Polymeric and lipid-based systems for controlled drug release: an engineering point of view

During the last century, scientists’ attention has been focused on the discovery of new potent drug formulations, with new biological activity. Nowadays this is still an important research area, however, during the last few decades a major focus has been devoted to the development of systems able to deliver these drugs in the desired way (Langer and Peppas, 1981). The most common way to realize a delivery system able to deliver a drug in a controlled manner is the incorporation of the drug in a solid polymer. The control of the drug release can be achieved mainly by two types of mechanisms: the temporal and the distribution control (Uhrich et al., 1999). With reference to the temporal control, controlled release over a given period of time is particularly useful for those drugs that are quickly metabolized and eliminated from the body after administration, that is, a system in which the drug release rate balances the drug elimination rate has to be realized, maintaining the drug concentration constant in the therapeutic window. For certain drugs, the site of their activities in the body is of crucial importance; for this reason a distribution control can be of great aid, that is, drugs for which the natural distribution forces the drug to encounter certain tissues causing major side effects, or drugs characterized by a natural distribution that does not allow the drug molecules to reach their site of action. Thus, the administration of a large number of drug classes can be improved by temporal or distribution controlled drug release, such as antiinflammatory drugs, steroids, opioids, and vaccines (Uhrich et al., 1999). When a polymer-based drug delivery system has to be developed, the selection of the polymer is one of the more challenging tasks due to the wide range of surface and bulk properties that a polymer system may have. These properties contribute to give the desired chemical, mechanical, and biological functions of the delivery system (Pillai and Panchagnula, 2001). On one hand, polymer surface properties (such as hydrophilicity, smoothness) determine the biocompatibility with the human body and influence the delivery system properties (such as durability, or permeability); on the other hand, the surface properties determine the water sorption capacity of the polymer, which is responsible of hydrolytic degradation, swelling, and erosion. Concerning the bulk properties of a polymer, they play an important role in the drug delivery, that is, they include adhesion and solubility, which confer peculiar characteristics to the system. Moreover, structural properties of a matrix, such as the pore size and the morphology, must be considered since they determine the mass transport phenomena. The choice of the polymer influences the final release rate from a drug delivery system, thus a series of polymer-related factors affecting drug release must be taken into account (Varma et al., 2004). Starting from the polymer type (i.e., water-soluble or water-insoluble polymer), some important parameters need consideration: the viscosity grade, which influences the diffusional and mechanical characteristics of the gel layer; the polymer ratio; and the particle properties (such as particle size, size distribution, number of particles), which influence the porosity, viscosity, and tortuosity of the matrix. However, it has to be considered that the polymer-related properties cannot alone influence the drug release rate but they must be combined with other properties (Caccavo et al., 2016a). The other factors influencing drug release can be divided into drug-related factors and formulation-related factors. The drug-related factors are the drug dose, solubility (which depends on the chemical structure of the molecule and its physicochemical nature), molecular weight and size, and particle size and shape. Undoubtedly, the formulation-related parameters have to be taken into account in the development of a delivery system: the formulation geometry, the processing technique, and the presence of additives or excipients contribute to the final release kinetics. Similar reasoning can be made in terms of lipids. Lipid-based drug delivery systems (LDDS) are safe and effective carriers that can be easily tailored to meet different disease conditions, routes of administration, costs, product stability, toxicity, and efficacy (Attama et al., 2012).