Synthesis and Characterization of Alginate Nanoparticles with Potential Application in Osteoporosis Therapy

Osteoporosis is a chronic disease characterized by an imbalance between bone resorption and formation, leading to the progressive reduction of bone mineral density [1]. A promising therapeutic approach involves drug encapsulation in nanostructures, which protect the active compound, enhance cellular uptake, and reduce toxicity and adverse effects. Sodium alginate, a natural, biocompatible, biodegradable, and low-cost polyelectrolyte, stands out as a versatile material capable of encapsulating both hydrophilic and lipophilic active compounds used in osteoporosis therapy [2,3]. Alginate forms egg-box structures through interactions with bivalent cations and its guluronate blocks. Strontium (Sr²⁺), in addition to acting as a gelling agent, exhibits therapeutic properties by inhibiting bone resorption and promoting bone formation [4]. The purpose of the study was to synthesize alginate nanoparticles (NP) crosslinked with Sr²⁺ aiming the development of a drug delivery system applied to bone pathologies. The NPs were synthesized via ionotropic gelation using a full factorial design with two levels and replication at the central point. Four input variables were selected: sodium alginate concentration (0.05%, 0.175% and 0.3% (w/v)), strontium chloride concentration (0,05%, 0,175% and 0,3% (w/v)), sonication amplitude (20%, 60% and 100%), and sonication time (2 min, 6 min and 10 min). The output variables evaluated were particle size (dynamic light scattering – DLS) and complexed strontium concentration (indirect method – atomic absorption spectroscopy). Alginate and SrCl₂ solutions were prepared at the aforementioned concentrations. SrCl₂ solution was kept under magnetic stirring and constant sonication (200 W, 24 kHz), while the alginate solution was added dropwise to promote NP formation. The concentration of Sr²⁺ had a statistically significant effect (p-value<0.05) on particle size. Concentrations of 0.05% and 0.175% yielded nanoparticles ranging from 330 to 612 nm, whereas 0.3% resulted in microparticles, regardless of alginate concentration. An empirical statistical model was developed to predict the average particle diameter, identifying SrCl₂ concentration as the most influential factor, with a synergistic effect observed with sonication amplitude. Experiments conducted at the central point demonstrated reproducibility and favorable outcomes: nanoparticles with an average diameter of 344.74 ± 14.57 nm and high strontium retention, without an increase in particle size. Therefore, ionotropic gelation induced by Sr²⁺ proves to be an effective method for producing alginate nanocarriers suitable for drug delivery in osteoporosis treatment.

[1] https://doi.org/10.3934/bioeng.2017.2.259
[2] https://doi.org/10.1016/j.ijantimicag.2005.12.009
[3] https://doi.org/10.3390/ph13110335
[4] https://doi.org/10.1038/nrendo.2011.146