ABSTRACT
Progress in both synthetic organic chemistry and molecular biology has led to an enormous increase in the number of active molecules which are candidates to become therapeutic or diagnostic agents. However, the physicochemical properties of these molecules often limit their potential. Many molecules derived from combinatorial chemistry libraries are poorly soluble in aqueous media and are therefore difcult to formulate and administer. Thus, although they may show good binding to specic targets in vitro, their bioavailability may be insufcient. On the other hand, molecules such as proteins, peptides, and nucleic acids are water-soluble but are often subject to degradation in biological uids. Furthermore, because these molecules are hydrophilic, they penetrate poorly through cell membranes, unless specic transporters exist. Appropriate drug carrier systems can help to
5.1 Introduction to Colloidal Drug Carriers ............................................................................... 123 5.1.1 Distribution of Nanocarriers after Intravenous Administration ...............................124 5.1.2 Distribution of Nanocarriers after Administration by the Oral Route ..................... 125 5.1.3 Distribution of Nanocarriers after Administration by Other Routes ....................... 125
5.2 Applications of “Conventional” NPs .................................................................................... 126 5.2.1 Intravenous Route ..................................................................................................... 126 5.2.2 Oral Route ................................................................................................................. 127 5.2.3 Other Routes ............................................................................................................. 127
5.3 Applications of Long-Circulating NPs ................................................................................. 128 5.3.1 Intravascular Applications ........................................................................................ 128 5.3.2 Delivery to Tumors ................................................................................................... 129 5.3.3 Delivery to Sites of Infection .................................................................................... 130 5.3.4 Other Applications .................................................................................................... 130
5.4 Targeted NPs......................................................................................................................... 130 5.4.1 Chemical Strategies to Obtain Targeted NPs ........................................................... 131
5.4.1.1 General Methodologies .............................................................................. 131 5.4.1.2 Covalent Coupling Strategies ..................................................................... 132 5.4.1.3 Non-Covalent Coupling Strategies ............................................................ 134
5.4.2 Applications of Targeted NPs ................................................................................... 135 5.4.2.1 Targeting to Tumors ................................................................................... 135 5.4.2.2 Targeting to Endothelium .......................................................................... 137 5.4.2.3 Targeting by Other Routes ......................................................................... 142
5.5 Conclusions ........................................................................................................................... 142 References ...................................................................................................................................... 143
transform candidate molecules into effective drugs. Nanoparticulate systems are particularly useful because, unlike microparticles, they can be administered by parenteral routes and are distributed by normal physiological processes. They present a large surface area, which can facilitate drug dissolution, and can be internalized by the majority of cell types. They differ from prodrugs in that there is usually no covalent linkage between the carrier and the drug.
