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

• Published in: International journal of pharmaceutics Vol. 518; no. 1-2; pp. 86 - 104
• Main Authors: Blanco-García, E., Otero-Espinar, F.J., Blanco-Méndez, J., Leiro-Vidal, J.M., Luzardo-Álvarez, A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 25.02.2017
• Subjects: Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - chemistry; Curcumin - administration & dosage; Curcumin - chemistry; Cytokines - metabolism; Dinoprostone - metabolism; Drug Liberation; Inflammatory Bowel Diseases; Inflammatory cell response; Intestinal delivery; Lipopolysaccharides; Maleates - chemistry; Mice; Mice, Inbred BALB C; Microspheres; Nitric Oxide - metabolism; Polymethacrylic Acids - chemistry; Polyvinyls - chemistry; PVMMA; RAW 264.7 Cells; Zein; Zein - chemistry; EE; PBS; NO; PGE2; TNFα; COX-2; Ms; NOS-2; Inflammatory cell response; FT-IR; IL-1β; LPS; Microspheres; ACT; ZN; PVMMA; DSC; PI; SEM; Zein; Intestinal delivery; CRM
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2016.12.057

[Display omitted] 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 6h 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.