Preparation of New Doxorubicin Hydrochloride Liposomes

[Objectives]To prepare protopanaxadiol type doxorubicin hydrochloride liposomes by replacing cholesterol with protopanaxadiol,a derivative of ginsenoside,which has a similar structure with cholesterol,to reduce the adverse reaction of adriamycin(doxorubicin)and improve the shortcomings of ordinary doxorubicin hydrochloride.[Methods]Liposomes were prepared by thin film dispersion-ammonium sulfate gradient method,and the optimal formulation was screened by Box-Behnken experiment with particle size and encapsulation efficiency as the evaluation indicator through single factor experiment,and the drug release in vitro was verified.[Results]The average particle size of the liposomes was(149.21±1.2)nm,the polydispersity index(PDI)was(0.22±0.02),and the potential was-(15.22±1.57)mV.The liposomes were spherical and uniform in size;the encapsulation efficiency and drug loading of the new doxorubicin hydrochloride liposomes were(89.71±4.4)%and(7.28±0.8)%,respectively.[Conclusions]The new doxorubicin hydrochloride liposomes was successfully prepared by a film dispersion-ammonium sulfate gradient method,the internal circulation of the doxorubicin hydrochloride liposomes was prolonged,and the new material has good stability.This study is expected to lay a foundation for the successful preparation of new doxorubicin hydrochloride liposomes in vitro and in vivo.

Nonclinical Study of the Active Components of Doxorubicin Hydrochloride Liposome Injection in Vivo

Objectives: A non-clinical study was performed to establish a LC-MS/MS method to determine the in vivo active components of doxorubicin hydrochloride liposome injection in the plasma of Sprague-Dawley rats. Methods: Ten male SD rats were administered tail vein with a single dose of 10 mg/kg, and the concentrations of doxorubicin hydrochloride in plasma, heart, liver, spleen, lung, and kidney were determined by liquid chromatography-tandem mass spectrometry, and the pharmacokinetic parameters were calculated. Results: The final concentration of doxorubicin hydrochloride ranged from 500 ng/mL to 250,000 ng/mL, and the lower limit of quantification was 500 ng/mL;the main pharmacokinetic parameters: T1/2 was (19.282 ± 10.305) h, Cmax was (118514.828 ± 26155.134) ng/mL, AUC0-24 and AUC0-∞ were (1216659.205 ± 192706.268) ng/mL⋅h and (2082244.523 ± 860139.487) ng/mL⋅h, MRT0-24 and MRT0-∞ were (9.237 ± 0.423) h and (26.52 ± 14.015) h, respectively, and clearance (CL) was (0.005 ± 0.002) mL/h⋅ng. Conclusions: The method is simple, rapid, and sensitive, which can be used for the determination of doxorubicin hydrochloride concentration in the plasma of SD rats and pharmacokinetic non-clinical studies.

Microwave ablation combined with transarterial chemoembolization containing doxorubicin hydrochloride liposome for treating primary and metastatic liver cancers

Aims:To determine the safety and efficacy of microwave ablation(MWA)and transarterial chemoembolization(TACE)with doxorubicin hydrochloride liposome(DHL)in patients with primary liver cancer(PLC)and metastatic liver cancer(MLC).Materials and methods:The medical records of patients with primary or metastatic liver cancer who underwent MWA combined with TACE containing DHL from March 2019 to March 2022 were collected and analyzed.Treatment-related adverse events(AEs)were recorded.Local tumor response was evaluated according to the modified RECIST criteria.Local tumor progression-free survival(LTPFS)and overall survival(OS)were calculated using the Kaplan-Meier method.Results:Altogether,96 patients with liver cancer were included(PLC,n=45;MLC,n=51).Forty(41.7%)patients experienced AEs during treatment,and eight(8.3%)patients developed grade 3 AEs.Compared to before treatment,the serum total bilirubin level and neutrophil to lymphocyte ratio significantly increased after treatment.The median LTPFS was 14.5 months in patients with PLC and 10.7 months in patients with MLC.The median OS was not reached in patients with PLC or MLC.The 1-month and 3-month disease control rates reached more than 80%in both groups.Conclusion:MWA combined with TACE with DHL may be a safe and effective method for the treatment of liver cancer.