Topical Treatment for Scarring and Non-Scarring Alopecia: An Overview of the Current Evidence

Figures & data

Figure 1 Progression of androgenic alopecia. The hair follicles are miniaturized due the increased concentration of dihydrotestosterone (DHT) in dermal papillae.

Table 1 Causes, Features, and Topical and Systemic Treatments of Scarring and Non-Scarring Alopecias

Scarring Alopecia
Type	Cause and Features	Treatments	Reference
Discoid lupus erythematosus	A chronic and common form of cutaneous lupus, in which the lesions typically occur on the scalp and other sun-exposed areas characterized by follicular plugging, atrophy, and hyperpigmentation.	Topical corticosteroids; intralesional corticosteroid; topical calcineurin inhibitors; antimalarial agents; oral retinoids; and methotrexate.	[^Citation13,Citation14]
Lichen planopilaris	Alopecia is characterized by multifocal and small lesions caused by a chronic and uncommon lymphocytic inflammation that leads to the selective destruction of hair follicles. Little Piccardi Lasseur syndrome, characterized by keratotic papules on the trunk and extremities, non-scarring alopecia of the axillary and pubic region, and cicatricial alopecia of the scalp.	Potent topical and intralesional corticosteroids; oral corticosteroids; hydroxychloroquine; oral retinoids; oral tetracyclines; cyclosporine; mycophenolate mofetil; azathioprine with concurrent systemic corticosteroids.	[^Citation15]
Central centrifugal cicatricial alopecia	A permanent hair loss in the crown region of the scalp caused by inflammation and scarring. Predominantly occurs in African descent women over 30 years old.	Potent topical or intralesional corticosteroids; systemic antibiotics; hydroxychloroquine; mycophenolate mofetil.	[^Citation16,Citation17]
Pseudopelade of Brocq	An idiopathic and slowly progressive form of cicatricial alopecia, which usually affects middle-aged Caucasian women. This condition is characterized by multiple small flash-toned alopecic areas with irregular borders without any signs of hyperkeratosis or inflammation.	Potent topical and intralesional corticosteroids; topical minoxidil; hydroxychloroquine; oral corticosteroids; isotretinoin; mycophenolate mofetil.	[^Citation18,Citation19]
Folliculitis decalvans	Uncommon scalp disease possibly triggered by Staphylococcus aureus and alteration of the patient’s local immune response. Erythematous patch, follicular pustules or papules, and follicular hyperkeratosis involving the vertex and the scalp’s occipital area are the clinical sign of this condition.	Combined topical and oral antibiotics; topical or intralesional corticosteroids; isotretinoin; topical antimicrobial or antiseptic therapy.	[^Citation11,Citation20]
Dissecting folliculitis	Rare alopecia characterized by a deep follicular occlusion, followed by follicular rupture and a deep inflammation of the hair follicle’s bulb.	Isotretinoin orally; topical or intralesional corticosteroids; oral or topical antibiotics; systemic corticosteroids; dapsone; and laser epilation.	[^Citation21,Citation22]
Acne keloidalis	A chronic form of scarring folliculitis that affects mostly African descent men. The exact cause remains unknown. The inciting agents are multifactorial such as androgens, inflammation, infection, trauma, genetics, and growing hair. This condition is characterized by papules, pustules, and, sometimes, tumorous masses in the scalp’s nuchal or occipital regions.	Potent topical or intralesional corticosteroids; oral antibiotics; and surgical excision.	[^Citation23]
Non-Scarring Alopecia
Type	Cause and Features	Treatments	Reference
Alopecia areata	Specific autoimmune disease of the hair follicle with a genetic basis. Acute patchy hair loss is frequently reported.	Intralesional corticosteroids; topical corticosteroids; and minoxidil.	[^Citation10,Citation24]
Tinea capitis	Alopecia caused by dermatophyte fungal infection on the scalp hair with predominance in children. Scaling with little hair loss to extensive alopecia, together with large inflammatory and pustular plaques.	Oral terbinafine, itraconazole, fluconazole, or griseofulvin. Topical antifungal as a complementary therapy to oral therapy.	[^Citation25]
Trichotillomania	Hair-pulling disorder producing hair loss and functional impairment.	Optimal treatment is unknown; selective serotonin reuptake inhibitors; behavioral therapy.	[^Citation26]
Telogen effluvium	Excessive shedding of hair, caused by an abnormality in the normal hair cycle, triggered by several factors such as drugs, physiological and emotional stress, and medical conditions.	Remove the underlying cause; topical corticosteroids.	[^Citation27]
Anagen effluvium	Chemotherapy-induced alopecia characterized by a diffuse hair loss days to weeks after exposure to a chemotherapeutic agent.	No pharmacologic intervention has been proven effective, although minoxidil may speed up the regrowth period.	[^Citation28]
Androgenic alopecia	The most common type of progressive hair loss with genetic causes. Men: typically involve frontal and vertex areas while preserving the occipital region. Women: diffuse hair thinning of the vertex with sparing of the frontal hairline.	Men: topical minoxidil (2% or 5% solution); oral finasteride. Women: topical minoxidil (1-5% solution).	[^Citation6,Citation29]

Table 2 Summary of the Encouraging Outcomes from Cutaneous Permeation Studies with Nanoparticles Carried with Drugs Indicated for Alopecia

