The manufacturing and characterization of pentamidine-loaded poly(lactic-co-glycolic acid) nanoparticles produced by microfluidic method

Abstract

In recent years, special attention has been paid to the study of manufacturing processes that can precisely control the physicochemical properties of nanoparticles (NPs) and reduce batch-to-batch variability. Microfluidics has recently emerged as an advanced production method that can manage NP properties by monitoring the diffusion/emulsification mechanism. Pentamidine free base (PTM-B), a diamidine compound positively charged at physiological pH, has already been used as a model drug for incorporation into poly(lactic-co-glycolic acid) (PLGA) via an ion-pairing strategy using a conventional bulk production method. The same formulation was chosen to study the scaling-up process and preparation using the microfluidic technique. The formulation of PLGA NP loaded with PTM-B by the microfluidic technique was optimized by adding 1 % Lutrol F68 as a surfactant agent to stabilize the nanosuspension during the solvent diffusion in the microchannel of the chip, and then, washed away in the final suspension. A thorough investigation of process parameters (i.e., total flow rate, flow rate ratio) was conducted to obtain a monodisperse suspension characterized by a mean diameter of less than 150 nm. In addition, in vitro studies on mammalian cancer cell lines demonstrated the potential antitumor activity of PTM-B-loaded NPs prepared by the microfluidic technique.