Synthesis and characterization of thermo-sensitive nanoparticles for drug delivery applications

被引：70

作者：

Biomedical Engineering Program, University of Texas Southwestern Medical Center, Dallas, TX, United States ^{[1
]}

不详 ^{[2
]}

不详 ^{[3
]}

不详 ^{[4
]}

机构：

[1] Biomedical Engineering Program, University of Texas Southwestern Medical Center, Dallas, TX

[2] Department of Bioengineering, University of Texas, Arlington

[3] Department of Chemistry, University of Texas, Arlington

[4] Biomedical Engineering Program, University of Texas, Arlington

来源：

J. Biomed. Nanotechnol. | 2008年 / 4卷 / 482-490期

关键词：

Drug delivery; Nanoparticles; Targeting; Temperature-sensitive polymers;

D O I：

10.1166/jbn.2008.014

中图分类号：

学科分类号：

摘要：

The aim of this research project was to develop new temperature sensitive nanoparticles that have a lower critical solution temperature (LCST) that is above body temperature and can be incorporated with various molecules at the surface. The poly(N-isopropylacrylamide-co-acrylamide-coallylamine) (NIPA-AAm-AH) nanoparticles were synthesized through a free radical polymerization method. NIPA was polymerized with AAm and AH to increase the LCST and to provide amine groups for functionalization, respectively. Using transmission electron microscopy (TEM) and laser scattering technology, the sizes of these nanoparticles were found to be inversely proportional to the surfactant concentrations. In addition, the LCST of the 100-nm NIPA-AAm-AH nanoparticles was approximately 40 °C measured by a spectrophotometer. The chemical composition of the NIPA-AAm-AH nanoparticles determined with Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) also confirmed the presence of functional groups of each monomer. Moreover the nanoparticles were successfully conjugated to bovine anti-rabbit lgG-Texas Red as a model for future bioconjugation. Furthermore, nanoparticles did not show significant cytotoxicity activity against human fibroblast cells. Finally, doxorubicin (DOX) was used in order to investigate the drug release profiles of the NIPA-AAm-AH nanoparticles at different temperatures. The results indicated that DOX was released more at 41 °C compared to that of 37 °C and 4 °C, which is evidence for temperature sensitivity of the nanoparticles. Future work will investigate the pharmacological and targeted capabilities of the synthesized nanoparticles conjugated to antibodies for possible application in controlled and targeted drug delivery. Copyright © 2008 American Scientific Publishers. All rights reserved.

引用

页码：482 / 490

页数：8

共 21 条

[1]

Chen H., Gu Y., Hub Y., Qian Z., Characterization of pH- and temperature-sensitive hydrogel nanoparticles for controlled drug release, PDA J. Pharm. Sci. Technol, 61, (2007)

[2]

Ozdemir N., Tuncel A., Kang M., Denkbas E.B., Preparation and characterization of thermosensitive submicron particles for gene delivery, J. Nanosci. Nanotechnol, 6, (2006)

[3]

Yan H., Tsujii K., Potential application of poly(N-isopropylacrylamide) gel containing polymeric micelles to drug delivery systems, Colloids Surf. B. Biointerfaces, 46, (2005)

[4]

Shimizu T., Yamato M., Isoi Y., Akutsu T., Setomaru T., Abe K., Kikuchi A., Umezu M., Okano T., Fabrication of pulsatile cardiac tissue grafts using a novel 3-dimensional cell sheet manipulation technique and temperature-responsive cell culture surfaces, Circ. Res, 90, (2002)

[5]

Vernon B., Gutowska A., Kim S.W., Bae Y.H., Thermally reversible polymer gels for biohybrid artificial pancreas, Macromol. Symp, 109, (1996)

[6]

Sarkhosh K., Tredget E.E., Uludag H., Kilani R.T., Karami A., Li Y., Iwashina T., Ghahary A.J., Temperature-sensitive polymer-conjugated IFN-γ induces the expression of IDO mRNA and activity by fibroblasts populated in collagen gel (FPCG), Cell. Physiol, 201, (2004)

[7]

Needham D., Dewhirst M.W., The development and testing of a new temperature-sensitive drug delivery system for the treatment of solid tumors, Adv. Drug Deliv. Rev, 53, (2001)

[8]

Ruel-Gariaepy E., Shive M., Bichara A., Berrada M., LeGarrec D., Chenite A., Leroux J.C., A thermosensitive chitosan-based hydrogel for the local delivery of paclitaxel, Eur. J. Pharm. Biopharm, 57, (2004)

[9]

Pochan D.J., Schneider J.P., Kretsinger J., Ozbas B., Rajagopal K., Haines L., Thermally reversible hydrogels via intramolecular folding and consequent self-assembly of a de novo designed peptide, J. Am. Chem. Soc, 125, (2003)

[10]

Tate M.C., Shear D.A., Hoffman S.W., Stein D.G., Laplaca M.C., Biocompatibility of methylcellulose-based constructs designed for intracerebral gelation following experimental traumatic brain injury, Biomaterials, 22, (2001)

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