Simulation and in vitro evaluations of microfluidically-fabricated clarithromycin-poly (ε-caprolactone) nanoparticles

Abstract

Clarithromycin (CLR)-loaded poly (ε-caprolactone) (PCL) nanoparticles (NPs) were synthesized using microfluidics (MF) with square-shaped (MF1), and three-channel (MF2), geometries as well as conventional bulk mixing (BM). Based on Comsol simulation results of MF chips, the flow rate ratio, non-solvent phase flow rate, and polymer solution concentration were optimized 0.05, 50 mL h−1, and 0.2 (%w/v), respectively; thereby, representing MF1 geometry with highest homogenous mixing. Characterization studies indicated that MF1-based NPs possessed smaller average diameter (∼91 nm), narrower polydispersity index (∼0.13) and higher zeta potential (-44 mV) compared to those NPs synthesized by MF2 and BM methods. Moreover, MF1-aided synthesis of NPs exhibited the encapsulation efficiency of approximately 81% and loading capacity of around 13%. Investigating CLR release behavior at different pHs also demonstrated that the MF1-based NPs experienced the most controlled release, followed the Fickian diffusion mechanism. The controlled release of MF1-based NPs was confirmed by evaluating their inhibitory effect against specific cytokines on BEAS-2B as bronchitis cell line via a series of in vitro experiments including real time-polymerase chain reaction and flow cytometry. Eventually, the antibacterial properties of the samples were studied on two prevalent bacterial strains and the obtained observations revealed that MF1-based NPs encompassed the best performance in controlled release of CLR with respect to the other samples.