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Hee-Kyoung Lee, Michael Onorato, Isaac Erickson, MaryJane Rafii, McKenna MARIE Drysdale, Brittany Coats, Thomas Zarembinski, Barbara M Wirostko; A Novel Carboxymethylated Hyaluronic Acid Polymer for Sustained Drug Delivery to Ocular Surface. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4139.
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© ARVO (1962-2015); The Authors (2016-present)
Jade Therapeutics uses a biocompatible, biodegradable cross-linked hyaluronic acid-based polymer for sustained drug delivery to enhance the treatment of ophthalmology disorders and improve visual outcomes. Jade's proprietary, thiolated carboxymethylated hyaluronic acid (CMHA) film requires infrequent application, and is easy to install "urgently" on-site by a physician. Films of four different cross-linked CMHA formulations were fabricated and the in vitro characteristics were determined and optimized to establish film drug release properties. The cytocompatibility of four CMHA film formulations was evaluated using two cell lines.
Films were fabricated varying the HA-based polymers (thiolated CMHA alone versus thiolated CMHA with thiolated gelatin). Poly(ethyleneglycol) diacrylate (PEGDA) or glutathione disulfide (GSSG) was used as cross-linkers. The polymerized gel in silicone mold was dried at room temperature overnight to create thin films. Swelling was assessed by analysis of film diameter and mass before and after hydration. Using carbazole assay, the integrity of CMHA-PEGDA film after ethylene oxide (EtO) sterilization was compared to the integrity of pre-sterilized film. Film’s mechanical property was measured under various levels of stress. Film-related effects on bone marrow derived mesenchymal stem cell (MSCs) and NIH 3T3 fibroblast viability and morphology were analyzed using fluorescence imaging and an alamarBlue® metabolic assay.
Six mm diameter films were created, and swelled to 8 mm in PBS within 30 min. The mass increased as much as 700% after 24 hrs. The CMHA-PEGDA film was the most favorable in terms of tensile strength, relaxation modulus, durability and flexibility. This film was also the closest to soft contact lens under various levels of stress. Based on the carbazole assay, the integrity of CMHA-PEGDA film remained the same after EtO sterilization. Cells readily proliferated over a 7-day period for each film and cell type with no significant reductions in metabolic activity or morphology as compared to the control.
Based on their physical characteristics, cytocompatability, comfort, and sterilizability, CMHA-PEGDA film shows the potential for use in sustained-release delivery of a wide range of molecules for treating various ocular surface conditions.
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