Cryo-emulsion gel patches as versatile platform for dual drug delivery to wounds

Cryo-emulsion gels (C-EGs) represent a promising drug delivery approach that combines the possibility to deliver both, hydrophilic and lipophilic drugs, with the mechanical stability of hydrogel matrices for dermal application. In this study, poly(vinyl alcohol) (PVA) was used as a multifunctional polymer acting as both a polymeric emulsifier and as a gelling agent for cryogelation to minimize formulation complexity. Medium-chain triglycerides, castor oil, and rapeseed oil were identified as suitable candidates for the dispersed phase of the emulsions. The influence of oil type and oil content on the rheological and mechanical properties of the patches was investigated, allowing the definition of a maximum oil content of 30%. Within this range, C-EGs with consistent droplet distribution were obtained. The two-phase structure enabled dual drug loading using hydrophilic N-acetylcysteine and lipophilic phenytoin, which complement each other in wound healing. The system showed controlled drug release over 48 h with release rates depending on the physicochemical properties of the drugs and their location within the patch. Ex vivo penetration studies on intact and wounded skin revealed different penetration profiles according to the drug and skin condition. Cytocompatibility studies demonstrated excellent tolerability of the PVA-based vehicle. Drug incorporation resulted in a synergistic effect between the C-EGs and the drugs, increasing cell viability up to 178%. Peel adhesion testing revealed very low adhesion of the C-EG patches on both bloody and dry wound surfaces. Overall, PVA-based C-EGs provide a stable and cytocompatible platform for incorporating emulsions into cryogel patches, representing an attractive strategy for advanced wound care applications.