Effect of physical stimuli on hair follicle deposition of clobetasol-loaded Lipid Nanocarriers

Abstract

Clobetasol propionate (CLO) is a potent glucocorticoid used to treat inflammation-based skin, scalp, and hair disorders. In such conditions, hair follicles (HF) are not only the target site but can also act as drug reservoirs when certain formulations are topically applied. Recently, we have demonstrated nanostructured lipid carriers (NLC) containing CLO presenting epidermal-targeting potential. Here, the focus was evaluating the HF uptake provided by such nanoparticles in comparison to a commercial cream and investigating the influence of different physical stimuli [i.e., infrared (IR) irradiation (with and without metallic nanoparticles-MNP), ultrasound (US) (with and without vibration) and mechanical massage] on their follicular targeting potential. Nanosystems presented sizes around 180 nm (PdI < 0.2) and negative zeta potential. The formulation did not alter skin water loss measurements and was stable for at least 30 days at 5 °C. Nanoparticles released the drug in a sustained fashion for more than 3 days and increased passively about 40 times CLO follicular uptake compared to the commercial cream. Confocal images confirmed the enhanced follicular delivery. On the one hand, NLC application followed by IR for heat generation showed no benefit in terms of HF targeting even at higher temperatures generated by metallic nanoparticle heating. On the other hand, upon US treatment, CLO retention was significantly increased in deeper skin layers. The addition of mechanical vibration to the US treatment led to higher follicular accumulation compared to passive exposure to NLC without stimuli. However, from all evaluated stimuli, manual massage presented the highest follicular targeting potential, driving more than double the amount of CLO into the HF than NLC passive application. In conclusion, NLC showed great potential for delivering CLO to HF, and a simple massage was capable of doubling follicular retention.Skin, hair, and scalp-related dermatological inflammatory pathologies have been treated for decades with oral and topical glucocorticoids. Among the topical drugs under study, clobetasol propionate (CLO) stands out as the most potent one 1 . Due to its vasoconstricting, anti-inflammatory, immunosuppressive and antiproliferative effects, the drug is useful in the treatment of conditions such as eczema, atopic dermatitis, alopecia areata, frontal fibrosing alopecia, psoriasis and lichen planopilaris 2-4 . Nevertheless, continuous use of typical CLO dermatological formulations may present local side effects as skin atrophy, pruritus, folliculitis, and telangiectasia 5-7 . Even though topical treatment results in fewer adverse effects when compared to oral or parenteral administration, formulations capable of controlling drug release while targeting and enhancing drug penetration to specific skin layers can provide additional therapeutic benefits.Previous studies from our group have shown CLO-loaded nanostructured lipid carriers (NLC), produced with 1/5 th of the drug dose used in commercial formulations, presented...

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

“…Additionally, a manual massage increased more than twice the amount of clobetasol accumulated into the hair follicles. 56 Indeed, the motion induced the nanosystem's deposition inside the hair follicles with maximal velocity, which stimulates the entrapped drug deposition in these structures, as revealed before. 77 Deformable nanoparticles have also been studied to topically deliver other drugs with undesirable systemic side effects, such as flutamide.…”

“… [ 47 ] 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. [ 56 ] 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. [ 57 ] 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.…”

Physical Enhancement? Nanocarrier? Current Progress in Transdermal Drug Delivery

“…Lipid nanoparticles have been used as an alternative TDDS for pharmaceutical drugs and cosmetic compounds since the early 1990s [ 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. A solid lipid nanoparticle (SLN) was prepared by the exchange of the liquid lipid oil of the emulsions by solid lipid, which remains at a solid-state at room temperature and body temperature [ 66 , 67 ].…”

“…For the improvement of these lipid-based nanocarriers, Park et al developed lipid nanoparticles composed of ceramide and succeeded in TDDS of apigenin [ 76 ]. Gratieri et al reported clobetasol-loaded lipid nanocarriers and investigated the effects on hair follicles [ 77 ]. In addition, Hamada et al successfully prepared ultra-small nanoparticles by using anionic phospholipids.…”

“…In particular, microneedles have been actively investigated, and clinical trials of delivery of macromolecules such as insulin, parathyroid hormone, and influenza vaccines were currently performed. Recently, nanocarrier-based TDDS [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , …”