Thiol-Michael Addition Microparticles: Their Synthesis, Characterization, and Uptake by Macrophages

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Nanotechnology

Background:

• Polymeric microparticles are investigated as platforms for disease treatment by targeting macrophages.
• Developing microparticles with controllable properties is crucial for effective macrophage targeting.

Purpose of the Study:

• To synthesize and characterize polymeric microparticles using thiol-Michael addition polymerization.
• To evaluate the impact of particle size, chemistry, and treatment time on macrophage uptake.
• To assess the inflammatory potential and lung-specific application of these microparticles.

Main Methods:

• Stepwise dispersion polymerization of dipentaerythritol hexa-3-mercaptopropionate (DPHMP) and di(trimethylolpropane) tetraacrylate (DTPTA).
• Off-stoichiometry thiol-acrylate reaction for secondary functionalization with amide, carboxyl, and thiol groups.
• Macrophage uptake studies using RAW 264.7 cell line and human alveolar macrophages.
• In vivo studies in mouse lungs to assess particle distribution and inflammation.

Main Results:

• Monodisperse microparticles (1-10 μm) with tunable properties were synthesized.
• Macrophage uptake was dependent on particle size, treatment time, and surface chemistry (amide, carboxyl, thiol).
• Amide-terminated particles demonstrated non-inflammatory profiles and significant uptake by macrophages in vitro and in vivo, including in mouse lungs.

Conclusions:

• Thiol-Michael addition polymerization offers a versatile method for creating functional polymeric microparticles.
• Amide-terminated microparticles are biocompatible, non-inflammatory, and effectively targeted by macrophages, showing promise for lung-specific applications.
• These microparticles represent a viable delivery vehicle for therapeutic interventions targeting macrophages.