Microfluidics-Assisted Size Tuning and Biological Evaluation of PLGA Particles

Abstract

Polymeric particles made up of biodegradable and biocompatible polymers such as poly(lactic-co-glycolic acid) (PLGA) are promising tools for several biomedical applications including drug delivery. Particular emphasis is placed on the size and surface functionality of these systems as they are regarded as the main protagonists in dictating the particle behavior in vitro and in vivo. Current methods of manufacturing polymeric drug carriers offer a wide range of achievable particle sizes, however, they are unlikely to accurately control the size while maintaining the same production method and particle uniformity, as well as final production yield. Microfluidics technology has emerged as an efficient tool to manufacture particles in a highly controllable manner. Here, we report on tuning the size of PLGA particles at diameters ranging from sub-micron to microns using a single microfluidics device, and demonstrate how particle size influences the release characteristics, cellular uptake and in vivo clearance of these particles. Highly controlled production of PLGA particles with ~100 nm, ~200 nm, and >1000 nm diameter is achieved through modification of flow and formulation parameters. Efficiency of particle uptake by dendritic cells and myeloid-derived suppressor cells isolated from mice is strongly correlated with particle size and is most efficient for ~100 nm particles. Particles systemically administered to mice mainly accumulate in liver and ~100 nm particles are cleared slower. Our study shows the direct relation between particle size varied through microfluidics and the pharmacokinetics behavior of particles, which provides a further step towards the establishment of a customizable production process to generate tailor-made nanomedicines.

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).…”

“…In this study, we adopted poly (D,L-lactic-co-glycolic acid) (PLGA) polymers as a carrier system, because they have shown the ability to protect the loaded drug or siRNA from inactivation, reduce unwanted side effects, and enhance the efficacy of the active pharmaceutical ingredient due to improved solubility and bioavailability. Notably, only nanoparticles (NPs) with a size of less than 200 nm have the ability to easily permeate through mucus without being immobilized by the natural size-filtering mechanism [30].…”

Ionizable lipid nanoparticles for in utero mRNA delivery

“…The use of PLGA NPs for nucleic acid delivery is supported by several benefits afforded by the NPs including high biocompatibility and biodegradability ( 29 ). Furthermore, recent studies have advanced techniques of polymeric NP formulation, such as microfluidic devices, which have allowed for precise control over the size of PLGA NPs, overcoming a previous limitation of size control ( 29 – 33 ). Although PLGA and other polymeric systems hold promise for drug delivery to fetuses, we were interested in developing nonviral, ionizable lipid nanoparticles (LNPs) for this application.…”

Ultrabright Green-Emitting Nanoemulsions Based on Natural Lipids-BODIPY Conjugates

“…Surprisingly, green BODIPYs have never been used as fluorescent cargos for NEs. However, different green BODIPYs successfully served to load nanomaterials ( Figure 1 ), including BODIPY 493/503 for poly(D,L-lactic acid) based nanoparticles [ 18 ], P-B and CholEsteryl BODIPY FL C12 for poly(lactic-co-glycolic acid) (PLGA) [ 19 , 20 ], PS-2 for silica NPs [ 21 ], and BDP-2C 8 for oil/polymer hybrid NPs [ 22 ]. Although the latter possesses enhanced hydrophobicity due to hydrophobic branched aliphatic chains, its biocompatibility remained limited and was only used for in vitro applications.…”