Ceftriaxone-Loaded Liposomal Nanoparticles for Pulmonary Delivery Against Lower Respiratory Tract Infections: Development and Characterization

<b>Background/Objectives:</b> Herein, we demonstrate the development and characterization of ceftriaxone (CTX)-loaded liposomal nanoparticles (NPs) intended to be applicable to the management of lower respiratory tract infections (LRTIs) associated with resistant bacteria. <b>Methods:</b> The CTX-loaded liposomal NPs were fabricated by a thin film hydration approach. <b>Results:</b> The particle size of the NPs, determined by a Zetasizer, was within the range of 90-536 nm. Microscopic examination by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) revealed that particles are spherical in shape and have retained their original morphology even after freeze-drying. Attenuated total reflection-Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC), thermogravimetric (TG), and powder X-ray diffraction (PXRD) spectra exhibited that CTX is incorporated into the liposomes with no possible interaction between drug and excipients. The formation of the CTX-loaded liposomal NPs was dependent on the concentrations of phospholipids, cholesterol and mannitol; however, no considerable differences were observed in entrapment efficiency and loading capacity of CTX formulations (F6-F10). Using a twin-stage impinger (TSI), the in vitro aerosolization of the formulations were carried out at a flow rate of 60 ± 5 L/min and CTX was determined by a validated HPLC method and the prepared liposomal formulations produced promising fine particle fraction (FPF) between 47 and 62%. The prepared formulation (F6) showed prolonged CTX release of 94.0% ± 5.7 and 95.9% ± 3.9 at 24 h and 48 h, respectively. The drug release followed the Hixon-Crowell model, with CTX being transported through Fickian diffusion. <b>Conclusions:</b> These results highlight the prepared CTX-loaded inhaled liposomal formulation would be suitable for pulmonary delivery and extend the successful antibiotic delivery strategies for the effective management of LRTIs.