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

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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.

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Abbreviations

PSi:

porous silicon

THCPSi:

thermally hydrocarbonized porous silicon

TOPSi:

thermally oxidized porous silicon

UnTHCPSi:

undecylenic acid treated thermally hydrocarbonized porous silicon

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ACKNOWLEDGMENTS & DISCLOSURES

This study was financially supported by Finnish Cultural Foundation (MK), Orion Farmos Research Foundation (MK), Graduate School of Pharmaceutical Research (JM), Academy of Finland – PEPBI consortium (#117906, #118002, #217547) and the strategic funding of the University of Eastern Finland (NAMBER consortium).

Author information

Authors and Affiliations

  1. School of Pharmacy, Pharmaceutical Technology, Faculty of Health Sciences, University of Eastern Finland, Po Box 1627, 70211, Kuopio, Finland

    Miia Kovalainen, Juha Mönkäre & Kristiina Järvinen

  2. Department of Physics and Astronomy, University of Turku, 20014, Turku, Finland

    Ermei Mäkilä & Jarno Salonen

  3. Faculty of Science and Forestry, Department of Applied Physics, University of Eastern Finland, 70211, Kuopio, Finland

    Vesa-Pekka Lehto

  4. Institute of Biomedicine, Biocenter of Oulu University of Oulu, 90014, Oulu, Finland

    Karl-Heinz Herzig

  5. Department of Psychiatry, Kuopio University Hospital, 70211, Kuopio, Finland

    Karl-Heinz Herzig

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  1. Miia Kovalainen
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Corresponding author

Correspondence to Miia Kovalainen.

Additional information

Miia Kovalainen and Juha Mönkäre share equal contribution.

Electronic Supplementary Materials

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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)

High Resolution Image (TIFF 8260 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)

High Resolution Image (TIFF 8939 kb)

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Kovalainen, M., Mönkäre, J., Mäkilä, E. et al. Mesoporous Silicon (PSi) for Sustained Peptide Delivery: Effect of PSi Microparticle Surface Chemistry on Peptide YY3-36 Release. Pharm Res 29, 837–846 (2012). https://doi.org/10.1007/s11095-011-0611-6

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  • DOI: https://doi.org/10.1007/s11095-011-0611-6

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