Enhancing Antibacterial Activity of Medinilla speciosa Blume Fruits Against Cutibacterium acnes Through Phytosome Delivery: An In Vivo Study

Background/Objectives: The fruit of Medinilla speciosa Blume fruit contains flavonoids with potent activity against Cutibacterium acnes, but their clinical application is hindered by poor bioavailability. This study aimed to develop, characterize, and evaluate a phytosome-based vesicular system to enhance the in vivo antibacterial efficacy of the fruit’s ethyl acetate fraction (EAFMS). Methods: Phytosomes were synthesized via antisolvent precipitation using a 1:3 EAFMS-to-phospholipid ratio. Formulations were characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE), and in vitro release. Antibacterial efficacy was assessed in C. acnes-induced Wistar rats over three days. Results: EAFMS showed superior antibacterial activity with a 93.5% relative potency compared to tetracycline. The optimized phytosomes exhibited favorable physicochemical properties: particle size of phytosome 244.60 ± 0.85 nm, PDI of phytosome 0.396 ± 0.08, zeta potensial of phytosome −56.70 ± 2.08 mV, and EE of phytosome 89.46 ± 0.45%. The formulation achieved a 76.504% cumulative release at 8 h. In vivo trials demonstrated that the phytosome cream significantly reduced bacterial colony counts and diminished inflammatory cell infiltration compared to the cream base. Conclusions: The phytosome system effectively improves the stability and delivery of M. speciosa flavonoids, significantly enhancing their antibacterial and anti-inflammatory performance against acne.