One- pot development of spray dried cationic proliposomal dry powder insufflation: Optimization, characterization and bio-interactions

In the present investigation, one-pot synthesis method has been reported for the preparation of tramadol loaded proliposomes (PLs) coated with chitosan (CCPLs) and carboxymethyl chitosan (CM-ChPLs) for intranasal administration. Spray drying method used for formulation of PLs was optimized using Design of Experiment (DoE). The formulated PLs were extensively characterized and evaluated. The formulation was assessed for biocompatibility using cell viability assay, along with estimation of inflammatory potential of PLs, in vitro drug permeation across nasal mucosa, in vitro mucoadhesion study, nasal mucosa penetration study and analysis of powder spray pattern. The prepared PLs were also assessed for their interactions and stability under various physiological conditions. The interaction of different PLs with serum protein and mucin was assessed using DLS and zeta potential measurement. The stability study demonstrated superiority of coated PLs over uncoated PLs. The cell viability study confirmed the biocompatibility of developed PLs while confocal microscopy confirmed enhanced permeation of coated PLs across nasal mucosa. All PLs were stable in simulated nasal fluid. The in vitro drug release studies demonstrated sustained release which was also supported by results obtained after ex vivo permeation study. The overall results confirmed that type of surface modification and surface charge along with particle size plays an important role in type and extent of interaction of PLs with proteins and mucin. This could directly or indirectly affect the diffusion or penetration of nanoliposomes across mucosa and ultimately affects in vivo results.