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Applying Microfluidics for the Production of the Cationic Liposome-Based Vaccine Adjuvant CAF09b

Subunit vaccines require particulate adjuvants to induce the desired immune responses. Pre-clinical manufacturing methods of adjuvants are often batch dependent, which complicates scale-up for large-scale good manufacturing practice (GMP) production. The cationic liposomal adjuvant CAF09b, composed...

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Autores principales: Schmidt, Signe Tandrup, Christensen, Dennis, Perrie, Yvonne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767004/
https://www.ncbi.nlm.nih.gov/pubmed/33352684
http://dx.doi.org/10.3390/pharmaceutics12121237
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author Schmidt, Signe Tandrup
Christensen, Dennis
Perrie, Yvonne
author_facet Schmidt, Signe Tandrup
Christensen, Dennis
Perrie, Yvonne
author_sort Schmidt, Signe Tandrup
collection PubMed
description Subunit vaccines require particulate adjuvants to induce the desired immune responses. Pre-clinical manufacturing methods of adjuvants are often batch dependent, which complicates scale-up for large-scale good manufacturing practice (GMP) production. The cationic liposomal adjuvant CAF09b, composed of dioctadecyldimethylammonium bromide (DDA), monomycoloyl glycerol analogue 1 (MMG) and polyinosinic:polycytidylic acid [poly(I:C)], is currently being clinically evaluated in therapeutic cancer vaccines. Microfluidics is a promising new method for large-scale manufacturing of particle-based medicals, which is scalable from laboratory to GMP production, and a protocol for production of CAF09b by this method was therefore validated. The influence of the manufacture parameters [Ethanol] (20–40% v/v), [Lipid] (DDA and MMG, 6–12 mg/mL) and dimethyl sulfoxide [DMSO] (0–10% v/v) on the resulting particle size, colloidal stability and adsorption of poly(I:C) was evaluated in a design-of-experiments study. [Ethanol] and [DMSO] affected the resulting particle sizes, while [Lipid] and [DMSO] affected the colloidal stability. In all samples, poly(I:C) was encapsulated within the liposomes. At [Ethanol] 30% v/v, most formulations were stable at 21 days of manufacture with particle sizes <100 nm. An in vivo comparison in mice of the immunogenicity to the cervical cancer peptide antigen HPV-16 E7 adjuvanted with CAF09b prepared by lipid film rehydration or microfluidics showed no difference between the formulations, indicating adjuvant activity is intact. Thus, it is possible to prepare suitable formulations of CAF09b by microfluidics.
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spelling pubmed-77670042020-12-28 Applying Microfluidics for the Production of the Cationic Liposome-Based Vaccine Adjuvant CAF09b Schmidt, Signe Tandrup Christensen, Dennis Perrie, Yvonne Pharmaceutics Article Subunit vaccines require particulate adjuvants to induce the desired immune responses. Pre-clinical manufacturing methods of adjuvants are often batch dependent, which complicates scale-up for large-scale good manufacturing practice (GMP) production. The cationic liposomal adjuvant CAF09b, composed of dioctadecyldimethylammonium bromide (DDA), monomycoloyl glycerol analogue 1 (MMG) and polyinosinic:polycytidylic acid [poly(I:C)], is currently being clinically evaluated in therapeutic cancer vaccines. Microfluidics is a promising new method for large-scale manufacturing of particle-based medicals, which is scalable from laboratory to GMP production, and a protocol for production of CAF09b by this method was therefore validated. The influence of the manufacture parameters [Ethanol] (20–40% v/v), [Lipid] (DDA and MMG, 6–12 mg/mL) and dimethyl sulfoxide [DMSO] (0–10% v/v) on the resulting particle size, colloidal stability and adsorption of poly(I:C) was evaluated in a design-of-experiments study. [Ethanol] and [DMSO] affected the resulting particle sizes, while [Lipid] and [DMSO] affected the colloidal stability. In all samples, poly(I:C) was encapsulated within the liposomes. At [Ethanol] 30% v/v, most formulations were stable at 21 days of manufacture with particle sizes <100 nm. An in vivo comparison in mice of the immunogenicity to the cervical cancer peptide antigen HPV-16 E7 adjuvanted with CAF09b prepared by lipid film rehydration or microfluidics showed no difference between the formulations, indicating adjuvant activity is intact. Thus, it is possible to prepare suitable formulations of CAF09b by microfluidics. MDPI 2020-12-19 /pmc/articles/PMC7767004/ /pubmed/33352684 http://dx.doi.org/10.3390/pharmaceutics12121237 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schmidt, Signe Tandrup
Christensen, Dennis
Perrie, Yvonne
Applying Microfluidics for the Production of the Cationic Liposome-Based Vaccine Adjuvant CAF09b
title Applying Microfluidics for the Production of the Cationic Liposome-Based Vaccine Adjuvant CAF09b
title_full Applying Microfluidics for the Production of the Cationic Liposome-Based Vaccine Adjuvant CAF09b
title_fullStr Applying Microfluidics for the Production of the Cationic Liposome-Based Vaccine Adjuvant CAF09b
title_full_unstemmed Applying Microfluidics for the Production of the Cationic Liposome-Based Vaccine Adjuvant CAF09b
title_short Applying Microfluidics for the Production of the Cationic Liposome-Based Vaccine Adjuvant CAF09b
title_sort applying microfluidics for the production of the cationic liposome-based vaccine adjuvant caf09b
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767004/
https://www.ncbi.nlm.nih.gov/pubmed/33352684
http://dx.doi.org/10.3390/pharmaceutics12121237
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