Light‐Triggered Pheophorbide A‐Based Protamine–Cinnamon Liposomes for Synergistically Enhanced Antibacterial Activity and Storage Stability

As delivery systems for natural antibacterial agents, liposomes exhibit limitations in targeting and environmental responsiveness, while many photosensitizers face issues of poor sustainability and low delivery efficiency. This study aims to develop an intelligent light-triggered liposome system for the synergistic co-delivery of natural antibacterial agents. Pheophorbide A serves as the phototrigger, encapsulating a protamine-cinnamon extract complex. Through systematic optimization of the preparation process, the resulting photosensitized liposomes achieved an encapsulation efficiency exceeding 70% and exhibited excellent colloidal stability (particle size = 169.6 nm; polydispersity index = 0.18; zeta potential = -47.47 mV). Release studies revealed that under 655 nm red light irradiation, the cumulative release rate of photosensitized liposomes reached 89.91% within 72 h-approximately four times that of conventional liposomes-following a second-order release model. Furthermore, the liposomes maintained structural integrity during 56 days of storage at both 4°C and 25°C. Antibacterial results demonstrated that the antibacterial efficacy of this system against Escherichia coli and Staphylococcus aureus was dependent on light irradiation time, thereby achieving a lower minimum inhibitory concentration and more durable antibacterial activity compared with conventional liposomes and free complexes. This light-triggered release system establishes a novel intelligent, on-demand delivery mechanism for protamine and cinnamon extract, significantly expanding the practical application potential of natural antibacterial agents while enhancing both antibacterial efficacy and stability.