Purchase this article with an account.
Darren Stirland, Christian Pompoco, Brenda Mann; Degradation assessment of crosslinked CMHA-S polymer products for ophthalmic applications. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5689.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Hyaluronic acid (HA) polymers naturally exist in the human body and are commonly used as biomaterials. This work involves crosslinked thiolated carboxymethyl hyaluronic acid (CMHA-S) with physicochemical properties for increased residence time on eye and drug delivery capabilities as a gel or film for ophthalmic applications. Ophthalmic products are especially sensitive to biocompatibility, of both the polymer and its degradation products. Although degradation of non-modified HA has been extensively studied, degradation and detection of crosslinked modified HA are more complicated. Thus, the purpose of this work was to determine the conditions in which crosslinked CMHA-S degrades, utilizing various detection methods.
Extreme conditions for degradation included acid, H2O2, and high heat. Biologically relevant conditions included hyaluronidase (HAase), H2O2, Simulated Tears Fluid (STF), and Fasted State Simulated Gastric Fluid (FaSSGF). Degradation was assessed with gel electrophoresis, size exclusion chromatography, multiangle light scattering, rheology, and gravimetric analysis.
Forced degradation conditions of acid, H2O2, and high heat resulted in a shift to smaller molecular weight products, indicating degradation of crosslinked CMHA-S, and confirmed degradation detection techniques. Crosslinked CMHA-S in STF, FaSSGF, and physiological concentrations of H2O2 and HAase showed no degradation out to 7 days. However, escalating concentrations of H2O2 and HAase revealed dose-dependent degradation of crosslinked CMHA-S.
Combining multiple detection methods compensates for analytical limitations and provides further confirmation of degradation results. Non-modified HA was used as a comparator for some of the experiments as a positive control. However, it cannot be used as a direct comparator as HA differs from crosslinked CMHA-S in terms of molecular interactions, size, charge, and rheological characteristics. No degradation in physiologically relevant conditions out to 7 days indicates that crosslinked CMHA-S likely has a longer residence time than HA. Future work will include longer time points, both physiological and for shelf-stability, and explore additional analytical methods such as capillary electrophoresis.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
This PDF is available to Subscribers Only