Co-delivery of a hydrophobic small molecule and a hydrophilic peptide by porous silicon nanoparticles

Dongfei Liu, Luis M. Bimbo, Ermei Mäkilä, Francesca Villanova, Martti Kaasalainen, Barbara Herranz-Blanco, Carla M. Caramella, Vesa-Pekka Lehto, Jarno Salonen, Karl-Heinz Herzig, Jouni Hirvonen, Hélder A. Santos

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Nanoparticulate drug delivery systems offer remarkable opportunities for clinical treatment. However, there are several challenges when they are employed to deliver multiple cargos/payloads, particularly concerning the synchronous delivery of small molecular weight drugs and relatively larger peptides. Since porous silicon (PSi) nanoparticles (NPs) can easily contain high payloads of drugs with various properties, we evaluated their carrier potential in multi-drug delivery for co-loading of the hydrophobic drug indomethacin and the hydrophilic human peptide YY3-36 (PYY3-36). Sequential loading of these two drugs into the PSi NPs enhanced the drug release rate of each drug and also their amount permeated across Caco-2 and Caco-2/HT29 cell monolayers. Regardless of the loading approach used, dual or single, the drug permeation profiles were in good correlation with their drug release behaviour. Furthermore, the permeation studies indicated the critical role of the mucus intestinal layer and the paracellular resistance in the permeation of the therapeutic compounds across the intestinal wall. Loading with PYY3-36 also greatly improved the cytocompatibility of the PSi NPs. Conformational analysis indicated that the PYY3-36 could still display biological activity after release from the PSi NPs and permeation across the intestinal cell monolayers. These results are the first demonstration of the promising potential of PSi NPs for simultaneous multi-drug delivery of both hydrophobic and hydrophilic compounds.

LanguageEnglish
Pages268-278
Number of pages11
JournalJournal of Controlled Release
Volume170
Issue number2
Early online date9 Jun 2013
DOIs
Publication statusPublished - 10 Sep 2013
Externally publishedYes

Fingerprint

Silicon
Nanoparticles
Peptides
Pharmaceutical Preparations
HT29 Cells
Caco-2 Cells
Mucus
Drug Delivery Systems
Indomethacin
Molecular Weight
Therapeutics
peptide YY (3-36)

Keywords

  • animals
  • anti-inflammatory agents
  • Caco-2 cells
  • cell line
  • cell survival
  • coculture techniques
  • drug carriers
  • HT29 cells
  • Hep G2 cells
  • humans
  • hydrophobic interactions
  • indomethacin
  • mice
  • nanoparticles
  • peptide fragments
  • peptide YY
  • permeability
  • porosity
  • silicon
  • hydrophilic interactions

Cite this

Liu, Dongfei ; Bimbo, Luis M. ; Mäkilä, Ermei ; Villanova, Francesca ; Kaasalainen, Martti ; Herranz-Blanco, Barbara ; Caramella, Carla M. ; Lehto, Vesa-Pekka ; Salonen, Jarno ; Herzig, Karl-Heinz ; Hirvonen, Jouni ; Santos, Hélder A. / Co-delivery of a hydrophobic small molecule and a hydrophilic peptide by porous silicon nanoparticles. In: Journal of Controlled Release. 2013 ; Vol. 170, No. 2. pp. 268-278.
@article{c977e80eb0a744f8bdb2d55261a83547,
title = "Co-delivery of a hydrophobic small molecule and a hydrophilic peptide by porous silicon nanoparticles",
abstract = "Nanoparticulate drug delivery systems offer remarkable opportunities for clinical treatment. However, there are several challenges when they are employed to deliver multiple cargos/payloads, particularly concerning the synchronous delivery of small molecular weight drugs and relatively larger peptides. Since porous silicon (PSi) nanoparticles (NPs) can easily contain high payloads of drugs with various properties, we evaluated their carrier potential in multi-drug delivery for co-loading of the hydrophobic drug indomethacin and the hydrophilic human peptide YY3-36 (PYY3-36). Sequential loading of these two drugs into the PSi NPs enhanced the drug release rate of each drug and also their amount permeated across Caco-2 and Caco-2/HT29 cell monolayers. Regardless of the loading approach used, dual or single, the drug permeation profiles were in good correlation with their drug release behaviour. Furthermore, the permeation studies indicated the critical role of the mucus intestinal layer and the paracellular resistance in the permeation of the therapeutic compounds across the intestinal wall. Loading with PYY3-36 also greatly improved the cytocompatibility of the PSi NPs. Conformational analysis indicated that the PYY3-36 could still display biological activity after release from the PSi NPs and permeation across the intestinal cell monolayers. These results are the first demonstration of the promising potential of PSi NPs for simultaneous multi-drug delivery of both hydrophobic and hydrophilic compounds.",
keywords = "animals, anti-inflammatory agents, Caco-2 cells, cell line, cell survival, coculture techniques, drug carriers, HT29 cells, Hep G2 cells, humans, hydrophobic interactions, indomethacin, mice, nanoparticles, peptide fragments, peptide YY, permeability, porosity, silicon, hydrophilic interactions",
author = "Dongfei Liu and Bimbo, {Luis M.} and Ermei M{\"a}kil{\"a} and Francesca Villanova and Martti Kaasalainen and Barbara Herranz-Blanco and Caramella, {Carla M.} and Vesa-Pekka Lehto and Jarno Salonen and Karl-Heinz Herzig and Jouni Hirvonen and Santos, {H{\'e}lder A.}",
note = "Copyright {\circledC} 2013 Elsevier B.V. All rights reserved.",
year = "2013",
month = "9",
day = "10",
doi = "10.1016/j.jconrel.2013.05.036",
language = "English",
volume = "170",
pages = "268--278",
journal = "Journal of Controlled Release",
issn = "0168-3659",
number = "2",

