The role of cells and their products in respiratory drug delivery: the past, present, and future

ABSTRACT

Introduction

Cell-based delivery systems offer considerable promise as novel and innovative therapeutics to target the respiratory system. These systems consist of cells and/or their extracellular vesicles that deliver their contents, such as anti-microbial peptides, micro RNAs, and even mitochondria to the lung, exerting direct therapeutic effects.

Areas covered

The purpose of this article is to critically review the status of cell-based therapies in the delivery of therapeutics to the lung, evaluate current progress, and elucidate key challenges to the further development of these novel approaches. An overview as to how these cells and/or their products may be modified to enhance efficacy is given. More complex delivery cell-based systems, including cells or vesicles that are genetically modified to (over)express specific therapeutic products, such as proteins and therapeutic nucleic acids are also discussed. Focus is given to the use of the aerosol route to deliver these products directly into the lung.

Expert opinion

The use of biological carriers to deliver chemical or biological agents demonstrates great potential in modern medicine. The next generation of drug delivery systems may comprise ‘cell-inspired’ drug carriers that are entirely synthetic, developed using insights from cell-based therapeutics to overcome limitations of current generation synthetic carriers.

Keywords:

• Cell therapy
• Exosomes
• microRNA
• microvesicles
• nebulized delivery
• ARDS

Article highlights

• The use of cells and cell-based vectors provide an alternative method for drug delivery which overcomes many of the challenges faced such as non-targeted biodistribution, poor longevity, and high toxicity.

• Multiple cell types have been investigated as drug delivery vehicles, each with their own advantages and disadvantages, however the definitive biological carrier may be cell derived rather than the whole cell itself.

• Methods of therapeutic loading include direct loading of the drug product or using the cells’ own endogenous machinery to generate the therapeutic of choice. Modes of drug release discussed include passive release, and other clever approaches incorporating chemogenetic and biomimetic strategies.

• The use of multidisciplinary skills from the fields of biology, chemistry, and engineering and steering research toward the generation of biosynthetic carriers which incorporate the beneficial properties of synthetic and biological particles for drug delivery.

• Delivery of the therapeutic carrier to the site of interest is also discussed with the cells own naïve characteristics often making them the carrier of choice. Considerations of size, localisation, paracrine effects, and longevity are needed when determining the route of administration. Nebulisation is discussed as a non-invasive, effective strategy for pulmonary delivery.

• There are a range of challenges and considerations to be addressed and overcome to further the research of biological carriers for drug delivery including commercialisation, up-scaling production, establishing guidelines, and development of specific regulatory bodies.

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

This paper was funded by the Science Foundation Ireland Grant 16-FRL-3845.