Alginate nanoparticle synthesis using n-heptane and isopropyl myristate/AOT reverse micelles: the impact of the non-polar solvent, water content, and pH on the particle size and cross-linking efficiency†

The synthesis of monodisperse and stable alginate nanoparticles (ALG-NPs) was achieved through the crosslinking of sodium alginate with Ca²⁺ ions within sodium bis(2-ethylhexyl)sulfosuccinate (AOT) reverse micelles (RMs) as nano-templates. This study addresses the challenge of controlling the size and stability of nanoparticles, which is critical for their applications in drug delivery and tissue engineering. We explored the effects of varying the water content, the choice of non-polar solvent, and the pH of the resuspension medium on nanoparticle formation. Using both n-heptane and isopropyl myristate (IPM) to form AOT RMs, we found that nanoparticle size increased with water content in both solvents, attributed to differing degrees of crosslinking efficiency influenced by the proximity of alginate and calcium ions at lower water content. Notably, IPM produced smaller and more crosslinked ALG-NPs than n-heptane, likely due to its impact on interfacial interactions. Additionally, raising the pH of the resuspension medium resulted in smaller NPs due to enhanced alginate availability for cross-linking. These findings highlight the potential of AOT RMs as versatile templates for generating polymeric nanoparticles with precise control over their characteristics. The significant role of solvent choice and pH in tailoring nanoparticle properties is underscored, providing valuable insights for future applications. The controlled size and stability of these ALG-NPs make them excellent candidates for drug delivery systems and tissue engineering, given their biocompatibility and biodegradability.