Controlled Drug Delivery: Historical perspective for the next generation

Abstract

The modern day drug delivery technology is only 60years old. During this period numerous drug delivery systems have been developed. The first generation (1950-1980) has been very productive in developing many oral and transdermal controlled release formulations for clinical applications. On the other hand, the second generation (1980-2010) has not been as successful in generating clinical products. This is in large part due to the nature of the problems to overcome. The first generation of drug delivery technologies dealt with physicochemical problems, while the second struggled with biological barriers. Controlled drug delivery systems can be made with controllable physicochemical properties, but they cannot overcome the biological barriers. The third generation (from 2010) drug delivery systems need to overcome both physicochemical and biological barriers. The physicochemical problems stem from poor water solubility of drugs, large molecular weight of peptide and protein drugs, and difficulty of controlling drug release kinetics. The biological barriers to overcome include distribution of drug delivery systems by the body rather than by formulation properties, limiting delivery to a specific target in the body. In addition, the body's reaction to formulations limits their functions in vivo. The prosperous future of drug delivery systems depends on whether new delivery systems can overcome limits set by human physiology, and the development process can be accelerated with new ways of thinking.

Keywords: Biological barriers; Drug delivery; History; Physicochemical barriers.

Figure 1

Examples of pharmacokinetic profiles of Nutropin Depot (A) and Trelstar (B) (obtained from the packaging inserts). The red arrow indicates the PK region resulting from the initial burst release of a drug, and the green arrow indicates the PK region of the therapeutically effective drug concentrations.

Figure 2

The number of articles on nanoparticle drug delivery systems published from 1995 to 2014. In SciFinder, the research topic of “drug delivery nanoparticle” was used for the initial search to find more than 30,000 references containing the concept. The search was further refined using the research topic of “target”.