title: 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 (pI 5.4) was loaded and released from the negatively charged thermally oxidized (TOPSi, pI 1.8) and thermally carbonized (TCPSi, pI 2.6) PSi microparticles and from the novel positively charged amine modified microparticles, designated as TOPSi-NH2-D (pI 8.8) and TCPSi-NH2-D (pI 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-NH2-D and TCPSi-NH2-D were not able to prolong the effect when compared to TOPSi, TCPSi or GLP-1 solution. However, TOPSi-NH2-D and TCPSi-NH2-D microparticles were able to carry improved payloads of active GLP-1 encouraging continuing further attempts to achieve sustained release.
authors.affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Huotari
authors.forename: Wujun
authors.initials: W
authors.lastname: Xu
authors.forename: Juha
authors.initials: J
authors.lastname: Mönkäre
authors.forename: Miia
authors.initials: M
authors.lastname: Kovalainen
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Herzig
authors.forename: Vesa-Pekka
authors.initials: VP
authors.lastname: Lehto
authors.forename: Kristiina
authors.initials: K
authors.lastname: Järvinen
mesh_terms: D000327:Adsorption; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D016062:Porosity; D012825:Silicon / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007004:Hypoglycemic Agents; D052216:Glucagon-Like Peptide 1; D012825:Silicon
keywords: Blood glucose levels; GLP-1; In vivo; Mesoporous silicon; Peptide delivery