Macromolecular engineering and stimulus response in the design of advanced drug delivery systems
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Introduction Particulate drug delivery systems are currently being developed to address shortcomings of conventional drug administration via tablets, injections, and other means. For instance, conventional methods lack selectivity and thus may cause deep serious damage to healthy tissues. The physicochemical characteristics of many drugs do not allow them to cross biological barriers, resulting in their rapid enzymatic decomposition and metabolization. However, therapeutic activity can be maximized and undesirable side-effects minimized by the proper design of nano-sized drug delivery systems, or “nanocarriers,”1 because of their capacity to meet a series of key criteria: 䊏 Encapsulation of poorly water-soluble drugs 䊏 Control of drug-release kinetics 䊏 Crossing of the physiological barriers by drugs protected from chemical and enzymatic degradation 䊏 Decreased drug toxicity toward healthy tissues and thus limited side effects 䊏 Improved comfort of patients by decreasing the number of injections and perfusions. Therefore, research is focusing on nanocarriers that can transport, protect, and target drugs toward a specific action site. For targeting tumors, several physiological differences between healthy and tumor tissues can be exploited (Figure 1). First, the vascularization of tumor tissue results in discontinuous
endothelium of the blood vessel walls, so that species as big as 100 nm in diameter can diffuse through. Therefore, macromolecules or macromolecular assemblies can accumulate within tumors. This effect, known as the “EPR-effect” (enhanced permeability and retention), allows size-regulated targeting. A free drug of a small enough size can diffuse within both healthy and tumor tissues. In contrast, the same drug selectively accumulates in the tumor tissues if encapsulated into nanocarriers of an adequate size. A second level of targeting is based on the difference in pH between healthy (pH = 7.4) and tumor tissues (pH as low as 6.5). The nanocarrier stability against pH is then the key criterion for the selective drug release at the tumor site.2 As a rule, the surface properties of nanocarriers are of utmost importance, because they dictate the interactions with the biological environment, and thus the biodistribution and, ultimately, the fate of the nanocarriers within living organisms. In this respect, polymeric micelles are very promising carriers, with a size of several tens of nanometers.3 They result from the supramolecular self-assembly of amphiphilic block copolymers into core-shell nanoparticles. The outer shell consists of the constitutive block of the copolymer that is selectively soluble in the dispersion medium. Because their composition and structure can be changed significantly, amphiphilic block copolymers are desirable precursors for particulate drug delivery systems. Indeed, techniques for
Christine Jérôme, Center for Education and Research on Macromolecules, University of Liège, Belgium, [email protected].
MRS BULLETIN • VOLUME 35 • SEPTEMBER 2010 • www.mrs.org/bulletin
665
MACROMOL
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