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TEDx Talks
Title: Nanoscience and drug delivery -- small particles for big problems | Taylor Mabe | TEDxGreensboro
Published: 2015-07-01
Source: https://www.youtube.com/watch?v=0wFwXUhHu5c
it was nineteen ninety and I was a seven year old prom into back on the family farm I was happy because I was in the row next to my grandfather he was there for the most grandpas but I think care I love that man he had these old weathered hands who big blue veins and when he wasn't paying attention poke at those things this particular day
we played our usual game who could get to the end of their tobacco road the fastest I want but when I finished I look down in the dirt see a Mason jar with a clear liquid and I picked it up and ask grandpa thought you were supposed that anymore these land around sun that's been there we go more Pat maybe in five or six days a
week or more five or six days as a seven year old even I knew how many days a week but that wasn't the first time a grandfather was confused Ralph may was a moonshine Macon lawbreaking cool grandpa he would sneak off into the woods where he ran a moonshine still now this lead grandpa going to college a lot that was our family slang for prison I
was twelve and we buried him and impacted me I remember crying in the attic of three seventeen some street that was the first time I dealt with death and with addiction but it wasn't my lack in my early twenties I moved to Wilmington North Carolina and I fell in love with that city there I met a guy named bridge who was my best friend is in
the audience today he was battling addiction and he told me of this implant that he had IBM off drugs this fascinated me this was my spark I felt like Sir Isaac Newton when that apple fail and he thought gravity been around Bridger saw the faces coming go of treatment centers of these people knew pain they would be happy and healthy one day relapse and become completely
consumed by their addiction I thought of grandpa treatment for addiction have improve psalm since that hot summer day nineteen ninety but not drastically of the people who seek treatment ninety three percent fail so we're doing a terrible job of treating this disease with good year tire be in business of ninety three percent of the product failed so it's time to think differently about this issue nanoscience
maybe the solution before we go down the narrow trail let's take a look at the challenges that current medications are up against so when you swallow a pill what happens to it he goes down the esophagus and from that point it has to get past five barriers think of this like a video game our character Peter pill head has appeal for head so you need to
pay attention to three areas for a video game strength indicator shown by that battery barrier he said ready to play he so the first barrier is the stomach this acidic environment can degrade our drug Peter this is an obstacle after thirty seven minutes Peter enters the intestines the intestinal wall to cross that we have to be small and chemically fit as you see by his head
Peter loses some of the pill the liver his the next barrier no this is the organ wrist that's responsible for eliminating the harmful effects of medication so the enzymes in here to great Peter sing by his decaying head level for our barrier for proteins and enzymes in the blood stream the proteins can bind to the drug and then psalms can put him in a headlock so
this will take us if we get past this you sing Peter are you lost most of his head a final barrier the blood brain barrier this is a protective barrier that only allow small fat soluble drugs to pass through for Peter this is a total loss he loses all of his head and the game's over we Las so if we can make it to this point
we still have issues the graph your scenes what's called peak and valley delivery so the medicine has to be ingested over and over again to remain effective in the body the blue dash line you're seeing is the level at which the medicine becomes effective in the green is the level at which the medicine comes harmful are toxic so the name of the game is to stay
in between those two lines think about taking a Tylenol if you don't take enough you had it doesn't go away but if you take too much it shut down your liver so this brings us to the issue of side effects side effects occur when medicines bind somewhere else other than their intended target now seen in our video game some of the medicine was lost along the
way so when you take a pill the dose could be a hundred times more than what's needed because so much of the medicine is lost along the way like we saw each barrier a massive dose is required so in some cases as much as ninety five percent of the medicines lost along the way a guy named David Anderson in his tape top had analogy an analogy
that I really like he said current medications like getting a can of oil and porn and all over your car engine some of that oil will dribble into the right spot but the majority of it is wasted and some even does harm so we need a way to target the medicine so that is only released at specific sites do this the dose would decrease and as
a result side effects would so we need a way for the medicine to not wonder off invited other sites in the body so there are two ways to solve this one we continue down the same rabbit trail where big pharma spends over a billion dollars in fifteen years to develop one single drug or two we could use the drugs are known to work that just have
a hard time getting to where they need to go change the way their delivery the latter has how nanoscience emerges as a potential solution so what is nanoscience not a science is the science of the small and we're using that to solve problems but how small the diameter of a baseball seven point five centimeters seventy five billion billion nanometer if you went down further in size
