Microfluidic Assembly of Poly(glutamic acid) Nanogels Through SPAAC Click Chemistry

Area of Science:

• Materials Science: Development of novel nanocarriers for advanced drug delivery systems.
• Chemical Engineering: Application of microfluidics for precise synthesis of polymeric nanostructures.
• Biotechnology: Utilizing click chemistry for controlled bioconjugation and nanogel formation.

Background:

• Nanogels (NGs) are versatile drug delivery vehicles due to their tunable properties and biocompatibility.
• Conventional batch synthesis methods for NGs often suffer from poor control over size distribution and encapsulation efficiency.
• There is a need for reproducible and scalable methods to produce well-defined nanogels for pharmaceutical applications.

Purpose of the Study:

• To develop a microfluidic platform for the reproducible synthesis of poly(α-glutamic acid) (PGA)-based nanogels.
• To utilize strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry for nanogel formation.
• To investigate the impact of microfluidic flow parameters on nanogel physicochemical properties and drug encapsulation.

Main Methods:

• Functionalized PGA (azide and DBCO) were co-injected in a microfluidic system with acetone to form NGs via SPAAC.
• Systematic screening of flow rate ratios (FRR) and total flow rates at different temperatures (25 °C and 50 °C).
• Evaluation of nanogel size, polydispersity index (PDI), zeta potential, and doxorubicin encapsulation efficiency (EE%).

Main Results:

• Tunable nanogel sizes (~50 nm to >170 nm) with low PDI (<0.1) were achieved under optimal microfluidic conditions.
• Higher FRR and total flow rates resulted in smaller and more uniform nanogels.
• Doxorubicin loading did not negatively impact nanogel characteristics, with EE% reaching up to ~65%; elevated temperature improved drug-loaded nanogel properties.

Conclusions:

• Microfluidic SPAAC synthesis provides precise and scalable fabrication of PGA nanogels with controlled size and drug loading.
• The microfluidic platform demonstrates superior reproducibility and size control compared to traditional batch synthesis.
• This technology holds promise for integration with on-chip purification and monitoring for clinical nanomedicine applications.