Citation: Xin Wu, Xinmei Chen, Xinyu Wang, Haisheng He, Jianming Chen, Wei Wu. Paclitaxel-lipid prodrug liposomes for improved drug delivery and breast carcinoma therapy[J]. Chinese Chemical Letters, ;2024, 35(2): 108756. doi: 10.1016/j.cclet.2023.108756 shu

Paclitaxel-lipid prodrug liposomes for improved drug delivery and breast carcinoma therapy

Xin Wu ^{a, b, c, 1} ,
Xinmei Chen ^{c, 1} ,
Xinyu Wang ^{b, 1} ,
Haisheng He ^{a, c} ,
Jianming Chen ^{b, c, *,} ,
Wei Wu ^{a, d, *,}

a.
Key Laboratory of Smart Drug Delivery of MOE, School of Pharmacy, Fudan University, Shanghai 201203, China
b.
Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China
c.
Shanghai Wei Er Lab, Shanghai 201707, China
d.
Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, China

chenjm0711@163.com

wuwei@shmu.edu.cn

Received Date: 26 April 2023
Revised Date: 24 June 2023
Accepted Date: 29 June 2023
Available Online: 1 July 2023

Figures(4)

Paclitaxel (PTX) is widely applied for the treatment of unresectable and metastasis breast carcinoma as well as other cancers, whereas its efficacy is always impeded by poor solubility. Liposomes are one kind of the most successful drug carriers which are capable of solubilizing PTX and improving patients' tolerance owing to excellent biocompatibility and biodegradability. However, poor compatibility between PTX and liposomes compromises the stability, drug loading and anti-tumor capacity of liposomal formulations. To address this issue, three lipids with various chain lengths, namely, myristic acid (MA, 14C), palmitic acid (PA, 16C) and stearic acid (SA, 18C), were conjugated to PTX via ester bonds and the synthesized prodrugs with high lipophilicity were further formulated into liposomes, respectively. All liposomes show high stability and drug loadings, as well as sustained drug release. The chain lengths of lipids are negatively correlated with drug release and enzymatic conversion rates, which further impact the pharmacokinetics, tumor accumulation, and anti-tumor efficacy of liposomal PTX. Neither rapid nor slow drug release facilitates high tumor accumulation as well as anti-tumor efficacy of PTX. Among all liposomes, PTX-PA-loaded liposomes show the longest circulation and highest tumor accumulation of PTX and exert the most potent anti-tumor capacities in vivo, owing to its moderate drug release and enzymatic conversion rate. Witnessing its superior safety, PTX-PA liposomes hold potential for further clinical translation.
- Paclitaxel,
- Lipids,
- Prodrugs,
- Liposomes,
- Drug release,
- Chemotherapy
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