Abstract
Drug carriers hold significant promise for precision medicine but face persistent challenges in balancing high encapsulation efficiency with structural preservation during active loading. In this study, we present a microelectromechanical system (MEMS)-driven platform that can generate gigahertz (GHz)-frequency acoustic streaming (1.55 GHz) to enable nondestructive, power-tunable drug encapsulation in lipid vesicles. Utilizing DSPE-PEG-modified bilayers with hydrodynamic shear forces, our method achieves transient membrane permeability that preserves membrane integrity while permitting controlled doxorubicin (DOX) influx. We developed the GHz acoustic MEMS platform and applied it to systematically investigate two drug loading strategies: (1) loading DOX into giant unilamellar vesicles (GUVs, >10 μm in diameter) prior to extrusion into small unilamellar vesicles (SUVs, 100 nm) versus (2) direct acoustic loading into pre-formed SUVs. The GUV-first approach demonstrated better performance, achieving 60.04% ± 1.55% encapsulation efficiency (EE%) at 250 mW acoustic power-a 5.93% enhancement over direct SUV loading (54.11% ± 0.72%). Structural analysis via TEM confirmed intact SUV morphology post-loading, while power-dependent EE% analysis showed a linear trend. This work bridges gaps in nanocarrier engineering by optimizing drug loading strategies, aiming to offer a potential drug carrier platform for drug delivery in biomedical treatment in future.