Characterization of Calcium- and Strontium-Polyphosphate Particles Toward Drug Delivery into Articular Cartilage

Macromol Biosci. 2024 Mar;24(3):e2300345. doi: 10.1002/mabi.202300345. Epub 2023 Oct 18.

Abstract

Drug delivery into articular cartilage poses many challenges due in part to its lack of vasculature. While intra-articular injections are effective for the local administration of drugs, small molecules are rapidly cleared from the synovial fluid. As such, there is a need to develop effective drug delivery strategies to improve the residence times of bioactive molecules in the joint and elicit a sustained therapeutic effect. In this study, calcium- and strontium-polyphosphate particles are synthesized and characterized as potential drug carriers into articular cartilage. Physicochemical characterization reveals that the particles exhibit a spherical morphology, have a negative zeta potential, and are nanoscale in size. Biological characterization in chondrocytes confirms cellular uptake of the particles and demonstrates both size and concentration-dependent cytotoxicity at high concentrations. Furthermore, treatment of chondrocytes with these particles results in a reduction in cell proliferation and metabolic activity, confirming biological effects. Finally, incubation with cartilage tissue explants suggests successful uptake, despite the particles exhibiting a negative surface charge. Therefore, from the results of this study, these polyphosphate-based particles have potential as a drug carrier into articular cartilage and warrant further development.

Keywords: articular cartilage; chondrocytes; drug delivery; inorganic polyphosphate; nanoparticles.

MeSH terms

  • Calcium / metabolism
  • Cartilage, Articular*
  • Chondrocytes
  • Drug Carriers / chemistry
  • Drug Delivery Systems
  • Polyphosphates

Substances

  • Calcium
  • Polyphosphates
  • Drug Carriers