Delivering More Minoxidil to Hair Follicles: What's possible and what possibly helps?

How can I deliver more minoxidil to my hair follicles?

Topical 2 and 5 % Minoxidil are FDA approved and Health Canada approved for treating androgenetic alopecia. The drug does not help everyone but certainly helps a proportion of users. Given the benefits of minoxidil, there is a tremendous interest in understanding how best to delivery the minoxidil down into the scalp so that hair follicles can use it to stimulate their growth.

In this article, we’ll take a look at 5 methods to deliver more minoxidil to follicles as well as the challenges and limitations associated with these methods.

1. Use the same amount and same concentration of minoxidil and use it with the same frequency…. but apply it properly. 

There’s a bit of a learning curve to applying minoxidil and some people just don’t apply it correctly. Minoxidil probably absorbs better when applied after the scalp is washed and is still a bit warm. But clearly this is impractical for everyone as many do not shampoo daily and many who do like to apply minoxidil at night and shampoo the hair clean in the morning.  Despite this, it’s probably more important to remember to apply the minoxidil every day that fuss about when to apply it and how clean the hair is.

Regardless of how it’s applied, the minoxidil needs to get on the skin of the scalp so it can begin its journey into the scalp. Getting minoxidil on the hair shafts does not help. Similarly, if there is a great deal of gunk blocking the scalp surface, it becomes more difficult for minoxidil to penetrate the scalp. Gunk includes excessive amounts of gel, oils and hair fibers.

2. Use the same concentration of minoxidil, but use more of it... or use it more often.

For some patients, using more minoxidil allows more to get into the scalp. This is especially true for males using minoxidil and may be true for some women as well. It’s clear that using 5 % minoxidil twice daily is better when treating male pattern balding than using 5 % minoxidil once daily. For some women - but not all - this may be true too. The downside of using more minoxidil is a greater chance of side effects. The chance of headaches, dizziness, and hair on the face all increase as the amount of minoxidil increases.

3. Expose the hairs to higher concentrations of topical minoxidil

Theoretically, using higher concentrations of minoxidil may help more get into the scalp. Studies that support the ideal minoxidil concentration are few and far between. In fact, one study suggested surprisingly that 5 % minoxidil was more effective than 10 %. Researchers from Egypt set out to compare the efficacy and safety of 5% topical minoxidil with 10% topical minoxidil and placebo in 90 males with balding. Surprisingly, after the 9 months, partipcants in the 5 % minoxidil group had higher vertex and frontal hair counts compared to study participants in the 10 % minoxidil group and the placebo group. Clearly, we still have a lot to learn and a long way to go. Higher concentrations of minoxidil are not necessarily better.

4. Compound the minoxidil with different topical agents or via other drug delivery strategies to allow minoxidil to penetrate the scalp better.

There is a major interest in the hair research community to figure out how best to get minoxidil into the scalp. Different vehicles, use of so called nanoparticles as well as other techniques are the focus of many studies. 

It’s also clear that use of adjuvants like retinoids can help make minoxidil more effective. Before we look at this concept further, it’s important to understand a few concepts. In order for minoxidil to do it’s job, it needs to be converted to minoxidil sulphate. Hair follicles have the machinery to help with this but some people’s hair follicles are not really that good at it. Scientifically, we say that some people’s hair follicles lack high levels of an enzyme known as “sulfotransferase” and so they cannot convert minoxidil into the active form that actually does all the work.  (The public does not yet have minoxidil sulfotransferase testing kits available to them but this technology may be coming at some point in the near future.) For year now, it has been known that mixing retinoids with minoxidil makes minoxidil work better. It has long been thought that retinoids irritate the scalp and somehow by doing so allow minoxidil to get into the scalp. Now, based on interesting work published by Sharma and colleagues in 2019 it’s realized that retinoids upregulate the minoxidil sulfotransferase enzyme and by doing so help generate greater amounts of active minoxidil sulphate in the scalp.

The use of derma rolling may be yet another strategy to get more minoxidil into the scalp. Scalp Micro-needling" (dermrolling) is a technique whereby a controlled injury is created in the scalp. Skin injury (at least in some situations) can stimulate the production of growth factors and inflammatory cytokines that promote skin healing and possibly hair growth. A "dermaroller" is one such device to cause controlled injury. A dermaroller consists of teeth of different lengths that are attached to a wheel. Dermarollers of 0.5 mm, 1 mm, 1.5 mm are common. These are "rolled" back and forth across the skin to create redness. A 2013 study of 100 patients supports benefit of dermarolling. The study set out to determine in patients who use topical minoxidil (Rogaine, etc) could achieve even further benefit by dermarolling. In the study, half the patients received daily minoxidil and the other half of the patients received weekly dermarolling sessions (using a 1.5 mm dermaroller) in addition to minoxidil treatment. Results showed that patients using a dermaroller achieved greater benefits than those using minoxidil alone. Specifically, 82 % of patients receiving dermarolling felt they achieved greater than a 50 % benefit in their hair compared to just 4.5 % receiving minoxidil alone. Physicians rated the improvements similarly. Hair counts (at an up close level) were increased in the dermarolling group compared to the minoxidil alone group (91.4 vs 22.2 respectively). These studies support the potential benefit of dermarolling - especially to increase the efficacy of minoxidil. More studies need to be done to verify or refute these results as well as to determine the optimal parameters for dermarolling. These include comparisons of daily vs weekly vs monthly treatment and comparisons of 0.5 mm needles, 1 mm or 1.5 mm needles. Studies are also needed to determine if any proportion of patient actually worsen with dermarolling.

5. Eat the minoxidil (or eat more).

If someone has androgenetic alopecia but is not able to achieve high enough concentrations of minoxidil deep under the scalp with use of topical minoxidil, switching from topical minoxidil to oral minoxidil could make sense.  As reviewed above, in order for minoxidil to do it’s job, it needs to be converted to minoxidil sulphate. Hair follicles have the machinery to help with this but some people’s hair follicles are not really that good at it. Scientifically, we say that some people’s hair follicles lack high levels of an enzyme known as “sulfotransferase” and so they cannot convert minoxidil into the active form that actually does all the work. When oral minoxidil is ingested, the liver does the job of converting the minoxidil to minoxidil sulphate - bypassing the need for the hair follicle to do this job.

Patients who don’t respond to topical minoxidil may respond to oral minoxdil. Similarly, patients who don’t respond to very low doses (like 0.25 mg to 0.5 mg) may respond to moderate doses (like 1-2-5 mg). Of course, increasing the dose may increase side effects like headaches, swelling, fluid retention, hives and excessive hair growth on the body.

References

Dhurat R, et al. A randomized evaluator blinded study of effect of microneedling in androgenetic alopecia: a pilot study. Int J Trichology. 2013.

Ghonemy S et al. Efficacy and safety of a new 10% topical minoxidil versus 5% topicalminoxidil and placebo in the treatment of male androgenetic alopecia: a trichoscopic evaluation. J Dermatolog Treat. 2019 Oct 21:1-6. doi: 10.1080/09546634.2019.1654070. [Epub ahead of print]

Jeong WY et al. Transdermal delivery of Minoxidil using HA-PLGA nanoparticles for the treatment in alopecia. Biomater Res. 2019 Oct 31;23:16. doi: 10.1186/s40824-019-0164-z. eCollection 2019.

Sharma A et al. Tretinoin enhances minoxidil response in androgenetic alopecia patients by upregulating follicular sulfotransferase enzymes. Dermatol Ther. 2019 May;32(3):e12915. doi: 10.1111/dth.12915. Epub 2019 Apr 23.