Targeted and pH-sensitive polyzwitterionic liposomes for oral anticancer drug delivery--颗粒学报PARTICUOLOGY

a Beijing Key Laboratory for Bioengineering and Sensing Technology, School of Chemistry and Biological Engineering, University of Science and Technology Beijing, Beijing, 100083, China
b State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Chemical Biology Center, Peking University, Beijing, 100191, China
c School of Materials Science and Engineering, University of Science and Technology Beijing, Beijing, 100083, China

10.1016/j.partic.2025.01.001

Volume 98, March 2025, Pages 13-20

Received 3 August 2024, Revised 5 December 2024, Accepted 4 January 2025, Available online 17 January 2025, Version of Record 28 January 2025.

E-mail: yaowenlong@bjmu.edu.cn; liyan310@ustb.edu.cn

Highlights

• Targeted and pH-sensitive polyzwitterionic liposomes overcome physiological barriers during oral anticancer drug delivery.

• Targeted and pH-sensitive polyzwitterionic liposomes with doxorubicin hydrochloride significantly inhibit tumor cells growth.

• Targeted and pH-sensitive polyzwitterionic liposomes provide a promising approach for oral cancer therapy.

Abstract

Compared to intravenous injection, oral administration is attractive due to its many advantages for cancer therapy. Taken physiological barriers and other profiles of oral anticancer drug carriers into consideration, targeted and pH-sensitive polyzwitterionic liposomes (ZL) based on zwitterionic poly(carboxybetaine) (PCB) were constructed for oral delivery of doxorubicin hydrochloride (DOX·HCl) for cancer therapy. The DOX-ZL with 40% trehalose had good lyophilization stability, which would be packaged into enteric capsules to enhance their stability in stomach. In addition, DOX-ZL exhibited good storage stability and serum stability. The DOX-ZL could achieve controlled release of DOX·HCl at the endosomal pH 5.0 due to the pH-sensitive of zwitterionic PCB. Importantly, DOX-ZL could targeted deliver DOX·HCl to Caco-2 cells to cross the intestinal epithelial cell layer. The empty ZL had good biocompatibility, while DOX-ZL significantly inhibited tumor cells growth due to their high cellular uptake and controlled drug release ability. Therefore, this work provided a promising approach for oral cancer therapy.

Graphical abstract

Keywords

Polyzwitterionic liposomes; Poly(carboxybetaine); Doxorubicin hydrochloride; Oral administration; Cancer therapy

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