Ultra-small starch microspheres with narrow size distribution prepared in aqueous two-phase system of starch-PVP

It is challenging to fabricate uniform starch microspheres (SMs) with sub-10 μm diameters in starch-polyethylene glycol (PEG) aqueous two-phase system (ATPS). To address this issue, a refined approach using starch- polyvinylpyrrolidone (PVP) ATPS is presented in this work. Phase diagrams were constructed for ATPSs con- taining PVPs of varying molecular weights, which provided crucial insights into the influence of PVP on SM formation. The results revealed that increasing both the molecular weight and concentration of PVP led to higher starch and PVP contents within the dispersed phase, significantly influencing the final yield of SMs. The morphology, size, crystallinity, and swelling behavior of SMs prepared in the starch-PVP ATPS were compre- hensively characterized. Increasing PVP molecular weight resulted in smaller SMs with enhanced crystallinity and reduced swelling capacity. Notably, SMs prepared with 58 kDa PVP exhibited an average particle size (D[4,3) of 5.13 μm, a narrow size distribution (Span value = 1.33), a B + V crystal type, and a relative crystallinity of 20.9 %. Furthermore, no residual PVP was detected in the final SMs. This innovative starch-PVP ATPS approach offers a promising route for the controlled fabrication of sub-10 μm SMs with tightly controlled size distributions. This method holds significant potential for applications demanding well-defined starch-based materials in various fields. This innovative starch-PVP ATPS approach offers a promising route for controlled fabrication of uniform SMs with sub-10 μm diameters, which could be advantageous for drug encapsulation and delivery systems requiring high structural stability.