Chitosan glycerophosphate-based semirigid dexamethasone eluting biodegradable stent.
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).


CONCLUSIONS
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.
Bleier
Benjamin S
BS
Department of Otorhinolaryngology-Head and Neck Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. benjamin.bleier@uphs.upenn.edu
Paulson
David P
DP
O'Malley
Bert W
BW
Li
Daqing
D
Palmer
James N
JN
Chiu
Alexander G
AG
Cohen
Noam A
NA
D020341:Absorbable Implants; D000818:Animals; D001672:Biocompatible Materials; D048271:Chitosan / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004338:Drug Combinations; D054855:Drug-Eluting Stents; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000494:pharmacology; D015523:Maxillary Sinusitis / Q000601:surgery; D015508:Nasal Obstruction / Q000209:etiology / Q000517:prevention & control*; D013517:Otorhinolaryngologic Surgical Procedures / Q000295:instrumentation*; D018583:Pliability; D011183:Postoperative Complications / Q000209:etiology / Q000517:prevention & control; D011474:Prosthesis Design; D011817:Rabbits; D016896:Treatment Outcome
D001672:Biocompatible Materials; D004338:Drug Combinations; D005938:Glucocorticoids; D003907:Dexamethasone; D048271:Chitosan