A facile and universal method to achieve liposomal remote loading of non-ionizable drugs with outstanding safety profiles and therapeutic effect

• 来源期刊: 药学学报（英文版）
• 年，卷（期）: 2021,（1）
• 所属期刊栏目: Original articles
• 页码范围: 258-270
• 页数: 13页
• 语种: 英文

摘要

Liposomes have made remarkable achievements as drug delivery vehicles in the clinic.Lipo-somal products mostly benefited from remote drug loading techniques that succeeded in amphipathic and/or ionizable drugs,but seemed impracticable for nonionizable and poorly water-soluble therapeutic agents,thereby impeding extensive promising drugs to hitchhike liposomal vehicles for disease therapy.In this study,a series of weak acid drug derivatives were designed by a simplistic one step synthesis,which could be remotely loaded into liposomes by pH gradient method.Cabazitaxel(CTX)weak acid derivatives were selected to evaluate regarding its safety profiles,pharmacodynamics,and pharmacoki-netics.CTX weak acid derivative liposomes were superior to Jevtana? in terms of safety profiles,including systemic toxicity,hematological toxicity,and potential central nerve toxicity.Specifically,it was demonstrated that liposomes had capacity to weaken potential toxicity of CTX on cortex and hippo-campus neurons.Significant advantages of CTX weak acid derivative-loaded liposomes were achieved in prostate cancer and metastatic cancer therapy resulting from higher safety and elevated tolerated doses.