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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2021
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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 |
work_keys_str_mv |
AT reneesvanderkooij microfluidicproductionofpolymericcoreshellmicrospheresforthedelayedpulsatilereleaseofbovineserumalbuminasamodelantigen AT robsteendam microfluidicproductionofpolymericcoreshellmicrospheresforthedelayedpulsatilereleaseofbovineserumalbuminasamodelantigen AT johanzuidema microfluidicproductionofpolymericcoreshellmicrospheresforthedelayedpulsatilereleaseofbovineserumalbuminasamodelantigen AT henderikwfrijlink microfluidicproductionofpolymericcoreshellmicrospheresforthedelayedpulsatilereleaseofbovineserumalbuminasamodelantigen AT wouterljhinrichs microfluidicproductionofpolymericcoreshellmicrospheresforthedelayedpulsatilereleaseofbovineserumalbuminasamodelantigen |
_version_ |
1718410797264142336 |