Preparation of Heat-Denatured Macroaggregated Albumin for Biomedical Applications Using a Microfluidics Platform

Area of Science:

• Biomaterials Science
• Nanotechnology
• Pharmaceutical Sciences

Background:

• Albumin microparticles are utilized in pharmaceuticals for drug delivery and imaging.
• Traditional methods for macroaggregated albumin (MAA) preparation yield particles with poor size control (CV ~50%).
• Precise control over albumin microparticle characteristics is crucial for optimizing drug delivery and diagnostic applications.

Purpose of the Study:

• To develop an integrated microfluidics platform for the controlled fabrication of albumin microparticles.
• To produce microfluidic-MAA (M2A2) particles with enhanced size uniformity and dispersity.
• To evaluate the pharmaceutical utility and biodistribution of M2A2 particles in vivo.

Main Methods:

• Fabrication of microfluidic chips using off-stoichiometry thiol-ene chemistry.
• Utilized a flow-focusing design followed by a heated curing channel (85 °C).
• Controlled particle size by adjusting flow rates of dispersed and continuous phases.

Main Results:

• Reliable preparation of M2A2 particles with diameters ranging from 70 to 300 μm.
• Achieved significantly improved size uniformity with coefficients of variation (CV) between 10% and 20%.
• In vivo studies with ¹¹¹In-M2A2 demonstrated lung uptake and subsequent clearance, similar to ^99mTc-MAA.

Conclusions:

• The developed microfluidics platform offers a controllable and precise method for preparing albumin microparticles.
• M2A2 particles exhibit improved characteristics over conventionally prepared MAA.
• This technology holds promise for advanced pharmaceutical applications, including drug delivery and medical imaging.