Hair follicle-penetrating nanoparticles offer a promising avenue for targeted antibiotic delivery, especially in challenging infections like acne inversa or folliculitis decalvans. However, demonstrating their efficacy with existing preclinical models remains difficult. This study presents an innovative approach using a 3D in vitro organ culture system with human hair follicles to investigate the hypothesis that antibiotic nanocarriers may reach bacteria within the follicular cleft more effectively than free drugs. Living human hair follicles were transplanted into a collagen matrix within a 3D printed polymer scaffold to replicate the follicle\'s microenvironment. Hair growth kinetics over 7 days resembled those of simple floating cultures. In the 3D model, fluorescent nanoparticles exhibited some penetration into the follicle, not observed in floating cultures. Staphylococcus aureus bacteria displayed similar distribution profiles postinfection of follicles. While rifampicin-loaded lipid nanocapsules were as effective as free rifampicin in floating cultures, only nanoencapsulated rifampicin achieved the same reduction of CFU/mL in the 3D model. This underscores the hair follicle microenvironment\'s critical role in limiting conventional antibiotic treatment efficacy. By mimicking this microenvironment, the 3D model demonstrates the advantage of topically administered nanocarriers for targeted antibiotic therapy against follicular infections.

Tofacitinib citrate (TC) has recently gained interest in treating skin disorders such as psoriasis, atopic dermatitis and baldness. Unfortunately, the oral administration shows side effects, such as decreased neutrophil counts. To this end, the topical delivery of TC can be used to reduce the risk associated with systemic exposure. However, TC shows minimal absorption via skin. Hence, the objective of this study is to enhance the skin delivery of TC using a non-invasive approach. The liposomes based on propylene glycol, named as proposomes, carrying TC, were studied. The vesicle characteristics and in vitro skin permeation were assessed. The proposomes enhanced the skin permeability of TC by 4-11 folds. The composition of proposomes was found to affect the skin permeation and deposition of TC. The proposomes were stable for at least 6 months. Overall, proposomes were effective for targeted topical drug delivery.

This overview on skin delivery considers the evolution of the principles of percutaneous absorption and skin products from ancient times to today. Over the ages, it has been recognised that products may be applied to the skin for either local or systemic effects. As our understanding of the anatomy and physiology of the skin has improved, this has facilitated the development of technologies to effectively and quantitatively deliver solutes across this barrier to specific target sites in the skin and beyond. We focus on these technologies and their role in skin delivery today and in the future.