Drug	Types of Nanoparticles	Particle Size (nm)	Test Model	Outcome	Reference
Cyclosporin A	PLA nanoparticles	150	Abdominal porcine skin	Cyclosporin A-loaded PLA nanoparticles were accumulated inside the hair follicles along the entire follicular duct. On the other hand, no staining was detected in skin sections treated with Cyclosporin A-containing non-particulate drug solution (control).	[^Citation55]
Clobetasol propionate	Polymeric nanospheres, nanocapsules, and lipid-core nanocapsules	100–260	Human heat-separated epidermis (HHSE)	All nanocarriers tested reduced the undesired transdermal permeability in comparison to the application of the free drug.	[^Citation47]
Clobetasol propionate	Nanostructured lipid carriers	180	Skin from porcine ears	Nanoparticles released the drug in a sustained fashion for more than 3 days and increased passively in about 40 times the clobetasol follicular uptake, compared to the commercial cream.	[^Citation56]
Diphencyprone	Nanostructured lipid carriers	208–265	Nude and hairy mouse dorsal skin	A more regular absorption of diphencyprone was achieved by applying nanostructured lipid carriers compared to the control.	[^Citation57]
Diphencyprone and Minoxidil	Nanostructured lipid carriers and nanoemulsions	177 and 194	Female nude mice (ICR-Foxn1nu)	Follicular uptake by squarticles was 2- and 7-fold higher for diphencyprone and minoxidil, respectively, compared to the free drug controls.	[^Citation58]
Dutasteride	Poly-(ɛ-caprolactone)-lipid-core, coated with chitosan nanoparticles	199	Skin from porcine ears	Both coated and non-coated nanoparticles targeted the hair follicles compared to a drug solution, which is appropriate aiming the topical treatment of alopecia	[^Citation59]
Finasteride	Liquid crystalline formulation	154–170	Dorsal skin of male hairless mice	Liquid crystalline formulation increased the drug penetration in the skin compared with control.	[^Citation34]
Finasteride	PLA nanoparticles	300	PDMS membrane as a simplified model of human epidermis	The nanoparticles prolonged the time finasteride remained on the skin.	[^Citation60]
Finasteride or Dutasteride	Metallic nanoparticles (iron oxide)	123	Skin from porcine ears	Metallic nanoparticles exhibited a higher skin drug penetration compared to each respective control solution.	[^Citation46]
Flutamide	Solid lipid nanoparticles	198	Male Wistar rats (in vitro) and young male hamsters (in vivo)	In vitro: flutamide-loaded solid lipid nanoparticles formulation exhibited significantly higher deposition of Flutamide in the skin (62.95 ± 6.2%) than the hydroalcoholic solution (35.83 ± 4.1%). In vivo: flutamide-loaded solid lipid nanoparticles increased the number of hair follicles more than the solution when applied to the skin.	[^Citation61]
Latanoprost	Poly-ε-caprolactone nanocapsules	198	Skin from porcine ears	The nanocapsules improved latanoprost accumulation into the hair follicles, delivering 30% more drug to these skin structures relative to the control solution.	[^Citation62]
Minoxidil	Solid lipid nanoparticles	190	Skin from porcine ears	Penetration experiments with porcine skin showed that the solid lipid nanoparticles suspension penetration into skin layers was statistically non-different to commercial products for formulation applied in excess.	[^Citation63]
Minoxidil	Nanostructured lipid carriers	281	Abdominal skin of male Sprague Dawley rats	Compared to the traditional formulation for the topical delivery of minoxidil, the nanostructured lipid carriers showed the highest skin retention.	[^Citation42]
Minoxidil	Niosomes	214 −1368	Fresh hairless mouse skin	Smaller niosomes (214–252 nm) achieved a higher minoxidil skin penetration than the larger ones (1160–1240 nm).	[^Citation64]
Minoxidil	Chitosan nanoparticles	235	Skin from porcine ears	Nanoparticles application resulted in a two-fold minoxidil increase into hair follicles after 6 h compared to the control solution.	[^Citation50]
Minoxidil	PLGA and hyaluronic acid-PLGA nanoparticles	PLGA: 159 HA-PLGA: 243	Rat skin	HA-PLGA nanoparticles were more permeable than PLGA nanoparticles and more efficient in transdermal delivery.	[^Citation31]
Minoxidil	Polymeric nanoparticles	90–300	Male 7-week-old C57BL/6 mice	The minoxidil content in the hair bulbs of mice treated with nanoparticles was 6.0- and 1.8-fold higher than in mice treated with the formulation based on minoxidil powder and the commercially available minoxidil formulation, respectively.	[^Citation65]
Minoxidil	Metallic nanoparticles (iron oxide)	150–200	Mice C57BL/6	The mice’s hair density exhibited an 800% improvement after being treated by microneedle, followed by an external magnetic field, compared to the mice without any treatments.	[^Citation66]
Minoxidil and Diphencyprone	Liposomes and niosomes	200–300 and 750–3200	Fresh human skin obtained fromm abdominoplasty	Liposome formulations increased drugs skin penetration compared to a propylene glycol–water–ethanol solution.	[^Citation67]
Minoxidil and Finasteride	Nanostructured lipid carriers	200	Porcine ear skin	Nanostructured lipid carriers loaded with minoxidil and finasteride had low penetration levels through pig ear skin under physiological conditions, which would avoid a toxic, systemic exposure.	[^Citation68]
Quercetin	PLGA and DPPC-PLGA nanoparticles	339	Male Sprague-Dawley rats (in vivo)	Hybrid nanoparticles improved the hair regrowth potential of quercetin, and the accumulation of nanoparticles at hair follicles end region inhibit hair follicles cells apoptosis.	[^Citation69]
Spironolactone	Nanostructured lipid carriers	216–834	Newly born albino mice	Fluorine-labeled nanostructured lipid carriers accumulated preferentially at the follicular region compared to the non-follicular region, indicating that the follicular pathway was the main penetration pathway of such nanoparticles	[^Citation70]

Figure 2 Scheme of the proposed mechanism for targeted drug delivery to the hair follicles provided by topical application of a nanoparticulate formulation.

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