title: In vivo toxicological evaluation of polymeric nanocapsules after intradermal administration.
abstract: Polymeric nanocarriers have shown great promise as delivery systems. An alternative strategy has been to explore new delivery routes, such as intradermal (i.d.), that can be used for vaccines and patch-based drug delivery. Despite their many advantages, there are few toxicity studies, especially in vivo. We report a safety assessment of biodegradable poly(ɛ-caprolactone) lipid-core nanocapsules (LNC) with a mean size of 245±10nm following single and repeated intradermal injections to Wistar rats. Suspensions were prepared by interfacial deposition of polymer. The animals (n=6/group) received a single-dose of saline solution (1.2ml/kg) or LNC (7.2×10(12)LNC/kg), or repeated-doses of two controls, saline solution or Tween 80 (0.9ml/kg), or three different concentrations of LNC (1.8, 3.6, and 5.4×10(12)LNC/kg) for 28 consecutive days. Clinical and physiological signs and mortality were observed. Samples of urine, blood, and tissue were used to perform toxicological evaluation. There were no clinical signs of toxicity or mortality, but there was a slight decrease in the relative body weights in the Tween 80-treated group (p<0.01) after repeated administration. No histopathological alterations were observed in tissues or significant changes in blood and urinary biomarkers for tissue damage. Mild alterations in white blood cells count with increases in granulocytes in the Tween-80 group (p<0.05) were found. Genotoxicity was evaluated through the comet assay, and no statistical difference was observed among the groups. Therefore, we conclude that, under the conditions of these experiments, biodegradable LNC did not present appreciable toxicity after 28 consecutive days of intradermal administration and is promising for its future application in vaccines and patch-based devices for enhancing the delivery of drugs.
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Brazil; Laboratório de Toxicologia (LATOX), Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors: Rachel P
authors: RP
authors: Bulcão
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Brazil; Laboratório de Toxicologia (LATOX), Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors: Fernando A
authors: FA
authors: de Freitas
authors: Departamento de Ciências Básicas da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil.
authors: Eliane
authors: E
authors: Dallegrave
authors: Departamento de Produção e Controle de Medicamentos, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors: Cristina G
authors: CG
authors: Venturini
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Brazil; Laboratório de Toxicologia (LATOX), Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors: Marília
authors: M
authors: Baierle
authors: Laboratório de Toxicologia (LATOX), Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors: Juliano
authors: J
authors: Durgante
authors: Laboratório de Toxicologia (LATOX), Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Instituto de Cardiologia, Fundação Universitária de Cardiologia, Porto Alegre, Brazil.
authors: Elisa
authors: E
authors: Sauer
authors: Instituto de Biotecnologia, Universidade de Caxias do Sul, Caxias do Sul, Brazil.
authors: Carina
authors: C
authors: Cassini
authors: Departamento de Patologia, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors: Carlos T
authors: CT
authors: Cerski
authors: Instituto de Cardiologia, Fundação Universitária de Cardiologia, Porto Alegre, Brazil.
authors: Paulo
authors: P
authors: Zielinsky
authors: Instituto de Biotecnologia, Universidade de Caxias do Sul, Caxias do Sul, Brazil.
authors: Mirian
authors: M
authors: Salvador
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Brazil; Departamento de Química Orgânica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors: Adriana R
authors: AR
authors: Pohlmann
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Brazil; Departamento de Produção e Controle de Medicamentos, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors: Sílvia S
authors: SS
authors: Guterres
authors: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Brazil; Laboratório de Toxicologia (LATOX), Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. Electronic address: solange.garcia@ufrgs.br.
authors: Solange C
authors: SC
authors: Garcia
mesh_terms: D000818:Animals; D002208:Caproates / Q000008:administration & dosage / Q000009:adverse effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000009:adverse effects; D016503:Drug Delivery Systems / Q000379:methods; D006098:Granulocytes / Q000187:drug effects; D007271:Injections, Intradermal / Q000379:methods; D007783:Lactones / Q000008:administration & dosage / Q000009:adverse effects; D008055:Lipids / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D053769:Nanocapsules / Q000008:administration & dosage* / Q000009:adverse effects*; D010316:Particle Size; D011108:Polymers / Q000008:administration & dosage* / Q000032:analysis*; D011136:Polysorbates / Q000008:administration & dosage / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D013535:Suspensions / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D002208:Caproates; D004337:Drug Carriers; D007783:Lactones; D008055:Lipids; D053769:Nanocapsules; D011108:Polymers; D011136:Polysorbates; D013535:Suspensions; C121056:caprolactone
keywords: Biodegradable nanocapsule; Genotoxicity; Nanotoxicology; Poly-(ε-caprolactone); Repeated-dose treatment; Single-dose treatment; Tween 80