Nanoparticles are extensively studied for drug delivery and are proving to be effective in drug delivery and the diagnostic field. Drug delivery to lungs has its advantages over other routes of administration. Inhalable powders consisting of nanoparticles are gaining much interest in respiratory research and clinical therapy. Particle engineering technique is a key factor to develop inhalable formulations that can successfully deliver drug with improved therapeutic effect and enhanced targeting. Inhalable nanoparticles in the solid-state dry powders for targeted pulmonary delivery offer unique advantages and are an exciting new area of research. Nasal delivery of inhalable nanoparticulate powders is gaining research attention recently, particularly in vaccine applications, systemic drug delivery in the treatment of pain, and non-invasive brain targeting. Fundamental aspects and recent advancements along with future prospects of inhalable powders consisting of nanoparticles in the solid-state for respiratory delivery are presented. The advance in nanotechnology has enabled the design of new drug delivery systems through inhalation, which has many advantages over traditional delivery systems. This comprehensive review describes and discusses the current status, drug design and modification for targeted delivery and challenges of the use of nanoparticles in the respiratory tract.

The number of pulmonary diseases that are effectively treated by aerosolized medicine continues to grow. These diseases include chronic obstructive pulmonary disease (COPD), lung inflammatory diseases (e.g., asthma) and pulmonary infections. Dry powder inhalers (DPIs) exhibit many unique advantages that have contributed to the incredible growth in the number of DPI pharmaceutical products. To improve the performance, there are a relatively large number of DPI devices available for different inhalable powder formulations. The relationship between formulation and inhaler device features on performance of the drug-device combination product is critical. Aerosol medicine products are drug-device combination products. Device design and compatibility with the formulation are key drug-device combination product aspects in delivering drugs to the lungs as inhaled powders. In addition to discussing pulmonary diseases, this review discusses DPI devices, respirable powder formulation and their interactions in the context of currently marketed DPI products used in the treatment of COPD, asthma and pulmonary infections. There is a growing line of product options available for patients in choosing inhalers for treatment of respiratory diseases. Looking ahead, combining nanotechnology with optimized DPI formulation and enhancing device design presents a promising future for DPI development.

Central nervous system (CNS) disorders, such as psychiatric disorders, neurodegeneration, chronic pain, stroke, brain tumor, spinal cord injury, and many other CNS diseases, would hugely benefit from specific and potent peptide pharmaceuticals and their low inherent toxicity. The delivery of peptides to the brain is challenging due to their low metabolic stability, which decreases their duration of action, poor penetration of the blood-brain barrier (BBB), and their incompatibility with oral administration, typically resulting in the need for parenteral administration. These challenges limit peptides’ clinical application and explain the interest in alternative routes of peptide administration, particularly nose-to-brain (N-to-B) delivery, which allows protein and peptide drugs to reach the brain noninvasively. N-to-B delivery can be a convenient method for rapidly targeting the CNS, bypassing the BBB, and minimizing systemic exposure; the olfactory and trigeminal nerves provide a unique pathway to the brain and the external environment. This review highlights the intranasal delivery of drugs, focusing on peptide delivery, illustrating various clinical applications, nasal delivery devices, and the scope and limitations of this approach.

Nanomedicine is making groundbreaking achievements in drug delivery. The versatility of nanoparticles has given rise to its use in respiratory delivery that includes inhalation aerosol delivery by the nasal route and the pulmonary route. Due to the unique features of the respiratory route, research in exploring the respiratory route for delivery of poorly absorbed and systemically unstable drugs has been increasing. The respiratory route has been successfully used for the delivery of macromolecules like proteins, peptides, and vaccines, and continues to be examined for use with small molecules, DNA, siRNA, and gene therapy. Phospholipid nanocarriers are an attractive drug delivery system for inhalation aerosol delivery in particular. Protecting these phospholipid nanocarriers from pulmonary immune system attack by surface modification by polyethylene glycol (PEG)ylation, enhancing mucopenetration by PEGylation, and sustaining drug release for controlled drug delivery are some of the advantages of PEGylated liposomal and proliposomal inhalation aerosol delivery. This review discusses the advantages of using PEGylated phospholipid nanocarriers and PEGylated therapeutics for respiratory delivery through the nasal and pulmonary routes as inhalation aerosols.