Advances in the use of cell penetrating peptides for respiratory drug delivery

ABSTRACT

Introduction

Respiratory diseases are leading causes of death in the world, still inhalation therapies are the largest fail in drug development. There is an evident need to develop new therapies. Biomolecules represent apotential therapeutic agent in this regard, however their translation to the clinic is hindered by the lack of tools to efficiently deliver molecules. Cell penetrating peptides (CPPs) have arisen as apotential strategy for intracellular delivery that could theoretically enable the translation of new therapies.

Areas covered

In this review, the use of CPPs as astrategy to deliver different molecules (cargoes) to treat lung-relateddiseases will be the focus. Abrief description of these molecules and the innovative methods in designing new CPPs is presented. The delivery of different cargoes (proteins, peptides, poorly soluble drugs and nucleic acids) using CPPs is discussed, focusing on benefits to treat different respiratory diseases like inflammatory disorders, cystic fibrosis and lung cancer.

Expert opinion

The advantages of using CPPs to deliver biomolecules and poorly soluble drugs to the lungs is evident. This field has advanced in the past few years toward targeted intracellular delivery, although further studies are needed to fully understand its potential and limitations in vitro and in vivo.

KEYWORDS:

• Lung
• cystic fibrosis
• poorly soluble drugs
• cancer
• inflammatory diseases
• asthma
• COPD
• designing tools
• machine-learning
• aerosol drug delivery

Article highlights

• Cationic and amphipathic CPPs have been used to enhance the delivery of proteins, peptides, nucleic acids and poorly soluble drugs to treat respiratory diseases. Amongst these diseases, lung cancer is the most studied with few studies addressing inflammatory diseases and cystic fibrosis

• Applications of CPPs for respiratory diseases range from the delivery of therapeutic biomolecules and drugs, to their use as an imaging tool and for the identification of intracellular pathways

• The development of ACPPs holds promising results to circumvent current CPPs targeting issues.

• Cell penetrating peptides hold great potential in delivering molecules intracellularly and should be further explored in combination to other formulation technologies to broaden the spectrum of therapeutic choices available to treat lung diseases

• With the heterogeneity observed in respiratory diseases, the availability of a tool that could be used to increase drug delivery, as well as to understand the role of molecules in the disease state is valuable, and should be explored

• The use of machine-learning techniques has increased the knowledge around CPPs, although further toxicity studies are still required to move forward.

This box summarizes key points contained in the article.

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.

Additional information

Funding

D Traini was the recipient of an Australian Research Council Future Fellowship [project number FT12010063].