Inhalation of nanoparticle-based drug for lung cancer treatment: Advantages and challenges

Abstract

Ever since the success of developing inhalable insulin, drug delivery via pulmonary administration has become an attractive route to treat chronic diseases. Pulmonary delivery system for nanotechnology is a relatively new concept especially when applicable to lung cancer therapy. Nano-based systems such as liposome, polymeric nanoparticles or micelles are strategically designed to enhance the therapeutic index of anti-cancer drugs through improvement of their bioavailability, stability and residency at targeted lung regions. Along with these benefits, nano-based systems also provide additional diagnostic advantages during lung cancer treatment, including imaging, screening and drug tracking. Nevertheless, delivery of nano-based drugs via pulmonary administration for lung cancer therapy is still in its infancy and numerous challenges are expected. Pharmacology, immunology, toxicology and large-scale manufacturing (stability and activity of drugs) are some aspects in nanotechnology that should be taken into consideration for the development of inhalable nano-based chemotherapeutic drugs. This review will focus on the current inhalable nano-based drugs for lung cancer treatment.

Multimodal Precision Imaging of Pulmonary Nanoparticle Delivery in Mice: Dynamics of Application, Spatial Distribution, and Dosimetry

“…The region of NM/NP deposition can have a significant impact on residence time, release kinetics, and hence bioactivity of the drug or toxicity of NPs . While NM/NP can be quickly (within minutes) removed from the upper airways by mucociliary transport, clearance of NM/NP from the alveolar epithelium mainly relies on uptake by alveolar macrophages (takes a few hours), which may be enough time for direct bioactivity/toxicity of the NM/NP or result in secondary drug release into or from the macrophages . Consequently, understanding the mechanisms of pulmonary NM/NP delivery and their relevance for tissue‐delivered NM/NP dose with cellular resolution is essential for the development of effective NM or minimizing health hazards of NPs .…”

“…For treatment of lung diseases, direct application of the drug to the lung via aerosol inhalation is widely used due to its high therapeutic index, i.e., high efficacy at the site of disease and low side effects in secondary organs. Currently, inhalation therapy is a cornerstone for the treatment of pulmonary infections, asthma, COPD, and cystic fibrosis, but also treatment of lung cancer or even nonpulmonary disease such as diabetes is within reach . Also nanotechnology enabled drugs (nanomedicines (NMs)) offer new diagnostic and therapeutic options for cancer and other diseases leveraging their unique features for controlled release, reduced drug toxicity, prolonged residence, and/or targeted delivery .…”

Inhalable nanotherapeutics to improve treatment efficacy for common lung diseases

“…Pulmonary delivery of nanomedicines enhances lung cancer treatment by transporting encapsulated poorly water-soluble, potent anticancer drugs directly to their intended site of action, facilitating targeted and controlled release at tumor sites and reducing the necessary dosage and mitigating off-target side-effects (Hitzman, Wattenberg, & Wiedmann, 2006;Koshkina et al, 2001;Tomoda et al, 2009); however, inhalation distributes these drugs evenly around the lungs, potentially exposing both healthy and diseased cells to chemotherapy and inducing undesirable adverse effects on the lungs (Lee, Loo, Traini, & Young, 2015a). Drug deposition and distribution is influenced by the physical occlusion of the respiratory track by tumors, where tumors reduce the cross-sectional area of the airway and thereby divert airflow to nonoccluded areas and reduce drug deposition on tumor tissue (Carvalho, Carvalho, & Mcconville, 2011;Mangal et al, 2017).…”

Carriers for the targeted delivery of aerosolized macromolecules for pulmonary pathologies

“…One of the ubiquitous approaches for active targeting generally involves the conjugation of the carrier or macromolecule to a targeting ligand, which is generally in the form of protein and peptides, polysaccharides, glycolipids, glycoproteins, or antibodies. Cell surface receptors may be overexpressed on specific cell groups according to the pathologies such as cancer, or expressed on a particular cell group that are useful targets for therapy [80]. …”

“…The epidermal growth factor receptor (EGFR) is known to be highly expressed in non-small cell lung cancer, and studies have been conducted investigating nano-formulations with EGFR targeting ligands for the delivery of cisplatin to the cancer tissue following inhalation [80]. These EGFR targeting particles were able to reduce tumor volume more effectively, as well as increase the bioavailability of cisplatin in the lung compared to the free drug [80]. Another target for lung cancer is carbonic anhydrase IX, which is expressed on tumor cells.…”