title: Pharmacological and toxicological assessment of innovative self-assembled polymeric micelles as powders for insulin pulmonary delivery.
abstract: Explore the use of polymeric micelles in the development of powders intended for pulmonary delivery of biopharmaceuticals, using insulin as a model protein.
  
  
  
  Formulations were assessed in vitro for aerosolization properties and in vivo for efficacy and safety using a streptozotocin-induced diabetic rat model.
  
  
  
  Powders presented good aerosolization properties like fine particle fraction superior to 40% and a mass median aerodynamic diameter inferior of 6 μm. Endotracheally instilled powders have shown a faster onset of action than subcutaneous administration of insulin at a dose of 10 IU/kg, with pharmacological availabilities up to 32.5% of those achieved by subcutaneous route. Additionally, micelles improved the hypoglycemic effect of insulin. Bronchoalveolar lavage screening for toxicity markers (e.g., lactate dehydrogenase, cytokines) revealed no signs of lung inflammation and cytotoxicity 14 days postadministration.
  
  
  
  Developed powders showed promising safety and efficacy characteristics for the systemic delivery of insulin by pulmonary administration.
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.|IBEC, Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.|School of Pharmacy, University of Barcelona, 08028 Barcelona, Spain.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Andrade
authors.affiliation: REQUIMTE, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.|CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, 4585-116 Gandra PRD, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Fonte
authors.affiliation: INEB Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal.|I3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Costa
authors.affiliation: CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, 4585-116 Gandra PRD, Portugal.
authors.forename: Cassilda Cunha
authors.initials: CC
authors.lastname: Reis
authors.affiliation: INEB Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal.|I3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.
authors.forename: Rute
authors.initials: R
authors.lastname: Nunes
authors.affiliation: INEB Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal.|I3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Almeida
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
authors.forename: Domingos
authors.initials: D
authors.lastname: Ferreira
authors.affiliation: IBEC, Institute for Bioengineering of Catalonia, 08028 Barcelona, Spain.|School of Pharmacy, University of Barcelona, 08028 Barcelona, Spain.|CIBER-BBN, Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine, 28029 Madrid, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Oliva
authors.affiliation: CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, 4585-116 Gandra PRD, Portugal.|INEB Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal.|I3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D004337:Drug Carriers / Q000737:chemistry / Q000633:toxicity*; D016503:Drug Delivery Systems; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008823:Micelles; D011108:Polymers / Q000737:chemistry / Q000633:toxicity*; D011208:Powders; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004337:Drug Carriers; D007004:Hypoglycemic Agents; D007328:Insulin; D008823:Micelles; D011108:Polymers; D011208:Powders
keywords: fine particle fraction; in vivo; inhalation; insulin; pharmacological availability; polymeric micelles; pulmonary toxicity