Formulation development and evaluation of lidocaine hydrochloride loaded in chitosan-pectin-hyaluronic acid polyelectrolyte complex for dry socket treatment

Abstract

The main purpose of this study was to assess a lidocaine hydrochloride-loaded chitosan-pectin-hyaluronic polyelectrolyte complex for rapid onset and sustained release in dry socket wound treatment. Nine formulations (LCs) of lidocaine hydrochloride (LH) loaded into a chitosan–pectin–hyaluronic polyelectrolyte complex (PEC) were assessed using full factorial design (two factors × three levels). The formulations ranged between 4 and 10% w/w LH and 0.5–1.5% w/w HA. The following physicochemical properties of LCs were characterized: size, zeta potential, % entrapment efficiency, viscosity, mucoadhesiveness, % drug release, morphology, storage stability, and cytotoxicity. The particle size, zeta potential, % EE, viscosity, and % mucoadhesion increased with increasing LH and HA concentrations. Rapid release of LH followed a zero-order model, and a steady-state percentage of the drug was released over 4 h. LCs were found to be non-cytotoxic compared to LH solution. LH loaded into PEC demonstrated appropriate characteristics—including suitable rate of release—and fit a zero-order model. Furthermore, it was not cytotoxic and showed good stability in a high-HA formula, making it a promising candidate for future topical oral formulations.

Colloidal Polyelectrolyte Complexes from Hyaluronic Acid: Preparation and Biomedical Applications

“…[19,20] Furthermore, HA can act synergistically with other biopolymers, namely CTS, in order to improve PEC mucoadhesiveness and offer more advantages for oral or nasal administration. [26,95,96] HA can also be chemically modified owing to the ubiquitous distribution of carboxyl, hydroxyl, and acetamido groups across the chain structure (Figure 1), leading to the perspectives of elaborating PECs with more interesting physicochemical and biological properties from HA derivatives. [97] For instance, the introduction of hydrophobic groups like phospholipids [98] or alkyl chains [99] can generate amphiphilic HA derivatives for better encapsulation of hydrophobic molecules.…”

“…[ 19,20 ] Furthermore, HA can act synergistically with other biopolymers, namely CTS, in order to improve PEC mucoadhesiveness and offer more advantages for oral or nasal administration. [ 26,95,96 ]…”

Polymeric Micelles Enhance Mucosal Contact Time and Deposition of Fluocinolone Acetonide

“…The formula–mucin bonding of FPMs was not very strong, and this could be due to hydrogen bonding between hydroxyl and carboxyl groups [ 11 ]. The non-ionic bonds of the formula–mucin complex could be involved, but the negative charges of the formulas and mucin provide weak bonds that may decrease over time [ 13 ]. Furthermore, external forces or stimuli (such as shaking) could create a stronger formula–mucin interaction, and this factor is likely essential in application.…”

“…Mucoadhesiveness was assessed by observing the interactions of FPMs and mucin type II and measuring the bond strength between the polymeric micelle solution and the glycoproteins in the mucus [ 11 , 12 ], according to the results of our previous study [ 13 ]. Each FPM (5 mL) was mixed with mucin type II (5 mL) in test tubes, and the tube was inverted 5 times without shaking.…”

“…Each FPM solution contained in a 5 mL syringe and weighing approximately 5 g, was loaded into a 35 × 50 mm dialysis membrane tube (dialysis membrane standard RC Tubing MWCO 3.5K Da, Spectra/Por ® , Waltham, MA, USA), avoiding the gas bubble and tided with dialysis tubing clamps with magnetic stirrers. Each dialysis bag was placed into a closed container, contained 250 mL of artificial saliva (composed of 0.17% sodium bicarbonate, 0.05% sodium dihydrogen orthophosphate, and 0.02% calcium chloride in water at pH 7.4 [ 13 ]), and was stirred at 600 rpm at 37 ± 2 °C.…”