Pulmonary drug and vaccine delivery: therapeutic significance and major challenges

1. Background and interests in this field; focus of my current research

Dr. Abdelwahab Omri obtained his PhD from Université de Montréal in 1995 in pharmacology focus on pulmonary drug and vaccine delivery. After completing postdoctoral fellowships at McGill University and the University of Toronto (1996 – 1998), he spent > 2 years as Research associate at NRC (institute of biological sciences in Ottawa) from 1998 to 2000. Dr. Omri is currently Full Professor in the Department of Chemistry and Biochemistry with a cross appointment to the Department of Biology, the Biomolecular Sciences PhD Programme, School of Rural and Northern Health PhD Programme and Medical Sciences Division, Northern Ontario School of Medicine (NOSM). Dr. Omri’s research interests are focused on lipid-based drug and vaccine delivery systems. His laboratory employs a multi-disciplinary approach to addressing the antimicrobial resistance to Gram negative bacteria in cystic fibrosis patients and in medical devices implants. Dr. Omri is also involved in the education of undergraduate and graduate students through the coordination of several calendar courses in biochemistry, pharmacology and toxicology and pharmaceutical technology. In addition to research, Dr. Omri is actively involved in the research training of both undergraduate and graduate students. Dr. Omri has served in administrative capacities in several international scientific societies. He has published > 80 peer-reviewed research articles over his career on various aspects of drug delivery and targeting in addition to several published book chapters and books (2). He has served on a number of Editorial Boards and Granting Agencies in Canada and abroad. Dr. Omri has two patents.

2. Brief history and relevance of this topic

Pulmonary administration have been used and still employed to manage numerous lung illness for centuries. These diseases include asthma, chronic obstructive pulmonary disease, diabetes, lung cancer and pulmonary infection.

This route involves the inhaling of a drug that is in a gas, liquid or powder form. The drug is absorbed through the alveoli to the lungs. The huge surface area of the alveoli and its good vascularization provide a non-invasive and effective drug delivery at the desired concentration while minimizing the drug toxic effect. The advantages of this route may include the avoidance of liver metabolism and the availability of reliable, metered nebulizer-based delivery systems capable of accurate dosage delivery, in powder, gas or liquid form.

3. Therapeutic significance and major challenges of drug delivery to the lung: why this themed issue is important?

In the last few decades, wide strides have been achieved for the pulmonary delivery of nucleic acids (e.g., siRNA), anticancer drugs (e.g., doxorubicin), and protein and peptide drugs (e.g., insulin). The use of liposomes, polymers, lipoplexes and mucoadhesive nanoparticles are currently the most promising carriers for the pulmonary delivery of biotherapeutics.

Pulmonary drug delivery permits straight delivery of inhaled drugs to specific sites in the lungs where they are needed. The major challenges of drug delivery to the lungs, in the case of lung delivery are:

• the development of innovative devices for a reliable and an efficient delivery to the target site within the lungs, of the active drugs

• clinical trials to demonstrate the benefit (ratio efficacy/toxicity, quality of life for patients with chronic diseases...) of aerosol delivery over other delivery routes.

4. Major discoveries in the last decade

Gene, peptide and protein delivery, nanoparticles, vaccines and cancer therapies are all relatively new areas of research in inhalation that have really taken up momentous in the past decade. Now that the research community has understood that the lung can be considered both a local and systemic portal for drug delivery, more and more its amazing properties will be exploited for the delivery of new inhaled therapies.

The major discoveries in pulmonary drug delivery could be:

• the compact and silent mesh nebulizer device allowing high drug delivery into the lungs

• the possibility to vaccine (against measles for example) by aerosol route avoiding injection therapy, particularly in developing countries.

In addition, in the past decade we have seen respiratory drug delivery applied to indications other than asthma and COPD, for example, lung infections and systemic delivery. We have also seen major advances in preclinical methods that allow a priori design of drugs, devices and formulations that achieve specific pre-specified design targets.

5. Opinion on the latest and most promising research avenues that are currently being pursued

Over the last decades, one of the most promising research avenues in inhalation drug delivery has been in the repurposing of drugs, given previously by other routes of administration, as inhalation products. This has open up novel therapeutic targets with many safety benefits, improved efficacy and patient compliance. Furthermore, the entry of biosimilars is likely to catalyze increased competition, renewing interest in this kind of product differentiation.

