Leveraging Colloidal Aggregation for Drug-Rich Nanoparticle Formulations

Molecular Pharmaceutics
Ahil N GaneshMolly S Shoichet

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, 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.

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Citations

Sep 27, 2018·Nano Today·Ahil N GaneshMolly S Shoichet
Jan 29, 2021·ChemMedChem·Marta GozziEvamarie Hey-Hawkins
Mar 25, 2021·Journal of Medicinal Chemistry·Parnian LakBrian K Shoichet
Mar 7, 2019·ACS Chemical Biology·Ahil N GaneshMolly S Shoichet
Aug 20, 2019·Journal of Medicinal Chemistry·Yann AyotteSteven R LaPlante
Jun 28, 2019·ACS Chemical Biology·Eric N DondersMolly S Shoichet

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