Liposomes have made remarkable achievements as drug delivery vehicles in the clinic. Liposomal 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 pharmacokinetics. 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 hippocampus 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.

脂质体作为临床上的药物输送工具已经取得了令人瞩目的成就。脂质体产品主要得益于成功的两亲性和/或可离子化药物的远程药物装载技术，但对于不可离子化和水溶性差的治疗剂似乎不可行，从而阻碍了广泛的有前途的药物搭便车脂质体媒介物的疾病治疗。在这项研究中，通过简单的一步合成设计了一系列弱酸药物衍生物，可以通过pH梯度法将其远程装载到脂质体中。选择卡巴他赛（CTX）弱酸衍生物以评估其安全性，药效学和药代动力学。CTX弱酸衍生物脂质体在安全性方面（包括全身毒性，血液学毒性，和潜在的中枢神经毒性。具体而言，已证明脂质体具有减弱CTX对皮层和海马神经元的潜在毒性的能力。由于更高的安全性和更高的耐受剂量，在前列腺癌和转移性癌症治疗中实现了CTX弱酸衍生物负载脂质体的显着优势。