Experimental Design Supported Liposomal Aztreonam Delivery: In Vitro Studies

The present study focuses on a systemic approach to develop liposomal aztreonam as a promising dosage form for inhalation therapy in the treatment of pneumonia and explores the in-vitro antimicrobial and cell uptake efficacy. Liposomes were prepared by ethanol injection method using the lipids - soya phosphatidylcholine (SP) and cholesterol (CH). A central composite design (CCD) was employed to optimize the lipid composition to evaluate the effect on vesicle size, zeta potential and entrapment efficiency of the formulation. A numerical and graphical optimization was carried out to predict the optimized blend. The optimized formulation was characterized for vesicle size, surface charge, encapsulation, surface morphology, differential scanning calorimetry (DSC), powder X Ray Diffraction (PXRD), thermogravimetric analysis (TGA), in vitro diffusion, accelerated stability studies, antimicrobial studies on Pseudomonas aeruginosa NCIM 2200 and in vitro cell uptake studies. The optimized formulation was found to have a particle size of 144 nm, a surface charge of -35 mV, with satisfactory drug entrapment. The surface morphology study proved the formation of nanosized vesicles. The drug release from liposomal matrix was biphasic in nature. The solid-state study revealed the reason for good encapsulation of drug. The moisture retention capacity was found to be minimum. The anti-microbial study revealed the potential antibacterial activity of the optimized formulation over the pure drug. The formulation was found to be safe on the epithelial cells and showed a marked increase in cellular uptake of aztreonam in a lipid carrier. It can be concluded that the optimized liposomal aztreonam could be considered as a promising approach for the delivery of aztreonam through inhalation.