Perfluorocarbon nanoemulsions in drug delivery: design, development, and manufacturing

Perfluorocarbons (PFCs) are formulated into kinetically stable nanoemulsions (NEs) having a droplet diameter less than 500 nm for biomedical applications. PFC NEs are developed for various applications, such as ¹⁹F magnetic resonance imaging tracers, ultrasound contrast agents, and oxygen carriers. They are an attractive platform for theranostic development, as PFC NEs can be designed to deliver a multitude of therapeutics, from small molecules to biologics. Although many reviews have been published on designing PFC NEs as imaging agents or oxygen carriers, there is no comprehensive review of the formulation strategies and manufacturing of PFC NEs as drug delivery platform. From a "formulator's perspective," the presented review addresses this gap as it describes the selection of formulation components such as the PFCs, surfactants, and hydrocarbon oils and provides an overview of manufacturing techniques. In this review, we will also identify potential shortcomings in the published literature on the manufacturing of PFC NEs. We will discuss the need for the implementing Quality by Design (QbD) approach in the manufacturing of PFC NEs to achieve scalability and necessary quality control for supporting both preclinical and clinical applications. Finally, we will review different surface-conjugation strategies for developing targeted PFC NEs. Overall, this article aims to increase understanding of PFC NEs designed for delivering drugs, including both small molecules and biologics.