I have a lot of soreness in certain muscles and people are recommending OTC topical analgesics. Well, before I even investigated them my thought was: skin, the largest organ of the body, is designed to do one particular thing above all others: keep things from getting into your body. Skin is supremely well-designed to block things from “penetrating”. So I’m immediately skeptical that some stinky cheap OTC cream with some aspirin in it is going to even be able to pass thorugh the barrier of my skin at all, much less do much good if it does.
But of course we all know there are patches designed to deliver medications through the skin’s bitchen barrierness.
I have since read up about “sports creams” and there’s no evidence to support the belief that they will provide relief. No shock there.
But what I would like to know is what is required in order for something to pass through the skin? Is the patch the only way, does the long contact with the skin make adifference? Is there a particular size particle that can pass through? I know somethings do and some things don’t, but I have no idea what properties make the difference between those things that can breech skin and those that cannot.
I would like to understand these things better, if anyone would like to weigh in about it.
I had questions about this one myself, but your skin(or any cell membrane like the mouth or anus) cells are mostly made of fat on the outside.(lipids) And some substances like drugs are lipid soluble, so that is how they diffuse through.
There are three different ways that a transdermal (through the skin) medication can work. The first is kind of cheating - use a bunch of teeny tiny needles to poke holes in the dry outer layers of the skin so the medicine can get in. Remember the old smallpox vaccine? Like that, only even smaller little microneedles, so scarring is minimal or nonexistent. This method isn’t used much, but there have been a couple of breakthroughs (no pun intended) lately that have gotten pharmacists and drug companies hopeful that it may be the Next Big Thing.
But without poking holes, you’ve got two other options:
Substances can pass transcellularly: into the first layer of cells across the cell membrane, move through the cytoplasm, out the cell membrane on the other side, across the cell membrane of the next cell down, through the cytoplasm, out the far cell membrane and so on, until it’s past all the skin cells and into subcutaneous tissue. It’s not very far, but the dried out nature of the top layers of skin (called the stratum corneum) makes it difficult for things to move well, but also and more importantly, the outside of a cell membrane is made of something that tends to keep water based liquids out (it’s hydrophobic), and the inside made of stuff that tends to keep oil based liquids out (it’s hydrophilic). So it’s a short path, but a challenging one.
OR a substance can pass intercellularly: go around the cells entirely, moving in the microscopic spaces between cells, like a tiny microscopic banking queue, until it’s past all the skin cells and into subcutaneous tissue. Just like a banking queue, this is a longer route, because it requires all sorts of switchbacks and turns to get around each cell.
As a result of the need to get through or around the many tightly packed dried out cells of the stratum corneum, the things that we can deliver transdermally tend to be very small on the molecular level (we call it “low-molecular weight”), and are largely hydrophobic and work at a very low dose.
Second generation transdermal medications add things that can help increase the permeability of the cell membranes. These are often chemicals that can penetrate the cell membrane and then act as channels - think of a bodyguard at a film premier clearing a path for a star. He can get in without being mobbed because the crowd (cell) doesn’t care much about him, and he holds the crowd back for the star to walk in unimpeded. On a cellular level, there are chemicals that can penetrate the cell membrane and allow the medication to cross into and out of the cell unimpeded. This is great except that, as you might expect, it can cause those cells to get grumpy, and the skin to be irritated. (The liver gets bilious and the kidneys downright pissed off sometimes, but that’s another story! ) Changing where you put the patch to different body sites can help to reduce this irritation (or, I suppose more accurately, spread the irritation around so it stays low level irritation.)
For less skin irritation, you can add not whole chemicals, but add specific molecules to the molecules of medication, molecules that help it to pass cell membranes better. Stick an alkyl side group on a drug molecule*, and it can then use a preexisting pore in the cell membrane that lets alkyls pass through. Sneaky sneaky… This tends to produce less skin irritation, but bigger headaches for the drug companies: because they’ve changed the chemical composition of the drug, they have to start over with testing for FDA approval. These are called “prodrugs” because the added molecule has to fall away at some point before the drug can be used by the body.
I hope this helps a little; I am a student, not a teacher. I’m sure I’ve screwed up many key points and glossed over others in my ignorance. We’ve got some pharmacists on the board, but they’re probably sleeping at this uncivilized hour and will be by shortly to correct me.
References:
*Good lord, please don’t ask me how one sticks atoms onto a molecule and gets them in the right spot. I’m in Biochem, not Pharmacology! I don’t know how it works on the big level, only the molecular level. I suspect enzymes or other catalysts are involved somehow. Or maybe magic.
) Changing where you put the patch to different body sites can help to reduce this irritation (or, I suppose more accurately, spread the irritation around so it stays low level irritation.)
