Porous silicon microcarriers for extended release of metformin: Design, biological evaluation and 3D kinetics modeling
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Nanostructured porous silicon microparticles (μPSip) synthesized by electrochemical etching were used as tunable carriers for sustained delivery of metformin hydrochloride (MET), an oral antihyperglycemic agent. The surface of native PSi microparticles was modified by thermal oxidation to enhance μPSip stability and MET physical adsorption. Morphological and physicochemical properties of the porous carrier were characterized by a combination of scanning electron microscopy, nitrogen adsorption–desorption, and zeta potential techniques. Drug loading was confirmed by ATR Fourier transform infrared spectroscopy, and loading efficiency was quantified by thermogravimetric analysis and UV–Vis. From MET released profiles, we demonstrated that thermally oxidized µPSip exhibited a sustained release during 26 h, with burst effect depending on pH of the microenvironment. Native PSi loaded particles showed a complete MET release within 6 h with a substantial burst effect at 1 h. The loading kinetics of MET at different initial concentrations were satisfactorily predicted with a 3D diffusional model based on surface diffusion. The proposed model showed that the surface diffusion coefficient (Ds) values increase exponentially as a function of MET loading. The mass transport parameters obtained from the loading kinetics were used to predict the release kinetics of MET. The comparison of experimental and predicted results showed an accurate representation of the data, highlighting the reliability of the model. Through in vivo studies, it was demonstrated that MET-μPSip microcarriers did not induce inflammatory processes. A sustained hypoglycemic effect was observed for 24 h after composite administration, which is a novel contribution of this work. © 2019 Elsevier B.V.
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3D modeling; Blood glucose; Drug delivery; Inflammation; Metformin; Porous silicon 3D modeling; Controlled drug delivery; Drug delivery; Drug products; Fourier transform infrared spectroscopy; Gas adsorption; Kinetics; Physicochemical properties; Scanning electron microscopy; Silicon compounds; Surface diffusion; Targeted drug delivery; Thermogravimetric analysis; Thermooxidation; Antihyperglycemic agent; Biological evaluation; Blood glucose; Inflammation; Inflammatory process; Initial concentration; Metformin hydrochlorides; Metformins; Porous silicon
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