Ke Wang,1,2,* Jinlu Shang,3,* Chao Tao,1,2,* Mingquan Huang,4 Daiqing Wei,5 Liuxuan Yang,1 Jing Yang,1 Qingze Fan,1 Qian Ding,6 Meiling Zhou1 

1Department of Pharmacy, the Affiliated Hospital, Southwest Medical University, Luzhou, People’s Republic of China; 2Department of Clinical Pharmacy, School of Pharmacy, Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Pharmacy, West China Hospital Sichuan University Jintang Hospital, Chengdu, People’s Republic of China; 4Sichuan Treatment Center for Gynaecologic and Breast Diseases (Breast Surgery), the Affiliated Hospital, Southwest Medical University, Luzhou, People’s Republic of China; 5Department of Orthopaedics, the Affiliated Hospital, Southwest Medical University, Luzhou, People’s Republic of China; 6Department of Clinical Pharmacy, the Third Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Meiling Zhou, Department of Pharmacy, the Affiliated Hospital, Southwest Medical University, No. 25, Taiping Street, Luzhou, Sichuan, 646000, People’s Republic of China, Email meilzhou@163.com Qian Ding, Department of Clinical Pharmacy, the Third Hospital of Mianyang, Sichuan Mental Health Center, No. 190, East Section of Jiannan Road, Mianyang, Sichuan, 621000, People’s Republic of China, Email dingqian0506@163.com

Abstract: Betulinic acid (BA) is a natural compound obtained from plant extracts and is known for its diverse pharmacological effects, including anti-tumor, antibacterial, anti-inflammatory, antiviral, and anti-atherosclerotic properties. Its potential in anti-tumor therapy has garnered considerable attention, particularly for the treatment of breast, lung, and liver cancers. However, the clinical utility of BA is greatly hindered by its poor water solubility, low bioavailability, and off-target toxicity. To address these issues, researchers have developed various BA-loaded nanoformulations, such as nanoparticles, liposomes, micelles, and nanofibers, aiming to improve its solubility and bioavailability, prolong plasma half-life, and enhance targeting ability, thereby augmenting its anti-cancer efficacy. In preparing this review, we conducted extensive searches in well-known databases, including PubMed, Web of Science, and ScienceDirect, using keywords like “betulinic acid”, “nanoparticles”, “drug delivery”, “tumor”, and “cancer”, covering the literature from 2014 to 2024. The review provides a comprehensive overview of recent advancements in the application of BA-loaded nano-delivery systems for anti-tumor therapy and offers insights into their future development prospects.

Keywords: betulinic acid, nanoformulations, anti-tumor, bioavailability, targeting