Thiolated chitosans

Osuna, IB Teutonico, D Arpicco, S. Characterization of chitosan thiolation and application to thiol quantification onto nanoparticle surface. International Journal of Pharmaceutics, 2007, 340, 173-181. 

A. H. Krauland, V. M. Leitner, V. Grabovac, and A. Bernkop-Schnurch. In vivo evaluation of a nasal insulin delivery system based on thiolated chitosan. J Pharm Sci 95 2463-2472 (2006). 

Roldo, M., et al., Mucoadhesive thiolated chitosans as platforms for oral controlled drug delivery synthesis antfi vitro evaluation,Eur. J. Pharm. Biopharm., 57, 115, 2004. 

Thiolated Chitosan as a Strongly Mucoadhesive Polymer and Its Applications... 

Bernkop-Schnurch, A., D. Guggi, and Y. Pinter. 2004. Thiolated chitosans development and in vitro evaluation of a mucoadhesive, permeation enhancing oral drug delivery system. J Control Release 94 177. 

Krauland, A.H., D. Guggi, and A. Bernkop-Schnurch. 2004. Oral insulin delivery The potential of thiolated chitosan-insulin tablets on non-diabetic rats. J Control Release 95 547. 

Werle, M., and M. Hoffer. 2006. Glutathione and thiolated chitosan inhibit multidrug resistance P-glycoprotein activity in excised small intestine. J Control Rel 111 41. 

Foger, F., T. Schmitz, and A. Bernkop-Schniirch. 2006. In vivo evaluation of an oral delivery system for P-gp substrates based on thiolated chitosan. Biomaterials 27 4250. 

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]. 

Fig. 10 Synthesis of thiolated chitosan. Figure reproduced with permission from [127]. 2004...

Bernkop-Schniirch A, Homof M, Guggi D (2004) Thiolated chitosans. Eur J Pharm Biopharm 57(1) 9— 17... 

Bernkop-Schnurch A, Marschtitz MK (1997) Development and in vivo evaluation of systems to protect peptide drugs from aminopeptidase N. Pharm Res 14 181-185 Bernkop-Schnurch A, Paikl C, Valenta C (1997) Novel bioadhesive chitosan-EDTA conjugate protects leucine enkephalin from degradation by aminopeptidase N. Pharm Res 14 917-922 Bernkop-Schnurch A, Thaler S (2000) Polycarbophil-cysteine conjugates as platforms for oral (poly)peptide delivery systems. J Pharm Sci 89 901-909 Bernkop-Schnurch A, Walker G, Zarti H (2001) Thiolation of polycarbophil enhances its inhibition of intestinal brush border membrane bound aminopeptidase N. J Pharm Sci 90 1907-1914... 

Bernkop-Schnurch, A., Hornof, M. and Zoidl, T. (2003) Thiolated polymers- thiomers modification of chitosan with 2-iminothiolane. Int. J. Pharm. 260 229-237. 

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. 

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., Kafedjiiski K., Hoyer H., Loretz B., Bernkop-Schnurch A. (2006b) Enhanced transport of P-glycoprotein substrate saquinavir in presence of thiolated chitosan. J Drug Targ, 15, (2), 132-139. 

Palmberger T.F., Hombach J., Bemkop-Schniirch A. (2008) Thiolated chitosan Development and in vitro evaluation of an oral delivery system for acyclovir. Int J Pharm, 348(l-2) 79-85. 

Fig. 8.4 Decrease in plasma calcium level as a biological response for the salmon calcitonin bioavailability in fasted rats after oral administration of chitosan minitablets ( ), chitosan/ chitosan-pepsin inhibitor conjugate minitablets ( ) and thiolated chitosan/chitosan-pepsin inhibitor conjugate minitablets (A), all containing 50 pg of the peptide drug. Indicated values are the mean results from five rats S.D. (Guggi et al. 2003)...

Further, the enhanced transport of the P-gp substrate acyclovir across excised rat intestinal mucosa and Caco-2 monolayers in the presence of thiolated chitosan was found to be due to efflux pump inhibition (Palmberger et al. 2008). Co-administration of paclitaxel and thiolated polycarbophil significantly improved paclitaxel plasma levels and led to a more constant pharmacokinetic profile and reduced tumour growth in mammary cancer-induced rats (Foger et al. 2008). 

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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