PERMEATION ENHANCEMENT
n order to improve the
bioavailability of non-invasively administered drugs permeation enhancing
drug delivery systems are often essential. Thiolated polymers have been
demonstrated to show a strong permeation enhancing effect for the uptake of
drugs from mucosal membranes such as the intestinal [Clausen, A.E.,
Kast, C.E. and Bernkop-Schnürch, A. (2002). The role of glutathione in the
permeation enhancing effect of thiolated polymers. Pharm. Res., 19, 602-608; Clausen, A.E.,
and Bernkop-Schnürch, A. (2001) Thiolated Carboxy- methylcellulose: In vitro
evaluation of its permeation enhancing effect on peptide drugs. Eur. J. Parm.
Biopharm., 51, 25-32; Kast, C.E.
and Bernkop-Schnürch, A. (2002) Influence of the molecular mass on the
permeation enhancing effect of different poly(acrylates). STP pharma, 12,
351-356] and nasal mucosa [Leitner V.M.,
Guggi D., Bernkop-Schnürch A. (2004) Thiomers in noninvasive polypeptide
delivery: in vitro and in vivo characterization of a polycarbophil-cysteine/glutathione
gel formulation for human growth hormone. J. Pharm. Sci. 93, 1682-169].
In comparison to most low
molecular weight permeation enhancers, thiolated polymers offer the
advantage of not being absorbed from the mucosal membrane. Hence, their
permeation enhancing effect can be maintained for a comparatively longer
period of time and systemic toxic side effects of the auxiliary agent can be
excluded. The mechanism being responsible for the permeation enhancing
effect of thiomers has been discovered within the last years showing a
reversible opening of the tight junctions and the role of glutathione as
permeation mediator [Clausen, A.E.,
Kast, C.E. and Bernkop-Schnürch, A. (2002). The role of glutathione in the
permeation enhancing effect of thiolated polymers. Pharm. Res., 19, 602-608].
As this permeation enhancing
mechanism differs from most conventionally used permeation enhancers such as
fatty acids, the effect can be even further improved by the combination of
both types of permeation enhancing systems. The
permeation enhancing properties of thiomers were also demonstrated in
various in vivo studies.
Uptake of a therapeutic peptide (PACAP) from
porcine buccal mucosa (grey graph). Click on the graph to see the improvement due to the addition of 1% thiomer [Langoth N., Bernkop-Schnürch A. and Kurka P. (2005)
In vitro evaluation of various buccal permeation enhancing systems for PACAP
(pituitary adenylate cyclase-activating polypeptide). Pharm. Res., 22,
2045-2050]. |
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Uptake of sodium fluorescein
from small intestinal mucosa (grey graph). The blue graph shows the
improvement due to the addition of 0.5% thiomer. Click on the graph. [Clausen, A.E.,
Kast, C.E. and Bernkop-Schnürch, A. (2002). The role of glutathione in the
permeation enhancing effect of thiolated polymers. Pharm. Res., 19, 602-608].
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Transport
of Leu-enkephalin across freshly excised bovine nasal mucosa in buffer
solution (grey graph). The blue graph shows the improvement due to the
addition of 0.5% thiomer. Click on the graph. [Bernkop-Schnürch A., Obermair K., Greimel A.
and Palmberger T.F. (2006) In vitro evaluation of the potential of
thiomers for the nasal administration of Leu-enkephalin. Amino Acids., 30,
417-423].
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