nano drugs in cystic fibrosis

Pulmonary inflammations such as chronic obstructive pulmonary disease and cystic fibrosis are widespread and can be fatal, especially when they are characterized by abnormal mucus accumulation. Inhaled corticosteroids are commonly used for lung inflammations despite their considerable side effects. By utilizing particle engineering techniques, a combined dry powder inhaler (DPI) comprising nanosized ketoprofen-embedded mannitol-coated microparticles was developed. A nanoembedded microparticle system means a novel advance in pulmonary delivery by enhancing local pulmonary deposition while avoiding clearance mechanisms...

Cystic fibrosis (CF) is a genetic disorder of the respiratory system caused by mutation of the Cystic Fibrosis Trans-Membrane Conductance Regulator (CFTR) gene that affects a huge number of people worldwide. It results in difficulty breathing due to a large accumulation of mucus in the respiratory tract, resulting in serious bacterial infections, and subsequent death. Traditional drug-based treatments face hindered penetration at the site of action due to the thick mucus layer. Nanotechnology offers possibilities for developing advanced and effective treatment platforms by focusing on drugs that can penetrate the dense mucus layer, fighting against the underlying bacterial infections, and targeting the genetic cause of the disease...

Asthma, lung cancer, cystic fibrosis, tuberculosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and COVID-19 are few examples of inflammatory lung conditions that cause cytokine release syndrome. It can initiate a widespread inflammatory response and may activate several inflammatory pathways that cause multiple organ failures leading to increased number of deaths and increased prevalence rates around the world. Nanotechnology-based therapeutic modalities such as nanoparticles, liposomes, nanosuspension, monoclonal antibodies, and vaccines can be used in the effective treatment of inflammatory lung diseases at both cellular and molecular levels...

In recent years, RNA-based therapies have gained much attention as biomedicines due to their remarkable therapeutic effects with high specificity and potency. Lung diseases offer a variety of currently undruggable but attractive targets that could potentially be treated with RNA drugs. Inhaled RNA drugs for the treatment of lung diseases, including asthma, chronic obstructive pulmonary disease, cystic fibrosis, and acute respiratory distress syndrome, have attracted more and more attention. A variety of novel nanoformulations have been designed and attempted for the delivery of RNA drugs to the lung via inhalation...

The rapid advancements in gene therapy have opened up new possibilities for treating genetic disorders, including Duchenne muscular dystrophy, thalassemia, cystic fibrosis, hemophilia, and familial hypercholesterolemia. The utilization of the clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) system has revolutionized the field of gene therapy by enabling precise targeting of genes. In recent years, CRISPR/Cas9 has demonstrated remarkable efficacy in treating cancer and genetic diseases...

BACKGROUND: Aquagenic wrinkling of palms (AWP) is emerging as a screening test for cystic fibrosis (CF). There is lack of normative data for the same in our population. OBJECTIVES: To generate normative data for AWP in children 1-15 years of age and to describe the factors associated with it. METHODS: Children aged 1-15 years were enrolled after obtaining informed consent and assent of the parent and child based on age. Information regarding age, gender, anthropometry, indications for visiting hospital and drug intake were noted down...

Microbes entrenched within biofilms can withstand 1000-fold higher concentrations of antibiotics, in part due to the viscous extracellular matrix that sequesters and attenuates antimicrobial activity. Nanoparticle (NP)-based therapeutics can aid in delivering higher local concentrations throughout biofilms as compared to free drugs alone, thereby enhancing the efficacy. Canonical design criteria dictate that positively charged nanoparticles can multivalently bind to anionic biofilm components and increase biofilm penetration...

A fatal hereditary condition, cystic fibrosis (CF) causes severe lung problems. Ibuprofen (IBU), a non-steroidal anti-inflammatory drug, slows the progression of disease without causing significant side effects. Considering the poor water-solubility of the drug, IBU nanoparticles are beneficial for local pulmonary administration. We aimed to formulate a carrier-free dry powder inhaler containing nanosized IBU. We combined high-performance ultra-sonication and nano spray-drying. IBU was dissolved in ethyl acetate; after that, it was sonicated into a polyvinyl alcohol solution, where it precipitated as nanoparticles...

A Dry Powder Inhaler (DPI) is a technique as well as a device used to inhale formulation which is in the form of dry powder, and is inhaled through the nose or mouth. It was developed for the purpose of treating conditions like chronic obstructive pulmonary disease (COPD), Asthma, and even cystic fibrosis etc. The aim of the review is to discuss the different methods of preparation of dry powders along with the characterization of DPI. Here we present the outline of different methods like supercritical fluid extraction (SCF), spray drying, and milling...

