Lin-Zhu Zhang,* Rui-Jie Du,* Duo Wang,* Juan Qin, Chao Yu, Lei Zhang, Hai-Dong Zhu

Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, Nanjing, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Lei Zhang; Hai-Dong Zhu, Center of Interventional Radiology & Vascular Surgery, Department of Radiology, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology (Southeast University), Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, Nanjing, 210009, People’s Republic of China, Email zhang_lei@seu.edu.cn; zhuhaidong@seu.edu.cn

Abstract: With the in-depth knowledge of the pathological and physiological characteristics of the intestinal barrier–portal vein/intestinal lymphatic vessels–systemic circulation axis, oral targeted drug delivery is frequently being renewed. With many advantages, such as high safety, convenient administration, and good patient compliance, many researchers have begun to explore targeted drug delivery from intravenous injections to oral administration. Over the past few decades, the fields of materials science and nanomedicine have produced various drug delivery platforms that hold great potential in overcoming the multiple barriers associated with oral drug delivery. However, the oral transport of particles into the systemic circulation is extremely difficult due to immune rejection and biochemical invasion in the intestine, which limits absorption and entry into the bloodstream. The feasibility of the oral delivery of targeted drugs to sites outside the gastrointestinal tract (GIT) is unknown. This article reviews the biological barriers to drug absorption, the in vivo fate and transport mechanisms of drug carriers, the theoretical basis for oral administration, and the impact of carrier structural evolution on oral administration to achieve this goal. Finally, this article reviews the characteristics of different nano-delivery systems that can enhance the bioavailability of oral therapeutics and highlights their applications in the efficient creation of oral anticancer nanomedicines.

Keywords: oral nanomedicine, oral targeted drug delivery, nanoparticles, cancer treatment, biological barriers