From micro to nano: evolution and impact of drug delivery in treating disease
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INSPIRATIONAL NOTE
From micro to nano: evolution and impact of drug delivery in treating disease Jeff Hrkach 1 & Robert Langer 2,3
# Controlled Release Society 2020
Abstract Over the past 50 years, drug delivery breakthroughs have enabled the approval of several important medicines. Often, this path starts with innovation from academic collaborations amongst biologists, chemists, and engineers, followed by the formation of a start-up company driving clinical translation and approval. An early wave featured injectable (i.e., intramuscular, subcutaneous) biodegradable polymeric microspheres to control drug release profiles for peptides and small molecules (e.g., Lupron Depot®, Risperdal Consta®). With these early successes for microspheres, research shifted to exploring systemic delivery by intravenous injection, which required smaller particle sizes and modified surface properties (e.g., PEGylation) to enable long circulation times. These new innovations resulted in the nanoparticle medicines Doxil® and Abraxane®, designed to improve the therapeutic index of cytotoxic cancer agents by decreasing systemic exposure and delivering more drug to tumors. Very recently, the first siRNA lipid nanoparticle medicine, Patisiran (Onpattro®), was approved for treating hereditary transthyretin-mediated amyloidosis. In this inspirational note, we will highlight the technological evolution of drug delivery from micro- to nano-, citing some of the approved medicines demonstrating the significant impact of the drug delivery field in treating many diseases. Keywords Drug delivery . Microsphere . Nanoparticle . Controlled release . siRNA . mRNA
Background The complexity of human disease biology presents many challenges for the development and approval of new medicines. It is very difficult to design drug molecules with activity specific for a single biological pathway unique to diseased cells; with a pharmacokinetic profile with optimal onset and/or duration of action; or without detrimental side effects due to systemic exposure. In addition, patient compliance in taking medicines can offer significant challenges. Drug delivery systems offer the possibility to design and engineer levels of control beyond
* Jeff Hrkach [email protected] 1
Frequency Therapeutics, 19 Presidential Way, Woburn, MA 01801, USA
2
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA 02139, USA
3
Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
the drug molecule’s inherent properties to overcome the aforementioned challenges.
Pioneering drug delivery with biodegradable PLGA microparticles Until the mid-1970s, many thought that controlled release drug delivery was limited to small molecules. Pioneering research by Folkman and Langer led the way for sustained release of proteins and other macromolecules [ 1]. Biodegradable polymers such as the poly(lactide-coglycolide) (PLG) family degrade by hydrolysis in
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