Surface functionalization of mesoporous silica nanoparticles controls loading and release behavior of mitoxantrone

Amit Wani, Elayaraja Muthuswamy, Galbokka H Layan Savithra, Guangzhao Mao, Stephanie Brock, David Oupicky

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Purpose To investigate the effect of surface functionalization of mesoporous silica nanoparticles (MSN) on crystallization, loading, release and activity of mitoxantrone (MTX). Methods Thiol-, amine-, and mixed thiol/amine-functionalized MSN were synthesized and characterized by electron microscopy, thermogravimetry, surface area analysis, elemental analysis and zeta potential. MTX loading and release kinetics were determined in phosphate and acetate buffers (pH 7.4 and 4.5). The crystalline state ofMTX inMSN was determined by differential scanning calorimetry and X-ray diffraction. Cytotoxicity and activity of MTX loaded MSN were determined by MTS assay in MDA-MB-231 cells. Results Our results demonstrate that loading of MTX depends strongly on the type of surface functional groups in MSN. Thiol-MSN showed the highest MTX loading (18 % w/w) when compared with thiol/amine-MSN (6 % w/w) and amine-MSN (1 % w/w). MTX release was strongly dependent on the pH of the release medium and the type of surface functional group. MTX was found in the amorphous form when loaded in thiolfunctionalized MSN. No significant effect of surface modification of MSN on particle toxicity was observed. MTX loaded in MSN exhibited comparable anticancer activity in vitro as free MTX. Conclusion Surface modifications of MSN have significant effect on MTX crystallization and release behavior.

Original languageEnglish (US)
Pages (from-to)2407-2418
Number of pages12
JournalPharmaceutical Research
Volume29
Issue number9
DOIs
StatePublished - Sep 1 2012

Fingerprint

Mitoxantrone
Silicon Dioxide
Nanoparticles
Sulfhydryl Compounds
Amines
Crystallization
Functional groups
Surface treatment
Thermogravimetry
Differential Scanning Calorimetry
Zeta potential
Cytotoxicity
X-Ray Diffraction
Electron microscopy
Toxicity
Thermogravimetric analysis
Differential scanning calorimetry
Assays
Electron Microscopy
Buffers

Keywords

  • Drug delivery
  • Drug release
  • Mesoporous silica
  • Mitoxantrone
  • Nanoparticles

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Organic Chemistry
  • Molecular Medicine
  • Pharmacology (medical)
  • Biotechnology
  • Pharmacology

Cite this

Surface functionalization of mesoporous silica nanoparticles controls loading and release behavior of mitoxantrone. / Wani, Amit; Muthuswamy, Elayaraja; Savithra, Galbokka H Layan; Mao, Guangzhao; Brock, Stephanie; Oupicky, David.

In: Pharmaceutical Research, Vol. 29, No. 9, 01.09.2012, p. 2407-2418.

Research output: Contribution to journalArticle

Wani, Amit ; Muthuswamy, Elayaraja ; Savithra, Galbokka H Layan ; Mao, Guangzhao ; Brock, Stephanie ; Oupicky, David. / Surface functionalization of mesoporous silica nanoparticles controls loading and release behavior of mitoxantrone. In: Pharmaceutical Research. 2012 ; Vol. 29, No. 9. pp. 2407-2418.
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abstract = "Purpose To investigate the effect of surface functionalization of mesoporous silica nanoparticles (MSN) on crystallization, loading, release and activity of mitoxantrone (MTX). Methods Thiol-, amine-, and mixed thiol/amine-functionalized MSN were synthesized and characterized by electron microscopy, thermogravimetry, surface area analysis, elemental analysis and zeta potential. MTX loading and release kinetics were determined in phosphate and acetate buffers (pH 7.4 and 4.5). The crystalline state ofMTX inMSN was determined by differential scanning calorimetry and X-ray diffraction. Cytotoxicity and activity of MTX loaded MSN were determined by MTS assay in MDA-MB-231 cells. Results Our results demonstrate that loading of MTX depends strongly on the type of surface functional groups in MSN. Thiol-MSN showed the highest MTX loading (18 {\%} w/w) when compared with thiol/amine-MSN (6 {\%} w/w) and amine-MSN (1 {\%} w/w). MTX release was strongly dependent on the pH of the release medium and the type of surface functional group. MTX was found in the amorphous form when loaded in thiolfunctionalized MSN. No significant effect of surface modification of MSN on particle toxicity was observed. MTX loaded in MSN exhibited comparable anticancer activity in vitro as free MTX. Conclusion Surface modifications of MSN have significant effect on MTX crystallization and release behavior.",
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N2 - Purpose To investigate the effect of surface functionalization of mesoporous silica nanoparticles (MSN) on crystallization, loading, release and activity of mitoxantrone (MTX). Methods Thiol-, amine-, and mixed thiol/amine-functionalized MSN were synthesized and characterized by electron microscopy, thermogravimetry, surface area analysis, elemental analysis and zeta potential. MTX loading and release kinetics were determined in phosphate and acetate buffers (pH 7.4 and 4.5). The crystalline state ofMTX inMSN was determined by differential scanning calorimetry and X-ray diffraction. Cytotoxicity and activity of MTX loaded MSN were determined by MTS assay in MDA-MB-231 cells. Results Our results demonstrate that loading of MTX depends strongly on the type of surface functional groups in MSN. Thiol-MSN showed the highest MTX loading (18 % w/w) when compared with thiol/amine-MSN (6 % w/w) and amine-MSN (1 % w/w). MTX release was strongly dependent on the pH of the release medium and the type of surface functional group. MTX was found in the amorphous form when loaded in thiolfunctionalized MSN. No significant effect of surface modification of MSN on particle toxicity was observed. MTX loaded in MSN exhibited comparable anticancer activity in vitro as free MTX. Conclusion Surface modifications of MSN have significant effect on MTX crystallization and release behavior.

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