title: Isotretinoin-loaded nanocapsules: stability and cutaneous penetration by tape stripping in human and pig skin.
abstract: The cutaneous penetration of isotretinoin-loaded poly(epsilon-caprolactone) nanocapsules (GEL-NCISO) was compared to that of free isotretinoin (GEL-FREE) incorporated in hydrogels by tape stripping in excised human and pig skin. The physicochemical stability of isotretinoin-loaded nanocapsules and a nanoemulsion (used as a control) was evaluated using multiple light scattering, quantifying drug content and determining particle size, polydispersion index, zeta potential and pH for 60 days. A photostability study was also carried out. GEL-FREE and GEL-NCISO were applied to human and pig skin and penetration was assessed by tape stripping in Franz diffusion cells. The isotretinoin-loaded nanocapsules showed suitable physicochemical characteristics for topical administration, physical stability for 2 months at room temperature and under UVA radiation. In vitro tape stripping in human and pig skin showed that no isotretinoin reaches the receptor compartment for both formulations up to 8 h. Nanoencapsulation increased isotretinoin skin penetration for both skin stratum corneum. Pig skin was more permeable than human since higher isotretinoin concentrations were found at human upper skin layers for both formulations. Similar proportion of cutaneous penetration for human and pig skin were observed although different amounts of drug were detected in the stratum corneum of both skin specimens in vitro. A positive Pearson product moment correlation coefficient (0.79) between human and pig skin penetration in vitro was obtained, thus, pig skin can be considered suitable for predicting cutaneous penetration of isotretinoin in humans in vitro.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, Porto Alegre - 90610-000, RS, Brazil.
authors.forename: Clarissa C
authors.initials: CC
authors.lastname: Bettoni
authors.forename: Cândice C
authors.initials: CC
authors.lastname: Felippi
authors.forename: Cristiane
authors.initials: C
authors.lastname: de Andrade
authors.forename: Renata P
authors.initials: RP
authors.lastname: Raffin
authors.forename: Alessandro
authors.initials: A
authors.lastname: Jager
authors.forename: Sílvia S
authors.initials: SS
authors.lastname: Guterres
authors.forename: Teresa Dalla
authors.initials: TD
authors.lastname: Costal
mesh_terms: D000269:Adhesives; D000818:Animals; D004355:Drug Stability; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D015474:Isotretinoin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D008027:Light; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D010782:Photolysis; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry; D012542:Scattering, Radiation; D012867:Skin / Q000737:chemistry / Q000378:metabolism*; D012869:Skin Absorption; D013552:Swine
chemical_list: D000269:Adhesives; D005782:Gels; D053769:Nanocapsules; D011091:Polyesters; C016240:polycaprolactone; D015474:Isotretinoin