Effect of surface chemistry of porous silicon microparticles on glucagon-like peptide-1 (GLP-1) loading, release and biological activity

Abstract Recently, mesoporous silicon (PSi) microparticles have been shown to extend the duration of action of peptides, reducing the need for frequent injections. Glucagon-like peptide 1 (GLP-1) is a potential novel treatment for type 2 diabetes. The aim of this study was to evaluate whether GLP-1 loading into PSi microparticles reduce blood glucose levels over an extended period. GLP-1 (p I 5.4) was loaded and released from the negatively charged thermally oxidized (TOPSi, p I 1.8) and thermally carbonized (TCPSi, p I 2.6) PSi microparticles and from the novel positively charged amine modified microparticles, designated as TOPSi-NH 2 -D (p I 8.8) and TCPSi-NH 2 -D (p I 8.8), respectively. The adsorption of GLP-1 onto the PSi microparticles could be increased 3–4-fold by changing the PSi surface charge from negative to positive, indicating that the positive surface charge of PSi promoted an electrostatic interaction between the negatively charged peptide. All the GLP-1 loaded PSi microparticles lowered the blood glucose levels after a single s.c. injection but surprisingly, TOPSi-NH 2 -D and TCPSi-NH 2 -D were not able to prolong the effect when compared to TOPSi, TCPSi or GLP-1 solution. However, TOPSi-NH 2 -D and TCPSi-NH 2 -D microparticles were able to carry improved payloads of active GLP-1 encouraging continuing further attempts to achieve sustained release.