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A. Clausen, M. Hornof, M. Hoffer; Thiolated Biopolymers: New Polymers for Ocular Use. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5770.
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Within recent years a new class of polymeric excipients has been introduced in the literature. Thiolated polymers or so-called thiomers are hydrophilic macromolecules exhibiting free thiol groups on the polymeric backbone. Due to these functional groups various features of well-established ophthalmic excipients such as hyaluronic acid and poly(acrylic acid) are strongly improved
Poly(acrylic acid), hyaluronic acid (HA) and Chitosan were modified with thiol groups via the covalent attachment of cysteine, cysteamine and N-acetyl-l-cysteine, respectively. The effect of this modification on polymer properties was tested in vitro:1. Cohesive Properties: Inserts were incubated in artificial tear fluid at 37°C and the time till disintegration was measured. 2. Mucoadhesive Properties: An isotonic aqueous formulation containing 0,5% thiomer adjusted to pH 6,6 was mixed with isolated mucin in artificial tear fluid. The rheological properties of the formulation, the isolated mucin in artificial tear fluid and the mixture of mucin and polymer solutions were determined. 3. Permeation enhancing properties: The permeation enhancing properties of the new polymers were measured in Ussing-type diffusion chambers in an atmosphere of 95% O2 and 5% CO2 at 37°C on excised rabbit corneas. As permeation markers dexamethasone phosphate and rhodamine were used. At predetermined time points samples were taken from the acceptor reservoir and analysed. Controls were performed using unmodified polymer for each test regime.
Ad. 1 The formation of intra- and interchain disulfide bonds within the polymeric network of the inserts led to a strongly improved stability of drug delivery systems. The disintegration time of inserts composed of thiolated polymer was more than one week, whereas inserts made from unmodified polymer dissolved within 30 min. Ad. 2 The results of the rheological tests clearly demonstrate a strong interaction between mucin and the thiomer via disulfide bond formation. The cross over point could be 2-fold increased compared to unmodified polymer, which clearly underlines the formation of a three-dimensional high stable network. Ad. 3 Thiolated polymers exhibit also a permeation enhancing effect for the paracellular uptake of drugs. This circumstance leads to 2.4-fold and 2-fold increased permeation values of the model substances compared to unmodified polymers.
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