In Vitro Release Dynamics of Atorvastatin-Loaded Alginate Particles for Enhanced Periodontal Treatment

Periodontitis is a chronic inflammatory condition of the periodontium, which often leads to tooth loss. Recently, statins have emerged as potent anti-inflammatory agents with pleiotropic effects that can potentially outperform conventional periodontal treatments. However, the clinical application of statins is limited by the lack of suitable drug carriers that fit the periodontal region and provide a controlled local drug release. In this study, we address the critical gap in localized periodontal drug delivery and introduce an ultrasound-assisted technique to encapsulate atorvastatin within alginate microparticles (10-400 µm in diameter)-a simple, scalable, and biocompatible solution. While ultrasound is widely used in polymer synthesis, its application in alginate polymerization remains underexplored. To mimic physiological conditions, particles were incubated in artificial saliva at 37 °C, with drug release being analyzed via high-performance liquid chromatography. A methylcellulose-based hydrogel served as a conventional reference product. Results revealed that alginate particles exhibited at least a 10-fold increase in mean dissolution time compared to the methylcellulose gel, indicating superior stability. Increasing atorvastatin concentration extended the time interval needed for 50% of the drug to be released (t_50%) from 1 h to 11 h, maintaining the overall drug diffusion level for several days. Further analysis showed that covalent cross-linking of alginate with divinyl sulfone significantly delayed the initial drug release by 3 h (p < 0.05) due to the additional molecular stabilization. These findings underscore the utility of ultrasonic atomization for the processing of alginate-based formulations. Given the ease of production, biocompatibility, and small size, successfully fabricated alginate particles represent a promising carrier for delivery of statins or other related drugs in clinical dentistry.