The future of hair loss therapy
Nanotechnology today, provides an added dimension of benefit conferred to many widely-used drugs. Perhaps unsurprisingly, nano formulations of nutritional supplements and cosmeceuticals are likewise being developed with the purpose of improving bioavailability, protecting active ingredients against degradation, reducing side effects and providing overall greater therapeutic utility. This review article will provide context and comparative data which may prove helpful in assessing how nano-enabled formulations may influence hair loss treatment options both today and in the coming years.
Background & Significance
Until quite recently, no viable treatments against pattern hair loss were
available. In the 1980s, and due to the serendipitous observation of an unusual side effect, minoxidil (an anti-hypertensive oral medication) was repurposed against androgenetic alopecia (AGA) also known as pattern hair loss. In the 1990s, finasteride, a benign prostatic hyperplasia (BPH) drug was likewise repurposed against AGA. However, due to frequent and sometimes significant negative side effect, safer treatment options were sought.
Among the first, was Generation 1, HAIRGENESIS®, a putative inhibitor of 5 alpha-reductase, the enzyme shown to convert testosterone to the more pathogenic metabolite 5 alpha-dihydrotestosterone. Key to the clinical success of Gen 1 HAIRGENESIS®, was the combinatorial approach wherein both topical and oral boluses of the formula were deployed. In 1999, HAIRGENESIS®, was first to demonstrate safety and efficacy of a natural, botanically-derived set of formulations tested under placebo-controlled, double-blind, clinical study. The positive results of this work, along with subsequent research was subjected to critical peer-review and ultimately published in well-respected medical Journals. Contemporaneous with this work, Rx drugs began metamorphosing into nano-enabled variations.
Mechanism of Action
It is widely understood that natural compounds demonstrate significant therapeutic effects. However, hindrances in their absorption, specificity, and bioavailability limit their clinical utility. Recent advances show that such limitations can be overcome using nanotechnology. Multiple well-designed studies demonstrate that nano formulations of naturally derived compounds [as bioactive agents] result in improved efficacy. These delivery systems provide higher penetration at the cellular level and exhibit a highly-controlled release of the therapeutic bolus.
Although synthetic nano-delivery systems include precious metals, carbon nanotubes, and other materials, several naturally-based nanoscale delivery vehicles are now available to protect, sequester, stabilize, and deliver therapeutic phytochemical compounds to the target tissue. These include chitosans, liposomes, and cyclodextrins. With a hydrophobic interior and hydrophilic exterior, cyclodextrins form stable, amphiphilic complexes with hydrophobic compounds. α-, β-, and γ-cyclodextrin are all generally recognized as safe by the FDA. Of note, β-cyclodextrin has emerged as the most versatile excipient among the cyclic oligosaccharides with proven utility in oral, rectal, dermal, ocular, and parenteral formulations. Multiple published reports have demonstrated safety and efficacy for β-cyclodextrin in the use of poorly soluble phytochemicals.
Relevant Published Research
AGA, a multi-factorial, complex trait disorder is thought to be linked to genetic, epigenetic, chronobiologic and biochemical precipitating triggers. Building upon the well-reported androgen-mediated pathophysiology, recent studies show that microinflammation appears to play a significant role in causing involution (shrinkage) of the functional anatomical and physiological hair follicle sub-structures. Based on this premise, thoughtfully educed, naturally-based formulations have been developed & tested (https://pubmed.ncbi.nlm.nih.gov/26990224/).
Subsequently, nano-enabled versions of the same proprietary multi-function formulations were tested both in-vitro and in-vivo. Here, recent advances in nanomaterial manipulation provided enhanced platforms [cyclodextrins] within which the compositions were enveloped and delivered with markedly enhanced clinical efficiency (https://www.mdpi.com/2079-9284/7/3/65).
Over the course of a recent nine-month uncontrolled, open label case series, two AGA-affected male subjects were treated with a cyclodextrin-complexed, phytochemically-based formula administered via concomitant oral and topical delivery. By treatment day 90, the negative growth cycle appeared to have been halted and reversed. As the study progressed fewer low caliber strands were evident with continued hair thickening in each patient noted on treatment day 180. Upon the final evaluation on treatment day 270, most hairs observed in both subjects were characterized as full thickness/terminal.
The utility of oral and topical drug-based hair loss treatment products has been reliably proven in well-controlled, peer-reviewed research studies. Considered to be an ectodermal appendage, the scalp hair follicle represents a particularly intriguing therapeutic target for concomitant local and systemic therapy. Although some have exploited this opportunity via combined topical minoxidil and oral finasteride, the literature-reported negative side effects of each drug has limited the widespread use of the drug-based approach. In light of their multi-faceted mechanisms, enhanced safety profile and potential utility across a spectrum of disorders, nano-stabilized, naturally derived chemicals appear to represent an abundant reservoir for the interrogation and development of safe and efficacious adjunctives or alternatives to drug-based monotherapy. The nine-month, two-subject, uncontrolled, open label case series reported in the peer-reviewed literature, and discussed here, appears to support the hypothesis.
In the current year 2022, nanotechnologies now contribute to almost every field of science, including physics, materials science, chemistry, biology, computer science, and engineering. Nano-encapsulation has proven useful to improve the physical and the chemical stability of naturally-derived compounds, as well as their bioavailability and efficacy, enabling their incorporation into a wide range of formulations aimed to enhance the utility of numerous products, including those designed to address pattern hair loss (AGA). Future efforts may involve nano-enhanced modulation of gene transcription markers responsible for homeostatic hair growth as well as broad-spectrum biochemical inhibition of negative factors shown to cause miniaturization and hair loss.