Recent advances in targeted drug delivery for the treatment of pancreatic ductal adenocarcinoma

ABSTRACT

Introduction

Pancreatic ductal adenocarcinoma (PDAC) has become a serious health problem with high impact worldwide. The heterogeneity of PDAC makes it difficult to apply drug delivery systems (DDS) used in other cancer models, for example, the poorly developed vascular system makes anti-angiogenic therapy ineffective. Due to its various malignant pathological changes, drug delivery against PDAC is a matter of urgent concern. Based on this situation, various drug delivery strategies specially designed for PDAC have been generated.

Areas covered

This review will briefly describe how delivery systems can be designed through nanotechnology and formulation science. Most research focused on penetrating the stromal barrier, exploiting and alleviating the hypoxic microenvironment, targeting immune cells, or designing vaccines, and combination therapies. This review will summarize the ways to reverse the malignant pathological features of PDAC and hopefully provide ideas for subsequent studies.

Expert opinion

Drug delivery systems designed to achieve penetrating functions or to alleviate hypoxia and activate immunity have achieved good therapeutic results in animal models in several studies. In future studies, there is a need to deliver PDAC therapeutics in a more precise manner, or the use of drug carriers for multiple functions simultaneously, are potential therapeutic strategy.

KEYWORDS:

• Pancreatic ductal adenocarcinoma
• Drug delivery systems
• Stromal barriers penetration
• Harnessing the hypoxia microenvironment
• Re-education of the immune microenvironment

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Article highlights

• Pancreatic cancer is difficult to treat mainly due to its stromal barrier that prevents drug entry.

• The presence of the stromal barrier leads to an internal hypoxic microenvironment and a state of immunosuppression.

• Size conversion and charge reversal are two strategies to increase the permeation efficiency of drug delivery systems.

• The hypoxic and immunosuppressive microenvironment can be improved by transporting oxygen or immunotherapeutic agents.

• Combination therapies that combine multiple strategies are promising treatments.

This box summarizes key points contained in the article.

Additional information

Funding

This paper was supported by the National Natural Science Foundation of China (32030059, 82121002), Key Projects of Shanghai Science Foundation (19JC1410800), and Shanghai Municipal Science and Technology Major Project (Grant 2018SHZDZX01) and ZJLab.