title: Preparation and characterization of PEG-coated silica nanoparticles for oral insulin delivery.
abstract: The present study reports the production and characterization of PEG-coated silica nanoparticles (SiNP-PEG) containing insulin for oral administration. High (PEG 20,000) and low (PEG 6000) PEG molecular weights were used in the preparations. SiNP were produced by sol-gel technology followed by PEG adsorption and characterized for in vitro release by Franz diffusion cells. In vitro permeation profile was assessed using everted rat intestine. HPLC method has been validated for the determination of insulin released and permeated. Insulin secondary structure was performed by circular dichroism (CD). Uncoated SiNP allowed slower insulin release in comparison to SiNP-PEG. The coating with high molecular weight PEG did not significantly (p> 0.05) alter insulin release. The slow insulin release is attributed to the affinity of insulin for silanol groups at silica surface. Drug release followed second order kinetics for uncoated and SiNP-PEG at pH 2.0. On the other hand, at pH 6.8, the best fitting was first-order for SiNP-PEG, except for SiNP which showed a Boltzmann behavior. Comparing the values of half-live, SiNP-PEG 20,000 showed a faster diffusion followed by Si-PEG 6000 and SiNP. CD studies showed no conformational changes occurring after protein release from the nanoparticles under gastrointestinal simulated conditions.
authors.affiliation: Department of Biology and Environment, University of Tras-os Montes e Alto Douro, UTAD, Quinta de Prados, P-5001-801 Vila Real, Portugal; Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), UTAD, Vila Real, Portugal; Research Centre for Biomedicine (CEBIMED), Fernando Pessoa University (UFP), Praça 9 de Abril, 349, 4249-004 Porto, Portugal.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Andreani
authors.affiliation: Department of Pharmaceutical Sciences, UNESP - Universidade Estadual Paulista, Rodovia Araraquara-Jau, Km. 01, Araraquara, São Paulo, Brazil.
authors.forename: Ana Luiza R
authors.initials: AL
authors.lastname: de Souza
authors.affiliation: Department of Pharmaceutical Sciences, UNESP - Universidade Estadual Paulista, Rodovia Araraquara-Jau, Km. 01, Araraquara, São Paulo, Brazil.
authors.forename: Charlene P
authors.initials: CP
authors.lastname: Kiill
authors.affiliation: Department of Biochemistry and Chemical Technology, Institute of Chemistry, UNESP - Universidade Estadual Paulista, Araraquara, São Paulo, Brazil.
authors.forename: Esteban N
authors.initials: EN
authors.lastname: Lorenzón
authors.affiliation: Research Centre for Biomedicine (CEBIMED), Fernando Pessoa University (UFP), Praça 9 de Abril, 349, 4249-004 Porto, Portugal; Faculty of Health Sciences, Fernando Pessoa University, Rua Carlos da Maia, 296, P-4200-150 Porto, Portugal.
authors.forename: Joana F
authors.initials: JF
authors.lastname: Fangueiro
authors.affiliation: Biopharmacy and Pharmacokicetic Unit, Pharmacy and Pharmaceutical Technology Department, School of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 8028 Barcelona, Spain.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Calpena
authors.affiliation: Sorocaba University, UNISO, Rodovia Raposo Tavares, Km. 92.5, 18023-000, Sorocaba, Brazil.
authors.forename: Marco V
authors.initials: MV
authors.lastname: Chaud
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, Barcelona University, Av. Joan XXIII s/n, 8028 Barcelona, Spain.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Garcia
authors.affiliation: Department of Pharmaceutical Sciences, UNESP - Universidade Estadual Paulista, Rodovia Araraquara-Jau, Km. 01, Araraquara, São Paulo, Brazil.
authors.forename: Maria Palmira D
authors.initials: MP
authors.lastname: Gremião
authors.affiliation: Department of Biology and Environment, University of Tras-os Montes e Alto Douro, UTAD, Quinta de Prados, P-5001-801 Vila Real, Portugal; Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), UTAD, Vila Real, Portugal.
authors.forename: Amélia M
authors.initials: AM
authors.lastname: Silva
authors.affiliation: Research Centre for Biomedicine (CEBIMED), Fernando Pessoa University (UFP), Praça 9 de Abril, 349, 4249-004 Porto, Portugal; Faculty of Health Sciences, Fernando Pessoa University, Rua Carlos da Maia, 296, P-4200-150 Porto, Portugal; Institute of Biotechnology and Bioengineering, Centre of Genomics and Biotechnology, UTAD, Vila-Real, Portugal. Electronic address: eliana@ufp.edu.pt.
authors.forename: Eliana B
authors.initials: EB
authors.lastname: Souto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D004339:Drug Compounding; D066298:In Vitro Techniques; D061386:Insulin, Regular, Human / Q000008:administration & dosage / Q000737:chemistry*; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D061386:Insulin, Regular, Human; D011092:Polyethylene Glycols; D012822:Silicon Dioxide
keywords: HPLC validation; Insulin; Mathematic modeling; Oral delivery; PEG adsorption; Silica nanoparticles