Maltodextrins as drying auxiliary agent for the preparation of easily resuspendable nanoparticles

To increase the long-term stability of poly(D,L-lactide-co-glycolide) nanoparticles (NP) a drying step is mandatory. Spray- and freeze-drying can induce their irreversible aggregation and, therefore, the use of a drying auxiliary agent is necessary. The aim of this work was to explore the ability of four grades of maltodextrins (MDX) as NP’s auxiliary agent in spray- and freeze-drying. PLGA NP were prepared by the solvent displacement method, using a polymer with a Tg of 36.5 °C. Compatibility was evaluated by DLS, after stirring NP with solutions of MDX (DE2, DE6, DE12 and DE38) at 2, 4 and 8% w/v concentrations using water or 0.9% NaCl as dispersants. Spray-drying process conditions were optimized by a Design of Experiment. Freeze-drying cycles were designed based on the thermal properties of MDX solutions. Dried products were reconstituted in water or 0.9% NaCl under gentle stirring and characterized by DLS after 5, 30 and 60 min. NP had a monomodal size distribution with a size of about 160 nm and a Z-potential (z) of -31 mV. NP were compatible with all the aqueous solutions of MDX at all concentrations, even if DLS revealed a slight increment of NP size as a function of MDX grade and concentration. A concomitant increase of z was less evident for MDX DE2 and DE38 compared to DE6 and DE12, with values of about -26 and -24 mV, respectively. In 0.9% NaCl solution, only MDX DE2 and DE38 did not induce NP aggregation. These results appeared related to the organization of MDX onto NP surface, since both the z and the apparent persistence length of hydrated MDX [1] followed the same trend. Independently of the drying method, after reconstitution of the dried products, MDX DE2 was not effective in preserving NP features (size>400 nm). Conversely, MDX DE38 allowed an easy and complete reconstitution of NP. Its optimal concentrations resulted in the 2-4% w/v range. Indeed, monodisperse NP were obtained after 5 min of reconstitution independently of medium ionic strength (spray-dried product prepared by 2%w/v MDX DE38: 172±12 nm; freeze-dried product prepared by 4%w/v MDX DE38: 188±6 nm). In conclusion, MDX DE38 appears an efficacious drying auxiliary agent for NP at concentrations lower than those reported in literature for polyols and sugars, independently of the drying process. References [1] Aeberhardt K., De Saint Laumer J.Y., Bouquerand P.E., Normand V. Ultrasonic wave spectroscopy study of sugar oligomers and polysaccharides in aqueous solutions: The hydration length concept. International Journal of Biological Macromolecules, 36(5), 275–282, 2005.