Micro and nanotechnologies: The little formulations that could

Abstract

The first publication of micro- and nanotechnology in medicine was in 1798 with the use of the Cowpox virus by Edward Jenner as an attenuated vaccine against Smallpox. Since then, there has been an explosion of micro- and nanotechnologies for medical applications. The breadth of these micro- and nanotechnologies is discussed in this piece, presenting the date of their first report and their latest progression (e.g., clinical trials, FDA approval). This includes successes such as the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines from Pfizer, Moderna, and Janssen (Johnson & Johnson) as well as the most popular nanoparticle therapy, liposomal Doxil. However, the enormity of the success of these platforms has not been without challenges. For example, we discuss why the production of Doxil was halted for several years, and the bankruptcy of BIND therapeutics, which relied on a nanoparticle drug carrier. Overall, the field of micro- and nanotechnology has advanced beyond these challenges and continues advancing new and novel platforms that have transformed therapies, vaccines, and imaging. In this review, a wide range of biomedical micro- and nanotechnology is discussed to serve as a primer to the field and provide an accessible summary of clinically relevant micro- and nanotechnology platforms.

Keywords: PEG; imaging agents; inorganic; lipid nanoparticles; nanoparticles; vaccines.

FIGURE 1

Scale of biological world. DNA, deoxyribonucleic acid; nm, nanometer

FIGURE 2

Timeline of first reports of micro and nanotechnology used for therapeutic, vaccine, and imaging applications. CAR T cells, chimeric antigen receptor T cells; NP, nanoparticle; PEG, polyethylene glycol; PEGylation/PEGylated, PEG covalently bound; PRINT, particle replication in nonwetting templates

FIGURE 3

Controlled release defined and illustrated with release of drug from polymeric particles

FIGURE 4

Graphic depicting administration route which compares systemic administration versus triggered release or local treatment. Triggered release or local treatment can concentrate a drug at one region or area of the body to mitigate potential off‐target toxicities.

FIGURE 5

Graphic highlighting the properties that PEGylation can impart on micro‐ and nanotechnology‐based formulations.,

FIGURE 6

Graphic contrasting passive and active targeting with two examples. Passive targeting is exemplified by using size to exclude uptake in most cells, for preferential uptake in phagocytic cells. Active targeting is illustrated by using an antibody fragment against a receptor (EGFR) that is upregulated on cancer cells.,

FIGURE 7

Illustration of passive targeting phenomena, the enhanced permeability and retention (EPR) effect. In intact capillaries, the NPs must transport between or through endothelial cells to traffic out of the vessel. In capillaries feeding inflamed and solid cancers, pores as large as 200 nm can form and allow NPs and other nano‐sized material in the blood to enter the surrounding tissue more easily. Over time, the lack of lymphatic drainage in solid tumors can result in buildup of material like cell waste, which results in a high intratumoral pressure. If the intratumoral pressure is greater than the pressure inside the capillary, then EPR no longer occurs.

FIGURE 8

PEG can activate B cells through (a–c) the alternative pathway of B cell activation, wherein surface B cell receptors are clustered, either in response to anti‐PEG IgM binding or the close proximity of multiple repeating PEG chain units. A second way PEG can activate B cells is via (d) complement fixation (particularly c3d protein). Although this type of activation has been shown in other mammals, it has not been illustrated in humans directly., , Figure not to scale