Advanced Materials and Processing for Drug Delivery: The Past and the Future Ying Zhang, Hon Fai Chan, and Kam W. Leong Drug delivery systems (DDS) are crucial for medicine and healthcare, with materials innovation and nanotechnology driving their advancement. These systems enable biodegradable, biocompatible, environment-responsive, and targeted delivery. Nanotechnology allows control over size, shape, and functionality of particulate DDS. This review discusses materials innovation and processing in DDS, highlighting their impact on past and future drug delivery. Keywords: Commercialized drug delivery system; nanoparticle; polyplex; natural polymers; polymer-drug conjugate; combinatorial chemistry; microfluidics; particle replication in non-wetting template; step-flash imprint lithography Drug delivery improves bioavailability, maintains therapeutic concentrations, and reduces side effects. Since 1990, over 10 DDS have been commercialized for various diseases. Developing a new DDS is less costly and time-consuming than a new drug. The market for advanced DDS has grown significantly. Advances in genomics and systems biology have identified new molecular targets, with future therapeutics being nucleic acid and peptidic in nature. Drug delivery is essential for their intracellular action. Innovations in materials chemistry have led to biodegradable, biocompatible, targeting, and stimulus-responsive carriers. Nanotechnology has enabled the development of more effective particulate DDS through nanofabrication. PLGA is a widely used biodegradable polymer for DDS due to its biodegradability, biocompatibility, and ease of processing. It can deliver various bioactive agents, including drugs, peptides, proteins, and DNA. PLGA NPs can be modified for targeting, PEGylation, and environment-responsive elements. Block copolymers, such as PEG-PEI and PEG-polylysine, have been used for drug delivery. They can form micelles, electrostatic complexes, or polymersomes. Challenges in blood stability have been addressed through various approaches, including increasing hydrophobicity, introducing hydrogen bonds, promoting electrostatic interactions, and crosslinking the micelle core. Polymer-drug conjugates have been developed to enhance pharmacokinetics. HPMA-doxorubicin and PGA-paclitaxel conjugates have shown promising results. However, some systems have shown unexpected release behavior and side effects. Natural polymers, such as polysaccharides, proteins, and DNA, are biocompatible and biodegradable. They have been used as drug carriers with significant clinical benefits. Nucleic acid-based structures, such as DNA nanotubes and nanoboxes, have been developed for drug delivery. Protein-based carriers, such as modified GFP, have been used for drug delivery and tracking. Recombinant proteins, such as ELPs and SLPs, have been developed for drug delivery. They are biodegradableAdvanced Materials and Processing for Drug Delivery: The Past and the Future Ying Zhang, Hon Fai Chan, and Kam W. Leong Drug delivery systems (DDS) are crucial for medicine and healthcare, with materials innovation and nanotechnology driving their advancement. These systems enable biodegradable, biocompatible, environment-responsive, and targeted delivery. Nanotechnology allows control over size, shape, and functionality of particulate DDS. This review discusses materials innovation and processing in DDS, highlighting their impact on past and future drug delivery. Keywords: Commercialized drug delivery system; nanoparticle; polyplex; natural polymers; polymer-drug conjugate; combinatorial chemistry; microfluidics; particle replication in non-wetting template; step-flash imprint lithography Drug delivery improves bioavailability, maintains therapeutic concentrations, and reduces side effects. Since 1990, over 10 DDS have been commercialized for various diseases. Developing a new DDS is less costly and time-consuming than a new drug. The market for advanced DDS has grown significantly. Advances in genomics and systems biology have identified new molecular targets, with future therapeutics being nucleic acid and peptidic in nature. Drug delivery is essential for their intracellular action. Innovations in materials chemistry have led to biodegradable, biocompatible, targeting, and stimulus-responsive carriers. Nanotechnology has enabled the development of more effective particulate DDS through nanofabrication. PLGA is a widely used biodegradable polymer for DDS due to its biodegradability, biocompatibility, and ease of processing. It can deliver various bioactive agents, including drugs, peptides, proteins, and DNA. PLGA NPs can be modified for targeting, PEGylation, and environment-responsive elements. Block copolymers, such as PEG-PEI and PEG-polylysine, have been used for drug delivery. They can form micelles, electrostatic complexes, or polymersomes. Challenges in blood stability have been addressed through various approaches, including increasing hydrophobicity, introducing hydrogen bonds, promoting electrostatic interactions, and crosslinking the micelle core. Polymer-drug conjugates have been developed to enhance pharmacokinetics. HPMA-doxorubicin and PGA-paclitaxel conjugates have shown promising results. However, some systems have shown unexpected release behavior and side effects. Natural polymers, such as polysaccharides, proteins, and DNA, are biocompatible and biodegradable. They have been used as drug carriers with significant clinical benefits. Nucleic acid-based structures, such as DNA nanotubes and nanoboxes, have been developed for drug delivery. Protein-based carriers, such as modified GFP, have been used for drug delivery and tracking. Recombinant proteins, such as ELPs and SLPs, have been developed for drug delivery. They are biodegradable