title: Biological assessment of self-assembled polymeric micelles for pulmonary administration of insulin.
abstract: Pulmonary delivery of drugs for both local and systemic action has gained new attention over the last decades. In this work, different amphiphilic polymers (Soluplus®, Pluronic® F68, Pluronic® F108 and Pluronic® F127) were used to produce lyophilized formulations for inhalation of insulin. Development of stimuli-responsive, namely glucose-sensitive, formulations was also attempted with the addition of phenylboronic acid (PBA). Despite influencing the in vitro release of insulin from micelles, PBA did not confer glucose-sensitive properties to formulations. Lyophilized powders with aerodynamic diameter (<6 μm) compatible with good deposition in the lungs did not present significant in vitro toxicity for respiratory cell lines. Additionally, some formulations, in particular Pluronic® F127-based formulations, enhanced the permeation of insulin through pulmonary epithelial models and underwent minimal internalization by macrophages in vitro. Overall, formulations based on polymeric micelles presenting promising characteristics were developed for the delivery of insulin by inhalation.
  
  
  BACKGROUND
  The ability to deliver other systemic drugs via inhalation has received renewed interests in the clinical setting. This is especially true for drugs which usually require injections for delivery, like insulin. In this article, the authors investigated their previously developed amphiphilic polymers for inhalation of insulin in an in vitro model. The results should provide basis for future in vivo studies.
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Porto, Portugal; Department of Pharmacy & Pharmaceutical Technology, School of Pharmacy, University of Barcelona, Barcelona, Spain; Nanoprobes and Nanoswitches Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain. Electronic address: fersilandrade@gmail.com.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Andrade
authors.affiliation: I3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; INEB, Instituto de Engenharia Biomédica, Biocarrier Group, Universidade do Porto, Porto, Portugal; CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: das Neves
authors.affiliation: CIBBIM-Nanomedicine, Hospital Universitari Vall d'Hebrón and Vall d'Hebrón Institut de Recerca, Universitat Autónoma de Barcelona, Barcelona, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors.forename: Petra
authors.initials: P
authors.lastname: Gener
authors.affiliation: CIBBIM-Nanomedicine, Hospital Universitari Vall d'Hebrón and Vall d'Hebrón Institut de Recerca, Universitat Autónoma de Barcelona, Barcelona, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors.forename: Simó
authors.initials: S
authors.lastname: Schwartz
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Porto, Portugal.
authors.forename: Domingos
authors.initials: D
authors.lastname: Ferreira
authors.affiliation: Department of Pharmacy & Pharmaceutical Technology, School of Pharmacy, University of Barcelona, Barcelona, Spain; Nanoprobes and Nanoswitches Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Oliva
authors.affiliation: I3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; INEB, Instituto de Engenharia Biomédica, Biocarrier Group, Universidade do Porto, Porto, Portugal; CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Portugal. Electronic address: bruno.sarmento@ineb.up.pt.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
mesh_terms: D000280:Administration, Inhalation; D001897:Boronic Acids / Q000008:administration & dosage / Q000737:chemistry; D018929:Cell Culture Techniques; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry; D008823:Micelles; D010539:Permeability / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D001897:Boronic Acids; D007328:Insulin; D008823:Micelles; D011108:Polymers; D005947:Glucose; C010686:benzeneboronic acid
keywords: Cytotoxicity; Inhalation; Permeability; Phagocytosis; Polymeric micelles; Protein delivery