Systemic macromolecular delivery

In macromolecular dmg delivery systems, dmgs are attached to polymeric compounds, such as synthetic polymers [60], dendrimers [61], and antibodies [62], in order to enhance the delivery of the active substance to the diseased tissue and to reduce the toxicity to healthy tissue. The use of macromolecular delivery systems provides several advantages extension of the half-life of the dmg, the ability to introduce targeting moieties into the carrier, the possibility of triggered dmg release, and the aforementioned reduced cytotoxicity. 

A detailed discussion of particulate and soluble macromolecular delivery systems is presented in the following sections. 

Classical carrier-linked prodrugs Site-specific chemical delivery systems Macromolecular prodrugs Drug-antibody conjugates... 

Stevenson CL. Delivery of Proteins from Implantable Systems. Macromolecular Drug Delivery Conference, Breckenridge, CO, 1999. 

Rujiravanit, R., Kruaykitanon, S., Jamieson, A. M., and Tokura, S. (2003). Preparation of cross-linked chitosan/silk fibroin blend films for drug delivery system. Macromolecular Bioscience 3, 604 11. 

Scheuch G, KohUiaeufl MJ, Brand P, Siekmeier R. Clinical perspectives on pulmonary systemic and macromolecular delivery. Adv Drug Deliv Rev. 2006 58(9-10) 996-1008. 

Another very important site for drug delivery is the central nervous system (CNS). The blood-brain barrier presents a formidable barrier to the effective delivery of most agents to the brain. Interesting work is now advancing in such areas as direct convective delivery of macromolecules (and presumably in the future macromolecular drug carriers) to the spinal cord [238] and even to peripheral nerves [239]. For the interested reader, the delivery of therapeutic molecules into the CNS has also been recently comprehensively reviewed... 

E. Goldberg, in Polymeric Delivery Systems, Midland Macromolecular Symposium (R. J. Kostelnek, ed.), Gordon and Breach, New York, 1978, p. 227. 

Soluble Macromolecular and Other Drug-Delivery Systems... 

Table 15 Suggested Soluble Macromolecular Drug-Delivery Systems and Their Uses...

Kim, S. W., Temperature Sensitive Polymers for Delivery of Macromolecular Drugs, in Advanced Biomaterials in Biomedical Engineering and Drug Delivery Systems (N. Ogata, et al., Eds.), pp. 125-133. Springer, Tokyo (1996). 

The copolymer-based systems possessing the core-shell structure in solutions are known and studied rather well (see, e.g., [14-16]). These copolymers in aqueous media tend to form polymeric micelles, which are often considered as promising drug delivery nano-vehicles [ 17,18], i.e., these macromolecular systems are not only of scientific, but also of considerable applied significance. Among such systems there are interesting examples, whose properties are very similar to the properties that should be inherent in the protein-like copolymers. All of these macromolecules possess the primary structure of... 

Kostelnik, R. J., Ed. "Polymeric Delivery Systems Midland Macromolecular Monographs, Vol. 5 Gordon Breach New York, 1977. 

A special group of carrier-linked prodrugs are the site-specific chemical delivery systems [23], Macromolecular prodrugs are synthetic conjugates of drugs covalently bound (either directly or via a spacer) to proteins, polypeptides, polysaccharides, and other biodegradable polymers [24],... 

To conclude this long chapter, we give here a brief and schematic survey of prodrugs that have a macromolecule as the pro-moiety [253], There is considerable interest in some of these systems for selective delivery and improved therapy [254], From the pharmacochemical perspective, macromolecular prodrugs can be approached from three angles ... 

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