Current Pharmaceutical Design - Volume 27, Issue 12, 2021

Drug-resistant tuberculosis (TB) can be considered the man-made result of interrupted, erratic or inadequate TB therapy. As reported in WHO data, resistant Mycobacterium tuberculosis (Mtb) strains continue to constitute a public health crisis. Mtb is naturally able to survive host defence mechanisms and to resist most antibiotics currently available. Prolonged treatment regimens using the available first-line drugs give rise to poor patient compliance and a rapid evolution of strains resistant to rifampicin only or to both rifampicin and isoniazid (multi drug-resistant, MDR-TB). The accumulation of mutations may give rise to extensively drug-resistant strains (XDR-TB), i.e. strains with resistance also to fluoroquinolones and to the injectable aminoglycoside, which represent the second-line drugs. Direct lung delivery of anti-tubercular drugs, as an adjunct to conventional routes, provides high concentrations within the lungs, which are the intended target site of drug delivery, representing an interesting strategy to prevent or reduce the development of drug-resistant strains. The purpose of this paper is to describe and critically analyse the most recent and advanced results in the formulation development of WHO second-line drug inhalation products, with particular focus on dry powder formulation. Although some of these formulations have been developed for other lung infectious diseases (Pseudomonas aeruginosa, nontuberculous mycobacteria), they could be valuable to treat MDR-TB and XDR-TB.

Pulmonary mycoses are associated with high morbidity and mortality. The current standard treatment by systemic administration is limited by inadequate local bioavailability and systemic toxic effects. Aerosolisation of antifungals is an attractive approach to overcome these problems, but no inhaled antifungal formulation is currently available for the treatment of pulmonary mycoses. Hence, the development of respirable antifungals formulations is of interest and in high demand. In this review, the recent advances in the development of antifungal formulations for pulmonary delivery are discussed, including both nebulised and dry powder formulations. Although the clinical practices of nebulised parenteral amphotericin B and voriconazole formulations (off-label use) are reported to show promising therapeutic effects with few adverse effects, there is no consensus about the dosage regimen (e.g. the dose, frequency, and whether they are used as single or combination therapy). To maximise the benefits of nebulised antifungal therapy, it is important to establish standardised protocol that clearly defines the dose and specifies the device and the administration conditions. Dry powder formulations of antifungal agents such as itraconazole and voriconazole with favourable physicochemical and aerosol properties are developed using various powder engineering technologies, but it is important to consider their suitability for use in patients with compromised lung functions. In addition, more biological studies on the therapeutic efficacy and pharmacokinetic profile are needed to demonstrate their clinical potential.

Asthma and chronic obstructive pulmonary disease (COPD) are obstructive lung diseases which are characterized by chronic inflammation and an increase in mucus production, and are highly prevalent conditions. Despite recent advances and multiple available therapies, there remains a significant unmet medical need. Over the past 40 years, the introduction of new classes of safe and effective therapy is insufficient. In spite of the high burden of asthma and COPD among patients, there are fewer new approved therapies in comparison to cardiovascular, metabolic and neurological diseases due to few drug candidates and a higher failure rate in the development of respiratory medicine. Lung diseases are amongst the leading causes of death globally with asthma being one of the most prevalent respiratory diseases, which affects people of all ages but, despite effective therapies available, many patients are poorly controlled and have a low quality of life. COPD is currently ranked as the fourth cause of death worldwide and predicted to become the third leading cause of death in 2030. The development of more effective treatments is urgently needed in order to reduce the high mortality rate and the enormous suffering from asthma and COPD. Various inhalation devices with different classes of medications are the foundation as therapies in both asthma and COPD. This article gives a comprehensive review of the promising inhaled therapies in the treatment of asthma and COPD. However, the lack of disease control in asthma and COPD patients may be due to numerous reasons. The association between non-adherence to guidelines on the part of the health care provider and poor inhalation technique and/or non-adherence to the prescribed treatment plan by the patients is common. It is therefore essential to discuss the different delivery systems and the methods used in asthma and COPD patients.

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Due to the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: The study aims to perform a summary of advances in the understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers can more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for the potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

Solid dispersions offer many advantages for oral drug delivery of poorly water-soluble drugs over other systems, including an increase in drug solubility and drug dissolution. An improvement in drug absorption and the higher bioavailability of active pharmaceutical ingredients in the gastrointestinal tract have been reported in various studies. In certain circumstances, a rapid pharmacological effect is required for patients. Fastdissolving solid dispersions provide an ideal formulation in such cases. This report will provide an overview of current studies on fast-dissolving solid dispersions, including not only solid dispersion powders with fast dissolution rates but also specific dose form for the controlled release of poorly water-soluble drugs. Specifically, the applications of fast-dissolving solid dispersions will be described in every specific case. Moreover, pharmaceutical approaches and the utilization of polymers will be summarized. The classification and analysis of fastdissolving solid dispersions could provide insight into strategies and potential applications in future drug delivery developments.

Alzheimer’s and Parkinson’s are the two most rampant neurodegenerative disorders worldwide. Existing treatments have a limited effect on the pathophysiology but are unable to fully arrest the progression of the disease. This is due to the inability of these therapeutic molecules to efficiently cross the blood-brain barrier. We discuss how nanotechnology has enabled researchers to develop novel and efficient nano-therapeutics against these diseases. The development of nanotized drug delivery systems has permitted an efficient, site-targeted, and controlled release of drugs in the brain, thereby presenting a revolutionary therapeutic approach. Nanoparticles are also being thoroughly studied and exploited for their role in the efficient and precise diagnosis of neurodegenerative conditions. We summarize the role of different nano-carriers and RNAi-conjugated nanoparticle-based therapeutics for their efficacy in pre-clinical studies. We also discuss the challenges underlying the use of nanomedicine with a focus on their route of administration, concentration, metabolism, and any toxic effects for successful therapeutics in these diseases.