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Leveraging colloidal aggregation for drug-rich nanoparticle formulations Ahil N. Ganesh, Jennifer Logie, Christopher K. McLaughlin, Benjamin L. Barthel, Tad H Koch, Brian K. Shoichet, and Molly S Shoichet Mol. Pharmaceutics, Just Accepted Manuscript • Publication Date (Web): 14 May 2017 Downloaded from http://pubs.acs.org on May 15, 2017
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Molecular Pharmaceutics
Leveraging colloidal aggregation for drug-rich nanoparticle formulations Ahil N. Ganesh1,2,#, Jennifer Logie1,2,#, Christopher K. McLaughlin1,2,#, Benjamin L. Barthel3, Tad H. Koch3, Brian K. Shoichet4, Molly S. Shoichet1,2,5,* 1 Department
of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario, Canada M5S 3E5
2 Institute
of Biomaterials and Biomedical Engineering, University of Toronto, 164 College Street, Toronto, Ontario, Canada M5S 3G9
3
Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309-0215, United States
4 Department
of Pharmaceutical Chemistry & Quantitative Biology Institute, University of California,
San Francisco, 1700 Fourth Street, Mail Box 2550, San Francisco, California 94143, United States 5 Department
of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, Canada M5S 3H6
# These
authors contributed equally
*to whom correspondence should be addressed:
[email protected] 1 ACS Paragon Plus Environment
Molecular Pharmaceutics
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ABSTRACT
While limited drug loading continues to be problematic for chemotherapeutics formulated in nanoparticles, we found that we could take advantage of colloidal drug aggregation to achieve high loading when combined with polymeric excipients. We demonstrate this approach with two drugs fulvestrant and pentyl-PABC Doxazolidine (PPD) – a prodrug of doxazolidine, a DNA crosslinking anthracycline; and two polymers, respectively - polysorbate 80 (UP80) and poly(D,L-lactide-co-2methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol) (PLAC-PEG) – a customsynthesized, self-assembling, amphiphilic polymer. In both systems, drug-loaded nanoparticles had diameters
