Heat Enhanced Follicular Delivery of Isotretinoin to the Skin

Abstract

The aim of this work was to evaluate the use of short durations of externally applied heat with chemical penetration enhancers to improve delivery of isotretinoin to the skin and in particular via the follicular route. Methods: A range of chemical penetration enhancers were screened for their ability to improve isotretinoin delivery into human skin with heat using infinite dose, Franz cell experiments conducted in a water bath at a higher temperature to simulate heated conditions. Following this a prototype external heating system was developed that provided short durations of heat and its ability to improve delivery of finite doses into the skin and hair follicles was assessed. Results: The magnitude of the effect of heat on drug delivery was influenced by the choice of vehicle with changes in isotretinoin flux across skin ranging from not statistically significant to 25 fold increases with heat in the infinite dose studies. The prototype heating system provided significant increases in the total delivery of isotretinoin into the skin from an optimised vehicle. Drug distribution in the skin revealed significant increases in isotretinoin delivery to the hair follicles, and deeper skin layers, but not to the stratum corneum, providing strong evidence that the enhancement in delivery occurred mainly via the hair follicles. Conclusion: These data indicate that the use of short durations of heat combined with chemical penetration enhancers offers a valuable strategy for improving the delivery of drugs such as isotretinoin to the skin via the hair follicles.

Enhanced Follicular Delivery of Finasteride to Human Scalp Skin Using Heat and Chemical Penetration Enhancers

“…In most cases the largest amounts of drug were extracted from the dermis though DMI provided a greater level of drug delivery to the epidermis. The overall magnitude of the increases in finasteride total delivery with heat are similar to those obtained for isotretinoin from a range of vehicles with heat across abdominal skin (15). However the vehicles performed differently with the different drugs, for example heat did not significantly increase isotretinoin delivery from PG, whereas finasteride delivery to scalp skin was increased 2.6 fold.…”

“…As before the Franz cells had been preequilibrated in water baths maintained at either 37°C or 50°C to keep the skin surface at approximately 32± 1°C and 45± 1°C respectively. Additionally, the effect of controlled local heating on drug permeation across skin was determined as described previously (15). To summarise, after applying the formulation prepared at 32°C to the donor chamber, 2.5 mL or 5 mL of Sodium thiosulfate pentahydrate (ST) solution was introduced into the donor chamber to produce a membrane surface temperature of~43°C -44°C for approximately 20 and 30 min respectively.…”

“…However, features such as the high follicular density of scalp skin are thought to increase drug absorption to a greater extent for hydrophilic drugs in comparison to lipophilic molecules such as finasteride making it difficult to predict how effective follicular delivery of finasteride from topical administration would be (12,13). Recently the use of a heating system that can provide a physiologically tolerable increase in the skin temperature for relatively short periods of time along with selected chemical penetration enhancers has shown promise for delivery of drugs to the hair follicles, including for lipophilic molecules such as isotretinoin (14,15). An understanding of the effects of this enhancement approach on clinically relevant,…”

The effect of silymarin on liver enzymes in patients taking isotretinoin: A randomized clinical trial

“…One of the treatments of the severe and resistant type of acne that is not treated with conventional methods is administering oral isotretinoin, which has been proven to have therapeutic effects in various studies (Farah, Brown, & McAuley, ; Ianhez, Pinto, Miot, & Bagatin, ; Öktem, Hayran, Arı, & Yalçın, ). Like other medicines, this drug has a number of side effects, including dry lips, dry eyes, increased level of triglycerides (Brzezinski, Borowska, Chiriac, & Smigielski, ) and altered levels of liver enzymes (Ahmad, ).…”

Bcl‐2‐associated athanogene 5 overexpression attenuates catecholamine‐induced vascular endothelial cell apoptosis

“…buffered saline for 10 min each (Farah et al, 2019). Slides were blocked with 3% goat serum and incubated with primary antibodies at 4°C overnight (Dassanayaka et al, 2019).…”