title: Solid state formulations composed by amphiphilic polymers for delivery of proteins: characterization and stability.
abstract: Nanocomposite powders composed by polymeric micelles as vehicles for delivery proteins were developed in this work, using insulin as model protein. Results showed that size and polydispersity of micelles were dependent on the amphiphilic polymer used, being all lower than 300 nm, while all the formulations displayed spherical shape and surface charge close to neutrality. Percentages of association efficiency and loading capacity up to 94.15 ± 3.92 and 8.56 ± 0.36, respectively, were obtained. X-ray photoelectron spectroscopy (XPS) measurements confirmed that insulin was partially present at the hydrophilic shell of the micelles. Lyophilization did not significantly change the physical characteristics of micelles, further providing easily dispersion when in contact to aqueous medium. The native-like conformation of insulin was maintained at high percentages (around 80%) after lyophilization as indicated by Fourier transform infrared spectroscopy (FTIR) and far-UV circular dichroism (CD). Moreover, Raman spectroscopy did not evidenced significant interactions among the formulation components. The formulations shown to be physically stable upon storage up to 6 months both at room-temperature (20 °C) and fridge (4 °C), with only a slight loss (maximum of 15%) of the secondary structure of the protein. Among the polymers tested, Pluronic(®) F127 produced the carrier formulations more promising for delivery of proteins.
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; Department of Pharmacy & Pharmaceutical Technology, School of Pharmacy, University of Barcelona, Joan XXIII s/n, 08028 Barcelona, Spain; Nanoprobes and Nanoswitches Group, Institute for Bioengineering of Catalonia (IBEC), Edifici Hèlix, Baldiri Reixac 15-21, 08028 Barcelona, Spain. Electronic address: fersilandrade@gmail.com.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Andrade
authors.affiliation: REQUIMTE, Department of Chemistry, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal; CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Fonte
authors.affiliation: Department of Pharmacy & Pharmaceutical Technology, School of Pharmacy, University of Barcelona, Joan XXIII s/n, 08028 Barcelona, Spain; Nanoprobes and Nanoswitches Group, Institute for Bioengineering of Catalonia (IBEC), Edifici Hèlix, Baldiri Reixac 15-21, 08028 Barcelona, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Calle Monforte de Lemos 3-5, Pabellón 11, 28029 Madrid, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Oliva
authors.affiliation: iMed. ULisboa - Research Institute for Medicines and Pharmaceutical Sciences, School of Pharmacy, University of Lisbon, Av. Professor Gama Pinto, 1649-003 Lisboa, Portugal.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Videira
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
authors.forename: Domingos
authors.initials: D
authors.lastname: Ferreira
authors.affiliation: CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal; INEB - Instituto de Engenharia Biomédica, Biocarrier Group, Universidade do Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; I3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto,Rua do Campo Alegre, 823, 4150-180 Porto, Portugal. Electronic address: bruno.sarmento@ineb.up.pt.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
mesh_terms: D002152:Calorimetry, Differential Scanning; D002942:Circular Dichroism; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D005612:Freeze Drying; D007328:Insulin / Q000737:chemistry*; D008823:Micelles; D056951:Photoelectron Spectroscopy; D020442:Poloxamer / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D007328:Insulin; D008823:Micelles; D020442:Poloxamer
keywords: Amphiphilic polymers; Insulin; Insulin (PubChem CID 70678557); Lyophilization; Phenylboronic acid (PubChem CID 66827); Pluronic(®) (PubChem CID 24751); Polymeric micelles; Stability