In addition, tumor-specific oncolytic viruses and immunotherapy tools could be applied to lung cancer therapy via aerosol delivery. For effective cancer therapy, vector engineering using tumor-specific promotor could also be enhancing therapeutic specificity.

This special issue has received 11 papers of recent advances in research and development from the best experts all over the world working on the challenging area of pulmonary drug and vaccine delivery to treat various lung diseases.

The opening article of this issue by Dr. Hak-Kim Chan and his team addresses some of the future perspectives of natural materials for pulmonary drug delivery and lung tissue engineering [1]. The use of these natural materials in pulmonary drug delivery and tissue regeneration opens up tantalizing possibilities first to enhance the efficacy of drug delivery with reduced drug dose due to the synergistic action of drug and the carrier, and second to regenerate and replace injured tissues in the lungs.

Dr. Warren H Finlay and his colleague discuss the basic aspects of nebulization technologies, including jet nebulizers, various high-frequency vibration techniques, and the use of colliding liquid jets [2]. They described various fundamental droplet formation processes used in both traditional and newer nebulizers, before considering use of nebulizers in various settings. In so doing, they aim to link nebulization fundamentals and device design to applications and limitations of current nebulizer use. In another paper, Dr. Warren H Finlay and his colleagues describe the influence of device and formulation variables on pMDI performance metrics [3].

Dr. Fakhrul Ahsan and colleagues summarized the newer devices and advanced formulations of inhaled insulin: the authors discussed the challenges to develop inhaled insulin delivery systems, encapsulated the discontinued, recently approved and investigational devices for oral inhalation of insulin, and described the various formulation approaches for inhalational insulin [4].

Dr. Alf Lamprecht and his team summarize and discuss the investigated formulation approaches for the pulmonary delivery of anti-inflammatory agents, including: inhalation of actives as suspensions or dry powder formulations, with polymeric micro- and nano-delivery carriers, or within liposomes and lipid nanoparticles [5].

Dr. Heidi M Mansour and her colleagues discuss the application of dry powder inhalers (DPIs) in pulmonary diseases of COPD, lung inflammation, and pulmonary infections [6]. The relationship between formulation properties in the solid state and DPI device features on aerosol performance of the powder formulation–inhaler device combination product is described.

Dr. Bhumika Aggarwal and his group compare the efficacy and tolerability with salmeterol and fluticasone given individually, and with other fixed-dose combinations namely formoterol/fluticasone, formoterol/beclometasone and formoterol/mometasone furoate, all delivered via pMDI [7].

Dr. Myung-Haing Cho and his collaborators summarize recent advances in airway gene delivery for lung cancer treatment in animal models using viral vectors or cationic polymers [8]. Viral vectors including lentiviruses and adenoviruses have been used for airway gene delivery because of their high transfection efficiency. Cationic polymers have also been developed for aerosol gene therapy owing to their biocompatibility and ease of modification.

Dr. Daniela Traini and her team discuss the development of a dry powder inhaler formulation of simvastatin (SV), and the effects of SV on the respiratory epithelium [9]. This therapy could potentially be used for the local treatment of diseases such as chronic obstructive pulmonary disease, cystic fibrosis, and bronchiectasis given its anti-inflammatory effects and ability to reduce mucus production.

Dr. Abdelwahab Omri, Dr. Lakshmi Krishnan and colleague discuss the common causes of respiratory infections, the induction of mucosal and systemic responses and current respiratory vaccination advantages and challenges [10]. The influence of various particulate formulations including lipid-based particles, polymers, dry powder aerosol and others on pulmonary vaccine delivery is also elaborated.

Dr. Lee and his team summarize the development of nanotechnology-based drug delivery systems to target alveolar macrophages in association with intracellular infections, cancer and lung inflammation [11]. All aspects of particle engineering through exploitation of particles’physicochemical characteristics such as particle size, surface charge and geometry of particles are discussed.

The last article of this issue by Dr. Nathalie Heuzé-Vourc’h and her group provide an overview of the pharmacological properties of antibody-based treatments, describe those for respiratory diseases and discusses preclinical/clinical results of aerosolized antibody-based therapeutics [12]. The advantages and limitations of aerosol devices and the formulation for the administration of aerosolized mAbs are also detailed.

We believe that this special issue will introduce the readers to the challenging and exciting area of lung delivery systems of drugs and vaccines.

Acknowledgments

We thank the authors for their contributions and effort in the preparation of these high-quality articles.

Declaration of interest

The author has 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.