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Mol Pharm. 2017 Jun 5;14(6):1852-1860. doi: 10.1021/acs.molpharmaceut.6b01015. Epub 2017 May 19.

Leveraging Colloidal Aggregation for Drug-Rich Nanoparticle Formulations.

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Department of Chemical Engineering and Applied Chemistry, University of Toronto , 200 College Street, Toronto, Ontario, Canada M5S 3E5.
Institute of Biomaterials and Biomedical Engineering, University of Toronto , 164 College Street, Toronto, Ontario, Canada M5S 3G9.
Department of Chemistry and Biochemistry, University of Colorado , Boulder, Colorado 80309-0215, United States.
Department of Pharmaceutical Chemistry & Quantitative Biology Institute, University of California, San Francisco , 1700 Fourth Street, Mail Box 2550, San Francisco, California 94143, United States.
Department of Chemistry, University of Toronto , 80 St. George Street, Toronto, Ontario, Canada M5S 3H6.


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, which is a DNA cross-linking anthracycline), and two polymers, polysorbate 80 (UP80) and poly(d,l-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol) (PLAC-PEG; a custom-synthesized, self-assembling amphiphilic polymer). In both systems, drug-loaded nanoparticles had diameters < 200 nm and were stable for up to two days in buffered saline solution and for up to 24 h in serum-containing media at 37 °C. While colloidal drug aggregates alone are typically unstable in saline and serum-containing media, we attribute the colloid stability observed herein to the polymeric excipients and consequent decreased protein adsorption. We expect this strategy of polymer-stabilized colloidal drug aggregates to be broadly applicable in delivery formulations.


colloids; drug delivery; polymers; self-assembly; solvent exchange

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