Pharmaceutical Research

, Volume 29, Issue 9, pp 2407–2418

Surface Functionalization of Mesoporous Silica Nanoparticles Controls Loading and Release Behavior of Mitoxantrone

Authors

  • Amit Wani
    • Department of Pharmaceutical SciencesWayne State University
  • Elayaraja Muthuswamy
    • Department of ChemistryWayne State University
  • Galbokka H. Layan Savithra
    • Department of ChemistryWayne State University
  • Guangzhao Mao
    • Department of Chemical Engineering and Materials ScienceWayne State University
  • Stephanie Brock
    • Department of ChemistryWayne State University
    • Department of Pharmaceutical SciencesWayne State University
Research Paper

DOI: 10.1007/s11095-012-0766-9

Cite this article as:
Wani, A., Muthuswamy, E., Savithra, G.H.L. et al. Pharm Res (2012) 29: 2407. doi:10.1007/s11095-012-0766-9

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 of MTX in MSN 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 thiol-functionalized 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.

KEY WORDS

drug deliverydrug releasemesoporous silicamitoxantronenanoparticles

ABBREVIATIONS

APTES

3-aminopropyltriethoxysilane

CTAB

N-cetyltrimethylammonium bromide

DSC

differential scanning calorimetry

MPTMS

3-mercaptopropyltrimethoxysilane

MSN

mesoporous silica nanoparticles

MTX

mitoxantrone

PBS

phosphate buffered saline

RPMI

Roswell Park Memorial Institute medium

TEOS

tetraethylorthosilicate

TGA

thermogravimetric analysis

XRD

X-ray diffraction.

Supplementary material

11095_2012_766_MOESM1_ESM.docx (100 kb)
Figure S1Particle size distribution of SH-MSN (top), NH2-MSN (bottom left) and mixed SH/NH2-MSN (bottom right). (DOCX 99 kb)
11095_2012_766_MOESM2_ESM.docx (102 kb)
Figure S2Adsorption-Desorption isotherm of (A) SH-MSN (B) mixed SH/NH2-MSN and (C) NH2-MSN for BET surface area measurement. (DOCX 101 kb)
11095_2012_766_MOESM3_ESM.docx (21 kb)
Table S3Zeta Potential of unloaded and MTX-loaded SH-MSN, SH/NH2-MSN and NH2-MSN at pH 4.5. Results are represented in mean and standard deviation (n=10). (DOCX 20 kb)
11095_2012_766_MOESM4_ESM.docx (1.9 mb)
Figure S4Confirmation of presence of PBS after freeze drying (from top to bottom) SH-MSN stirred in PBS, Freeze dried PBS, MTX/SH-MSN, SH-MSN. (DOCX 1924 kb)

Copyright information

© Springer Science+Business Media, LLC 2012