Artigo
Preparation and characterization of PEG-coated silica nanoparticles for oral insulin delivery
Registro en:
International Journal Of Pharmaceutics. Amsterdam: Elsevier Science Bv, v. 473, n. 1-2, p. 627-635, 2014.
0378-5173
10.1016/j.ijpharm.2014.07.049
WOS:000342656800069
Autor
Andreani, Tatiana
Souza, Ana Luiza R. de [UNESP]
Kiill, Charlene P. [UNESP]
Lorenzon, Esteban N. [UNESP]
Fangueiro, Joana F.
Cristina Calpena, Ana
Chaud, Marco V.
Garcia, Maria L.
Gremiao, Maria Palmira D. [UNESP]
Silva, Amelia M.
Souto, Eliana B.
Resumen
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. (C) 2014 Elsevier B.V. All rights reserved. Fundacao para a Ciencia e Tecnologia (FCT, Portugal) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Univ Tras Os Montes & Alto Douro, Dept Biol & Environm, UTAD, P-5001801 Vila Real, Portugal UTAD, Ctr Res & Technol Agroenvironm & Biol Sci CITAB, Vila Real, Portugal Fernando Pessoa Univ UFP, Res Ctr Biomed CEBIMED, P-4249004 Oporto, Portugal Univ Estadual Paulista, Dept Pharmaceut Sci, UNESP, Sao Paulo, Brazil Univ Estadual Paulista, Inst Chem, UNESP, Dept Biochem & Chem Technol, Sao Paulo, Brazil Fernando Pessoa Univ, Fac Hlth Sci, P-4200150 Oporto, Portugal Univ Barcelona, Sch Pharm, Pharm & Pharmaceut Technol Dept, Biopharm & Pharmacokicet Unit, Barcelona 8028, Spain Sorocaba Univ, UNISO, BR-18023000 Sorocaba, Brazil Univ Barcelona, Fac Pharm, Dept Phys Chem, Barcelona 8028, Spain UTAD, Ctr Genom & Biotechnol, Inst Biotechnol & Bioengn, Vila Real, Portugal Univ Estadual Paulista, Dept Pharmaceut Sci, UNESP, Sao Paulo, Brazil Univ Estadual Paulista, Inst Chem, UNESP, Dept Biochem & Chem Technol, Sao Paulo, Brazil Fundacao para a Ciencia e Tecnologia (FCT, Portugal)SFRH/BD/60640/2009 Fundacao para a Ciencia e Tecnologia (FCT, Portugal)SFRH/BD/80335/2011 FAPESP: 12/10174-3