Skip to Content
Merck
  • Genipin-crosslinked catechol-chitosan mucoadhesive hydrogels for buccal drug delivery.

Genipin-crosslinked catechol-chitosan mucoadhesive hydrogels for buccal drug delivery.

Biomaterials (2014-12-03)
Jinke Xu, Satu Strandman, Julian X X Zhu, Jake Barralet, Marta Cerruti
ABSTRACT

Drug administration via buccal mucosa is an attractive drug delivery strategy due to good patient compliance, prolonged localized drug effect, and avoidance of gastrointestinal drug metabolism and first-pass elimination. Buccal drug delivery systems need to maintain an intimate contact with the mucosa lining in the wet conditions of the oral cavity for long enough to allow drug release and absorption. For decades, mucoadhesive polymers such as chitosan (CS) and its derivatives have been explored to achieve this. In this study, inspired by the excellent wet adhesion of marine mussel adhesive protein, we developed a buccal drug delivery system using a novel catechol-functionalized CS (Cat-CS) hydrogel. We covalently bonded catechol functional groups to the backbone of CS, and crosslinked the polymer with a non-toxic crosslinker genipin (GP). We achieved two degrees of catechol conjugation (9% and 19%), forming Cat9-CS/GP and Cat19-CS/GP hydrogels, respectively. We confirmed covalent bond formation during the catechol functionalization and GP crosslinking during the gel formation. The gelation time and the mechanical properties of Cat-CS hydrogels are similar to those of CS only hydrogels. Catechol groups significantly enhanced mucoadhesion in vitro (7 out of the 10 Cat19-CS hydrogels were still in contact with porcine mucosal membrane after 6 h, whereas all of the CS hydrogels lost contact after 1.5 h). The new hydrogel systems sustained the release of lidocaine for about 3 h. In-vivo, we compared buccal patches made of Cat19-CS/GP and CS/GP adhered to rabbit buccal mucosa. We were able to detect lidocaine in the rabbit's serum at concentration about 1 ng/ml only from the Cat19-CS patch, most likely due to the intimate contact provided by mucoadhesive Cat19-CS/GP systems. No inflammation was observed on the buccal tissue in contact with any of the patches tested. These results show that the proposed catechol-modified CS hydrogel is a promising mucoadhesive and biocompatible hydrogel system for buccal drug delivery.

MATERIALS
Product Number
Brand
Product Description

Procaine hydrochloride, European Pharmacopoeia (EP) Reference Standard
Supelco
Procaine hydrochloride, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Dehydrated Alcohol, United States Pharmacopeia (USP) Reference Standard
Supelco
Ethanol solution, certified reference material, 2000 μg/mL in methanol
Sigma-Aldrich
Lidocaine hydrochloride monohydrate, solid
Sigma-Aldrich
Procaine hydrochloride, ≥97%
Supelco
Dehydrated Alcohol, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Procaine hydrochloride, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Ethanol, tested according to Ph. Eur.
Supelco
1,2-Dichloroethane, analytical standard
Sigma-Aldrich
3,4-Dihydroxyhydrocinnamic acid, 98%
Sigma-Aldrich
Ethyl alcohol, Pure, 190 proof, ACS spectrophotometric grade, 95.0%
Sigma-Aldrich
1,2-Dichloroethane, anhydrous, 99.8%
Sigma-Aldrich
β-D-Allose, rare aldohexose sugar
Sigma-Aldrich
Ethanol, for residue analysis
Sigma-Aldrich
Ethyl alcohol, Pure, 190 proof, for molecular biology
Sigma-Aldrich
1,2-Dichloroethane, ACS reagent, ≥99.0%
Sigma-Aldrich
Ethanol, BioUltra, for molecular biology, ≥99.8%, (absolute alcohol, without additive, A15 o1)
Sigma-Aldrich
Ethanol, purum, absolute ethanol, denaturated with 2% 2-butanone, A15 MEK1, ≥99.8% (based on denaturant-free substance)
Sigma-Aldrich
Ethanol, purum, fine spirit, denaturated with 4.8% methanol, F25 METHYL1, ~96% (based on denaturant-free substance)
Sigma-Aldrich
Ethanol, purum, absolute ethanol, denaturated with 4.8% isopropanol, A15 IPA1, ≥99.8% (based on denaturant-free substance)
Sigma-Aldrich
Ethyl alcohol, Pure, 200 proof, for molecular biology
Sigma-Aldrich
Ethyl alcohol, Pure, 200 proof, meets USP testing specifications
Sigma-Aldrich
Ethyl alcohol, Pure, 200 proof, ACS reagent, ≥99.5%