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

作者：Blanco Garcia E; Otero Espinar F J; Blanco Mendez J; Leiro Vidal J M; Luzardo Alvarez A

来源：International Journal of Pharmaceutics, 2017, 518(1-2): 86-104.

DOI：10.1016/j.ijpharm.2016.12.057

• Microspheres
• Zein
• PVMMA
• Intestinal delivery
• Inflammatory cell response

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 (R) AN119 (PVMMA) were prepared by spray-drying and coated with a pH-sensitive polymer (Eudragit (R) 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, zeta 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 a.-helix structure for ZN when formulated and also, a strong interaction between components. The stabilization of alpha-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 (R) 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 PGE(2) production. However, a reduction in NO and PGE(2) 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 (TNF alpha, IL-1 beta, 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.

• 出版日期2017-2-25