Carbopol coated mucoadhesive PLGA nanoparticles for the sustained delivery of pilocarpine in the buccal cavity

Abstract

This study investigates a new nanoparticulate (NP) formulation for local buccal administration of pilocarpine (PIL) to treat xerostomia, aiming to improve patient compliance and reduce side effects. PIL-loaded NPs were prepared using poly (d,l-lactic-co-glycolic acid) (PLGA) as a matrix/carrier and carbopol (CRB) as a mucoadhesive agent at various concentrations at ratios of 0.05%, 0.10% and 0.15% w/v. The NPs were characterized in terms of size, morphology, drug loading, thermophysical and physicochemical properties, in vitro dissolution performance, and mucoadhesion. Smooth spherical drug-loaded NPs (200-300 nm) were prepared in all cases. CRB coating did not impact particle size or polydispersity index (PDI) but increased NPs’ negative surface charges. Good storage stability, high production yields (72.0%-83.7%), and adequate drug loading efficiencies (9.0%-9.7%) were achieved, in all cases. DSC and pXRD measurements confirmed the amorphous drug dispersion, while ATR-FTIR studies revealed strong molecular interactions between the matrix/carrier and the mucoadhesive agent. In vitro drug release studies showed sustained release profiles for all NPs, whereas the application of a CRB-coating enhanced mucoadhesion performance through the formation of electrostatic ionic interactions and physical entanglement with mucin. The preparation of a new PLGA-based NP formulation may present itself as a promising strategy for the buccal administration of PIL, while the use of CRB coating could be considered as a useful approach for enhancing the mucus adhesion of NPs.