}

Liu, D, Bimbo, LM, Mäkilä, E, Villanova, F, Kaasalainen, M, Herranz-Blanco, B, Caramella, CM, Lehto, V-P, Salonen, J, Herzig, K-H, Hirvonen, J & Santos, HA 2013, 'Co-delivery of a hydrophobic small molecule and a hydrophilic peptide by porous silicon nanoparticles' Journal of Controlled Release, vol. 170, no. 2, pp. 268-278. https://doi.org/10.1016/j.jconrel.2013.05.036

Co-delivery of a hydrophobic small molecule and a hydrophilic peptide by porous silicon nanoparticles. / Liu, Dongfei; Bimbo, Luis M.; Mäkilä, Ermei; Villanova, Francesca; Kaasalainen, Martti; Herranz-Blanco, Barbara; Caramella, Carla M.; Lehto, Vesa-Pekka; Salonen, Jarno; Herzig, Karl-Heinz; Hirvonen, Jouni; Santos, Hélder A.

In: Journal of Controlled Release, Vol. 170, No. 2, 10.09.2013, p. 268-278.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Co-delivery of a hydrophobic small molecule and a hydrophilic peptide by porous silicon nanoparticles

AU - Liu, Dongfei

AU - Bimbo, Luis M.

AU - Mäkilä, Ermei

AU - Villanova, Francesca

AU - Kaasalainen, Martti

AU - Herranz-Blanco, Barbara

AU - Caramella, Carla M.

AU - Lehto, Vesa-Pekka

AU - Salonen, Jarno

AU - Herzig, Karl-Heinz

AU - Hirvonen, Jouni

AU - Santos, Hélder A.

N1 - Copyright © 2013 Elsevier B.V. All rights reserved.

PY - 2013/9/10

Y1 - 2013/9/10

N2 - Nanoparticulate drug delivery systems offer remarkable opportunities for clinical treatment. However, there are several challenges when they are employed to deliver multiple cargos/payloads, particularly concerning the synchronous delivery of small molecular weight drugs and relatively larger peptides. Since porous silicon (PSi) nanoparticles (NPs) can easily contain high payloads of drugs with various properties, we evaluated their carrier potential in multi-drug delivery for co-loading of the hydrophobic drug indomethacin and the hydrophilic human peptide YY3-36 (PYY3-36). Sequential loading of these two drugs into the PSi NPs enhanced the drug release rate of each drug and also their amount permeated across Caco-2 and Caco-2/HT29 cell monolayers. Regardless of the loading approach used, dual or single, the drug permeation profiles were in good correlation with their drug release behaviour. Furthermore, the permeation studies indicated the critical role of the mucus intestinal layer and the paracellular resistance in the permeation of the therapeutic compounds across the intestinal wall. Loading with PYY3-36 also greatly improved the cytocompatibility of the PSi NPs. Conformational analysis indicated that the PYY3-36 could still display biological activity after release from the PSi NPs and permeation across the intestinal cell monolayers. These results are the first demonstration of the promising potential of PSi NPs for simultaneous multi-drug delivery of both hydrophobic and hydrophilic compounds.

AB - Nanoparticulate drug delivery systems offer remarkable opportunities for clinical treatment. However, there are several challenges when they are employed to deliver multiple cargos/payloads, particularly concerning the synchronous delivery of small molecular weight drugs and relatively larger peptides. Since porous silicon (PSi) nanoparticles (NPs) can easily contain high payloads of drugs with various properties, we evaluated their carrier potential in multi-drug delivery for co-loading of the hydrophobic drug indomethacin and the hydrophilic human peptide YY3-36 (PYY3-36). Sequential loading of these two drugs into the PSi NPs enhanced the drug release rate of each drug and also their amount permeated across Caco-2 and Caco-2/HT29 cell monolayers. Regardless of the loading approach used, dual or single, the drug permeation profiles were in good correlation with their drug release behaviour. Furthermore, the permeation studies indicated the critical role of the mucus intestinal layer and the paracellular resistance in the permeation of the therapeutic compounds across the intestinal wall. Loading with PYY3-36 also greatly improved the cytocompatibility of the PSi NPs. Conformational analysis indicated that the PYY3-36 could still display biological activity after release from the PSi NPs and permeation across the intestinal cell monolayers. These results are the first demonstration of the promising potential of PSi NPs for simultaneous multi-drug delivery of both hydrophobic and hydrophilic compounds.

KW - animals

KW - anti-inflammatory agents

KW - Caco-2 cells

KW - cell line

KW - cell survival

KW - coculture techniques

KW - drug carriers

KW - HT29 cells

KW - Hep G2 cells

KW - humans

KW - hydrophobic interactions

KW - indomethacin

KW - mice

KW - nanoparticles

KW - peptide fragments

KW - peptide YY

KW - permeability

KW - porosity

KW - silicon

KW - hydrophilic interactions

UR - http://www.sciencedirect.com/science/journal/01683659

U2 - 10.1016/j.jconrel.2013.05.036

DO - 10.1016/j.jconrel.2013.05.036

M3 - Article

VL - 170

SP - 268

EP - 278

JO - Journal of Controlled Release

T2 - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 2

ER -