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.

Autor: Reyna D; TSRL, Inc., 540 Avis Dr., Suite A, Ann Arbor, MI 48108, USA., Bejster I; TSRL, Inc., 540 Avis Dr., Suite A, Ann Arbor, MI 48108, USA., Chadderdon A; TSRL, Inc., 540 Avis Dr., Suite A, Ann Arbor, MI 48108, USA., Harteg C; TSRL, Inc., 540 Avis Dr., Suite A, Ann Arbor, MI 48108, USA., Kurnia Anjani Q; School of Pharmacy, Queen's University Belfast, BT9 7BL, United Kingdom., Hidayat Bin Sabri A; School of Pharmacy, Queen's University Belfast, BT9 7BL, United Kingdom., Brown AN; College of Medicine, University of Florida, Orlando, FL 32827, USA., Drusano GL; College of Medicine, University of Florida, Orlando, FL 32827, USA., Westover J; Institute for Antiviral Research, Utah State University, 5600 Old Main Hill, Logan, Utah 84322, USA., Bart Tarbet E; Institute for Antiviral Research, Utah State University, 5600 Old Main Hill, Logan, Utah 84322, USA., Vora LK; School of Pharmacy, Queen's University Belfast, BT9 7BL, United Kingdom., Donnelly RF; School of Pharmacy, Queen's University Belfast, BT9 7BL, United Kingdom., Lipka E; TSRL, Inc., 540 Avis Dr., Suite A, Ann Arbor, MI 48108, USA. Electronic address: elipka@tsrlinc.com.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2023 Jun 25; Vol. 641, pp. 123081. Date of Electronic Publication: 2023 May 23.
DOI: 10.1016/j.ijpharm.2023.123081
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘Ryan Donnelly has patent licensed to TSRL, Inc.’
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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