title: Improved photostability and reduced skin permeation of tretinoin: development of a semisolid nanomedicine.
abstract: The aims of this work were to increase the photostability and to reduce the skin permeation of tretinoin through nanoencapsulation. Tretinoin is widely used in the topical treatment of various dermatological diseases such as acne, psoriasis, skin cancer, and photoaging. Tretinoin-loaded lipid-core polymeric nanocapsules were prepared by interfacial deposition of a preformed polymer. Carbopol hydrogels containing nanoencapsulated tretinoin presented a pH value of 6.08±0.14, a drug content of 0.52±0.01 mg g(-1), pseudoplastic rheological behavior, and higher spreadability than a marketed formulation. Hydrogels containing nanoencapsulated tretinoin demonstrated a lower photodegradation (24.17±3.49%) than the formulation containing the non-encapsulated drug (68.64±2.92%) after 8h of ultraviolet A irradiation. The half-life of the former was seven times higher than the latter. There was a decrease in the skin permeability coefficient of the drug by nanoencapsulation, independently of the dosage form. The liquid suspension and the semisolid form provided K(p)=0.31±0.15 and K(p)=0.33±0.01 cm s(-1), respectively (p≤0.05), while the samples containing non-encapsulated tretinoin showed K(p)=1.80±0.27 and K(p)=0.73±0.12 cm s(-1) for tretinoin solution and hydrogel, respectively. Lag time was increased two times by nanoencapsulation, meaning that the drug is retained for a longer time on the skin surface.
authors.affiliation: Programa de Pós-Graduação em Nanotecnologia Farmacêutica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Aline Ferreira
authors.initials: AF
authors.lastname: Ourique
authors.forename: Ana
authors.initials: A
authors.lastname: Melero
authors.forename: Cristiane
authors.initials: C
authors.lastname: de Bona da Silva
authors.forename: Ulrich F
authors.initials: UF
authors.lastname: Schaefer
authors.forename: Adriana Raffin
authors.initials: AR
authors.lastname: Pohlmann
authors.forename: Silvia Stanisçuaski
authors.initials: SS
authors.lastname: Guterres
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Kostka
authors.forename: Ruy Carlos Ruver
authors.initials: RC
authors.lastname: Beck
mesh_terms: D000005:Abdomen / Q000502:physiology; D000287:Administration, Topical; D000328:Adult; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D005260:Female; D006601:Hexoses / Q000737:chemistry; D006801:Humans; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry; D007641:Keratolytic Agents / Q000008:administration & dosage / Q000737:chemistry*; D008055:Lipids; D053769:Nanocapsules / Q000737:chemistry*; D010316:Particle Size; D010539:Permeability; D010782:Photolysis; D011091:Polyesters / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000737:chemistry; D012867:Skin; D013535:Suspensions; D014212:Tretinoin / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D005079:Excipients; D006601:Hexoses; D020100:Hydrogels; D007641:Keratolytic Agents; D008055:Lipids; D053769:Nanocapsules; D011091:Polyesters; D011108:Polymers; D013535:Suspensions; C016240:polycaprolactone; D014212:Tretinoin; C009298:sorbitan monostearate