Successes and Challenges: Inhaled Treatment Approaches Using Magnetic Nanoparticles in Cystic Fibrosis

Abstract

Magnetic nanoparticles have been largely applied to increase the efficacy of antibiotics due to passive accumulation provided by enhancing permeability and retention, which is essential for the treatment of lung infections. Recurring lung infections such as in the life-shortening genetic disease cystic fibrosis (CF) are a major problem. The recent advent of the CF modulator drug ivacaftor, alone or in combination with lumacaftor or tezacaftor, has enabled systemic treatment of the majority of patients. Magnetic nanoparticles (MNPs) show unique properties such as biocompatibility and biodegradability as well as magnetic and heat-medicated characteristics. These properties make them suitable to be used as drug carriers and hyperthermia-based agents. Hyperthermia is a promising approach for the thermal activation therapy of several diseases, including pulmonary diseases. The benefits of delivering CF drugs via inhalation using MNPs as drug carriers afford application of sufficient therapeutic dosages directly to the primary target site, while avoiding potential suboptimal pharmacokinetics/pharmacodynamics and minimizing the risks of systemic toxicity. This review explores the multidisciplinary approach of using MNPs as vehicles of drug delivery. Additionally, we highlight advantages such as increased drug concentration at disease site, minimized drug loss and the possibility of specific cell targeting, while addressing major challenges for this emerging field.

Insights Into Patient Variability During Ivacaftor-Lumacaftor Therapy in Cystic Fibrosis

“…In CF care, screening for potential drug-drug interactions is of the paramount importance to identify and potentially substitute co-medications that alter drug bioavailability via cytochrome P450 (CYP450) induction or inhibition of CYP450. Clinically relevant drug interactions are metabolized by CYP450 enzymes and are divided into families ( Condren and Bradshaw, 2013 ; Tan et al, 2020 ; Elborn, 2016 ), sub-families (A-E) and individual gene number. Genetic polymorphisms in a given CYP450 gene result in variations in the enzyme activity leading to poor metabolizers, extensive metabolizers, or ultra-rapid metabolizers.…”

“…Cystic fibrosis (CF) is an autosomal recessive genetic disorder that affects chloride transport throughout the epithelial cells of the body, resulting in abnormalities in the respiratory, endocrine, gastrointestinal, and reproductive systems ( Condren and Bradshaw, 2013 ; Tan et al, 2020 ). The dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) channel causes dehydration of mucosal surfaces subsequently increasing viscous mucus that obstructs luminal compartments in lung, pancreas and intestine ( Elborn, 2016 ; Schneider et al, 2017a ).…”

Advantages and Disadvantages of Using Magnetic Nanoparticles for the Treatment of Complicated Ocular Disorders

“…It helps to increase the drug circulation time into the organism and to get the target site. Furthermore, these functionalized magnetic nanoparticles can act as hyperthermia agents, providing a more potent therapeutic effect since the increase in temperature in a specific site promote tumor cell death without altering normal cells [65,66]. Besides, magnetic nanoparticles can be easily visualized by magnetic resonance imaging (useful for diagnosis) by the application of an external magnetic field [67] and amblyopia), early and regular eye examinations for all children with CF remain essential.…”

“…Magnetic hyperthermia can be effectively used to decrease biofilm and mucus viscosity, while enhancing drug and immune cell penetration into the target areas [ 100 ]. Moreover, the produced increase in temperature noticeably reduces the formation and growth of biofilms [ 66 ]. Thus, magnetic hyperthermia results in increased bacterial membrane permeability, resulting in enhanced targeted killing of bacteria [ 101 ].…”

Stability and In Vitro Aerodynamic Studies of Inhalation Powders Containing Ciprofloxacin Hydrochloride Applying Different DPI Capsule Types

“…Furthermore, it should be emphasized that it is much more advantageous compared to oral administration in terms of side effect profile, as the first-pass effect of the liver and the enzymatic inactivation of the gastrointestinal tract as metabolic pathways are avoided by the inhaled drug, requiring a lower therapeutic dose [ 4 , 5 ]. It is noteworthy that great emphasis is placed on the development of inhaled antibiotic products as, for example, they can be used effectively in the treatment of cystic fibrosis [ 6 ]. A number of inhaled antibiotics are currently available on the market, such as amikacin (Arikayce ® , Insmed Incorporated, Bridgewater, NJ, USA), aztreonam (Cayston ® , Cayston Gilead Sciences Ireland UC, Carrigtohill, Ireland), colistimethate sodium (Colobreathe ® , Forest Laboratories UK Ltd., Whiddon Valley, UK), levofloxacin hemihydrate (Quinsair ® , Chiesi Farmaceutici S.p.A., Parma, Italy), and tobramycin (TOBI ® /TOBI ® Podhaler ® , Novartis International AG, Basel, Switzerland; Bramitob ® , Chiesi Farmaceutici S.p.A., Parma, Italy) [ 7 , 8 ].…”