Rational design and engineering of delivery systems for therapeutics: biomedical exercises in colloid and surface science

Engineering delivery systems of therapeutic agents has grown into an independent field, transcending the scope of traditional disciplines and capturing the interest of both academic and industrial research. At the same time, the acceleration in the discovery of new therapeutic moieties (chemical, biological, genetic and radiological) has led to an increasing demand for delivery systems capable of protecting, transporting, and selectively depositing those therapeutic agents to desired sites. The vast majority of delivery systems physically reside in the colloidal domain, while their surface properties and interfacial interactions with the biological milieu critically determine the pharmacological profiles of the delivered therapeutic agents. Interestingly though, the colloidal and surface properties of delivery systems are commonly overlooked in view of the predominant attention placed on the therapeutic effectiveness achieved. Moreover, the development and evaluation of novel delivery systems towards clinical use is often progressed by serendipity rather than a systematic design process, often leading to failure. The present article will attempt to illustrate the colloid and interfacial perspective of a delivery event, as well as exemplify the vast opportunities offered by treating, analysing and manipulating delivery systems as colloidal systems. Exploring and defining the colloid and surface nature of the interactions taking place between the biological moieties in the body and an administered delivery vehicle will allow for the rational engineering of effective delivery systems. A design scheme is also proposed on the way in which the engineering of advanced delivery systems should be practiced towards their transformation from laboratory inventions to clinically viable therapeutics. Lastly, three case studies are presented, demonstrating how rational manipulation of the colloidal and surface properties of delivery systems can lead to newly engineered systems relevant to chemotherapy, gene therapy and radiotherapy.