ABSTRACT
In order to exert a therapeutic effect, a drug should have high affinity and
selectivity for its intended biological target (for example, a protein or a
protein complex in or on a particular cells type) and also reach a sufficient
concentration at that site [1]. In general, to match this goal, the drug has to be
released from the delivery system, transported from the site of application to
the site of action, biotransformed and finally eliminated (metabolism) from
the body [2]. Thus, the whole process can be divided into the pharmaceutical
phase (where drug liberation takes place) and the pharmacokinetic phase
describing the course of the drug in the body and its metabolism. Undoubt-
edly, both the first and the second phases are strongly dependent on mass
transport and that is why it plays a central role in determining delivery system
reliability and effectiveness. Indeed, in the pharmaceutical phase, regardless
the delivery system considered (in passive preprogrammed systems, release rate is predetermined and it is irresponsive to external biological stimuli; in
active preprogrammed systems, release rate can be controlled by a source external to the body; in active self-programmed systems, release rate is driven by external physiological stimuli [3]) release kinetics depends on mass
transport characteristics both in the case of diffusion and convection con-
trolled processes. While in passive preprogrammed systems, release kinetics
is usually controlled by drug or water diffusion in the polymeric network, in
self-programmed systems, both diffusion and convection can play an import-
ant role. For example, Siegel [4], approaching insulin delivery by means of an
implantable mechanochemical pump, makes use of both convection and
diffusion. Indeed, this device is made up by a housing containing three
chambers (Figure 4.1). While chamber I contains an insulin solution, chamber
II contains aqueous fluid, and chamber III is made up by a glucose-sensitive
swellable hydrogel separated by the external environment by means of a
rigid membrane permeable only to small molecules and impermeable to
large molecules such as plasma proteins. As soon as blood glucose concentra-
tion increases, glucose permeates through the rigid membrane causing
further hydrogel expansion (diffusive mass transport). This, in turn, provokes
the forward movement of the diaphragm and of the partition separating,
respectively, chamber III from chamber II and chamber II from chamber I.
Accordingly, chamber I volume reduces and insulin solution is sent in the
