Mesoporous silicon (PSi) for sustained peptide delivery: effect of psi microparticle surface chemistry on peptide YY3-36 release.
OBJECTIVE
To achieve sustained peptide delivery via mesoporous silicon (PSi) microparticles and to evaluate the effects of different surface chemistries on peptide YY3-36 (PYY3-36) delivery.


METHODS
PYY3-36 was loaded into thermally oxidized (TOPSi), thermally hydrocarbonized (THCPSi) and undecylenic acid treated THCPSi (UnTHCPSi) microparticles with comparable porous properties. In vitro, PYY3-36 release was investigated by centrifuge. In vivo, PYY3-36 plasma concentrations were analyzed after delivery in microparticles or solution.


RESULTS
Achieved loading degrees were high (12.2 - 16.0% w/w). PYY3-36 release was sustained from all microparticles; order of PYY3-36 release was TOPSi > THCPSi > UnTHCPSi both in vitro and in vivo. In mice, PSi microparticles achieved sustained PYY3-36 release over 4 days, whereas PYY3-36 solution was eliminated in 12 h. In vitro, only 27.7, 14.5 and 6.2% of loaded PYY3-36 was released from TOPSi, THCPSi and UnTHCPSi, respectively. Absolute PYY3-36 bioavailabilities were 98, 13, 9 and 38% when delivered subcutaneously in TOPSi, THCPSi, UnTHCPSi and solution, respectively. The results clearly demonstrate improved bioavailability of PYY3-36 via TOPSi and the importance of surface chemistry of PSi on peptide release.


CONCLUSIONS
PSi represents a promising sustained and tailorable release system for PYY3-36.
School of Pharmacy, Pharmaceutical Technology, Faculty of Health Sciences, University of Eastern Finland, Po Box 1627, 70211, Kuopio, Finland. Miia.Kovalainen@uef.fi
Miia
M
Kovalainen
Juha
J
Mönkäre
Ermei
E
Mäkilä
Jarno
J
Salonen
Vesa-Pekka
VP
Lehto
Karl-Heinz
KH
Herzig
Kristiina
K
Järvinen
D000595:Amino Acid Sequence; D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry*; D006801:Humans; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D019894:Peptide YY / Q000008:administration & dosage* / Q000097:blood* / Q000737:chemistry; D016062:Porosity; D012825:Silicon / Q000737:chemistry*
D003692:Delayed-Action Preparations; D019894:Peptide YY; D012825:Silicon