Drug delivery technology has made the development of many drug products possible, by enhancing the delivery of therapeutic drugs to their target areas, minimizing off target accumulation, thereby promoting patient compliance and improving patient health. With the expansion of treatment methods from small molecules to include nucleic acids, peptides, proteins, antibodies, and live cells, drug delivery technologies have also been adjusted to address new challenges
The development of drug delivery technology can be described in different ways, such as the types of treatments and delivery modes. Figure 2 reviews the milestone development history of drug delivery systems through the introduction of new technologies using FDA approved products.
With Spansule ® The emergence of sustained-release capsule technology and modern drug delivery technology began in 1952. Spansule ® The sustained-release capsule technology can release the drug through the initial immediate dose for 12 hours after oral administration, and then gradually release the remaining drug. By the 1980s, oral and transdermal preparations provided a treatment duration of up to 24 hours for small molecule drugs and dominated the field and market of drug delivery.
In 1989, Lupron Depot ® The launch of has opened the door to long-acting injections and implants, and has extended drug release times from a few days to several months, sometimes even several years. This new long-acting injection formulation is closely followed by other systems that deliver various small molecules, peptides, and proteins. All FDA approved polymer based, biodegradable long-acting injection formulations are based on PLGA polymers due to their long-standing safety. Although PLGA formulations have been developed for over 30 years, as shown in Figure 3, there are currently no FDA approved generic drugs for long-acting injection formulations on the market, one of the reasons being that PLGA polymers have not been thoroughly characterized.
The first PEG protein Adagen in 1990 ® The emergence of PEG marked a new era for PEG based drugs, and Figure 4 shows the development history of FDA approved PEG based protein drugs. Over the past 30 years, approximately 20 PEG protein drug formulations have been developed. PEGylation is a process of attaching polyethylene glycol to protein molecules, thereby reducing the uptake and degradation of reticuloendothelial cells, increasing the time for proteins to circulate in the bloodstream, and greatly reducing immunogenicity reactions. Polyethylene glycol also reduces the biological activity of protein drugs by reducing binding to the target site, but the longer the circulation time, the better the therapeutic effect. The significance of polyethylene glycol technology lies not only in increasing the cycle time of modified proteins, but also in Doxil in 1995 ® The approval of polyethylene glycol liposome delivery of doxorubicin has begun, and its application in lipid delivery systems is the beginning of other important formulations. Lipid nanoparticles containing polyethylene glycol functionalized lipids successfully delivered oligonucleotides, such as Onpattro, in 2018 ® SiRNA in polyethylene glycol lipid nanoparticles. Polyethylene glycol functionalized lipid nanoparticles have also been rapidly developed based on mR
