Chemical delivery system

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],... 

N. Bodor, Novel Approaches to the Design of Safer Drugs Soft Drugs and Site-Specific Chemical Delivery Systems , in Advances in Drug Research , Ed. B. Testa, Academic Press, London, Vol. 13, 1984, p. 255-331. 

K. Prokai-Tatrai, E. Pop, W. Anderson, J.-L. Lin, M. E. Brewster, N. Bodor, Redox Derivatives of Tranylcypromine Syntheses, Properties, and Monoamine Oxidase Inhibitor Activity of Some Chemical Delivery Systems ,./. Pharm. Sci. 1991, 80, 255-261. 

The oxidation of dihydropyridine-based chemical delivery systems (CDSs) pioneered by Bodor and co-workers [176] has been discussed in a previous book (Chapt. 13 in [81]). There, we examined the principles by which such compounds function to deliver drugs to the brain. Here, we focus our attention to the last step in the activation of these double prodrugs, namely hydrolysis to release the drug. 

Fig. 8.14. Stepwise activation of dihydrotrigonelline-based chemical delivery systems, first by oxidation to a pyridinium cation (Reaction a), and then by hydrolysis to trigonelline and the drug ROH (Reaction b). Direct hydrolysis (Reaction c) is slow in comparison to the Reactions...

E. Shek, Chemical Delivery Systems and Prodrugs of Anticonvulsive Drugs , Adv. Drug Delivery Rev. 1994, 14, 227-241. 

L. Prokai, K. Prokai-Tatrai, N. Bodor, Targeting Drugs to the Brain by Redox Chemical Delivery Systems , Med. Res. Rev. 2000, 20, 367-416. 

Furthermore, by in vitro experiments, it has been verified that stereospecific activation of alprenoxime is organ-specific, occurring in the eye and not systemically. When administered locally to rabbits, marked decreases in intra-ocular pressure were observed, whereas oral administration elicited almost no cardiac effects. Such ketoximes represent promising chemical delivery systems in the treatment of glaucoma However, a major limitation is their poor stability in solution, seemingly due to hydrolysis of the oxime function. 

Cyclic. S -Mannich bases are rarely encountered in medicinal chemistry. The (R)-thiazolidine-4-carboxylic acids (11.113, Fig. 11.15), which are used as derivatives and chemical delivery systems for L-cysteine (11.114), provide an excellent example of S-Mannich bases. These compounds underwent activation by two distinct mechanisms, directly by nonenzymatic hydrolysis to cysteine and the original aldehyde (Fig. 11.15, Pathway a), and oxidatively (Pathway b) [138]. The latter route involved first oxidation by mitochondrial enzymes to the (f )-4,5-dihydrothiazole-4-carboxylic acid (11.115), followed by (presumably nonenzymatic) hydrolysis to /V-acylcysleine, and, finally, cytosolic hydrolysis to cysteine (11.114). 

Rrokai, L., K. Rrokai-Tatrai, and N. Bodor, Targeting drugs to the brain by redox chemical delivery systems. Med Res Rev, 2000. 20(5) 367 16. 

By the term chemical delivery system (CDS) we shall here refer to all derivatives of a parent drug which enhance access to the intended site of action by modification of physicochemical properties, and which deliver the parent by chemical or enzymic action in the biophase itself. The term prodrug is also often used, but this term really has a wider meaning ... 

Novel approaches to the design of safer drugs Soft drugs and site-specific chemical delivery systems, 13, 255... 

Free-on-Loan and Patented Chemical Delivery Systems... 

Yoshikawa T., Sakaeda T., Sugawara T., Hirano K., and Stella V. J. (1999). A novel chemical delivery system for brain targeting. Adv. Drug Deliv. Rev. 36 255-275. 

Bodor, N., et al. 2002. In vitro and in vivo evaluations of dihydroquinoline- and dihydroisoquinoline-based targetor moieties for brain-specific chemical delivery systems. J Drug Target 10 63. 

Brewster ME, Loftson T. The use of chemically modified cyclodextrins in the development of formulations for chemical delivery systems. Pharmazie 2002 57 94-101. 

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