Gelatin Stabilizes Nebulized Proteins in Pulmonary Drug Delivery against COVID-19

Abstract

Delivering medication to the lungs via nebulization of pharmaceuticals is a noninvasive and efficient therapy route, particularly for respiratory diseases. The recent worldwide severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic urges the development of such therapies as an effective alternative to vaccines. The main difficulties in using inhalation therapy are the development of effective medicine and methods to stabilize the biological molecules and transfer them to the lungs efficiently following nebulization. We have developed a high-affinity angiotensin-converting enzyme 2 (ACE2) receptor-binding domain (RBD-62) that can be used as a medication to inhibit infection with SARS-CoV-2 and its variants. In this study, we established a nebulization protocol for drug delivery by inhalation using two commercial vibrating mesh (VM) nebulizers (Aerogen Solo and PARI eFlow) that generate similar mist size distribution in a size range that allows efficient deposition in the small respiratory airway. In a series of experiments, we show the high activity of RBD-62, interferon-α2 (IFN-α2), and other proteins following nebulization. The addition of gelatin significantly stabilizes the proteins and enhances the fractions of active proteins after nebulization, minimizing the medication dosage. Furthermore, hamster inhalation experiments verified the feasibility of the protocol in pulmonary drug delivery. In short, the gelatin-modified RBD-62 formulation in coordination with VM nebulizer can be used as a therapy to cure SARS-CoV-2.

Atezolizumab Retains Cellular Binding to Programmed Death Ligand 1 Following AerosolizationviaMesh Nebulizer

“…Considering the future development of inhalable proteins, there are additional ways to protect protein during VM nebulization: e.g. by making a gelatinmodified RBD-62 formulation (30).…”

Pulmonary inhalation for disease treatment: Basic research and clinical translations

“…HCQ can be formulated as an inhalable dry powder by jet-grinding HCQ sulfate [ 271 ]. Li et al [ 272 ] developed an ACE2 receptor-binding domain that can inhibit SARS-CoV-2 infection and found that adding gelatin significantly stabilized the protein and increased the active protein fraction after aerosolization, minimizing the drug dose. A formulation of favipiravir SLN was prepared for pulmonary delivery using the thermal evaporation method [ 273 ].…”

Enhancing Mucoadhesive Properties of Gelatin through Chemical Modification with Unsaturated Anhydrides

“…1−3 Gelatin is commonly used as a major ingredient in many formulations, including hard and soft capsules, 4 vaginal and rectal suppositories, 5 as matrices in tissue engineering and regenerative medicine, 6 as a carrier in drug delivery (e.g., microspheres), 7 and in many other healthrelated applications. 8,9 This article is licensed under CC-BY 4 Mucoadhesion is defined as the ability of materials to adhere to mucosal membranes in the body for an extended period of time. The established routes for transmucosal drug administration include ocular (corneal and conjunctival), nasal, oromucosal (buccal and sublingual), gastrointestinal, rectal, vaginal, and intravesical.…”

“…Additionally, it exhibits a melting point close to body temperature. These distinctive properties are the key factors driving its extensive applications in pharmaceutical, food, and cosmetic industries. − Gelatin is commonly used as a major ingredient in many formulations, including hard and soft capsules, vaginal and rectal suppositories, as matrices in tissue engineering and regenerative medicine, as a carrier in drug delivery (e.g., microspheres), and in many other health-related applications. , …”

“… 1 − 3 Gelatin is commonly used as a major ingredient in many formulations, including hard and soft capsules, 4 vaginal and rectal suppositories, 5 as matrices in tissue engineering and regenerative medicine, 6 as a carrier in drug delivery (e.g., microspheres), 7 and in many other health-related applications. 8 , 9 …”