Abstract
The development of smart nanocarriers that enable controlled drug release in response to internal and external triggers is an emerging approach for targeted therapy. This study focused on designing pH-sensitive, ultrasound-responsive gelatin/perfluorohexane (PFH) nanodroplets loaded with berberine chloride as a model drug. The nanodroplets were prepared using an emulsion technique and optimized by varying process parameters like homogenization rate, polymer concentration, surfactant, drug, and perfluorocarbon content. The optimal formulation yielded nanodroplets with a particle size of 281.7 nm, a drug encapsulation efficiency of 66.8 ± 1.7, and a passive drug release of 15.4 ± 0.2 within 24 hours. Characterization confirmed successful encapsulation and pH-responsive behavior. Ultrasound stimulation significantly enhanced drug release, with 150 kHz being more effective than 1 MHz in triggering acoustic droplet vaporization while minimizing heat generation. After 10 minutes of radiation, the optimal formulation showed 89.4% cumulative drug release. The nanodroplets displayed stability over one month at 4°C. Overall, the dual-triggered nanodroplets demonstrate excellent potential for controlled delivery and targeted release of berberine chloride.