A five-day treatment course of zanamivir for the flu with a single, self-administered, painless microneedle array patch: Revolutionizing delivery of poorly membrane-permeable therapeutics

[Display omitted] Seasonal influenza virus infections cause a substantial number of deaths each year. While zanamivir (ZAN) is efficacious against oseltamivir-resistant influenza strains, the efficacy of the drug is limited by its route of administration, oral inhalation. Herein, we present the deve...

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Bibliographic Details
Published in:International journal of pharmaceutics 2023-06, Vol.641, p.123081-123081, Article 123081
Main Authors: Reyna, Dawn, Bejster, Ian, Chadderdon, Aaron, Harteg, Cheryl, Kurnia Anjani, Qonita, Hidayat Bin Sabri, Akmal, Brown, Ashley N., Drusano, George L., Westover, Jonna, Bart Tarbet, E., Vora, Lalitkumar K., Donnelly, Ryan F., Lipka, Elke
Format: Article
Language:English
Subjects:
Animals
Antiviral Agents
Controlled release delivery
Gelatin
Humans
Influenza treatment
Influenza, Human
PK/PD driven drug delivery
Preclinical pharmacokinetics
Rats
Swellable microarray patches
Swine
Trehalose
Zanamivir
Zanamivir - therapeutic use
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Summary:[Display omitted] Seasonal influenza virus infections cause a substantial number of deaths each year. While zanamivir (ZAN) is efficacious against oseltamivir-resistant influenza strains, the efficacy of the drug is limited by its route of administration, oral inhalation. Herein, we present the development of a hydrogel-forming microneedle array (MA) in combination with ZAN reservoirs for treating seasonal influenza. The MA was fabricated from Gantrez® S-97 crosslinked with PEG 10,000. Various reservoir formulations included ZAN hydrate, ZAN hydrochloric acid (HCl), CarraDres™, gelatin, trehalose, and/or alginate. In vitro permeation studies with a lyophilized reservoir consisting of ZAN HCl, gelatin, and trehalose resulted in rapid and high delivery of up to 33 mg of ZAN across the skin with delivery efficiency of up to ≈75% by 24 h. Pharmacokinetics studies in rats and pigs demonstrated that a single administration of a MA in combination with a CarraDres™ ZAN HCl reservoir offered a simple and minimally invasive delivery of ZAN into the systemic circulation. In pigs, efficacious plasma and lung steady-state levels of ∼120 ng/mL were reached within 2 h and sustained between 50 and 250 ng/mL over 5 days. MA-enabled delivery of ZAN could enable a larger number of patients to be reached during an influenza outbreak.
ISSN:0378-5173
1873-3476
1873-3476
DOI:10.1016/j.ijpharm.2023.123081