Investigating the role of Vehicle, Penetration Mechanisms and Skin Condition on Dermal Drug Delivery

This work systematically investigated the influence of vehicle composition, penetration enhancement strategies, and skin condition on dermal drug delivery using ex vivo porcine skin models and hydrophilic and lipophilic surrogate compounds. The work demonstrated that vehicle type critically determines penetration efficacy, affecting uptake, depth, and distribution, with novel carriers such as liposomes and marine collagen showing potential as alternatives to classical vehicles, albeit requiring further validation. Mechanical skin treatments revealed that microneedling most effectively enhanced penetration by bypassing the stratum corneum, while methods such as dermabrasion and tape stripping were moderately effective, and massage or ultrasound unexpectedly reduced penetration due to barrier compaction. Integration of vehicle type and skin condition highlighted complex interdependencies, where occlusive pretreatments facilitated lipophilic compound penetration, hydrogels supported hydrophilic delivery under hydrated conditions, and surfactants enhanced penetration at the expense of increased transepidermal water loss. Correlation analyses confirmed that optimal delivery requires balancing penetration enhancement with barrier preservation. Collectively, the findings underscore the multifactorial nature of dermal drug delivery, emphasize the need for mechanistic understanding of vehicle–skin interactions, and provide guidance for the rational design of safe and effective dermal formulations, while future work should aim to reduce formulation complexity and develop standardized models to refine vehicle selection and barrier modulation strategies.