Nasal delivery of encapsulated recombinant ACE2 as a prophylactic drug for SARS-CoV-2

Alberto Baldelli; Chun Yuen Jerry Wong; Hale Oguzlu; Hanieh Gholizadeh; Yigong Guo; Hui Xin Ong; Anika Singh; Daniela Traini; Anubhav Pratap-Singh

doi:10.1016/j.ijpharm.2024.124009

Nasal delivery of encapsulated recombinant ACE2 as a prophylactic drug for SARS-CoV-2

Alberto Baldelli, Chun Yuen Jerry Wong, Hale Oguzlu, Hanieh Gholizadeh, Yigong Guo, Hui Xin Ong, Anika Singh, Daniela Traini, Anubhav Pratap-Singh

Macquarie Medical School

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

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Abstract

Angiotensin-converting enzyme 2 (ACE2) is responsible for cell fusion with SARS-CoV viruses. ACE2 is contained in different areas of the human body, including the nasal cavity, which is considered the main entrance for different types of airborne viruses. We took advantage of the roles of ACE2 and the nasal cavity in SARS-CoV-2 replication and transmission to develop a nasal dry powder. Recombinant ACE2 (rhACE2), after a proper encapsulation achieved via spray freeze drying, shows a binding efficiency with spike proteins of SARS-CoV-2 higher than 77 % at quantities lower than 5 µg/ml. Once delivered to the nose, encapsulated rhACE2 led to viability and permeability of RPMI 2650 cells of at least 90.20 ± 0.67 % and 47.96 ± 4.46 %, respectively, for concentrations lower than 1 mg/ml. These results were validated using nasal dry powder containing rhACE2 to prevent or treat infections derived from SARS-CoV-2.

Original language	English
Article number	124009
Pages (from-to)	1-13
Number of pages	13
Journal	International Journal of Pharmaceutics
Volume	655
Early online date	16 Mar 2024
DOIs	https://doi.org/10.1016/j.ijpharm.2024.124009
Publication status	Published - 25 Apr 2024

Bibliographical note

Copyright the Author(s) 2024. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

Recombinant ACE2
Spray freeze drying
Nasal drug delivery
Nasal epithelium
SARS-CoV-2

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10.1016/j.ijpharm.2024.124009Licence: CC BY

Publisher version (open access)Final published version, 14.3 MBLicence: CC BY

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title = "Nasal delivery of encapsulated recombinant ACE2 as a prophylactic drug for SARS-CoV-2",

abstract = "Angiotensin-converting enzyme 2 (ACE2) is responsible for cell fusion with SARS-CoV viruses. ACE2 is contained in different areas of the human body, including the nasal cavity, which is considered the main entrance for different types of airborne viruses. We took advantage of the roles of ACE2 and the nasal cavity in SARS-CoV-2 replication and transmission to develop a nasal dry powder. Recombinant ACE2 (rhACE2), after a proper encapsulation achieved via spray freeze drying, shows a binding efficiency with spike proteins of SARS-CoV-2 higher than 77 % at quantities lower than 5 µg/ml. Once delivered to the nose, encapsulated rhACE2 led to viability and permeability of RPMI 2650 cells of at least 90.20 ± 0.67 % and 47.96 ± 4.46 %, respectively, for concentrations lower than 1 mg/ml. These results were validated using nasal dry powder containing rhACE2 to prevent or treat infections derived from SARS-CoV-2.",

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AU - Jerry Wong, Chun Yuen

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AU - Guo, Yigong

AU - Ong, Hui Xin

AU - Singh, Anika

AU - Traini, Daniela

AU - Pratap-Singh, Anubhav

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N2 - Angiotensin-converting enzyme 2 (ACE2) is responsible for cell fusion with SARS-CoV viruses. ACE2 is contained in different areas of the human body, including the nasal cavity, which is considered the main entrance for different types of airborne viruses. We took advantage of the roles of ACE2 and the nasal cavity in SARS-CoV-2 replication and transmission to develop a nasal dry powder. Recombinant ACE2 (rhACE2), after a proper encapsulation achieved via spray freeze drying, shows a binding efficiency with spike proteins of SARS-CoV-2 higher than 77 % at quantities lower than 5 µg/ml. Once delivered to the nose, encapsulated rhACE2 led to viability and permeability of RPMI 2650 cells of at least 90.20 ± 0.67 % and 47.96 ± 4.46 %, respectively, for concentrations lower than 1 mg/ml. These results were validated using nasal dry powder containing rhACE2 to prevent or treat infections derived from SARS-CoV-2.

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Nasal delivery of encapsulated recombinant ACE2 as a prophylactic drug for SARS-CoV-2

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