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M. Hornof, S. Höller; Toxicological Safety Evaluation of Hyaluronic Acid-Thiomer. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5337.
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A novel functionalized biodegradable biopolymer - hyaluronic acid-cysteamine conjugate (HA-thiomer) - has been developed by Croma-Pharma. It is postulated that modification of hyaluronic acid by the attachment of thiol groups allows (a) interaction between thiol groups of the HA-thiomer with cysteine-rich ocular surface mucins (MUC5AC) resulting in prolonged ocular residence time of the polymer formulation and (b) 3D stabilization of the polymer network via inter- and intramolecular disulfide bonds. Due to the versatility of this technology its use in different areas of the ophthalmic field is conceivable (dry eye treatment, ocular drug delivery, surgical implants). It was the aim of this study to evaluate the safety and biocompatibility of HA-thiomer material in pre-clinical tests and studies.
The following toxicity studies were conducted: a cytotoxicity study, a skin sensitization study (Guinea Pig Maximization Test), two acute irritation/corrosion studies (dermal and ocular) in rabbits, two acute toxicity studies (oral and subcutaneous) in rats and a long term implantation study with HA-thiomer implants for Non-Perforating Deep Sclerectomy (NPDS). All tests were performed according to ISO 10993 guideline.
HA-thiomer raw material had no cytotoxic effect on mouse embryo cells. The skin sensitization study and both irritation/corrosion studies indicated that the substance HA-thiomer is well tolerated. A dose of 1000mg/kg body weight did not cause any toxic effects after oral or subcutaneous administration in rats. Biodegradable HA-thiomer implants showed excellent biocompatibility.
First biocompatibility studies indicate that HA-thiomer has a very safe toxicological profile and seems to be well tolerated. Future studies will focus on the evaluation of the safety and efficacy of novel HA-thiomer based ophthalmic product developments such as lubricating eye drops, surgical implants (e.g. for NPDS) and ocular inserts for drug delivery and/or treatment of dry eye symptoms.
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