3:54 PM Abstract No. 171 - An in-situ forming resorbable hydrogel for endovascular drug delivery

Abstract

Purpose To evaluate drug load and release from a new in-situ gelable resorbable hydrogel and to assess its bioresorability. Materials and Methods Doxorubicin loaded hydrogels were prepared via mixing 1mL 2 wt% carboxymethyl chitosan (CCN), 0.5mL 2 mg/mL Doxorubicin, and 1 mL 2wt% oxidized carboxymethyl cellulose (OCMC) in 20 mL glass vials. Tetracycline loaded (10% payload) hydrogels were prepared in a similar fashion. Vials were placed in the refrigerator (5°C) for 20 hours for full gelation. 15 mL PBS (0.01M, pH=7.4) was added into each vial of drug-loaded hydrogel. Vials were then placed on a shaker (50 stroke/min) in incubator at 37°C. At fifteen predetermined time points, 0.5 mL aliquot was taken out from the vial and replaced with 0.5 mL fresh PBS. Drug concentrations in aliquots were measured by UV-Vis spectrophotometer. Tetracycline release was also measured at three different pH levels (2, 6, and 7.4) by adjusting the pH of PBS with HCl. Resorption study was performed with hydrogel pieces prepared from 0.5 mL CMC and 0.5 mL CCN solutions (2 wt%) at 37°C in a lysozyme solution (4 mg/mL in a PBS solution). On days 3, 5, 7 and 10, samples were retrieved, rinsed and freeze-dried. The percentage of weight loss was determined. All experiments were done in triplicates. Results Doxorubicin and tetracycline were successfully loaded into hydrogel without disruption of gel formation with no change in gelation time (p=NS). The drug release from doxorubicin loaded hydrogels peaked at 48 hours whereas it peaked at 24 hours for tetracycline release and continued to at least 96 hours. The release followed a curve indicating a gradual drug release which was seen across different pH levels. Tetracycline release followed more protracted course in more acidic solutions. Degradation occurred with 50% weight loss within approximately 4 days and total resorption in 12 days. Conclusion CCN/OCMC hydrogel possess the ability to slowly release drugs after loading. The resorbable hydrogel provides a novel delivery scaffold and completely degrades after delivery.