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J. Garrec, D. Dangl, M. Hornof; In vitro and in vivo Toxicological Safety Evaluation of Thiolated Chitosan. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4655.
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The biocompatibility of a novel thiolated chitosan derivative -chitosan-N-acetylcysteine (chitosan-NAC) - was evaluated. It is postulated that interaction between thiol groups of chitosan-NAC with cysteine-rich mucin (MUC5AC) will increase the residence time of the polymer on the ocular surface and enhance tear film stability. The use of chitosan-NAC in eye drops might be a promising new treatment strategy for dry eye.
Several in vitro and in vivo toxicity studies were conducted: a cytotoxicity study with balb/3T3 mouse embryo cells, a skin sensitisation study (Guinea Pig Maximisation Test), two acute irritation/corrosion studies (dermal and ocular) in rabbits and an acute oral toxicity study in rats. All tests were performed according to ISO 10993 guideline. During subsequent first efficacy studies in mice ocular tolerance of sterile, buffered and isotonic 0.3% and 0.5% chitosan-NAC formulations was monitored (blink rate, gross examination of ocular health, histopathological analysis of the ocular surface).
A mild cytotoxic effect of chitosan-NAC raw material was observed which was most likely caused by the gel formation of the test substance in the cell culture medium. The skin sensitization study and both irritation/corrosion studies indicated that the substance is well tolerated. The oral LD50 was determined to be > 1000mg/kg body weight in rats. No signs of irritation were observed during 4 weeks of twice daily chitosan-NAC eye drop application in mice.
In vitro and in vivo biocompatibility studies indicate that chitosan-NAC polymer has a safe toxicological profile and seems to be well tolerated. Subsequent efficacy studies during which ocular tolerance of chitosan-NAC eye drop formulations was additionally monitored confirm these results.
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