Development and characterization of cross-linked biopolymeric matrices for oral ulcers treatment

GARCÍA A.; BARRERA M. G; TEJADA, G.; CIANCIO, I.; LEONARDI, D.

Congreso; 7ma Reunión Internacional de Ciencias Farmacéuticas - RICIFA; 2023

One of the most frequent causes of ulcers in the oral mucosa is recurrent aphthous stomatitis (RAS) which is a chronic inflammatory disease of the mentioned mucosa. The treatment of RAS focuses on relieving pain, healing ulcers, and reducing severity and frequency of appearance. The options of treatments include local and systemic therapies, with topical treatments being preferred for reduced side effects. Examples include topical anaesthetics, antibiotics, antiseptics, anti-inflammatory agents, and topical corticosteroids like triamcinolone (TA). TA is formulated in several pharmaceutical dosage forms such as gels, pastes, mouthwashes, and sprays. However, these formulations are dislodged during speaking, swallowing, drinking, eating or by salivation, as well as by tongue movement. The dislodged of the formulations reduces patient compliance because of need to be applied several times a day. The aim of this work was to obtain mucoadhesive biopolymeric films based on modified chitosan, which prevent the drug from being washed away from the affected area, thus reducing the number of daily applications. To improve the properties of polysaccharides or to adapt them to a particular purpose, chemical modification of polysaccharides is often used. Chemical crosslinking has been found to be an effective method to improve the mechanical and water resistance of CH films. On the other hand, several crosslinking reactions of polysaccharides using polycarboxylic acids as a reagent have been reported. These reactions are based on the formation of the polycarboxylic acid anhydride by dehydration through heating in a medium with a minimum amount of water. To prepare the films: CH (1 % w/v) was solubilized in a 0.2 M aqueous solution of citric acid (CA) or lactic acid (LA). Each film-forming solution was kept under stirring at 25 °C for 12 h. The solutions were sonicated for 30 min to remove air bubbles. Subsequently, 30 g of the solution was poured onto glass plates and dried at 40 ◦C for 24 h. To perform the crosslinking reaction, the films were heated in an oven for 2 h at 90°C. To load the IFA onto the film, a solution of TA 0.3 % w/w in a mixture of ethanol-water-propylene glycol (62:30:8) was prepared. It was incorporated to each film 2 g of this solution (equivalent to 6 mg of TA). This preparation was dried at 40 ◦C for 24 h. The films retained their shape and uniform appearance after peeling from plates, after heating at 90°c and also after the addition of the TA-containing solution. In FT-IR spectra, the secondary amide bands at about 1583 cm-1 corresponded to amines (NH2) disappeared in the chitosan film, while two new bands at approximately 1533 and 1400 cm-1 were ascribed to symmetric N-H (–NH3+) bending vibration of chitosan and symmetrical stretching vibration of COO- groups of acids, suggesting the intermolecular interactions existed. In the spectra of the films containing TA, no characteristic signals of this drug were observed, probably due to the low concentration of this in the films. The cross-linked films prepared with CA presented improved mechanical properties and water resistance compared to those obtained with LA. The drying at 90 °C could facilitate amidation and the Maillard reaction in the membrane matrix, thus further improving their water resistance. CH-CA films had been successfully fabricated by a straightforward and effective method under the condition of heating at 90 ◦C.