ABSTRACT
BACKGROUND: Chitosan is a polysaccharide derived from chitin deacetylation, which can form a biodegradable matrix capable of reversibly binding dexamethasone. The purpose of this study was to optimize the chitosan formulation to produce a pliable sheet, to assess the innate longevity and inflammatory potential of the polymer, and to study the in vivo rate of dexamethasone release over time. METHODS: Chitosan glycerophosphate (CGP) sheets were produced with varying degrees of deacetylation (70-100%) and analyzed for structural integrity. Two-squared centimeter sheets of 91.7% deacetylated CGP were mixed with dexamethasone and implanted in 12 rabbit maxillary sinuses. Nasal lavage and peripheral blood samples were tested for dexamethasone levels by enzyme-linked immunosorbent assay (ELISA) over 15 days. Sinuses were examined histologically on postoperative days 3, 7, and 15 for persistence of the stent and degree of inflammation when compared with CGP alone. RESULTS: The 91.7% deacetylated CGP formulation was found to have optimal mechanical properties and remained present with moderate degradation and negligible inflammation through postoperative day 15. Dexamethasone levels were detectable in nasal lavage and blood samples through postoperative day 15 and decayed over time (lavage: day 0, 7.70 +/- 0.97 ng/mL, and day 15, 2.53 +/- 1.71 ng/mL; blood: day 3, 2.51 +/- 0.14 ng/mL, and day 15, 1.70 +/- 0.36 ng/mL). CONCLUSION: CGP may be used to create a semirigid sheet that is malleable, inert, and capable of eluting steroid over 15 days when implanted intranasally. This material may be used to create a pharmacologically active stent that spontaneously degrades over time.
Subject(s)
Absorbable Implants , Biocompatible Materials , Chitosan/pharmacology , Dexamethasone/pharmacology , Drug-Eluting Stents , Nasal Obstruction/prevention & control , Otorhinolaryngologic Surgical Procedures/instrumentation , Animals , Disease Models, Animal , Drug Combinations , Follow-Up Studies , Glucocorticoids/pharmacology , Maxillary Sinusitis/surgery , Nasal Obstruction/etiology , Pliability , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Prosthesis Design , Rabbits , Treatment OutcomeABSTRACT
PURPOSE: Our goal is to develop a novel drug delivery system that can potentially improve clinical outcomes compared to current methods of dosing drugs such as dexamethasone or gentamicin. This system focuses on a single local application to the inner ear via the round window membrane. HYPOTHESIS: A chitosan-glycerophosphate (CGP)-hydrogel based drug delivery system can be engineered to provide local and sustained drug release to the inner ear. STUDY DESIGN: In vitro: drug release and (CGP)-hydrogel matrix degradation were characterized using dexamethasone as a model drug. In vivo: dexamethasone laden CGP-hydrogel was placed in the round window niche of mice. Perilymph samples were obtained from the oval window and analyzed for dexamethasone. The impact of CGP-hydrogel on auditory function was evaluated. RESULTS: In vitro: A CGP-hydrogel was designed to release 92% of the dexamethasone load over 4 consecutive days with concurrent degradation of the hydrogel matrix. In vivo: After surgical placement of CGP-hydrogel to the round window niche, we detected elevated levels of dexamethasone in perilymph for 5 days. Auditory function testing revealed a temporary hearing loss in the immediate postoperative period, which resolved by the 10th postoperative day. CONCLUSIONS: We report the development of CGP-hydrogel, a biodegradable matrix that achieves local, sustained delivery of dexamethasone to the inner ear. There were no significant complications resulting from the surgical procedure or the administration of CGP-hydrogel to our murine model.
