390602 Polyethylene Glycol (PEG) Stabilized Cisplatin-Tethered Gold Nanoparticle Platform for Drug Delivery: Understanding Engineered Surface and Drug Performance

Sunday, November 16, 2014: 4:20 PM
211 (Hilton Atlanta)
Jiaojie Tan1, Tae Joon Cho2, De-Hao Tsai3, Jingyu Liu2, Vincent A. Hackley4 and Michael R Zachariah5, (1)University of Maryland, College park, MD, (2)NIST, Gaithersburg, MD, (3)National Tsing Hua University, Hsinchu City, Taiwan, (4)Materials Science & Engineering Laboratory, NIST, Gaithersbrug, MD, (5)Departments of Chemical Engineering and Chemistry, University of Maryland, College Park, MD

Design of nanoparticle drug delivery platforms through surface functionalization to achieve desirable therapeutic performance is a major challenge. In this presentation, we report on polyethylene glycol (PEG) stabilized cisplatin-tethered gold nanoparticles (AuNPs) for antitumor drug delivery. Assessment of surface modification and its influence on drug loading and colloidal stability was conducted.  To fabricate surface functionalized PtII-AuNPs, a dendrimer-like ligand, a dendron, was used to load cisplatin onto the AuNP surface through metal-carboxylate coordination. The branched structure of the dendron enables high loading capacity with respect to PtII pharmacophores, while providing steric resistance to aggregation. We showed that steric hindrance provided satisfactory colloidal stability at relatively low PtII loading, but is insufficient at high PtII loading due to increased charge neutralization.

In this context, further surface modification by PEGylation of AuNP-dendron conjugates was conducted. For the formulation, thiolated PEG at different concentrations relative to the dendron and of different molar masses was examined. On a quantitative basis, the extent of PEGylation was characterized and its influence on cisplatin drug payload was examined using an electrospray differential mobility analyzer (ES-DMA) coupled to a quadrapole inductively coupled plasma mass spectrometer (ICP-MS). We demonstrated that PEGylated AuNP conjugates (AuNP-dendron-SH-PEG-PtII) exhibited enhanced dispersion stability compared with native AuNP-dendron-PtII due to additional steric stabilization arising from the attached PEG.  Overall, the loading capacity for PtII was improved, indicating insignificant displacement of the complexing dendron by the PEG ligand on the surface. This was further confirmed by attenuated total reflectance Fourier transform infrared spectral analysis of deposited films. The conjugation of cisplatin on the PEG-stabilized AuNP vector was demonstrated to be stable under biologically relevant conditions (e.g., high ionic strength). Finally, the pH dependent drug release performance was evaluated.

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See more of this Session: Nanostructured Particles for Bio, Food and Pharma
See more of this Group/Topical: Particle Technology Forum