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Development of Adenovirus Containing Liposomes Produced by Extrusion vs. Homogenization: A Comparison for Scale-Up Purposes

Adenovirus (Ad) is a widely studied viral vector for cancer therapy as it can be engineered to cause selective lysis of cancer cells. However, Ad delivery is limited in treating cancers that do not have coxsackievirus and adenovirus receptors (CAR). To overcome this challenge, Ad-encapsulated liposo...

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Autores principales: Shah, Jaimin R., Dong, Tao, Phung, Abraham T., Reid, Tony, Larson, Christopher, Sanchez, Ana B., Oronsky, Bryan, Blair, Sarah L., Aisagbonhi, Omonigho, Trogler, William C., Kummel, Andrew C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687354/
https://www.ncbi.nlm.nih.gov/pubmed/36354531
http://dx.doi.org/10.3390/bioengineering9110620
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author Shah, Jaimin R.
Dong, Tao
Phung, Abraham T.
Reid, Tony
Larson, Christopher
Sanchez, Ana B.
Oronsky, Bryan
Blair, Sarah L.
Aisagbonhi, Omonigho
Trogler, William C.
Kummel, Andrew C.
author_facet Shah, Jaimin R.
Dong, Tao
Phung, Abraham T.
Reid, Tony
Larson, Christopher
Sanchez, Ana B.
Oronsky, Bryan
Blair, Sarah L.
Aisagbonhi, Omonigho
Trogler, William C.
Kummel, Andrew C.
author_sort Shah, Jaimin R.
collection PubMed
description Adenovirus (Ad) is a widely studied viral vector for cancer therapy as it can be engineered to cause selective lysis of cancer cells. However, Ad delivery is limited in treating cancers that do not have coxsackievirus and adenovirus receptors (CAR). To overcome this challenge, Ad-encapsulated liposomes were developed that enhance the delivery of Ads and increase therapeutic efficacy. Cationic empty liposomes were manufactured first, to which an anionic Ad were added, which resulted in encapsulated Ad liposomes through charge interaction. Optimization of the liposome formula was carried out with series of formulation variables experiments using an extrusion process, which is ideal for laboratory-scale small batches. Later, the optimized formulation was manufactured with a homogenization technique—A high shear rotor-stator blending, that is ideal for large-scale manufacturing and is in compliance with Good Manufacturing Practices (GMP). Comparative in vitro transduction, physicochemical characterization, long-term storage stability at different temperature conditions, and in vivo animal studies were performed. Ad encapsulated liposomes transduced CAR deficient cells 100-fold more efficiently than the unencapsulated Ad (p ≤ 0.0001) in vitro, and 4-fold higher in tumors injected in nude mice in vivo. Both extrusion and homogenization performed similarly–with equivalent in vitro and in vivo transduction efficiencies, physicochemical characterization, and long-term storage stability. Thus, two Ad encapsulated liposomes preparation methods used herein, i.e., extrusion vs. homogenization were equivalent in terms of enhanced Ad performance and long-term storage stability; this will, hopefully, facilitate translation to the clinic.
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spelling pubmed-96873542022-11-25 Development of Adenovirus Containing Liposomes Produced by Extrusion vs. Homogenization: A Comparison for Scale-Up Purposes Shah, Jaimin R. Dong, Tao Phung, Abraham T. Reid, Tony Larson, Christopher Sanchez, Ana B. Oronsky, Bryan Blair, Sarah L. Aisagbonhi, Omonigho Trogler, William C. Kummel, Andrew C. Bioengineering (Basel) Article Adenovirus (Ad) is a widely studied viral vector for cancer therapy as it can be engineered to cause selective lysis of cancer cells. However, Ad delivery is limited in treating cancers that do not have coxsackievirus and adenovirus receptors (CAR). To overcome this challenge, Ad-encapsulated liposomes were developed that enhance the delivery of Ads and increase therapeutic efficacy. Cationic empty liposomes were manufactured first, to which an anionic Ad were added, which resulted in encapsulated Ad liposomes through charge interaction. Optimization of the liposome formula was carried out with series of formulation variables experiments using an extrusion process, which is ideal for laboratory-scale small batches. Later, the optimized formulation was manufactured with a homogenization technique—A high shear rotor-stator blending, that is ideal for large-scale manufacturing and is in compliance with Good Manufacturing Practices (GMP). Comparative in vitro transduction, physicochemical characterization, long-term storage stability at different temperature conditions, and in vivo animal studies were performed. Ad encapsulated liposomes transduced CAR deficient cells 100-fold more efficiently than the unencapsulated Ad (p ≤ 0.0001) in vitro, and 4-fold higher in tumors injected in nude mice in vivo. Both extrusion and homogenization performed similarly–with equivalent in vitro and in vivo transduction efficiencies, physicochemical characterization, and long-term storage stability. Thus, two Ad encapsulated liposomes preparation methods used herein, i.e., extrusion vs. homogenization were equivalent in terms of enhanced Ad performance and long-term storage stability; this will, hopefully, facilitate translation to the clinic. MDPI 2022-10-27 /pmc/articles/PMC9687354/ /pubmed/36354531 http://dx.doi.org/10.3390/bioengineering9110620 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shah, Jaimin R.
Dong, Tao
Phung, Abraham T.
Reid, Tony
Larson, Christopher
Sanchez, Ana B.
Oronsky, Bryan
Blair, Sarah L.
Aisagbonhi, Omonigho
Trogler, William C.
Kummel, Andrew C.
Development of Adenovirus Containing Liposomes Produced by Extrusion vs. Homogenization: A Comparison for Scale-Up Purposes
title Development of Adenovirus Containing Liposomes Produced by Extrusion vs. Homogenization: A Comparison for Scale-Up Purposes
title_full Development of Adenovirus Containing Liposomes Produced by Extrusion vs. Homogenization: A Comparison for Scale-Up Purposes
title_fullStr Development of Adenovirus Containing Liposomes Produced by Extrusion vs. Homogenization: A Comparison for Scale-Up Purposes
title_full_unstemmed Development of Adenovirus Containing Liposomes Produced by Extrusion vs. Homogenization: A Comparison for Scale-Up Purposes
title_short Development of Adenovirus Containing Liposomes Produced by Extrusion vs. Homogenization: A Comparison for Scale-Up Purposes
title_sort development of adenovirus containing liposomes produced by extrusion vs. homogenization: a comparison for scale-up purposes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9687354/
https://www.ncbi.nlm.nih.gov/pubmed/36354531
http://dx.doi.org/10.3390/bioengineering9110620
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