Follicular Penetration of Caffeine from Topically Applied Nanoemulsion Formulations Containing Penetration Enhancers: In vitro Human Skin Studies

Abstract

Background/Aims: This study aimed to investigate transfollicular delivery enhancement of caffeine from nanoemulsion formulations incorporating oleic acid (OA) and eucalyptol (EU) as chemical penetration enhancers. Methods: Caffeine permeation was evaluated from nanoemulsions containing OA or EU and an aqueous control solution through excised human full-thickness skin with hair follicles opened, blocked, or left untreated. Differential tape stripping was performed, followed by cyanoacrylate skin surface biopsies to determine the amount of caffeine in the hair follicles, and skin extraction to determine the retention of caffeine in the skin. Results: Nanoemulsions significantly increased caffeine permeation through open and untreated skin over control (untreated: 36- and 42-fold for OA and EU, respectively; open: 40- and 49-fold). The follicular route contributed 53.7% of caffeine permeation for the OA nanoemulsion and 51% for EU when follicles were opened. Nanoemulsions promoted 4- and 3.4-fold increases in caffeine retention in open follicles, for OA and EU, respectively. Retention of caffeine in the stratum corneum and skin was almost equal in all cases. Conclusions: This study demonstrated effective delivery of caffeine as a hydrophilic model drug into and through hair follicles and showed that follicles and surrounding regions may be targeted by optimised formulations for specific treatments.

Deformable liposomes as enhancer of caffeine penetration through human skin in a Franz diffusion cell test

“…The cotton buds were mixed overnight with 2 mL of methanol to extract caffeine. To measure the amount of caffeine that penetrated and was retained in the stratum corneum, differential tape stripping was then performed according to the method developed and validated by Teichmann et al [21] and previously used in our laboratory [26]. Strips of adhesive tape designed for this purpose (D‐Squame tapes, CuDerm Corp., TX, USA) were applied to the exposed skin surface 20 times for about 5 s before being carefully removed.…”

Nanoemulsion: A Review on Mechanisms for the Transdermal Delivery of Hydrophobic and Hydrophilic Drugs

“…Caffeine NE was developed using OA and eucalyptol, which both serve a dual function of being an oil phase and a PE, showing a 51% and 54% passage of caffeine, compared to 27% penetration of a topical caffeine solution when the follicles were opened. On the other hand, the percentage of penetrated drug was only 18.9% through blocked follicles [139]. Follicular delivery is tricky in vitro, since human skin follicles tend to collapse, becoming blocked with dry sputum, and secretion pathways become inactive.…”

“…Moreover, the animal skin model used to evaluate this route is not always consistent with the release profile when applied to human skin [140]. However, certain in vivo human studies with the hydrophilic molecule caffeine NE showed that the transfollicular route contributed to over a third of the total penetration [139,148,149].…”

Laser scanning microscopy for control of skin decontamination efficacy from airborne particulates using highly absorbent textile nanofiber material in combination with PEG‐12 dimethicone

“…On the contrary, for non‐particulate substances, the hair follicle is a very fast and efficient penetration pathway. Lademann et al21 and Abd et al22 could demonstrate, for example, for caffeine and minoxidil, an efficient transfollicular penetration. The hair follicle is surrounded by a dense network of blood capillaries and immune cells; therefore, transfollicularly penetrating substances are easily absorbed by the blood circulation and are able to provoke immune reactions.…”