Research Paper

Pharmaceutical Research

, Volume 29, Issue 3, pp 837-846

First online:

Mesoporous Silicon (PSi) for Sustained Peptide Delivery: Effect of PSi Microparticle Surface Chemistry on Peptide YY3-36 Release

  • Miia KovalainenAffiliated withSchool of Pharmacy, Pharmaceutical Technology, Faculty of Health Sciences, University of Eastern Finland Email author 
  • , Juha MönkäreAffiliated withSchool of Pharmacy, Pharmaceutical Technology, Faculty of Health Sciences, University of Eastern Finland
  • , Ermei MäkiläAffiliated withDepartment of Physics and Astronomy, University of Turku
  • , Jarno SalonenAffiliated withDepartment of Physics and Astronomy, University of Turku
  • , Vesa-Pekka LehtoAffiliated withFaculty of Science and Forestry, Department of Applied Physics, University of Eastern Finland
  • , Karl-Heinz HerzigAffiliated withInstitute of Biomedicine, Biocenter of Oulu University of OuluDepartment of Psychiatry, Kuopio University Hospital
  • , Kristiina JärvinenAffiliated withSchool of Pharmacy, Pharmaceutical Technology, Faculty of Health Sciences, University of Eastern Finland

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ABSTRACT

Purpose

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.

KEY WORDS

in vivo mesoporous silicon peptide delivery pharmacokinetics PYY3-36