Tailoring Mesalazine Nanosuspension Using Chitosan Polyelectrolyte Complexes with Alginate and Alginate/Hydroxypropyl-Methylcellulose Phthalate

<b>Background/Objectives</b>: This study evaluated how the relative proportion of chitosan (CS) to the polyanions alginate (ALG) and hydroxypropyl-methylcellulose phthalate (HP) affects the colloidal properties of mesalazine (MSZ) nanosuspensions as a strategy to produce particles with specific characteristics. <b>Methods</b>: Nanosuspensions were prepared using a bottom-up approach based on acid-base reactions and were modified with CS in a binary mixture with ALG or a ternary mixture with ALG and HP. The particle size, polydispersity index (PDI), zeta potential, morphology, and drug association efficiency were analyzed. <b>Results</b>: Higher proportions of CS relative to the polyanions resulted in smaller, less polydisperse particles. The zeta potential inversion was influenced by the relative proportion of CS in the system. These results were consistent over 30 days and pH exerted an influence on the magnitude of the observed effect. The optimized NS modified with binary CS/ALG blends had the following properties at pH 6.0: an average particle size of 324.9 nm, PDI of 0.5, and zeta potential of +40.8 mV; at pH 4.0, it had an average particle size of 310.4 nm, PDI of 0.4, and zeta potential of +43.6 mV. The optimized NS modified with ternary CS/ALG/HP had the following properties at pH 6.0: an average particle size of 316.7 nm, PDI of 0.5, and zeta potential of +33.9 mV; at pH 4.0, it had an average particle size of 363.5 nm, PDI of 0.6, and zeta potential of +33.9 mV. <b>Conclusions</b>: CS-based polyelectrolyte complexes with ALG and ALG/HP offer an approach to modulating the properties of MSZ nanosuspensions, enabling the production of particles with tailored characteristics.