Nanomanufacturing through microfluidic-assisted nanoprecipitation: Advanced analytics and structure-activity...

Area of Science:

• Nanotechnology
• Materials Science
• Pharmaceutical Sciences

Background:

• Traditional methods for nanoparticle preparation can lack reproducibility and scalability.
• Controlling nanoparticle formation and purification is crucial for effective drug delivery.

Purpose of the Study:

• To develop and optimize a microfluidic method for producing drug-loaded poly(lactic acid-co-glycolic acid) nanoparticles.
• To assess the reproducibility and scalability of the microfluidic approach compared to batch methods.
• To investigate methods for purifying nanoparticles and analyze their drug release characteristics.

Main Methods:

• Utilized a microfluidic cross-shaped chip with flow focusing for controlled precipitation of poly(lactic acid-co-glycolic acid) from acetone.
• Employed PEGylated surfactants and varied acetone/water ratios to optimize nanoparticle formation.
• Applied advanced characterization techniques including flow-through dynamic light scattering and field flow fractionation with light scattering detection for quality control and impurity analysis.
• Investigated the release profile of paclitaxel from nanoparticles formulated with different poly(lactic acid-co-glycolic acid) and surfactant types.

Main Results:

• Microfluidic preparation demonstrated superior reproducibility and scalability compared to batch methods, with strong dependence on the acetone/water ratio.
• Field flow fractionation successfully detected free surfactant micelles in nanoparticle mixtures, a challenge for standard dynamic light scattering.
• The choice of poly(lactic acid-co-glycolic acid) molecular weight and surfactant type significantly impacted paclitaxel release, with higher molecular weight polymer and lower molecular weight surfactant leading to accelerated release.

Conclusions:

• Microfluidics offers a robust, operator-independent platform for scalable nanoformulation development.
• Advanced characterization techniques are essential for comprehensive quality control, including the detection of residual surfactants.
• Formulation parameters, specifically polymer and surfactant selection, critically influence nanoparticle drug release kinetics, impacting therapeutic efficacy.