Pharmaceutical Research

, Volume 29, Issue 3, pp 837–846

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

  • Miia Kovalainen
  • Juha Mönkäre
  • Ermei Mäkilä
  • Jarno Salonen
  • Vesa-Pekka Lehto
  • Karl-Heinz Herzig
  • Kristiina Järvinen
Research Paper

DOI: 10.1007/s11095-011-0611-6

Cite this article as:
Kovalainen, M., Mönkäre, J., Mäkilä, E. et al. Pharm Res (2012) 29: 837. doi:10.1007/s11095-011-0611-6

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 vivomesoporous siliconpeptide deliverypharmacokineticsPYY3-36

ABBREVIATIONS

PSi

porous silicon

THCPSi

thermally hydrocarbonized porous silicon

TOPSi

thermally oxidized porous silicon

UnTHCPSi

undecylenic acid treated thermally hydrocarbonized porous silicon

Supplementary material

11095_2011_611_Fig5_ESM.jpg (71 kb)
Supplementary data S1

TG measurements of thermally oxidized PSi (TOPSi), hydrocarbonized PSi (THCPSi) and undecylenic acid treated thermally hydrocarbonized PSi (UnTHCPSi) and PYY3-36 loaded TOPSi. Reduction in weight correlates with the decomposed surface moieties desorbing from the samples. (JPEG 71 kb)

11095_2011_611_MOESM1_ESM.tif (8.1 mb)
High Resolution Image (TIFF 8260 kb)
11095_2011_611_Fig6_ESM.jpg (88 kb)
Supplementary data S2

FTIR spectra of TOPSi, THCPSi, UnTHCPSi shown in Supplementary data S1. Spectra have been shifted to clarify the figure. (JPEG 88 kb)

11095_2011_611_MOESM2_ESM.tif (8.7 mb)
High Resolution Image (TIFF 8939 kb)

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Miia Kovalainen
    • 1
  • Juha Mönkäre
    • 1
  • Ermei Mäkilä
    • 2
  • Jarno Salonen
    • 2
  • Vesa-Pekka Lehto
    • 3
  • Karl-Heinz Herzig
    • 4
    • 5
  • Kristiina Järvinen
    • 1
  1. 1.School of Pharmacy, Pharmaceutical Technology, Faculty of Health SciencesUniversity of Eastern FinlandKuopioFinland
  2. 2.Department of Physics and AstronomyUniversity of TurkuTurkuFinland
  3. 3.Faculty of Science and Forestry, Department of Applied PhysicsUniversity of Eastern FinlandKuopioFinland
  4. 4.Institute of Biomedicine, Biocenter of Oulu University of OuluOuluFinland
  5. 5.Department of PsychiatryKuopio University HospitalKuopioFinland