title: Surface engineering of silica nanoparticles for oral insulin delivery: characterization and cell toxicity studies.
abstract: The present work aimed at studying the interaction between insulin and SiNP surfaced with mucoadhesive polymers (chitosan, sodium alginate or polyethylene glycol) and the evaluation of their biocompatibility with HepG2 and Caco-2 cell lines, which mimic in vivo the target of insulin-loaded nanoparticles upon oral administration. Thus, a systematic physicochemical study of the surface-modified insulin-silica nanoparticles (Ins-SiNP) using mucoadhesive polymers has been described. The surfacing of nanoparticle involved the coating of silica nanoparticles (SiNP) with different mucoadhesive polymers, to achieve high contact between the systems and the gut mucosa to enhance the oral insulin bioavailability. SiNP were prepared by a modified Stöber method at room temperature via hydrolysis and condensation of tetraethyl orthosilicate (TEOS). Interaction between insulin and nanoparticles was assessed by differential scanning calorimetry (DSC), X-ray and Fourier-transform infrared (FTIR) studies. The high efficiency of nanoparticles' coating resulted in more stable system. FTIR spectra of insulin-loaded nanoparticles showed amide absorption bands which are characteristic of α-helix content. In general, all developed nanoparticles demonstrated high biocompatible, at the tested concentrations (50-500 μg/mL), revealing no or low toxicity in the two human cancer cell lines (HepG2 and Caco-2). In conclusion, the developed insulin-loaded SiNP surfaced with mucoadhesive polymers demonstrated its added value for oral administration of proteins.
authors.affiliation: Department of Biology and Environment, University of Trás-os Montes e Alto Douro,UTAD, Quinta de Prados, 5001-801 Vila Real, Portugal; Centre for Research and Technology of Agro-Environmental and Biological Sciences, CITAB, UTAD, Vila Real, Portugal; Fernando Pessoa University, UFP, Praça 9 de Abril, 349, 4249-004 Porto, Portugal.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Andreani
authors.affiliation: Faculty of Pharmaceutical Sciences, Universidade Estadual Paulista, UNESP, Rodovia Araraquara-Jau, Km. 01, Araraquara, São Paulo, Brazil.
authors.forename: Charlene P
authors.initials: CP
authors.lastname: Kiill
authors.affiliation: Faculty of Pharmaceutical Sciences, Universidade Estadual Paulista, UNESP, Rodovia Araraquara-Jau, Km. 01, Araraquara, São Paulo, Brazil.
authors.forename: Ana Luiza R
authors.initials: AL
authors.lastname: de Souza
authors.affiliation: Fernando Pessoa University, UFP, Praça 9 de Abril, 349, 4249-004 Porto, Portugal; Research Centre for Biomedicine, CEBIMED, Fernando Pessoa University, UFP, Porto, Portugal.
authors.forename: Joana F
authors.initials: JF
authors.lastname: Fangueiro
authors.affiliation: Electron Microscopy Unit, UTAD, Vila Real, Portugal.
authors.forename: Lisete
authors.initials: L
authors.lastname: Fernandes
authors.affiliation: Research Institute For Medicines and Pharmaceutical Sciences-iMed.UL, Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Slavomira
authors.initials: S
authors.lastname: Doktorovová
authors.affiliation: Department of Biology and Environment, University of Trás-os Montes e Alto Douro,UTAD, Quinta de Prados, 5001-801 Vila Real, Portugal; Centre for Research and Technology of Agro-Environmental and Biological Sciences, CITAB, UTAD, Vila Real, Portugal.
authors.forename: Dario L
authors.initials: DL
authors.lastname: Santos
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, Barcelona University, Av. Joan XXIII s/n, 08028 Barcelona, Spain.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Garcia
authors.affiliation: Faculty of Pharmaceutical Sciences, Universidade Estadual Paulista, UNESP, Rodovia Araraquara-Jau, Km. 01, Araraquara, São Paulo, Brazil.
authors.forename: Maria Palmira D
authors.initials: MP
authors.lastname: Gremião
authors.affiliation: Departament of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra (FFUC), Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
authors.forename: Eliana B
authors.initials: EB
authors.lastname: Souto
authors.affiliation: Department of Biology and Environment, University of Trás-os Montes e Alto Douro,UTAD, Quinta de Prados, 5001-801 Vila Real, Portugal; Centre for Research and Technology of Agro-Environmental and Biological Sciences, CITAB, UTAD, Vila Real, Portugal. Electronic address: amsilva@utad.pt.
authors.forename: Amélia M
authors.initials: AM
authors.lastname: Silva
mesh_terms: D000284:Administration, Oral; D000464:Alginates / Q000737:chemistry; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry*; D020723:Glucuronic Acid / Q000737:chemistry; D056945:Hep G2 Cells; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry*; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000009:adverse effects / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000464:Alginates; D004337:Drug Carriers; D006603:Hexuronic Acids; D007328:Insulin; D011108:Polymers; D011092:Polyethylene Glycols; D012822:Silicon Dioxide; D020723:Glucuronic Acid; D048271:Chitosan
keywords: Caco-2 cell; Coated-SiNPs; HepG2 cell; Insulin; Mucoadhesive polymers; Silica nanoparticles