Intraoral Drug Delivery: Highly Thiolated κ-Carrageenan as Mucoadhesive Excipient
Aim: This study aims to design a novel thiolated κ-carrageenan (κ-CA-SH) and evaluate its potential as an excipient for the design of mucoadhesive drug delivery systems.
Methods: Native κ-carrageenan (κ-CA) was thiolated with phosphorous pentasulfide in sulfolane and characterized via 1H NMR, FTIR, as well as Ellman’s test. Cytotoxicity was assessed via resazurin assay. In vitro release of the model drug, benzydamine hydrochloride, was determined. Tensile and mucosal residence time studies were performed on buccal and small intestinal mucosa. Mucoadhesive features were investigated via rheological studies with freshly isolated porcine mucus.
Results: Thiolated κ-CA (κ-CA-SH) with 1213.88 ± 52 µmol/g thiol groups showed no cytotoxicity at a concentration of 1% (m/v) and low cytotoxicity up to 2% (m/v). Benzydamine hydrochloride showed slow release in solution for both polymers. Tensile studies on buccal and intestinal mucosa showed an up to 2.7-fold and 7.7-fold enhancement in the maximum detachment force (MDF) and total work of adhesion (TWA) of κ-CA-SH vs. κ-CA, respectively. The κ-CA-SH exhibited an up to 4.4-fold improved dynamic viscosity with mucus and significantly prolonged residence time on mucosa compared to native κ-CA.
Conclusion: Since highly thiolated κ-CA shows a slow release of positively charged active pharmaceutical ingredients and enhanced mucoadhesive properties, it might be a promising excipient for local drug delivery in the oral cavity.
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Materials
Kappa-carrageenan (κ-CA), phosphorus pentasulfide (P4S10, 99%), tetramethylene sulfone (sulfolane, 99%), dimethyl sulfoxide-d6 (DMSO-d6, 99.9%), benzydamine hydrochloride, 5,5′-dithiobis(2-nitrobenzoic acid) (Ellman’s reagent), and sodium borohydride (NaBH4, ≥98%), dibutyltin dilaurate (DBTDL) and fluorescein isothiocyanate isomer 1 (FITC, ≥90%) were purchased from Sigma-Aldrich, Wien, Austria. Dialysis tubes of ZelluTrans from Carl Roth, Osterreich, Austria, with MWCO 3500 Da, were used. All the used chemicals were received from commercial sources and used without purification. Porcine small intestine was a donation from a slaughterhouse in Innsbruck.
Kali, G.; Fürst, A.; Efiana, N.A.; Dizdarević, A.; Bernkop-Schnürch, A. Intraoral Drug Delivery: Highly Thiolated κ-Carrageenan as Mucoadhesive Excipient. Pharmaceutics 2023, 15, 1993. https://doi.org/10.3390/pharmaceutics15071993