title: Lipid nanoparticles for topical and transdermal application for alopecia treatment: development, physicochemical characterization, and in vitro release and penetration studies.
abstract: Alopecia is a dermatological disorder, commonly known as hair loss, which affects up to half of the Caucasian male population by middle age, and almost all (95%) Caucasian men by old age. Considering that alopecia affects so many people and that there is currently no scientifically proven treatment with few side effects, new drug-delivery systems able to improve alopecia therapy are urgently required. With this purpose in mind, the present study aimed to develop lipid nanoparticles (nanostructured lipid carriers) with the ability to incorporate and deliver anti-alopecia active compounds (minoxidil and finasteride) into the dermis and hair follicles. Lipid nanoparticles, prepared by ultrasonication method, showed mean particle sizes around 200 nm, which is sufficient for reaching the dermis and hair follicles, and zeta potential values around -30 mV, which indicates good physical stability. Over 28 days of storage, no significant variations in these parameters were observed, which indicates that all nanoformulations are stable in storage over that period. Cryo-scanning electron microscope measurements showed that all the lipid nanoparticles exhibited a spherical shape and a smooth surface regardless of their composition. Differential scanning calorimetry studies allowed the determination of phase transition temperatures and confirmed the recrystallization of the lipid nanoparticles (recrystallization index between 11% and 86%). A high loading efficiency was achieved for finasteride (between 70% and 90%), while less than 30% was achieved for minoxidil nanoparticles, over 28 days. Controlled release assays in physiological conditions demonstrated that nanoparticles loaded with minoxidil yielded a prolonged release, as desired. Penetration assays through pig ear skin demonstrated that nanoparticles loaded with minoxidil and finasteride had low levels of penetration. These results suggest that the proposed novel formulation presents several good characteristics indicating their suitability for dermal delivery of anti-alopecia active compounds.
authors.affiliation: REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Maria João
authors.initials: MJ
authors.lastname: Gomes
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal ; Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark.
authors.forename: Susana
authors.initials: S
authors.lastname: Martins
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Domingos
authors.initials: D
authors.lastname: Ferreira
authors.affiliation: REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Marcela A
authors.initials: MA
authors.lastname: Segundo
authors.affiliation: REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
mesh_terms: D000287:Administration, Topical; D000505:Alopecia / Q000188:drug therapy*; D000818:Animals; D003692:Delayed-Action Preparations; D003879:Dermatologic Agents / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D004355:Drug Stability; D018120:Finasteride / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008914:Minoxidil / Q000008:administration & dosage / Q000493:pharmacokinetics; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology; D010316:Particle Size; D012867:Skin / Q000378:metabolism; D013499:Surface Properties; D013552:Swine
chemical_list: D003692:Delayed-Action Preparations; D003879:Dermatologic Agents; D008055:Lipids; D018120:Finasteride; D008914:Minoxidil
keywords: alopecia; anti-alopecia therapy; finasteride; minoxidil; nanostructured lipid carriers (NLC)