Publication: Development of niosomes containing deep eutectic solvents to enhance curcumin bioavailability.
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Date
2025-05
Authors
Thaaranni A/P Bashkeran
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Abstract
Curcumin, a potent medicinal compound, exhibits poor aqueous solubility and low oral bioavailability, limiting its therapeutic potential. This study aims to enhance curcumin’s bioavailability by encapsulating it in niosomal formulations incorporating natural deep eutectic solvents (NADES). NADES were synthesized using betaine as the hydrogen bond acceptor (HBA) and various hydrogen bond donors (HBD), with betaine-glucose (BG), betaine-fructose (BF), and betaine-xylose (BX) exhibiting the highest curcumin solubility at 6.16±0.61 mg/g, 6.03±0.25 mg/g, and 5.57±0.14 mg/g, respectively. These NADES were integrated into curcumin niosomes, formulated in four different mass variations (25 mg, 50 mg, 75 mg, and 100 mg). Characterization studies confirmed the spherical shape of the niosomes, with entrapment efficiency ranging from 82.20±0.46% (BX1) to 97.61±0.67% (BG4), significantly exceeding blank niosomes (74.27±0.20%). Zeta potential measurements indicated enhanced electrostatic stability in eutectic-based niosomes (-45.50±2.55 mV to -53.70±1.63 mV) compared to blank niosomes (-17.57±0.90 mV). Raman spectroscopy revealed optimal molecular interactions in BG4, with an intensity ratio (I2930/I2850) of 0.3106. Stability studies demonstrated that NADES-niosome formulations retained their physicochemical properties over 28 days under various temperature conditions, with BG4 exhibiting the longest photochemical half-life (158.56 days). Antioxidant assays indicated improved activity in NADES-based niosomes, reflected in lower IC50 values. In vitro drug release studies showed a sustained release profile where Korsmeyer-Peppas model indicated a non-Fickian diffusion mechanism, with swelling and dissolution influencing curcumin release. The Peppas-Sahlin model further confirmed an initial diffusion-dominated release, shifting to relaxation-driven release over time, particularly in eutectic-based niosomes. Furthermore, the effect of cryoprotectants on freeze-dried niosomes was examined, revealing that mannitol at 10 g/g significantly improved physicochemical properties, reducing particle size (870.0 ± 15.52 nm to 418.07 ± 5.95 nm), decreasing polydispersity index (0.34 ± 0.016 to 0.12 ± 0.04), and increasing entrapment efficiency (75.75 ± 6.12% to 93.24 ± 3.21%). The zeta potential also increased from -38.87 ± 0.32 mV to -45.33 ± 3.99 mV. This study presents a novel approach for enhancing curcumin delivery by integrating NADES into niosomal formulations and optimizing freeze-drying with mannitol, offering a promising strategy for improving curcumin’s stability and bioavailability.