Microfluidics as tool to prepare size-tunable PLGA nanoparticles with high curcumin encapsulation for efficient mucus penetration

Abstract

Great challenges still remain to develop drug carriers able to penetrate biological barriers (such as the dense mucus in cystic fibrosis) and for the treatment of bacteria residing in biofilms, embedded in mucus. Drug carrier systems such as nanoparticles (NPs) require proper surface chemistry and small size to ensure their permeability through the hydrogel-like systems. We have employed a microfluidic system to fabricate poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with a muco-penetrating stabilizer (Pluronic), with a tunable hydrodynamic diameter ranging from 40 nm to 160 nm. The size dependence was evaluated by varying different parameters during preparation, namely polymer concentration, stabilizer concentration, solvent nature, the width of the focus mixing channel, flow rate ratio and total flow rate. Furthermore, the influence of the length of the focus mixing channel on the size was evaluated in order to better understand the nucleation–growth mechanism. Surprisingly, the channel length was revealed to have no effect on particle size for the chosen settings. In addition, curcumin was loaded (EE% of ≈68%) very efficiently into the nanoparticles. Finally, the permeability of muco-penetrating PLGA NPs through pulmonary human mucus was assessed; small NPs with a diameter of less than 100 nm showed fast permeation, underlining the potential of microfluidics for such pharmaceutical applications.

p47phox siRNA-Loaded PLGA Nanoparticles Suppress ROS/Oxidative Stress-Induced Chondrocyte Damage in Osteoarthritis

“…In addition, Zetasizer measurements revealed the formation of monodisperse particles (PDI ≤ 0.2) within the desired size range on scrambled or siRNA encapsulation. It should be noted that although PDI values smaller than 0.3 are considered acceptable for drug delivery applications, more specific standards and guidelines have yet to be established by regulatory authorities [30,41]. Furthermore, the uniformity and morphology of the NPs were confirmed by using scanning electron microscopy ( Figure 3E).…”

Nanostructured Lipid Carriers for Delivery of Chemotherapeutics: A Review

“…Microfluidics have been recently introduced as a novel approach to produce NPs that can optimize their uniformity [52]. In this technique, liquid reagents are forced into a microfluidics chip at precisely controlled flow rates leading to collision and rapid mixing of nanoliter amounts of these reagents under highly controlled pressure [53].…”

Targeted delivery of functionalized PLGA nanoparticles to macrophages by complexation with the yeast Saccharomyces cerevisiae

“…The nanoparticles were prepared using the solvent‐diffusion evaporation technique as similar to Nafee et al () in a one‐pot approach. In brief, 50 mg of rhodamine‐labeled PLGA (prepared as described by Lababidi et al, ) were dissolved in 4.5 ml ethyl acetate (Thermo Fisher Scientific, Schwerte, Germany). In parallel 7.5 ml of an aqueous 2% polyvinyl alcohol (PVA; Mowiol 4‐88, Kuraray Europe, Hattersheim, Germany) solution containing 22 mg of chitosan (Protasan UP CL 113, NovaMatrix, Dupont, Sandvika, Norway) was prepared.…”

“…The nanoparticles were prepared using the solvent-diffusion evaporation technique as similar to Nafee et al (2007) in a one-pot approach. In brief, 50 mg of rhodamine-labeled PLGA (prepared as described by Lababidi et al, 2019) To obtain the particles dispersed at nearly isotonic conditions, 67 mg NaCl (Carl Roth, Karlsruhe, Germany) was added to the 2% PVA solution (with or without chitosan) before combining with the PLGA containing phase. After particle formation, the volume was increased by adding 45 ml of 0.9% NaCl.…”