Macromolecular prodrugs

Probably the most promising polymeric drug carrier system involves polysaccharide molecules. These are natural polymers and are often biodegradable to products that are useful to the host or easily eliminated by the host. Dextrans have been the most extensively used polysaccharide for macromolecular prodrug preparations (79). These materials are biocompatible and the in vivo fate is directly related to their molecular weight. Moreover these macromolecules can be easily targetted to the hepatocytes with D-mannose or L-fucose (20). 

So, in order to provide a macromolecular prodrug of 5FU with reduced side-effects, having affinity for tumor cells and exhibiting a high antitumor activity, the present paper is concerned with the design of hybrid type conjugates of chitin-... 

F Harboe, C Larsen, MJ Johansen, HP Olesen. Macromolecular prodrugs. XV. Colon-targeted delivery—Bioavailability of naproxen from orally administered dextran-naproxen ester prodrugs varying in molecular size in the pig. Pharm Res 6(11) 919—923, 1989. 

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

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 ... 

P. Jaksic, K. Mlinaric-Majerski, B. Zorc, M. Dumic, Macromolecular Prodrugs. VI. Kinetic Study of Poly[a,/T(V-2-hydroxyethyl-DL-aspartamide)]-ketoprofen Hydrolysis , Int. J. Pharm. 1996, 135, 177-182. 

DESIGN OF MACROMOLECULAR PRODRUG OF CISPLATIN ATTACHED TO DEXTRAN THROUGH COORDINATE BOND... 

Design of Macromolecular Prodrug of Cisplatin Attached to Dextran through Coordinate Bond... 

Filipovic-Grcic, J., D. Maysinger, B. Zorc, and I. Jalsenjak. 1995. Macromolecular prodrugs. IV. 

Ichikawa, H., et al. 1993. Evaluation of the conjugate between N4-(4-carboxybutyryl)-l-beta-D-arabinofuranosylcytosine and chitosan as a macromolecular prodrug of 1-beta-D-arabinofurano-sylcytosine. Drug Des Discov 10 343. 

Soyez, H., Schacht, E., and Vanderkerken, S. The crucial role of spacer groups in macromolecular prodrug design. Adv. Drug Del. Rev. 21 81-106, 1996. 

C. Larsen, E. Harboe, M. Johansen, and H. P. Olesen, Macromolecular prodrugs Naproxen-dextran esters, Pharm. Res. 6 919-923, 995-999 (1989). 

One of the serious problems in chemotherapy is the limited selectivity of most of the common anticancer drugs. Because of the low cell selectivity, they do not only interfere with tumour cells but also with healthy cells, and lead therefore to serious side effects. New macromolecular prodrugs were synthesised that are composed of CMD, Gly - Gly - Gly linker, and camptothens (CPTs), one of the most promising classes of anticancer drugs [318]. 

When using macromolecular prodrugs it is advisable that the macromolecular carrier after fullfilling its function should be cleared... 

Takakura, Y., and Hashida, M. (1995), Macromolecular drug carrier systems in cancer chemotherapy Macromolecular prodrugs, Crit. Rev. OncoL/Hematol., 18, 207-231. 

Steyger, P.S. Baban, D.F. Brereton, M. Ulbrich, K. Seymour, L.W. Intratumoral distribution as a determinant of tumor responsiveness to therapy using polymer-based macromolecular prodrugs. Journal of Controlled Release... 

It is clear that macromolecule-drug conjugates or, more accurately, macromolecular prodrugs may well alter the pharmacological and immunological activity of the parent compound. The macromolecular transport vector may vary considerably in size, electrical charges, hydrophobicity and hydrophilicity, and its ability to act as a substrate for transmembrane transport mechanisms. 

---