title: Comedolytic effect and reduced skin irritation of a new formulation of all-trans retinoic acid-loaded solid lipid nanoparticles for topical treatment of acne.
abstract: Novel drug delivery systems, such as solid lipid nanoparticles (SLN), have been proposed to reduce retinoic acid (RA)-induced skin irritation. However, one question still remains: could it be accomplished without reducing efficacy? To evaluate this question the comedolytic effects and epidermal thickening of RA-loaded SLN were compared to the conventional RA formulations (gel or cream), as well as the potential of these formulations to induce skin irritation. The comedolytic effects and epidermal thickening of these formulations, both containing RA at 0.01 or 0.05%, were investigated in a rhino mouse model, while the studies of RA-induced skin irritation were evaluated through rabbit skin irritation tests and in the rhino mouse model. RA-loaded SLN, as compared to the placebo, produced a comedolytic effect with a significant reduction of the utricle diameter, which proved to be similar to that observed for marketed gels or creams regardless of the RA concentration. RA formulations (SLN or marketed cream) also induced an epidermal proliferation leading to a thickened epidermis in treated animals. In both animals studied (rhino mice and rabbits), the RA-loaded SLN, when compared to conventional formulations, promoted a significant reduction in RA-induced skin irritation (erythema and scaling). Then, RA-loaded SLN represents an interesting alternative to reduce RA-induced skin irritation without reducing efficacy, and constitutes an innovative approach for the topical treatment of acne with RA.
authors.affiliation: Department of Pharmaceutics, Federal University of Minas Gerais, Campus Pampulha-UFMG, Belo Horizonte, MG, Brazil.
authors.forename: G A
authors.initials: GA
authors.lastname: Castro
authors.forename: C A
authors.initials: CA
authors.lastname: Oliveira
authors.forename: G A B
authors.initials: GA
authors.lastname: Mahecha
authors.forename: L A M
authors.initials: LA
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D003877:Dermatitis, Contact / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004890:Erythema; D005782:Gels / Q000008:administration & dosage*; D005971:Glutamates / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008055:Lipids / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D011817:Rabbits; D023422:Skin Irritancy Tests; D014212:Tretinoin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D005782:Gels; D005971:Glutamates; D008055:Lipids; C546472:retinoyl glutamate; D014212:Tretinoin