Immobilization of protein-coated drug nanoparticles in nanofibrillar cellulose matrices

Enhanced stability and release

Hanna Valo (Corresponding Author), Miia Kovalainen, Päivi Laaksonen, Merja Häkkinen, Seppo Auriola, Leena Peltonen, Markus Linder, Kristiina Järvinen, Jouni Hirvonen, Timo Laaksonen

Research output: Contribution to journalArticleScientificpeer-review

76 Citations (Scopus)

Abstract

Nanosizing is an advanced approach to overcome poor aqueous solubility of active pharmaceutical ingredients. One main problem in pharmaceutical nanotechnology is maintaining of the morphology of the nanometer sized particles during processing and storage to make sure the formulation behaves as originally planned. Here, a genetically engineered hydrophobin fusion protein, where the hydrophobin (HFBI) was coupled with two cellulose binding domains (CBDs), was employed in order to facilitate drug nanoparticle binding to nanofibrillar cellulose (NFC). The nanofibrillar matrix provides protection for the nanoparticles during the formulation process and storage. It was demonstrated that by enclosing the functionalized protein coated itraconazole nanoparticles to the external nanofibrillar cellulose matrix notably increased their storage stability. In a suspension with cellulose nanofibrils, nanoparticles around 100 nm could be stored for more than ten months when the specific cellulose binding domain was fused to the hydrophobin. Also freeze-dried particles in the cellulose nanofibrils matrix were preserved without major changes in their morphology. In addition, as a consequence of formation of the immobilized nanodispersion, dissolution rate of itraconazole was increased significantly, which also enhanced the in vivo performance of the drug.
Original languageEnglish
Pages (from-to)390-397
JournalJournal of Controlled Release
Volume156
Issue number3
DOIs
Publication statusPublished - 2011
MoE publication typeA1 Journal article-refereed

Fingerprint

Cellulose
Immobilization
Nanoparticles
Pharmaceutical Preparations
Proteins
Itraconazole
Nanotechnology
Solubility
Suspensions

Keywords

  • Pharmaceutical nanotechnology
  • nanoparticles
  • hydrophobins
  • fusion proteins
  • drug release
  • nanofibrillar cellulose

Cite this

Valo, H., Kovalainen, M., Laaksonen, P., Häkkinen, M., Auriola, S., Peltonen, L., ... Laaksonen, T. (2011). Immobilization of protein-coated drug nanoparticles in nanofibrillar cellulose matrices: Enhanced stability and release. Journal of Controlled Release, 156(3), 390-397. https://doi.org/10.1016/j.jconrel.2011.07.016
Valo, Hanna ; Kovalainen, Miia ; Laaksonen, Päivi ; Häkkinen, Merja ; Auriola, Seppo ; Peltonen, Leena ; Linder, Markus ; Järvinen, Kristiina ; Hirvonen, Jouni ; Laaksonen, Timo. / Immobilization of protein-coated drug nanoparticles in nanofibrillar cellulose matrices : Enhanced stability and release. In: Journal of Controlled Release. 2011 ; Vol. 156, No. 3. pp. 390-397.
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Valo, H, Kovalainen, M, Laaksonen, P, Häkkinen, M, Auriola, S, Peltonen, L, Linder, M, Järvinen, K, Hirvonen, J & Laaksonen, T 2011, 'Immobilization of protein-coated drug nanoparticles in nanofibrillar cellulose matrices: Enhanced stability and release', Journal of Controlled Release, vol. 156, no. 3, pp. 390-397. https://doi.org/10.1016/j.jconrel.2011.07.016

Immobilization of protein-coated drug nanoparticles in nanofibrillar cellulose matrices : Enhanced stability and release. / Valo, Hanna (Corresponding Author); Kovalainen, Miia; Laaksonen, Päivi; Häkkinen, Merja; Auriola, Seppo; Peltonen, Leena; Linder, Markus; Järvinen, Kristiina; Hirvonen, Jouni; Laaksonen, Timo.

In: Journal of Controlled Release, Vol. 156, No. 3, 2011, p. 390-397.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Immobilization of protein-coated drug nanoparticles in nanofibrillar cellulose matrices

T2 - Enhanced stability and release

AU - Valo, Hanna

AU - Kovalainen, Miia

AU - Laaksonen, Päivi

AU - Häkkinen, Merja

AU - Auriola, Seppo

AU - Peltonen, Leena

AU - Linder, Markus

AU - Järvinen, Kristiina

AU - Hirvonen, Jouni

AU - Laaksonen, Timo

PY - 2011

Y1 - 2011

N2 - Nanosizing is an advanced approach to overcome poor aqueous solubility of active pharmaceutical ingredients. One main problem in pharmaceutical nanotechnology is maintaining of the morphology of the nanometer sized particles during processing and storage to make sure the formulation behaves as originally planned. Here, a genetically engineered hydrophobin fusion protein, where the hydrophobin (HFBI) was coupled with two cellulose binding domains (CBDs), was employed in order to facilitate drug nanoparticle binding to nanofibrillar cellulose (NFC). The nanofibrillar matrix provides protection for the nanoparticles during the formulation process and storage. It was demonstrated that by enclosing the functionalized protein coated itraconazole nanoparticles to the external nanofibrillar cellulose matrix notably increased their storage stability. In a suspension with cellulose nanofibrils, nanoparticles around 100 nm could be stored for more than ten months when the specific cellulose binding domain was fused to the hydrophobin. Also freeze-dried particles in the cellulose nanofibrils matrix were preserved without major changes in their morphology. In addition, as a consequence of formation of the immobilized nanodispersion, dissolution rate of itraconazole was increased significantly, which also enhanced the in vivo performance of the drug.

AB - Nanosizing is an advanced approach to overcome poor aqueous solubility of active pharmaceutical ingredients. One main problem in pharmaceutical nanotechnology is maintaining of the morphology of the nanometer sized particles during processing and storage to make sure the formulation behaves as originally planned. Here, a genetically engineered hydrophobin fusion protein, where the hydrophobin (HFBI) was coupled with two cellulose binding domains (CBDs), was employed in order to facilitate drug nanoparticle binding to nanofibrillar cellulose (NFC). The nanofibrillar matrix provides protection for the nanoparticles during the formulation process and storage. It was demonstrated that by enclosing the functionalized protein coated itraconazole nanoparticles to the external nanofibrillar cellulose matrix notably increased their storage stability. In a suspension with cellulose nanofibrils, nanoparticles around 100 nm could be stored for more than ten months when the specific cellulose binding domain was fused to the hydrophobin. Also freeze-dried particles in the cellulose nanofibrils matrix were preserved without major changes in their morphology. In addition, as a consequence of formation of the immobilized nanodispersion, dissolution rate of itraconazole was increased significantly, which also enhanced the in vivo performance of the drug.

KW - Pharmaceutical nanotechnology

KW - nanoparticles

KW - hydrophobins

KW - fusion proteins

KW - drug release

KW - nanofibrillar cellulose

U2 - 10.1016/j.jconrel.2011.07.016

DO - 10.1016/j.jconrel.2011.07.016

M3 - Article

VL - 156

SP - 390

EP - 397

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 3

ER -