Current Trends and Challenges in the Clinical Translation of Nanoparticulate Nanomedicines: Pathways for Translational Development and Commercialization

Abstract

The use of nanotechnology in medicine has the potential to have a major impact on human health for the prevention, diagnosis, and treatment of diseases. One particular aspect of the nanomedicine field which has received a great deal of attention is the design and development of nanoparticulate nanomedicines (NNMs) for drug delivery (i.e., drug-containing nanoparticles). NNMs are intended to deliver drugs via various mechanisms: solubilization, passive targeting, active targeting, and triggered release. The NNM approach aims to increase therapeutic efficacy, decrease the therapeutically effective dose, and/or reduce the risk of systemic side effects. In order to move a NNM from the bench to the bedside, several experimental challenges need to be addressed. This review will discuss the current trends and challenges in the clinical translation of NNMs as well as the potential pathways for translational development and commercialization. Key issues related to the clinical development of NNMs will be covered, including biological challenges, large-scale manufacturing, biocompatibility and safety, intellectual property (IP), government regulations, and overall cost-effectiveness in comparison to current therapies. These factors can impose significant hurdles limiting the appearance of NNMs on the market, irrelevant of whether they are therapeutically beneficial or not.

Keywords: biological; challenges; clinical translation; commercialization; drug delivery systems; nanomedicine; nanoparticles; regulations.

Figure 1

Schematic representation of different strategic designs for nanoparticulate nanomedicines (NNMs). (A) Conventional NNM—These NNMs can be modified with charged lipids/polymers, thermosensitive lipids/polymers and/or components for triggered release (e.g., pH-sensitive coating). (B) PEGylated NNM—Nanoparticle characteristics and behavior in vivo can be modified by the addition of a hydrophilic polymer coating, polyethylene glycol (PEG), to the NNM surface to confer steric stabilization. (C) Ligand-targeted NNM—Nanoparticles can be used for active targeting by attaching ligands (e.g., antibodies, peptides and carbohydrates) to its surface or to the terminal end of the attached PEG chains. (D) Theranostic NNM – These NNM systems consist of an imaging component and a therapeutic component, and may include a targeting element.