Synthesis of Paclitaxel Derivatives for Remote Loading into Liposomes and Improved Therapeutic Effect.

ABSTRACT: A series of novel paclitaxel derivatives modified by boronic acid according to the characteristics of the interaction between RB(OH)₂ and different strapping agents of intraliposomal aqueous phase were designed and synthesized, which were then used to develop remote poorly water-soluble drugs loading into liposomes. Meanwhile, we screened nineteen paclitaxel boronic acid derivatives for their cytotoxic activities against three cancer cell lines (A549, HCT-116 and 4T1) and one normal cell line (LO2), and performed liposome formulation screening of active compounds. Among all the compounds, the liposome of 4d, with excellent drug-encapsulated efficiency (>95% for drug-to-lipid ratio of 0.1 w/w), was the most stable. Furthermore, the liposomes of compound 4d (8 mg/kg, 4 times) and higher dose of compound 4d (24 mg/kg, 4 times) showed better therapeutic effect than paclitaxel (8 mg/kg, 4 times) in the 4T1 tumor model in vivo, and the rates of tumor inhibition were 74.3%, 81.9% and 58.5%, respectively. This study provided a reasonable design strategy for the insoluble drugs to improve their drug loading into liposomes and anti-tumor effect in vivo.

SUBMITTER: Xu X 

PROVIDER: S-EPMC9694711 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature