Aerosol Biologics for the Treatment of Eosinophilic Asthma

Asthma is a heterogeneous chronic airway disease comprising of distinct phenotypes characterized by different immunopathophysiologic pathways, clinical features, disease severity, and response to treatment. The phenotypes of asthma include eosinophilic, neutrophilic, mixed cellularity, and paucigranulocytic asthma. Eosinophilic asthma is principally a T helper type 2 (Th2)-mediated airway disease. However, several other immune and structural cells secrete the cytokines implicated in the pathogenesis of eosinophilic asthma. Innate type 2 lymphoid cells, mast cells, basophils, and eosinophils secrete Th2 cytokines, such as interleukin-4 (IL-4), IL-13, and IL-5. Additionally, airway epithelial cells produce alarmin cytokines, including IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). Alarmins are the key initiators of allergic inflammation at the sentinel mucosal surfaces. Innovative biotherapeutic research has led to the discovery of monoclonal antibodies which target and inhibit the immunopathological effects of the cytokines involved in the pathogenesis of eosinophilic asthma. Parenteral biologics targeting the inciting interleukins, include mepolizumab and reslizumab (anti-IL-5), benralizumab (anti-IL-5Rα), dupilumab (anti-4Rα), and tezelizumab (anti-TSLP). They have been shown to significantly reduce annualized exacerbation rates, improve asthma control, lung function, and quality of life. Currently, there are no pulmonary delivered aerosol biologics for topical treatment of asthma. CSJ117 is a potent neutralizing antibody Fab fragment against TSLP, formulated as a PulmoSol TM engineered powder, and is delivered to the lungs by a dry powder inhaler. Phase 2 placebo-controlled clinical trial evaluated the efficacy and safety of CSJ117. CSJ117 delivered as an inhaler attenuated the late asthmatic response (LAR), and the early asthmatic response (EAR) after allergen inhalation challenge (AIC) at day 84 of treatment. The maximum decrease in FVE1 from pre-AIC were significantly lower in the CSJ117 group compared to placebo (P = 029), during LAR. CSJ117 also significantly reduced fractional exhaled nitric oxide before AIC at day 83; and significantly reduced the allergen-induced increase in % sputum eosinophil count. Pulmonary delivery of biologics directly to the airway mucosal surface has several advantages over parenteral routes, particularly in treating airway diseases such as asthma. Inhaler delivered biologics, such as CSJ117 are innovative and attractive methods of future precision treatment of asthma, and other respiratory diseases.

Inhaled ciprofloxacin-loaded poly(2-ethyl-2-oxazoline) nanoparticles from dry powder inhaler formulation for the potential treatment of lower respiratory tract infections

Lower respiratory tract infections (LRTIs) are one of the fatal diseases of the lungs that have severe impacts on public health and the global economy. The currently available antibiotics administered orally for the treatment of LRTIs need high doses with frequent administration and cause dose-related adverse effects. To overcome this problem, we investigated the development of ciprofloxacin (CIP) loaded poly(2-ethyl-2-oxazoline) (PEtOx) nanoparticles (NPs) for potential pulmonary delivery from dry powder inhaler (DPI) formulations against LRTIs. NPs were prepared using a straightforward co-assembly reaction carried out by the intermolecular hydrogen bonding among PEtOx, tannic acid (TA), and CIP. The prepared NPs were characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction analysis (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The CIP was determined by validated HPLC and UV spectrophotometry methods. The CIP loading into the PEtOx was between 21–67% and increased loading was observed with the increasing concentration of CIP. The NP sizes of PEtOx with or without drug loading were between 196–350 nm and increased with increasing drug loading. The in vitro CIP release showed the maximum cumulative release of about 78% in 168 h with a burst release of 50% in the first 12 h. The kinetics of CIP release from NPs followed non-Fickian or anomalous transport thus suggesting the drug release was regulated by both diffusion and polymer degradation. The in vitro aerosolization study carried out using a Twin Stage Impinger (TSI) at 60 L/min air flow showed the fine particle fraction (FPF) between 34.4% and 40.8%. The FPF was increased with increased drug loading. The outcome of this study revealed the potential of the polymer PEtOx as a carrier for developing CIP-loaded PEtOx NPs as DPI formulation for pulmonary delivery against LRTIs.

Evaluating the technique of using MDI and DPI in patients with respiratory disease

Inhalation therapy plays a major role in treatment of respiratory diseases. Correct inhalation technique is crucial for effective clinical outcomes. The aim of this study was to evaluate and analyse technique of use of Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) in patients with respiratory disease. This observational study was conducted at pulmonary outpatient department of a tertiary care hospital. 30 patients were enrolled using convenience sampling. Participants’ demographic and disease specific data was recorded. Participants were asked to use their inhaler just as they would at home. The technique of device use was observed and recorded using inhaler specific checklists. Data collected was analyzed using descriptive statistics. Out of 30 patients 26 were using MDI, 23 of which (92%) performed at least 1 error. Among 4 patients using DPI, 3 (75%) performed at least 1 error. Patients using MDI for more than 1 year performed less errors compared to those who had been using MDI for less than 1 year, however the difference observed was not significant (n=26, p= 0.304). 29 patients (96%) received education about inhaler device use. The most common incorrectly performed steps were “complete exhalation” and “breath hold.” 92% of MDI and 75% of DPI users made at least one error during the inhalation maneuver despite majority being educated about inhaler technique. The most frequently performed incorrect steps for MDI and DPI were “Complete exhalation” and “Breath hold”.

A Novel Curcumin-Based Drug Powder Inhalation Medicine for Chronic Obstructive Pulmonary Disease

The dry powder inhaler is a new form of drug delivery that is widely used as an alternative to traditional drug delivery methods, addressing the shortcomings of traditional drug delivery methods and obtaining better therapeutic results. This mode of delivery is also one of the most rational ways to treat pulmonary diseases such as chronic obstructive pulmonary disease (COPD). Curcumin, a natural polyphenol, has been shown to be effective in the treatment of COPD. In this study, different concentrations of curcumin ethanol solution were spray dried with mannitol as a carrier to obtain dry powder particles with different particle size distribution for the preparation of curcumin dry powder inhaler. The solubility and physicochemical properties were further characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy. The characterization results showed that the product obtained in the experiment had reasonable particle size distribution and excellent solubility properties, which were positive for the treatment of COPD or other pulmonary diseases.