PLA/PLGA nanocarriers fabricated by microfluidics-assisted nanoprecipitation and loaded with Rhodamine or gold can be efficiently used to track their cellular uptake and distribution.

This study represents a pioneering investigation into using microfluidic technology for manufacturing PLA and PLGA nanocarriers (NCs) loaded with tracer molecules or metals through a co-precipitation protocol that involves saturating the water phase. The effects of total flow rate (TFR), flow rate ratio (FRR), surfactant amount, and polymer concentration on particle sizes and distributions were examined. The average size of PLA-NCs varied from 349 ± 175 nm to 170 ± 64 nm, with surface charges ranging from -13 to -6 mV. In contrast, PLGA-NCs had an average size between 192 ± 46 nm and 100 ± 34 nm, with surface charges from -23 mV to -53 mV. Increasing the TFR from 6 to 10 mL/min with a fixed FRR of 1:1 and reducing polymer concentrations in the organic phase from 20 to 5 mg/mL generally resulted in smaller NC sizes and distributions (monodispersed), with PLGA-NCs consistently exhibiting smaller dimensions. Under these specific conditions, Rhodamine B (Rhod) and gold (Au) were successfully loaded, achieving encapsulation efficiencies exceeding 50 %. Electron microscopy analysis confirmed that the nanocarriers exhibited a consistent spherical shape with smooth surface morphology. X-ray energy-dispersive spectroscopy (EDX) revealed a uniform distribution of gold within the polymer matrix. PLA-NCs were effectively internalized by various cell types, including human Peripheral Blood Mononuclear Cells (PBMCs), HT-29 colon cancer cells, and C6 glioma cells. Uptake occurred in a dose-dependent manner for PLA-NCs sized at 260 ± 51 nm, with only 30 % internalization at 2 mg/mL concentration after 24 to 48 h. Notably, smaller PLA-NCs with a mean size of 170 ± 64 nm achieved nearly 100 % uptake across all tested cell types after 48 h, indicating that particle size significantly influenced cellular uptake.