Citation: Qingling Song, Huirui Wang, Junfei Yang, Hui Gao, Ke Wang, Hao Wang, Yun Zhang, Lei Wang. A "cluster bomb" oral drug delivery system to sequentially overcome the multiple absorption barriers[J]. Chinese Chemical Letters, ;2022, 33(3): 1577-1583. doi: 10.1016/j.cclet.2021.08.113 shu

A "cluster bomb" oral drug delivery system to sequentially overcome the multiple absorption barriers

Qingling Song ^{b, d, 1} ,
Huirui Wang ^{a, c, 1} ,
Junfei Yang ^{b, d} ,
Hui Gao ^{b, d} ,
Ke Wang ^{b, d} ,
Hao Wang ^b ,
Yun Zhang ^{b, d, e, *,} ,
Lei Wang ^{a, b, c, d, e, *,}

a.
Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471009, China
b.
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China
c.
Tumor Immunity and Biomaterials Advanced Medical Center, Zhengzhou University, Luoyang 471009, China
d.
Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou 450001, China
e.
Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education, Zhengzhou 450001, China

zhang_yun@ymail.com

wanglei1@zzu.edu.cn

Received Date: 9 June 2021
Revised Date: 18 August 2021
Accepted Date: 24 August 2021
Available Online: 29 August 2021

Figures(7)

Oral drugs have been widely used in clinical therapy, but their developments were severely limited by the side effects of drug exposure as well as the multiple biological barriers. In this study, we constructed a "cluster bomb" oral drug delivery system (DOX@PFeL@L100) with core-shell structure to overcome the complex absorption barriers. The inner core termed as "bomb" that contains a lot of ultra-small diameter Fe₃O₄ nanoparticles (DOX@PFeL NPs) loaded with doxorubicin (DOX) and modified with l-valine, which can efficiently penetrate the epithelial cells via PePT1 receptor mediated endocytosis. The outer shell of this "cluster bomb" is a layer of pH-sensitive polymer (Eudragit®L100) that can be served as a pH-responsive switch and effectively control the "bomb" release in the intestinal microenvironment to improve the antitumor efficiency by the Fenton like reaction of DOX and Fe²⁺/Fe³⁺. This study demonstrates that the "cluster comb" oral drug delivery system can sequentially overcome the multiple biological barriers, providing a safe and effective approach for tumor therapy.
- Oral drug delivery,
- Absorption barrier,
- Cluster bomb,
- pH-sensitive,
- PePT1 receptor
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