I suspect if we could get our hands on a good liposomal vehicle it might be okay:
I just wish this was easier said than done.
it is in fact pretty easy to make a basic liposomal vehicle. the problem is however that liposomal is not that great either and depending on particle size(refer to figure 3 in the paper at the bottom), zeta potential or charge of the particles, loaded drug and its interactions with the particle all have a drastic influence on how it behaves. there is lots of research on this topic from in vitro and animal studies. for example for a liposomal additional excipients and size of the particles(should not be too big or small) have a major impact on how it behaves in the skin. one carrier that works for finasteride might not work for pyrilutamide due to molecule size, if they are lipohile or not etc.
ive been saying this for half a year, people here are sleeping on the idea of better delivery with a targeted vehicle. thats the future. maintenance drugs will all be anti androgenic in nature and carry the potential for systemic sexual side effects. furthermore they are not as effective on the scalp as they could be if they accumulated there. additionally new treatments from different angles won't be here for many years. I am mostly interested in what hutera from Korea or Japan is doing with their patented nanostructure lipid carrier that promises to deliver dutasteride right down the hair shaft and release it there with little systemic concentrations. this carrier could be used for other anti androgenic drugs as well. I recall a study that showed 7 times more minoxidil accumulation in the hair follicle as opposed to a standard vehicle with less transdermal(we dont want this) flux. this kind of carrier would allow using 7 times less drug to have the same local effect. additionally is has less transdermal flux so you use less and additionally less goes systemic.
but people aren't interested in this kind of stuff, most certainly big Pharma is not interested in better delivery of existing drugs because how could they make additional money off of it? they cannot. and so the research is super slow but I think it is quite promising. it also seems to have picked up in recent years based on paper publications.
lots of studies in the past 4 years on the topic of targeted delivery in dermatological diseases.
one study from2020 used dutasteride in a pig study with a Franz diffusion cells, they showed now transdermal flux(into deeper layers of the skin or "past" the skin) while having 7 times the accumulation right in the follicle (around the dermal papilla and bulb, directly where dht acts) compared to other carrier. they used some super advanced ion metallic nanoparticles to encapsulate it there. the particle had an affinity primarily for the hair follicle entrance. study: (
https://www.sciencedirect.com/science/article/pii/S0378517320306931 )
indeed we want something like this
https://ars.els-cdn.com/content/image/1-s2.0-S0378517320306931-gr6.jpg where there is increased concentration of the carrier primarily in the follicle as opposed to other parts of the skin. while this alone does not limit how much goes systemic, it allows using a much smaller dose due to increased targeting.
...more importantly, the nanosystem's efficiency can be established by the drug increase within the hair follicles, as it is the target for treating alopecia. dutasteride-ION provided a 3.4-fold drug increase in the hair follicles compared to the control solution (2.23 ± 0.26 and 0.66 ± 0.14 µg.cm−2, corresponding to 0.89 ± 0.11 and 0.27 ± 0.06%.cm−2), while finasteride-ION increase was of approximately only 1.5-fold
despite that I dont think there will be any commercialization(maybe hutera). this is something for the future though and targeted delivery of existing drugs is much more promising than all the new drugs bullshit that have the same up and downsides as existing ones
Imagine you can not tolerate 0.5% pyrilutamide, maybe you can tolerate 0.1%, get a good carrier for it that increases the local concentration around the follicle 5 times, has a slow release and suddenly you can get away with using 0.1% once a day opposed to 0.5% twice a day.
for more information on the major 3 different skin delivery pathways (
https://www.researchgate.net/public...tes-for-a-molecule-to-cross-the-skin_W640.jpg) and the potential to deliver hair loss drugs directly to the follicle in higher amounts, refer to this review paper from 2022
what im saying is, liposomal is not the easy answer, a lot of thought must go into the design of such a delivery system. but technically I think it can be done and it is my opinion much more realistic than to get a good drug from big pharma that does not have the same negative properties like finasteride(pyrilutamide should be that drug and it didn't seem to deliver in terms of tolerability).
a nano carrier encapsulated pyril however might
seekingalpha.com
