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Preparation of Aggregation Stable Block Copolymer Nanoparticles for Simultaneous Drug Delivery and Imaging

M.E. Gindy, R.K. Prud’homme
Princeton University, US

Keywords:
nanoparticle, dodecanethiol gold, coumarin, beta-carotene, methoxy poly(ethylene glycol), poly(caprolactone)

Abstract:
We have developed a nanoparticle formation process based on rapid micromixing to produce high supersaturations, which we term Flash NanoPreciptiation.4, 5 This work introduces a novel approach that expands the applications of the Flash NanoPrecipitation process to pre-formed solutes in conjunction with organically dissolved molecules, and permits the formation of nanoparticle formulations with limited recrystallization, and stable size distributions. In this system, an amphiphilic diblock copolymer, methoxy poly(ethylene glycol)-b-poly(-caprolactone), a model hydrophobic drug, -carotene, a preformed imaging agent, dodecanethiol capped gold (1-3 nm), and a fluorescent molecule, 7-amino-4-methyl coumarin, are dissolved or suspended in a water-miscible solvent such as tetrahydrofuran and subsequently impingement mixed against an opposing water stream using the confined impingement jets (CIJ) mixer. The collision of the two incoming jets provides a region of high intensity micromixing where solute supersaturation is rapidly achieved and precipitation of drug, imaging agent and block copolymer occurs without diffusional limitations. The result is the formation of polymer protected nanoparticles containing both the drug compound as well as the imaging agent. This process yields nanoparticles with controlled-size, narrow particle size distributions, high encapsulation efficiencies, and long term stability. Additionally, the amphiphilic polymer-based delivery vehicles detailed in the present work may be used for parenteral, nasal, subcutaneous, intramuscular, aerosol and oral administration.

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