The potential of intra-venous gallium nitrate (GaN) administration against Pseudomonas aeruginosa pneumonia was recently demonstrated in mice and in cystic fibrosis (CF) patients. Likewise, the added value of direct lung delivery of Ga(III) has been shown in rats. Therefore, the design of a drug delivery system specifically engineered for Ga(III) inhalation is imperative to improve its accumulation in lungs. To this purpose, Ga(III) was efficiently encapsulated into hyaluronic acid/chitosan nanoparticles (Ga_HA/CS NPs), whose features were tuned to facilitate access to the target by overcoming mucus and biofilm surrounding bacteria...

Liposomes are nano-structured vesicles, made up of phospholipids that provide active ingredients at the site of action at a predetermined rate and add the advantage of the sustained-release formulation. Liposomes have stability issues that tend to agglomerate and fuse upon storage, which reflects their drawback. Hence to overcome the aggregation, fusion, hydrolysis, and/or oxidation problems associated with liposomes a new technology named Proliposomes has been introduced. Proliposomes are defined as carbohydrate carriers coated with phospholipids, which upon addition of water generate liposomes...

Pulmonary delivery has high bioavailability, a large surface area for absorption, and limited drug degradation. Particle engineering is important to develop inhalable formulations to improve the therapeutic effect. In our work, the poorly water-soluble meloxicam (MX) was used as an active ingredient, which could be useful for the treatment of non-small cell lung cancer, cystic fibrosis, and chronic obstructive pulmonary disease. We aimed to produce inhalable "nano-in-micro" dry powder inhalers (DPIs) containing MX and additives (poly-vinyl-alcohol, leucine)...

Introduction : Cystic fibrosis (CF), is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and affects thousands of people throughout the world. Lung disease is the leading cause of death in CF patients. Despite the advances in treatments, the management of CF mainly targets symptoms. Recent CFTR modulators however target common mutations in patients, alleviating symptoms of CF. Unfortunately, there is still no approved treatments for patients with rare mutations to date...

Nanotechnology in medicine-nanomedicine-is extensively employed to diagnose, treat, and prevent pulmonary diseases. Over the last few years, this brave new world has made remarkable progress, offering opportunities to address historical clinical challenges in pulmonary diseases including multidrug resistance, adverse side effects of conventional therapeutic agents, novel imaging, and earlier disease detection. Nanomedicine is also being applied to tackle the new emerging infectious diseases, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East Respiratory Syndrome Coronavirus (MERS-CoV), influenza A virus subtype H1N1 (A/H1N1), and more recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)...

In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action...

Aim: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine, which has been shown to promote disease severity in cystic fibrosis. Methods : In this study, aerosolized drug-loaded nanoparticles containing SCD-19, an inhibitor of MIF's tautomerase enzymatic activity, were developed and characterized. Results: The aerosolized nanoparticles had an optimal droplet size distribution for deep lung deposition, with a high degree of biocompatibility and significant cellular uptake. Conclusion: For the first time, we have developed an aerosolized nano-formulation against MIF's enzymatic activity that achieved a significant reduction in the inflammatory response of macrophages, and inhibited Pseudomonas aeruginosa  biofilm formation on airway epithelial cells...

Previous studies have shown that combining colistin (Col), a cationic polypeptide antibiotic, with ivacaftor (Iva), a cystic fibrosis (CF) drug, could achieve synergistic antibacterial effects against Pseudomonas aeruginosa. The purpose of this study was to develop dry powder inhaler (DPI) formulations for co-delivery of Col and Iva, aiming to treat CF and lung infection simultaneously. In order to improve solubility and dissolution for the water insoluble Iva, Iva was encapsulated into bovine serum albumin (BSA) nanoparticles (Iva-BSA-NPs)...

Chronic airway inflammation is a hallmark of chronic obstructive airway diseases, including chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and asthma. Airway inflammation and mucus obstruction present major challenges to drug or gene delivery and therapeutic efficacy of nano-based carriers in these chronic obstructive airway conditions. To achieve targeted drug delivery of NPs to the diseased cells, NPs need to bypass the obstructive airway and circumvent the airway's defense mechanisms...

Host defense peptides (HDP) are small cationic molecules released by the immune systems of the body, having multidimensional properties including anti-inflammatory, anticancer, antimicrobial and immune-modulatory activity. These molecules gained importance due to their broad-spectrum pharmacological activities, and hence being actively investigated. Presently, respiratory infections represent a major global health problem, and HDP has an enormous potential to be used as an alternative therapeutics against respiratory infections and related inflammatory ailments...

Although the lung is an obvious target for site-specific delivery of many therapeutics for respiratory airway diseases such as asthma, COPD, and cystic fibrosis, novel strategies are needed to avoid key physiologic barriers for efficient delivery and controlled release of therapeutics to the lungs. Specifically, deposition into the deep lung requires particles with a 1-5 µm aerodynamic diameter; however, particles with a geometric diameter less than 6 µm are rapidly cleared by alveolar macrophages. Additionally, epithelial, endothelial, and fibroblast cells prefer smaller (< 300 nm) nanoparticles for efficient endocytosis...