative for delivering CRM to reduce the inflammatory activity at intestinal regions affected by inflammatory bowel diseases.