The evolution of commercial drug delivery technologies

Drug delivery technologies have enabled the development of many pharmaceutical products that improve patient health by enhancing the delivery of a therapeutic to its target site, minimizing off-target accumulation and facilitating patient compliance. As therapeutic modalities expanded beyond small molecules to include nucleic acids, peptides, proteins and antibodies, drug delivery technologies were adapted to address the challenges that emerged.

Delivery strategies have greatly helped convert promising therapeutics into successful therapies. As the therapeutic landscape evolved, delivery strategies and technologies quickly adapted to reflect changing drug delivery needs. A few decades ago, small-molecule drugs were the primary class of therapeutic. Because the delivery of small molecules is largely dictated by their physicochemical properties, which heavily influence the bioavailabilities of the drugs, delivery efforts first focused on improving the solubility of the drugs, controlling their release, broadening their activity and adjusting their pharmacokinetics (PKs). Over time, new generations of therapeutics, including proteins and peptides, monoclonal antibodies (mAbs), nucleic acids and live cells, have provided new therapeutic functions. The new functions brought about additional challenges, notably in stability (for proteins and peptides, in particular), intracellular delivery requirements (especially for nucleic acids) and viability and expansion (for live cells). Drug delivery strategies had to evolve to address these challenges.

In this Review Article, we evaluate how delivery challenges associated with the five classes of therapeutic—small molecules, nucleic acids, peptides, proteins and cells—led to the development of drug delivery approaches and of commercial products. By carrying out this analysis, we identify three core paradigms that have been used to overcome drug delivery challenges for each class of therapeutic: modification of the drug itself; alteration of the environment around the drug; and creation of an interface (that is, a drug delivery system) that facilitates delivery by controlling the interactions between the drug and its microenvironment. For each paradigm, we outline how it can be used to push the boundaries of drug delivery and to address emerging challenges in the delivery of therapeutic live cells. We also discuss how the evolution of drug delivery technologies has been catalysed by each new class of therapeutic.

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Article information: Vargason, A.M., Anselmo, A.C. & Mitragotri, S. The evolution of commercial drug delivery technologies. Nat Biomed Eng (2021). https://doi.org/10.1038/s41551-021-00698-w