https://orcid.org/0000-0002-7507-1159
There are reportedly over five million annual deaths worldwide due to lung-related diseases. A majority of these subjects suffer from asthma and chronic obstructive pulmonary diseases. It has been predicted that the prevalence rates of chronic respiratory diseases (CRDs) are destined for a monumental rise in the coming years, with chronic obstructive pulmonary disease leading the line with significantly higher mortality and morbidity rates. Similarly, other chronic lung diseases are becoming highly prevalent, and there is a steady rise in the incidence rates every year. These CRDs include lung cancer, pulmonary fibrosis and infections such as influenza and COVID-19. In all lung diseases, inflammation is one of the key pathophysiological events that governs the severity of these diseases. These facts suggest that there is an utmost need for targeted drug-delivery systems that can mitigate the inflammation associated with lung diseases.
The application and visibility of novel drug-delivery systems are constantly gaining massive attention due to their merits such as sustained or extended release, targeted effects, need for a lesser dose, minimal side and adverse effects and better patient compliance. The recent developments and the advent of ‘smart’ nano systems have enabled drug-delivery scientists to deliver any specific target drug to a given location in the body. These nanoparticle-associated molecules have enhanced shelf life, superior physico–chemical parameters and extended stability.
This special focus issue covers cutting-edge and emerging approaches that can be beneficial in managing lung diseases in the form of review and research articles. This special focus issue will be highly relevant and beneficial to respiratory drug delivery and translational researchers, as well as to pulmonary clinicians. The issue includes critical content on novel tools such as nanotechnology, polymeric, lipid and biocomposite-based, extracellular vesicles, mucoadhesive particles and surface functionalized polymeric micelles, important biophysical interactions, which are as important as pharmacological interactions at the lung air interface. The evaluation of such effects can lead to the invention of new treatments using nanotechnology.
This special issue was run by editorial experts, namely Raimar Loebenberg, Kamal Dua and Dinesh Kumar Chellappan with each editor focusing on their respective field of expertise. Loebenberg covered the sections on advanced drug-delivery systems and biophysical interactions with the biological systems. Dua focused on the sections targeting the behavior and activities of drug delivery on a cellular and molecular level. Chellappan managed the sections covering the aspects of pathophysiological involvement of respiratory diseases and characterization of targeted delivery formulations.
In recent decades, the tremendous potential of extracellular vesicles, that could transport therapeutically active drugs to target organs and tissues, has been demonstrated. Extracellular vesicles boast greater stability and minimal side effects, as well as enhanced therapeutic benefits in both cell line-based and in vivo lung disease studies, when compared with existing therapeutic modalities. Extracellular vesicles that were derived from stem cells have shown significant therapeutic effects in lung disease studies; these vesicles may be administered alongside conventional drugs in encapsulated forms. Additional in-depth studies in this area may assist in the development of promising treatment strategies for individuals with chronic lung diseases.
There has been considerable attention given toward the development of specific lipid-based biomaterials in the production and establishment of effective treatment modalities for lung diseases. Lipid-based therapies were introduced for treatment in early 1960s in the form of liposomes, which constituted phospholipids that were arranged in a double layer. The introduction of liposomes created a therapeutic revolution leading to the development of several lipid-oriented drug-delivery techniques. These strategies paved the path for establishing advanced drug-delivery systems in CRDs, which was previously considered impossible. Furthermore, the introduction of specific surfactants provided additional impetus, especially in terms of localized lung delivery. There are several other advantages with lipid-based systems, as they boast improved solubilization and permeation of the target agent. In addition, they are compatible, easily degradable and are known to possess limited immunogenicity. Lipid-based systems further protect the active drug from the surrounding microenvironment of the tissue, thereby ensuring that sufficient load of the active drug reaches the target cells. With the enhanced absorption of the active drug, the need for a higher dose also reduces. Moreover, a higher degree of precision in drug delivery is possible with the provision offered to modify the surface parameters that may enable to overcome the biological barriers. One of the major drawbacks outlining lipid-based systems is reproducibility of the applications in clinical settings. Other challenges with lipid-based drug-delivery systems are their lack of physiological resemblance and the difficulty to scale-up the formulations due to lack of suitable equipment. Degradation of the lipid components, loss of active drug from vesicles due to leaks and drug stability are other notable challenges with lipid systems.
Surface functionality of the developed drug-delivery systems plays a major role in the actual transport of the active drug to the target site in the tissues. Physicochemical parameters namely the pH of the system, dissolution potential and temperature may affect the overall outcomes in drug delivery. Nanocomposites may possess the inherent potential to modify such parameters to enable delivery of active substances to the target site. These substances could alter surface functionality and engineer the biological barrier for effective transport of the drug substance. This approach may also enhance the efficiency of nanoparticles in deactivating the activities of enzymes that may signal various inflammatory cascades in CRDs such as asthma and COPD. The advantage of such a system lies also in its ability to deter toxicity and produce an effective transport mechanism for active therapeutic substances. This is of paramount significance when it comes to inhalable nanomaterials. Therefore, nanocomposite-based delivery systems may play a significant role in the near future especially in the therapeutics of lungs.
There has been a renewed interest on mucoadhesive particles in the past decade. These advanced materials form a formidable component in the current drug delivery landscape. In addition to their function as excipients, these materials have also been employed in the production of vehicles for nasal delivery. They also assist in overcoming the challenges associated with lung delivery especially with regards to the penetration of substances through the mucus membrane barrier. Mucoadhesive drugs and deliverables have therefore led to the effective management of CRDs and have tremendously improved patient compliance. Mucoadhesive substances present themselves as promising candidates in the delivery of vaccines and other biologicals to counter respiratory ailments.
The current drug-delivery technology is rendered highly successful, primarily also owing to the contribution of polymeric micelles. Bioactive polymers offer a wide range of shapes, sizes and charges. These polymers have benefitted formulation scientists to overcome challenges, such as limited tissue specificity and bioavailability. The surface functionalization role of polymeric micelles has also contributed vastly to the success of polymeric micelles. This has also contributed to the increase in enhanced mucoadhesiveness. However, several challenges and drawbacks still persist. The majority of the polymers employed in the preparation of polymeric micelles are essentially manufactured from substances like polyvinyl alcohol and PEG, which also possess toxic characteristics. Homogeneity in the distribution of the active molecule across the tissues is another potential challenge with polymeric micelles, which may result in variations of dose distribution. This may potentially lead to reduced efficacy and outcome of the desired treatment. In addition, only a limited number of studies have been conducted on the effectiveness of polymeric micelles in diseases. Several of these studies are conducted in laboratory in vivo models with very few studies being carried out in clinical models. Therefore, additional studies are required to overcome these challenges and to make these substances therapeutically attractive.
Conclusion
The complexity of CRDs has been on the rise. The availability of several drug delivery modalities has provided scientists with an impetus to conduct additional in-depth analyses and detailed mechanistic studies, to advance drug-delivery strategies. Several drug-delivery strategies are being employed currently with a varying range of advantages and drawbacks. These have made an enormous impact on the fields of drug delivery and drug discovery. The advent of advanced materials has further pushed the quality of the deliverables to the next level.
Financial & competing interests disclosure
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.
No writing assistance was utilized in the production of this manuscript.