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Characterizing Environmentally Responsive Polymer-Based Nanoparticles for Drug Delivery

Fox, Tara L
http://rave.ohiolink.edu/etdc/view?acc_num=case1459341789

Abstract Details

2016, Doctor of Philosophy, Case Western Reserve University, Pharmacology.
Polymeric nanoparticles have shown promise in addressing issues surrounding poor solubility of hydrophobic drugs, helping to facilitate dispersion of drug molecules throughout the body. This work describes the characterization of a novel class of polymeric nanoparticles, mixed brush-grafted nanoparticles, for drug delivery. Mixed poly(acrylic acid) (PAA)/polystyrene (PS) brush-grafted silica nanoparticles are directly visualized by cryoelectron microscopy (cryoEM) in organic and aqueous solvents. These amphiphilic nanoparticles are predicted to be environmentally responsive and adopt distinct morphologies in different solvent environments. The morphology of mixed PAA/PS brush-grafted particles has been studied previously in a dried state but never in a solvent environment. CryoEM allows imaging the sample in a frozen solvated state at the resolution of a transmission electron microscope. Cryoelectron tomograms (cryoET) were generated for PAA/PS nanoparticles in both N,N-dimethylformamide (DMF, a nonselective good solvent) and water (a selective solvent for PAA). Different morphologies were observed in these two solvents. In DMF, mixed PAA/PS brushes are observed to form laterally separated bundles, whereas in water PAA chains form a near-complete shell, shielding collapsed PS chains that form surface-tethered micelles against the silica core. These cryoET results confirm the predicted environmentally responsive nature of PAA/PS mixed brush-grafted nanoparticles. These structural findings suggested a possible loading and release mechanism for hydrophobic compounds, which was tested in loading and release experiments with two hydrophobic fluorescent dyes, Nile Red and Nile Blue. Of these two compounds, Nile Blue is retained the best and released in a slow release phase with a half-life of ~13 days. The hydrophobic dye-loading capability of mixed brush-grafted nanoparticles with varying percentages of PS was also compared. The results indicate that a high percentage of hydrophobic PS is required for retention of Nile Blue. Finally, Nile Blue-loaded mixed brush-grafted nanoparticles were shown to mediate delivery of dye to HeLa cells. Altogether, these experiments represent the initial characterization of mixed brush-grafted nanoparticles for drug delivery applications.
Phoebe L. Stewart, Ph.D. (Advisor)
Jason Mears, Ph.D. (Committee Chair)
Johannes von Lintig, Ph.D. (Committee Member)
Nicole F. Steinmetz, Ph.D. (Committee Member)
Derek Taylor, Ph.D. (Committee Member)
185 p.
Pharmacology

Recommended Citations

Citations

  • Fox, T. L. (2016). Characterizing Environmentally Responsive Polymer-Based Nanoparticles for Drug Delivery [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1459341789

    APA Style (7th edition)

  • Fox, Tara. Characterizing Environmentally Responsive Polymer-Based Nanoparticles for Drug Delivery. 2016. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1459341789.

    MLA Style (8th edition)

  • Fox, Tara. "Characterizing Environmentally Responsive Polymer-Based Nanoparticles for Drug Delivery." Doctoral dissertation, Case Western Reserve University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1459341789

    Chicago Manual of Style (17th edition)

case1459341789
222
© 2016, some rights reserved.Creative Commons License Characterizing Environmentally Responsive Polymer-Based Nanoparticles for Drug Delivery by Tara L Fox is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.