Pulse-Heat Aerosol Reactor (PHAR): Processing Thermolabile Biomaterials and Biomolecules into Nanoparticles with Controlled Properties

Abstract

This work addresses the challenge of processing thermolabile biomaterials and biomolecules into nanoparticles without compromising structural integrity and activity. Control of size, structure, and crystallinity of nanoparticles is desirable for drug targeting and controlled release applications. An innovation using pulse-heat aerosol processing is demonstrated through a design of a pulse-heat aerosol reactor. Nanoparticle aerosol lipid matrices (NALM), of stearic acid, were synthesized under different processing conditions, obtained through pulse heating (fixed duration, three heat-pulse levels) and solvent selection. Operation with continuous heating resulted in ill-conditioned, multimodal size distributions. Pulse heating resulted in the synthesis of NALM with mean mobility diameter in the range of 56–183 nm and narrow unimodal size distributions (geometric size distribution, GSD = 1.5–1.7). Under higher pulse levels, particles with larger mean mobility diameter were formed, which had shell-type structures, compared with smaller, solid particles under operation with low level or no heating. NALM with different degree of crystallinity were produced under different processing conditions, at which different drop temperature is expected to result. The activity of glucose oxidase enzyme was preserved, when subjected to high pulse-heat (gas temperature of 110°C) aerosol processing. These results establish pulse-heat aerosol processing as a single-step, continuous method to process heat-sensitive biomaterials and biomolecules into nanoparticles with controlled properties, while avoiding thermal damage.