Design Considerations for Polymer–Deep Eutectic Solvent Hybrid Systems for Transdermal Drug Delivery

ABSTRACT

Polymer‐based transdermal drug delivery systems (TDDS) require precise control of solubility, permeability, mechanical integrity, and stability to achieve effective and patient‐friendly therapy. Deep eutectic solvents (DESs) and therapeutic DES (THEDES) have emerged as versatile, potentially sustainable and composition‐tunable excipients capable of modulating these properties within polymer matrices used in patches, films, hydrogels, nanoparticles, and microneedles. Through extensive hydrogen‐bond networks, DESs interact with polymer functional groups to regulate crystallinity, plasticization, viscosity, and drug–polymer affinity, thereby influencing drug loading, release kinetics, and transdermal flux. This review presents a polymer‐centric, design‐oriented framework that links DES composition with polymer compatibility and formulation performance. DESs are highlighted as active modulators of polymer structure–property relationships, enabling simultaneous control over drug solubilization, permeation enhancement, and matrix stability. The interplay between DES physicochemical descriptors, including polarity, viscosity, and hydrogen‐bonding capacity, and polymer characteristics is critically analyzed to guide rational formulation design. Emerging in silico approaches, including molecular dynamics, quantitative structure–property relationship (QSPR), and quantitative structure–toxicity relationship (QSTR) models, are discussed as predictive tools for screening DES–polymer compatibility and accelerating optimization. Key challenges related to safety, regulatory uncertainty, scalability, and long‐term stability are also addressed. Overall, polymer–DES hybrid systems represent a promising platform for developing efficient, stable, and customizable TDDS.