Microfluidic Design of Ultradeformable Liposomes for Advanced Skin Delivery of Stellaria media Phytocomplex.

Background/Objectives: Ultradeformable liposomes represent an established platform for topical delivery of antioxidant compounds, thanks to their structural flexibility and ability to enhance skin permeation, but standardized manufacturing protocols are still lacking. This study presents a microfluidic-based strategy for the scalable production of ultradeformable liposomes encapsulating Stellaria media extract, a polyphenol-rich phytocomplex with strong antioxidant activity. Methods: Liposomes were produced with a GMP-like microfluidic platform enabling fine control of formulation parameters and high reproducibility under conditions directly transferable to continuous manufacturing. Process optimization tested different total flow rates. Characterization included particle size and distribution, encapsulation efficiency, colloidal stability and kinetics of release. Permeation was assessed with Franz diffusion cells using human stratum corneum and epidermidis membranes. Results: Optimal conditions were a flow rate ratio of 3:1 and a total flow rate of 7 mL/min, yielding ultradeformable liposomes with a mean size of 89 ± 1 nm, a polydispersity index < 0.25, and high encapsulation efficiency (72%). The resulting formulation showed long-term colloidal stability and controlled release. Diffusion studies demonstrated a 2-fold increase in permeation rate compared to the free extract. Conclusions: These findings highlight the potential of microfluidics as a robust and scalable technology for the industrial production of ultradeformable liposomes designed to enhance the dermal delivery of bioactive phytocomplex for both pharmaceutical and cosmeceutical applications.