Microfluidic Production of Polymeric Core-Shell Microspheres for the Delayed Pulsatile Release of Bovine Serum Albumin as a Model Antigen

For many vaccines, multiple injections are required to confer protective immunity against targeted pathogens. These injections often consist of a primer administration followed by a booster administration of the vaccine a few weeks or months later. A single-injection vaccine formulation that provide...

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Autores principales: Renée S. van der Kooij, Rob Steendam, Johan Zuidema, Henderik W. Frijlink, Wouter L. J. Hinrichs
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/bda5dc6c013847dc8c076d0c0e07e904
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spelling oai:doaj.org-article:bda5dc6c013847dc8c076d0c0e07e9042021-11-25T18:41:11ZMicrofluidic Production of Polymeric Core-Shell Microspheres for the Delayed Pulsatile Release of Bovine Serum Albumin as a Model Antigen10.3390/pharmaceutics131118541999-4923https://doaj.org/article/bda5dc6c013847dc8c076d0c0e07e9042021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1854https://doaj.org/toc/1999-4923For many vaccines, multiple injections are required to confer protective immunity against targeted pathogens. These injections often consist of a primer administration followed by a booster administration of the vaccine a few weeks or months later. A single-injection vaccine formulation that provides for both administrations could greatly improve the convenience and vaccinee’s compliance. In this study, we developed parenterally injectable core-shell microspheres with a delayed pulsatile release profile that could serve as the booster in such a vaccine formulation. These microspheres contained bovine serum albumin (BSA) as the model antigen and poly(<span style="font-variant: small-caps;">dl</span>-lactide-<i>co</i>-glycolide) (PLGA) with various <span style="font-variant: small-caps;">dl</span>-lactide:glycolide monomer ratios as the shell material. Highly monodisperse particles with different particle characteristics were obtained using a microfluidic setup. All formulations exhibited a pulsatile in vitro release of BSA after an adjustable lag time. This lag time increased with the increasing lactide content of the polymer and ranged from 3 to 7 weeks. Shell thickness and bovine serum albumin loading had no effect on the release behavior, which could be ascribed to the degradation mechanism of the polymer, with bulk degradation being the main pathway. Co-injection of the core-shell microspheres together with a solution of the antigen that serves as the primer would allow for the desired biphasic release profile. Altogether, these findings show that injectable core-shell microspheres combined with a primer are a promising alternative for the current multiple-injection vaccines.Renée S. van der KooijRob SteendamJohan ZuidemaHenderik W. FrijlinkWouter L. J. HinrichsMDPI AGarticlecontrolled releasecore-shell microspheresdelayed pulsatile releasemicrofluidicspoly(<span style="font-variant: small-caps">dl</span>-lactide-<i>co</i>-glycolide)single-injection vaccinePharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1854, p 1854 (2021)
institution DOAJ
collection DOAJ
language EN
topic controlled release
core-shell microspheres
delayed pulsatile release
microfluidics
poly(<span style="font-variant: small-caps">dl</span>-lactide-<i>co</i>-glycolide)
single-injection vaccine
Pharmacy and materia medica
RS1-441
spellingShingle controlled release
core-shell microspheres
delayed pulsatile release
microfluidics
poly(<span style="font-variant: small-caps">dl</span>-lactide-<i>co</i>-glycolide)
single-injection vaccine
Pharmacy and materia medica
RS1-441
Renée S. van der Kooij
Rob Steendam
Johan Zuidema
Henderik W. Frijlink
Wouter L. J. Hinrichs
Microfluidic Production of Polymeric Core-Shell Microspheres for the Delayed Pulsatile Release of Bovine Serum Albumin as a Model Antigen
description For many vaccines, multiple injections are required to confer protective immunity against targeted pathogens. These injections often consist of a primer administration followed by a booster administration of the vaccine a few weeks or months later. A single-injection vaccine formulation that provides for both administrations could greatly improve the convenience and vaccinee’s compliance. In this study, we developed parenterally injectable core-shell microspheres with a delayed pulsatile release profile that could serve as the booster in such a vaccine formulation. These microspheres contained bovine serum albumin (BSA) as the model antigen and poly(<span style="font-variant: small-caps;">dl</span>-lactide-<i>co</i>-glycolide) (PLGA) with various <span style="font-variant: small-caps;">dl</span>-lactide:glycolide monomer ratios as the shell material. Highly monodisperse particles with different particle characteristics were obtained using a microfluidic setup. All formulations exhibited a pulsatile in vitro release of BSA after an adjustable lag time. This lag time increased with the increasing lactide content of the polymer and ranged from 3 to 7 weeks. Shell thickness and bovine serum albumin loading had no effect on the release behavior, which could be ascribed to the degradation mechanism of the polymer, with bulk degradation being the main pathway. Co-injection of the core-shell microspheres together with a solution of the antigen that serves as the primer would allow for the desired biphasic release profile. Altogether, these findings show that injectable core-shell microspheres combined with a primer are a promising alternative for the current multiple-injection vaccines.
format article
author Renée S. van der Kooij
Rob Steendam
Johan Zuidema
Henderik W. Frijlink
Wouter L. J. Hinrichs
author_facet Renée S. van der Kooij
Rob Steendam
Johan Zuidema
Henderik W. Frijlink
Wouter L. J. Hinrichs
author_sort Renée S. van der Kooij
title Microfluidic Production of Polymeric Core-Shell Microspheres for the Delayed Pulsatile Release of Bovine Serum Albumin as a Model Antigen
title_short Microfluidic Production of Polymeric Core-Shell Microspheres for the Delayed Pulsatile Release of Bovine Serum Albumin as a Model Antigen
title_full Microfluidic Production of Polymeric Core-Shell Microspheres for the Delayed Pulsatile Release of Bovine Serum Albumin as a Model Antigen
title_fullStr Microfluidic Production of Polymeric Core-Shell Microspheres for the Delayed Pulsatile Release of Bovine Serum Albumin as a Model Antigen
title_full_unstemmed Microfluidic Production of Polymeric Core-Shell Microspheres for the Delayed Pulsatile Release of Bovine Serum Albumin as a Model Antigen
title_sort microfluidic production of polymeric core-shell microspheres for the delayed pulsatile release of bovine serum albumin as a model antigen
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/bda5dc6c013847dc8c076d0c0e07e904
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AT robsteendam microfluidicproductionofpolymericcoreshellmicrospheresforthedelayedpulsatilereleaseofbovineserumalbuminasamodelantigen
AT johanzuidema microfluidicproductionofpolymericcoreshellmicrospheresforthedelayedpulsatilereleaseofbovineserumalbuminasamodelantigen
AT henderikwfrijlink microfluidicproductionofpolymericcoreshellmicrospheresforthedelayedpulsatilereleaseofbovineserumalbuminasamodelantigen
AT wouterljhinrichs microfluidicproductionofpolymericcoreshellmicrospheresforthedelayedpulsatilereleaseofbovineserumalbuminasamodelantigen
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