title: Stable Colloidal Drug Aggregates Catch and Release Active Enzymes.
abstract: Small molecule aggregates are considered nuisance compounds in drug discovery, but their unusual properties as colloids could be exploited to form stable vehicles to preserve protein activity. We investigated the coaggregation of seven molecules chosen because they had been previously intensely studied as colloidal aggregators, coformulating them with bis-azo dyes. The coformulation reduced colloid sizes to <100 nm and improved uniformity of the particle size distribution. The new colloid formulations are more stable than previous aggregator particles. Specifically, coaggregation of Congo Red with sorafenib, tetraiodophenolphthalein (TIPT), or vemurafenib produced particles that are stable in solutions of high ionic strength and high protein concentrations. Like traditional, single compound colloidal aggregates, the stabilized colloids adsorbed and inhibited enzymes like β-lactamase, malate dehydrogenase, and trypsin. Unlike traditional aggregates, the coformulated colloid-protein particles could be centrifuged and resuspended multiple times, and from resuspended particles, active trypsin could be released up to 72 h after adsorption. Unexpectedly, the stable colloidal formulations can sequester, stabilize, and isolate enzymes by spin-down, resuspension, and release.
authors.affiliation: 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.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: McLaughlin
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco , 1700 Fourth Street, San Francisco, California 94158-2550, United States.
authors.forename: Da
authors.initials: D
authors.lastname: Duan
authors.affiliation: 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.
authors.forename: Ahil N
authors.initials: AN
authors.lastname: Ganesh
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco , 1700 Fourth Street, San Francisco, California 94158-2550, United States.
authors.forename: Hayarpi
authors.initials: H
authors.lastname: Torosyan
authors.affiliation: Department of Pharmaceutical Chemistry, University of California, San Francisco , 1700 Fourth Street, San Francisco, California 94158-2550, United States.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Shoichet
authors.affiliation: 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.
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
mesh_terms: D003102:Colloids / Q000008:administration & dosage*; D010316:Particle Size; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D003102:Colloids; D001618:beta-Lactamases