title: Therapeutic surfactant-stripped frozen micelles.
abstract: Injectable hydrophobic drugs are typically dissolved in surfactants and non-aqueous solvents which can induce negative side-effects. Alternatives like 'top-down' fine milling of excipient-free injectable drug suspensions are not yet clinically viable and 'bottom-up' self-assembled delivery systems usually substitute one solubilizing excipient for another, bringing new issues to consider. Here, we show that Pluronic (Poloxamer) block copolymers are amenable to low-temperature processing to strip away all free and loosely bound surfactant, leaving behind concentrated, kinetically frozen drug micelles containing minimal solubilizing excipient. This approach was validated for phylloquinone, cyclosporine, testosterone undecanoate, cabazitaxel and seven other bioactive molecules, achieving sizes between 45 and 160 nm and drug to solubilizer molar ratios 2-3 orders of magnitude higher than current formulations. Hypertonic saline or co-loaded cargo was found to prevent aggregation in some cases. Use of surfactant-stripped micelles avoided potential risks associated with other injectable formulations. Mechanistic insights are elucidated and therapeutic dose responses are demonstrated.
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.|Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
authors.forename: Yumiao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
authors.forename: Wentao
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
authors.forename: Jumin
authors.initials: J
authors.lastname: Geng
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
authors.forename: Upendra
authors.initials: U
authors.lastname: Chitgupi
authors.affiliation: Department of Chemistry; University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
authors.forename: Hande
authors.initials: H
authors.lastname: Unsal
authors.affiliation: Department of Chemistry; University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Federizon
authors.affiliation: Department of Chemistry; University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
authors.forename: Javid
authors.initials: J
authors.lastname: Rzayev
authors.affiliation: Department of Chemistry; University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Sukumaran
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
authors.forename: Paschalis
authors.initials: P
authors.lastname: Alexandridis
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.|Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, New York 14260, USA.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Lovell
mesh_terms: D004337:Drug Carriers; D005615:Freezing; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D020442:Poloxamer; D013501:Surface-Active Agents
chemical_list: D004337:Drug Carriers; D008823:Micelles; D013501:Surface-Active Agents; D020442:Poloxamer