to like a marble marbles about one point five in the meters in the pack from the can see it in a marvelous fifteen billion nanometers if we went down even further to a BBC enough glued one onto a piece of cardboard from the kids BB gun that's half of a centimeter five billion nanometers across so in our lab we make nanoparticles between two and twenty nanometers
so these things are really really small a cool about that school is that you can put things inside of them even though they're small a single drug molecules smaller so I've made a model just to show you all what I'm holding who'd be our nanoparticle that blue ball on the inside would be like a drug molecule this really isn't an accurate size description if you wanted
to see something more accurate it would be like putting say this is our nanoparticle and these are our drugs if this was hollow we could fit a lot of babies inside there right so these things are small and they can carry a large payload of drugs they can go through the body function like a vehicle like a truck for our cases Collenette of drug it can
travel through the bloodstream carry drugs in the truck bed it has a GPS that we program to go where we desire scientists call this targeting so that aims to deliver medicine only at specific places so we only at diseased sites this is achieved by adding compounds on the outside function like molecular keys Sir how do we make the same well I spent months trying to make
a unique nanoparticle no matter what I did this it's this was unsuccessful my father always says that the struggle is in the details he's right after months botched experiments a family found out that the pipette I was using was contaminating my nanoparticles synthesis like this can read very tedious so was going through all this trouble would it be great if the nanoparticle could just make itself
itself a I can't think of all in water what happens when you pour oil into water they don't mix but if we had a heavy oil that we go to the bottom of the water it would self assemble into these little balls so let's see a lab video of just that so that those red balls would be the oil like substance so what we do is
we take that mixed drugs with it drop both of them in water and those little balls would form the drug molecules on the inside from that point we could start reducing the size and decorating the outside with the the homing molecules that GPS now this is a very simplified version of how the nanoparticle consensually make itself Sir I'm not inventing a new drug here all we're
doing is making little bitty vehicles that transport current drugs actually teaching old dogs will %HESITATION drugs new tricks so chemistry still magic to me it still gets me excited I love piddling around in the lab the benefits of this research our vast and could potentially save millions of lives so it can also be this passes five barriers you remember them let's play a game again I
hate losing I do not like losing I'm very competitive I think some of people in the audience will attest to that but are spare video game again this time let me introduce you to our new character Superman %HESITATION super nano right so now our medicines encased in our little nanoparticle is protected the outsides decorated with fat like molecules so level one or barrier one is the
stomach the acid degraded the pill from before so this time were protected by Superman and glad right through fully intact level two was the intestinal wall for Peter could really get through that Superman kinda knows the secret handshake he's got that oil on the outside so he can pass right through to barrier three bay area three is deliver it has enzymes in it that degraded the
pill from before Superman passes right through this level four or proteins and enzymes in the bloodstream member before they put Peter in a headlock Superman passes right through this on to the fifth barrier that was the blood brain barrier then we had to be small fat soluble to get through this we decorate the outside of Superman with those fat like molecules so we can pass right
through now we're inside the brain Fernando the mission and that's to go around identify the bad guys bad cells egos good so good so good so good sale bad self target acquired so then like a Trojan horse it moves inside opens and releases the drugs so let's see a video or animation of just that so we so you know I so here's our video this is
our nana vehicle the blue sails of the healthy ones the red is the bat we target the little drug molecules they test cricket but as you can see by the video the the blue sails were to simply ignored and beyond the red ones were targeted or the red one was targeted so now let's compare the delivery profile that the nanomedicine to that of traditional so remember
the pecan valley a profile in the name of the game was to stay in between the effective and toxic level clearly evident by the grass the nanomedicine does is far better it would eventually fall but we can program that to last days weeds or months San chronic medicine he would wanna medicine inside of a person for for a long period of time so it to achieve
this you can either make the delivery profile stay for months or we could put in an implant like bridge had and work on making those last longer his only worked for for about two months but we desire them to last much longer so a personal goal of mine is to make a drug delivery system that last about twelve months so how was this currently impacting our
world this technology can be applied to any drug for any disease the drug talk so high doxo is already being applied to cancer and that's RTC in the benefits type two diabetes has a drug called by Dearie on which is already showing the benefits of system and releases well so my passion to unravel addiction is what what drives me since so many talented people experience senseless
pain was upsetting a good friend told me that addiction is when you can't get enough of what you do not want I love that he said addiction is when you can't get enough of which you don't want I'm sure Ralph made didn't want that masons are hiding in the dirt and I'm sure you don't let his family down over and over again I'm sure it will
