In view of the limitations of amikacin intravenous administration, including poor permeability in lung tissue and significant toxic and side effects, this study adopted the reverse-phase evaporation method to prepare and optimize the formulation and process of amikacin liposomes, and systematically evaluated their physical and chemical properties, in order to provide experimental basis for lung targeted delivery.

Amikacin liposomes were prepared by the reverse-phase evaporation method using dipalmitoylphosphatidylcholine (DPPC) and cholesterol as lipid materials. The encapsulation efficiency was determined by ultrafiltration centrifugation-HPLC. Based on the single factor investigation, the formulation and process parameters were optimized by the Box-Behnken response surface method with encapsulation efficiency as the evaluation index, and their encapsulation efficiency, morphology, particle size, polydispersity index (PDI), Zeta potential and in vitro release behavior were studied.

The optimum prescription process parameters were as follows: the phospholipid-to-cholesterol ratio was 4, the phospholipid concentration was 53.79 mg·mL^-1, the ratio of lipid to drug was 3.78, the amount of organic solvent (chloroform) was 24.4 mL, the ultrasonic frequency was 40 times, and the rotary evaporation pressure was 600 mbar. The average encapsulation efficiency of the liposomes was (50.40 ± 0.89)%, the average particle size was (218.37 ± 2.47) nm, the PDI was (0.24 ± 0.01), and the Zeta potential was (-0.684 ± 0.21) mV. The in vitro release showed an obvious sustained release effect, with a cumulative release rate of 52.99% at 48 h, which was consistent with the Higuchi model.

The optimized preparation process of amikacin liposomes has good stability and reproducibility. The product has uniform particle size, stable morphology and sustained-release property. It has the potential advantages of achieving pulmonary targeted delivery, improving local efficacy and reducing toxic and side effects, thus laying a foundation for subsequent pharmacodynamics and safety studies.