Enhanced Curcumin Delivery and Stability through Natural Deep Eutectic Solvent-Based Niosomes

Abstract

Curcumin, a highly sought-after medicinal compound with diverse health benefits, encounters limitations regarding its oral bioavailability and aqueous solubility. To overcome these challenges, curcumin can be encapsulated within niosomal formulations, allowing controlled drug release and improving encapsulation efficacy. In this study, incorporating a natural deep eutectic solvent (NADES) with curcumin-loaded niosomes was investigated to enhance the bioavailability of curcumin. Initially, NADESs were synthesized using betaine as a hydrogen bond acceptor and a range of hydrogen bond donors. Among the different combinations tested, the NADES formed with betaine and glucose, fructose, or xylose exhibited the highest solubility of 6.16 ± 0.61 mg/g, 6.03 ± 0.25 mg/g and 5.57 ± 0.14 mg/g, respectively. Subsequently, these NADESs with the ideal combination were utilized to incorporate with curcumin niosomes denoted by the formulation abbreviations BG, BF, and BX. These formulations were prepared at varying masses, including 25 mg (BG1, BF1, and BX1), 50 mg (BG2, BF2, and BX2), 75 mg (BG3, BF3, and BX3), and 100 mg (BG4, BF4, and BX4). Optical microscopy results revealed that curcumin-loaded niosomes with NADES displayed a spherical morphology. The entrapment efficiency of eutectic-based curcumin niosomes ranged from 82.20 ± 0.46 % (BX1) to 97.61 ± 0.67 % (BG4), significantly outperforming blank niosomes, which achieved a mere 74.27 ± 0.20 %. The zeta potential measurements reveal distinct differences where the blank curcumin niosomes exhibit a relatively modest value of −17.57 ± 0.90 mV, whereas the eutectic-based niosomes display markedly elevated zeta potentials, spanning from −45.50 ± 2.55 mV to −53.70 ± 1.63 mV. Raman spectroscopy studies were performed to examine the interactions between the NADES and curcumin in the niosome, providing insights into the molecular interactions and potential improvements in drug delivery where BG4 achieved the optimum intensity ratio (I2930/I2850) at 0.3106. Stability investigations were conducted to evaluate the enduring stability of the NADES-niosome formulation, affirming its capacity to preserve its electrostatic coherence and underscoring its resilience across varying temperature conditions under 28 days. Moreover, comprehensive experiments were conducted to assess the photochemical stability, revealing that BG4 boasts the lengthiest half-life, reaching an impressive 158.56 days. The antioxidant assay results indicate that niosomes incorporating NADES exhibit lower IC50 values. Furthermore, in vitro studies coupled with Korsmeyer-Peppas and Peppas-Sahlin’s model fitting were performed to evaluate curcumin’s release profile and dissolution behavior from the NADES-niosome system. Overall, this study explores the potential of incorporating NADES with curcumin-loaded niosomes to enhance the bioavailability of curcumin. The comprehensive analysis and characterization techniques provide valuable insights into the formulation’s stability, efficiency, and drug release behavior, paving the way for potential advancements in curcumin delivery systems.