Thiolated polymers

For example, Wuelfing et al. reported on the synthesis of Au NPs using the thiolated polymer, a-methoxy-co-mercapto-poly(ethylene glycol) (PEG-SH), as stabilizer in a modification of the Brust-Schiffrin method using a 1/12 polymer thiol/ AuC14 ratio. Transmission electron microscopy showed that the product had modestly polydisperse Au cores of average diameter 2.8 1 nm. This nanomaterial led to characteristics uniquely different from alkanethiolate MPCs, notably aqueous solubility, thermal and chemical stability, ligand footprint size, and ionic conductivity [66]. 

Marschiiz, M.K. and Bernkop-Schnirch, A., Thiolated polymers self-crosslinking properties of thi-olated 450 kDa poly(acrylic acid) and their in uence on mucoadhdsim l. Pharm. Sci., 15, 387,... 

Clausen, A.E., C.E. Kast, and A. Bernkop-Schnurch. 2002. The role of glutathione in the permeation enhancing effect of thiolated polymers. Pharm Res 19 602. 

In order to improve the mucosal absorption of poorly absorbed drugs such as peptides and proteins, newer delivery systems with higher mucoadhesive and permeation-enhancing polymers have been developed. While the first generation of mucoadhesive polymers provided adhesion to the mucus gel layer via secondary bonds, the new generation of mucoadhesive polymers is able to form covalent bonds with the mucous layer. The immobilization of thiol groups on mucoadhesive polymers results in thiolated polymers or thiomers that can form disulfide bonds with cysteine-rich subdomains of mucus glycoproteins [84,85]. 

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. 

Langoth, N., et al. 2003. Development of buccal drug delivery systems based on a thiolated polymer. Int J Pharm 252 141. 

In a recent study, some authors proposed the employment of thiolated polymers obtained by the immobilization of thiol groups on well-established multifunctional polymers such as poly(acrylates) and chitosans as functional agents having mucoadhesive, penetration enhancement, and enzyme-inhibiting properties [94,95]. 

Thiolated polymers are synthesized by immobilizing thiol groups on polyacrylates or cellulose derivatives by the group of Bernkop-Schnurch and Steiniger (2000), Bernkop-Schnurch et al. (2000), Leitner et al. (2003a, b), Clausen et al. (2000), and Bernkop-Schnurch (2005). The main purpose of introducing free... 

Bernkop-Schnurch, A. and Steiniger, S. (2000) Synthesis and characterization of mucoadhe-sive thiolated polymers. Int. J. Pharm. 194 239-247. 

Bernkop-Schnurch, A., Scholler, S. and Biebel, R.G. (2000) Development of controlled drug release systems based on thiolated polymers. J. Control. Release 66 39-48. 

Kast, C.E. and Bernkop-Schniirch, A. (2001) Thiolated polymers - thiomers development and in vitro evaluation of chitosan-thioglycolic arid conjugates. Biomaterials 22 2345-2352. Kotze, A.F., LueBen, H.L., de Leeuw, B.J., de Boer, A.G., Verhoef, J.C. and Junginger, H.E. 

Leitner,. V.M., Walker, G.F. and Bernkop-Schniirch, A. (2003b) Thiolated polymers evidence for the formation of disulphide bonds with mucus glycoproteins. Eur. 

Limited local inhibition of these transporters by using polymeric inhibitors could reduce such systemic risks and side effects. Efflux pump modulating polymers and surfactants mentioned in this review have been distinguished between nonionic, ionic and thiolated polymers. 

Bypassing intestinal transmembrane transporters mainly by a paracellular absorption would avoid or limit exposure of the substrate to these efflux pumps. Improved paracellular uptake can be achieved by using fatty acids, calcium chelators such as EDTA, papain, bromelain, surfactants, chitosans, polyacrylic acid or thiolated polymers. 

Foger F., Malaivijitnond S., Wannaprasert T., Huck C., Bernkop-Schnurch A., Werle M. (2008) Effect of oral paclitaxel in presence of a thiolated polymer on absorption and tumor growth in rats. J Drug Targeting, 16, (2), 149-55. 

Grabovac V., Bernkop-Schnurch A. (2006) Thiolated polymers as effective inhibitors of intestinal Mrp2 efflux pump transporters. Sci Pharm, 74. 

Bernkop-Schniirch, A. and Steininger, S. Synthesis and characterisation of mucoadhesive thiolated polymers. Int J Pharm 2000 194, 2, 239-247. 

Foger, F., Malaivijitnond, S., Wannaprasert, T., Fluck, C., Bernkop-Schnurch, A., and Werle, M. Effect of a thiolated polymer on oral paclitaxel absorption and tumor growth in rats. J. Drug Target 2008 16, 2, 149-155. 

Kast, C. E. and Bernkop-Schnurch, A. Thiolated polymers - thiomers development and in vitro evaluation of chitosan-thioglycolic acid conjugates. Biomaterials 2001 22, 17, 2345-2352. 

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