Novel Production Methods for Incorporating Nanoparticles into Polymeric Microparticles: A Morphological Analysis

Abstract

Biologics, which include peptide or protein-based therapeutics, are one of the most rapidly expanding classes of pharmaceuticals due to their high potency and specificity toward targets in the body as well as generally lowered toxicity. However, biologics must be delivered parenterally and are also subject to rapid clearance from the bloodstream in vivo. A common solution to extend the release of biologics entails the use of microparticles (MPs) composed of hydrophobic polymer scaffolds loaded with biologics. However, the most common method of MP production introduces challenges such as low encapsulation efficiency and heterogeneous distributions of biologic within the MPs. This would yield undesirable drug release kinetics and larger MP injections. Embedding a fine and stable dispersion of biologics with high loading, such as nanoparticles (NPs) produced via inverted Flash NanoPrecipitation, into the larger polymeric MPs is a potential solution to many of the aforementioned problems. Flow-focusing microfluidic devices may also be used to prepare MPs with a monodisperse size distribution, allowing for reproducible drug release kinetics.This work examines the mechanics of NP loading within the larger polymeric MP scaffolds using both microfluidics and the existing “hand-mixing” methods for assembly of MPs. Although microfluidic devices show promise as a novel MP production procedure, higher concentrations of lysozyme NPs resulted in wetting of the PAA-lined channel walls. MPs prepared using varying concentrations of fluorophore-loaded NPs and polystyrene scaffold were imaged by confocal microscopy. This work shows that despite small voids and NP aggregates, NPs are relatively homogenously distributed throughout the polymer scaffold of the MPs. This work will also ultimately allow for the optimized manufacture of MPs loaded with a fine and stable dispersion of NPs, leading to drug release kinetics studies.