Transplant immunology · 2025
Oral cyclosporine a nanosuspension for improved immunosuppressive efficacy: In vivo cytokine profiling in rats.
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Tan Çağman, Gülbağ Pınar Sıla, Çelebi Nevin
Аннотация
BACKGROUND: Cyclosporine A (CycA) is a cornerstone immunosuppressant in transplantation, but its poor solubility and variable bioavailability limit therapeutic efficacy. Nanosuspension technology offers an innovative formulation strategy to enhance oral absorption and potentially improve immunomodulatory effects.
METHODS: Wistar rats (n = 4/group) received oral CycA as coarse powder, physical mixture, commercial product, or nanosuspension. Serum cytokines and chemokines (IL-4, IL-5, IL-10, IL-13, IL-17 A, Eotaxin, GRO-α, IP-10, MCP-1, MCP-3, MIP-1α, MIP-2, Rantes) were quantified on days 7, 14, and 21. Data were expressed as mean ± SD. Statistical analysis was performed using Mann-Whitney U test with Benjamini-Hochberg correction for multiple comparisons.
RESULTS: At day 21, IL-10 levels were significantly higher in the nanosuspension group compared to control and coarse powder (adjusted p = 0.041), confirming nanosuspension-mediated IL-10 upregulation. IL-13 was also elevated in nanosuspension and commercial product groups versus control (p_adj = 0.048). IL-4 was significantly reduced in the nanosuspension group at both day 7 (p_adj = 0.042) and day 21 (p_adj = 0.049). IL-5 levels increased in the nanosuspension group at day 21 compared to control and coarse powder (p_adj = 0.037). No statistically significant differences were detected for IL-17 A or chemokines, although descriptive trends suggested altered profiles in the nanosuspension group.
CONCLUSION: CycA nanosuspension selectively modulates cytokine networks by elevating IL-10, fine-tuning Th2 cytokines (IL-4, IL-5, IL-13), and trending toward chemokine regulation. These findings highlight nanosuspension technology as a promising strategy to enhance CycA's immunosuppressive efficacy, with potential implications for transplantation.
METHODS: Wistar rats (n = 4/group) received oral CycA as coarse powder, physical mixture, commercial product, or nanosuspension. Serum cytokines and chemokines (IL-4, IL-5, IL-10, IL-13, IL-17 A, Eotaxin, GRO-α, IP-10, MCP-1, MCP-3, MIP-1α, MIP-2, Rantes) were quantified on days 7, 14, and 21. Data were expressed as mean ± SD. Statistical analysis was performed using Mann-Whitney U test with Benjamini-Hochberg correction for multiple comparisons.
RESULTS: At day 21, IL-10 levels were significantly higher in the nanosuspension group compared to control and coarse powder (adjusted p = 0.041), confirming nanosuspension-mediated IL-10 upregulation. IL-13 was also elevated in nanosuspension and commercial product groups versus control (p_adj = 0.048). IL-4 was significantly reduced in the nanosuspension group at both day 7 (p_adj = 0.042) and day 21 (p_adj = 0.049). IL-5 levels increased in the nanosuspension group at day 21 compared to control and coarse powder (p_adj = 0.037). No statistically significant differences were detected for IL-17 A or chemokines, although descriptive trends suggested altered profiles in the nanosuspension group.
CONCLUSION: CycA nanosuspension selectively modulates cytokine networks by elevating IL-10, fine-tuning Th2 cytokines (IL-4, IL-5, IL-13), and trending toward chemokine regulation. These findings highlight nanosuspension technology as a promising strategy to enhance CycA's immunosuppressive efficacy, with potential implications for transplantation.