Hybrid patch based on fast-dissolving electrospun nanocomposite membrane for local inflammation treatment

The topical delivery of Ketoprofen (Ket) has some limitations depending on its poor water solubility, low skin permeability, and related side effects. In this study, a novel hybrid patch was developed by embedding Ket-loaded lipid nanovesicles (NVs) within electrospun polyethylene oxide (PEO) nanofibers. The resulting dry patch (Ket-HP) was designed to enhance percutaneous Ket permeation, improve its effectiveness and patient compliance. NVs had a mean size of approximately 95 nm and a narrow size distribution (PDI<0.1), endorsing suitable features for topical application. Electrospinning was used to obtain a homogeneous dispersion of drug-loaded NVs within polymeric nanofibers. Morphological and spectroscopic analyses endorsed the successful integration of drug-loaded NVs and their homogeneous distribution in the Ket-HP. The NVs supramolecular integrity, after electrospinning process, was confirmed by cryo-TEM analysis. In vitro release studies demonstrated a sustained and controlled release of Ket from the Ket-HP over 48 h, outperforming both Ket-loaded NVs and PEO-based patches containing free drug (Ket-P). In vitro permeation studies through human stratum corneum epidermidis demonstrated that the Ket-HP improved the Ket permeation of 10- to 30-fold than conventional Ket-gel. In vivo tolerability tests on healthy volunteers showed safe profile of Ket-HP and higher anti-inflammatory effectiveness than conventional Ket-gel dosage. The hygroscopic property of Ket-HP allowed its rapid conversion in gel-like structure upon the contact with moist skin, improving the application on difficult anatomical sites. The resulting Ket-HP combines the advantages of NVs and electrospinning and could represent a promising patient-oriented platform for the topical treatment of inflammation disease.