Penetration enhancer-containing vesicles (PEVs): from deformable liposomes to barrier-modulating delivery platforms across multiple administration routes.

Abstract

Introduction: Penetration enhancer-containing vesicles (PEVs) were developed as lipid-based nanocarriers integrating vesicle deformability with controlled modulation of barrier architecture to improve drug permeation and tissue deposition.

Areas covered: This review provides an overview of the composition, mechanism of actions and applications of PEVs. Initially introduced for dermal and transdermal delivery, PEVs have demonstrated superior performance than conventional liposomes in enhancing skin penetration of synthetic and natural bioactive. Evidence supports extension of the PEV concept to oral, mucosal, nasal, and pulmonary delivery, where permeability, stability, and epithelial interaction represent critical challenges. Particular emphasis is placed on the barrier-oriented design of PEVs, and on the possibility of tailoring penetration enhancer selection according to drug physicochemical properties and target tissues.The literature included in this review was identified in PubMed, Scopus, and Web of Science, focusing on 2000 to 2025 and prioritizing recent studies.

Expert opinion: PEVs should not be considered merely as improved deformable liposomes but as adaptable barrier-modulating platforms. Their future clinical translation will depend on safety assessment of penetration enhancers, scalable manufacturing strategies, and standardized pharmacokinetic and toxicological evaluation. If supported by systematic translational studies, PEVs may represent a versatile approach for the design of next-generation noninvasive drug delivery systems.