Using microfluidic platforms to develop CNS‐targeted polymeric nanoparticles for HIV therapy

ABSTRACT The human immunodeficiency virus (HIV) uses the brain as reservoir, which turns it as a promising target to fight this pathology. Nanoparticles (NPs) of poly(lactic‐co‐glycolic) acid (PLGA) are potential carriers of anti‐HIV drugs to the brain, since most of these antiretrovirals, as efavirenz (EFV), cannot surpass the blood‐brain barrier (BBB). Forasmuch as the conventional production methods lack precise control over the final properties of particles, microfluidics emerged as a prospective alternative. This study aimed at developing EFV‐loaded PLGA NPs through a conventional and microfluidic method, targeted to the BBB, in order to treat HIV neuropathology. Compared to the conventional method, NPs produced through microfluidics presented reduced size (73nm versus 133nm), comparable polydispersity (around 0.090), less negative zeta‐potential (−14.1mV versus −28.0mV), higher EFV association efficiency (80.7% versus 32.7%) and higher drug loading (10.8% versus 3.2%). The microfluidics‐produced NPs also demonstrated a sustained in vitro EFV release (50% released within the first 24h). NPs functionalization with a transferrin receptor‐binding peptide, envisaging BBB targeting, proved to be effective concerning nuclear magnetic resonance analysis (&dgr; = −0.008ppm; &dgr; = −0.017ppm). NPs demonstrated to be safe to BBB endothelial and neuron cells (metabolic activity above 70%), as well as non‐hemolytic (1–2% of hemolysis, no morphological alterations on erythrocytes). Finally, functionalized nanosystems were able to interact more efficiently with BBB cells, and permeability of EFV associated with NPs through a BBB in vitro model was around 1.3‐fold higher than the free drug.