Preparation of mitoxantrone hydrochloride-loaded liposomes and investigation of pharmacodynamics and pharmacokinetics / 中国药学杂志

ABSTRACT

OBJECTIVE: To prepare mitoxantrone-loaded liposomes using copper ion gradient method and compare the pharmacodynamics (PD) and pharmacokinetics (PK) of liposomal mitoxantrone (Mit-lipo) with free mitoxantrone (Mit-free). METHODS: Orthogonal design was adopted to screen the preparation process and formulation of Mit-lipo, using encapsulation efficiency (EE) as the evaluation index. The antineoplastic effect of Mit-lipo was evaluated in L1210/BDF1 ascites tumor model. The PK study of Mit-lipo and Mit-free was performed in KM mice followed a single intravenous injection. RESULTS: The optimal preparation process and formulation were as follows; the weight proportion of mitoxantrone to HSPC was 110. Mit-lipo was prepared by copper ion gradient method using 0.3 mol · L-1 copper sulfate (pH 7.5) as the inner phase solution. The drug loading process was performed at 60°C for 30 min. The particle size of Mit-lipo was (99.5±1.9) nm, and the EE was (95.0±0.6)%. The PK study showed that the AUC and t1/2 values of Mit-lipo were higher than those of Mit-free in KM mice, suggesting Mit-lipo had a long circulation characteristic. The PD study showed that Mit-lipo could significantly prolong the survival time of tumor-bearing mice with lower toxicity than Mit-free. CONCLUSION: The developed preparation method for Mit-lipo has a high EE. The PK of Mit-lipo changes obviously compared to Mit-free, resulting in an increase of the therapeutic index.