Enzyme-controlled Drug Release

Pro-drugs are conjugates of drugs with carrier molecules mostly of inert nature. The microbial enzymes in the colon are responsible for the cleavage of the drug-carrier bond. A variety of pro-drugs have been synthesized, mainly azo compounds, glycosides, esters and amides [24]. 

Pro-drugs must not be cleaved by digestive enzymes of the upper GI tract and should not be susceptible to chemical hydrolysis. Moreover, pro-drug absorption in the small intestine should be negligible. Because of these requirements, the hydrophUicity, the molecular weight and the charge of the carrier molecules have to be regarded as critical parameters. 

The Drug Delivery Index (DDI) ahows a quantification of the reduction in the drug dose and the systemic exposure observed after drug release specificahy to the colon [37]. It may be calculated using AUC (Area l/nder the plasma drug concentration-time Curve) data or drug concentrations in blood and colonic tissues under steady-state conditions  

6 A Practical Approach in the Design of Colon-specific Drug Delivery Systems 

If a biodegradable polymer does not exhibit satisfactory film-forming properties, it may also be used as a compression coat requiring a compaction process onto a drug-containing core [62-64]. 

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Phase transition in gels in response to biochemical reactions [27,28]. Polymer gels were synthesized in which an enzyme (urease) or a biologically active protein (lectin) was immobilized. The volume phase transitions were observed in such gels when biochemical reactions took place. Such mechano-biochemical gels will be used in devices such as, sensors, selective absorbers, and biochemically controlled drug release. 

Langoth et al. [86] studied the properties of matrix-based tablets containing the novel pentapeptide leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) that has been shown to have pain-modulating properties. The matrix-based tablets were made with the thiolated polymer PCP. The covalent attachment of cysteine to the anionic polymer PCP leads to an improvement of the stability of matrix tablets, enhances the mucoadhesive properties, and increases the inhibitory potency of PCP towards buccal enzymes. All these factors lead to stability of the peptide and a controlled drug release for the peptide was obtained for more than 24 h. Also, the tablets based on thiolated PCP remained attached on freshly excised porcine mucosa 1.8 times longer than the corresponding unmodified polymer. 

Heller, J., and Trescony, P. Controlled drug release by polymer dissolution 11. Enzyme-mediated delivery device. J. Pharm. Sci. 68 919—921, 1979. 

Grafted chitosans have great utility in controlled drug release [115], tissue engineering [116], wound-healing [117] and cardiovascular applications [118-119]. Moreover, there are several reports regarding the use of enzymes in polymer s)m-thesis and modification [120-121]. In fact, enz)mies offer the potential advantage... 

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