Dual targeting powder formulation of antiviral agent for customizable nasal and lung deposition profile through single intranasal administration

Neutralisation of SARS-CoV-2 by monoclonal antibody through dual targeting powder formulation

“…To prepare dual targeting formulations, spray dried WKS13 powders that were produced with the same feed solution but different nozzle were mixed at different weight ratios using a Turbula® shaker-mixer type T2F (Willy A. Bachofen AG Maschinenfabrik, Basel, Switzerland) ( Table 1 ). A total of 50 mg of powder was weighed into a 50 mL glass vial and subjected to a constant rotational speed of 49 rpm for 10 min [ 12 ].…”

“…The volumetric size distribution of the spray dried WKS13 powders was measured using a HELOS/KR laser diffractometer (Sympatec, Germany) as previously described [ 12 ]. In brief, a nasal powder device (Unit Dose System Powder Nasal Spray, Aptar Pharma, France) was filled with 3.0 ± 0.5 mg of powder and manually dispersed.…”

“…The most representative volumetric particle size distribution of each formulation were plotted for comparison. The aerodynamic size distribution of the spray dried WKS13 powders was evaluated using a Next Generation Impactor (NGI) coupled with a 1 L glass expansion chamber (Copley, Nottingham, UK) as previously described [ 12 ]. Briefly, 6 mg of powder was loaded into a nasal powder device (Unit Dose System Powder Disposable Nasal Spray, Aptar Pharma, France) and dispersed at a flow rate of 15 L/min.…”

“…WKS13 is a broad-spectrum humanised mAb that was recently discovered to exhibit potent neutralisation activity against different SARS-CoV-2 variants in hamsters through intraperitoneal administration [manuscript under revision]. The aim of this study was to develop an optimal formulation of WKS13 for potential clinical application by employing the dual targeting formulation strategy [ 12 ], in which a dry powder aerosol can be deposited in both the upper and lower respiratory tract simultaneously for antiviral activity through intranasal administration. A dual targeting formulation which contained particles with bimodal size distribution was prepared by blending spray dried powder of WKS13 of two different particle sizes, with the large particles (> 10 μm) for nasal deposition whilst the small particles (< 5 μm) for lung deposition.…”

Inhalable neutralizing antibodies – promising approach to combating respiratory viral infections

“…This is an area that remains to be investigated to develop an optimal formulation for the best clinical outcome. The concept of delivering antiviral drugs to the nasal and lower airways simultaneously through intranasal administration has been proposed [73], and this could be explored for neutralizing antibody therapy.…”