氧化苦参碱与黄芪甲苷 IV 共载脂质体：放大生产目的及其对乳腺癌抗 PD-1 疗效的增强

The response rate of programmed cell death protein-1 (PD-1) inhibitors in breast cancer remains unsatisfactory, primarily due to the limited infiltration and activity of tumor-infiltrating T lymphocytes (TILs). Previous studies demonstrated that oxymatrine (Om) and astragaloside IV (As) could enhance TIL infiltration and function by inhibiting cancer-associated fibroblasts (CAFs) and promoting mitochondrial activity in TILs, respectively.

Thus, combining Om and As may be a promising strategy to improve the antitumor effects of PD-1 inhibitors in breast cancer.

However, co-delivery above drugs into breast cancer tissue is challenging due to their low bioavailability and distinct physicochemical properties.

This study addresses this challenge by formulating Om and As co-loaded liposomes (Om-As-Lip) and comparing the scale-up production methods: high-pressure homogenization (EP-HPH) and microfluidics. Om-As-Lip prepared via microfluidics demonstrated superior entrapment efficiency (As: 99. 03 0. 04 %, Om: 67. 01 0. 02 %) and a significantly higher production rate (22. 12 mL/min) compared to EP-HPH (1. 19 mL/min).

Additionally, Om-As-Lip produced by microfluidics increased the area under the curve (AUC) (Om: 6. 17-fold, As: 2. 07-fold) and maximum concentration (Cmax) (Om: 1. 58-fold, As: 3. 49-fold) compared to the free drugs.

Importantly, Om-As-Lip enhanced the antitumor efficacy of -PD-1 by inhibiting CAF activation and boosting TIL activity, resulting in a tumor inhibition rate of 61. 2 % and extended survival in mice. This work presents a novel perspective for scaling up co-delivered formulations of drugs with differing polarities to improve breast cancer immunotherapy.