Development of benzydamine HCl loaded-cellulose acetate butyrate in situ forming gels for periodontal treatment

Abstract

Benzydamine hydrochloride (Bz), classified as a nonsteroidal anti-inflammatory drug, has limited its application to topical administration. Bz emerges as a promising candidate for development of solvent removal in-situ forming gel (ISG) in this research aimed at addressing periodontitis treatment. The 40 % w/w cellulose acetate butyrate (CAB) was evaluated as an ISG matrix-forming agent, with varying concentrations of Bz to examine the role of drug concentration on ISG's physicochemical attributes. The drug release kinetics, antimicrobial efficacy, and anti-inflammatory performance of developed ISG were assessed. The formulations, all featuring identical percentages of CAB, exhibited consistent physicochemical characteristics and matrix formation properties triggered by solvent exchange and removal in macroscopic and microscopic examinations. Fluorescence probes tracking with sodium fluorescein and Nile red indicated a delay in solvent movement from CAB matrix formation. X-ray tomographic microscopy and scanning electron microscopy revealed the scaffold CAB-based ISG morphology after Bz release from solvent and drug diffusions. The 3 % w/w Bz-loaded CAB-ISG prolonged drug release spanning over 7 days involving the relaxation of the polymeric network and exhibiting non-Fickian diffusion. Numerical simulations indicated that the CAB matrix effectively modulated the Bz release rate. The ISG showcased heightened antimicrobial efficacy against standard microbes and periodontitis pathogen. Additionally, the anti-inflammatory effects were attained by inhibiting protein denaturation in egg albumin and efficiently reducing the expression of IL-1β from LPS-induced human U937 macrophage assay. Consequently, the solvent removal Bz-loaded CAB-ISG stands out as a promising treatment option for periodontitis, offering sustained drug delivery and effective microbial inhibition and especially anti-inflammatory.