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Some drugs such as nicotine can be administered through skin. I thought the layers of skin are designed to prevent in-flow of any chemical/germs. Not all drugs get absorbed in this fashion. So do drugs like nicotine have any specialities(such as a special chemical group) that fool the sentries of skin? A link to an article/site would be very helpful, or even a book recommendation.

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  • $\begingroup$ Looks like size is the largest factor: en.wikipedia.org/wiki/Transdermal_patch $\endgroup$ – Astrolamb Aug 18 '18 at 12:12
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    $\begingroup$ "...that fool the sentries of skin..." The skin doesn't have sentries. It doesn't know anything, much less possess the ability to recognize drugs and let them in or keep them out. Finally, bacteria are much, much, much larger than the molecules that comprise the drugs. $\endgroup$ – anongoodnurse Aug 18 '18 at 17:19
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According to a review (Prausnitz2004), marketed drugs with a dermal route of administration tend to fulfil the following criteria :

  • Small molecular size (< 500 Da)
  • High lipophilicity
  • Small required dose (up to ~milligram)

This is a consequence of the structure of the skin (with a lipophilic stratum corneum, and low diffusion speed) and practical concerns (everything else equal, a higher dose would need more surface area).

Beyond "pure" diffusion, there has been much work on improving drug delivery through other means : chemical enhancers (ethanol or DMSO being classical member of this class), medical devices (microneedle patch, ultrasonic device), and other more exotic methods mentionned in the paper.

These criteria are also mentionned in (GoodmanGillman2006, chapter 26), with emphasis on concentration gradient being the driving force behind diffusion across the skin. This chapter also contain a list of commonly used transdermal/dermatological drug, and their use.

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