Formation of albumin manganese carbonate hybrid microparticles by confined impinging jet mixing with a tubular maturation section.

Abstract

Hybrid protein inorganic microparticles are promising carriers for controlled drug delivery because their size, composition, and surface chemistry can be tailored to therapeutic requirements. In this study, human serum albumin-manganese(II) carbonate hybrid microparticles (MPs) were synthesized for the first time by continuous coprecipitation in a confined impinging jet mixer (CIJM) equipped with a tubular maturation section. Equimolar precursor solutions containing 10 mg·mL^-1 HSA were mixed at total flow rates between 2 and 20 mL·min^-1, and mean maturation residence times of 0, 6, and 12 s were achieved using capillaries of defined length. Particle characteristics were quantified by dynamic light scattering, laser Doppler electrophoresis, confocal laser scanning microscopy, and UV-vis spectrophotometry. Increasing flow rate reduced both the Kolmogorov length scale and the MPs' hydrodynamic diameter, yielding MPs of 240-800 nm with polydispersity indices below 0.25. In contrast, residence time did not significantly affect size but increased the encapsulation efficiency from 43% to 65% and shifted the zeta potential to more negative values, indicating enhanced protein incorporation. These results show that CIJM hydrodynamics determine MP size, while the maturation section provides an independent lever to tune loading and surface properties, offering a robust route for engineering hybrid MPs for biomedical applications.