Controlling stability and size of amorphous magnesium calcium phosphate particles

Abstract

The development of nanoparticles with tunable size and stability is crucial for the development of safe and effective drug delivery systems. Amorphous Magnesium Calcium Phosphate (AMCP) nanoparticles offer a promising solution due to their biocompatibility, biodegradability, and ability to load bioactive substances. However, their successful application is hindered by two main limitations: the tendency of the metastable amorphous phase to crystallize into more thermodynamically stable forms and the propensity for aggregation in the absence of stabilizing agents, which compromises their nanoscale properties. This study focuses on the preparation and characterization of AMCP nanoparticles stabilized with polyacrylic acid (PAA), with the purpose of understanding whether variations in the synthetic Ca/Mg ratio and PAA molecular weight (M_w) influence nanoparticles’ physico-chemical properties such as size, crystallinity, dispersibility and stability, along with their solubility in different pH environments, to explore potential applications in the pharmacological field.

The results reveal that PAA acts as a remarkable stabilizing agent for AMCPs, significantly reducing aggregation and enhancing dispersibility. Stability and size were strongly influenced by Ca/Mg ratio and PAA M_w, demonstrating the crucial interplay between these factors in nanoparticles design. Incorporating PAA not only delayed the thermal crystallization process but also improved the resistance of AMCPs to dissolution in acidic environments, highlighting their potential for pH-responsive drug delivery applications. Additionally, a higher magnesium content was found to enhance the stability of the amorphous phase, while PAA effectively prevented the transformation of AMCP into hydroxyapatite under physiological conditions, further reinforcing its role in achieving the desired nanoparticle properties.