PMID- 34834269
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211130
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 13
IP  - 11
DP  - 2021 Nov 3
TI  - Microfluidic Production of Polymeric Core-Shell Microspheres for the Delayed 
      Pulsatile Release of Bovine Serum Albumin as a Model Antigen.
LID - 10.3390/pharmaceutics13111854 [doi]
LID - 1854
AB  - 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(dl-lactide-co-glycolide) (PLGA) with various 
      dl-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.
FAU - van der Kooij, Renee S
AU  - van der Kooij RS
AD  - Department of Pharmaceutical Technology and Biopharmacy, Groningen Research 
      Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV 
      Groningen, The Netherlands.
FAU - Steendam, Rob
AU  - Steendam R
AD  - InnoCore Pharmaceuticals, L.J. Zielstraweg 1, 9713 GX Groningen, The Netherlands.
FAU - Zuidema, Johan
AU  - Zuidema J
AD  - InnoCore Pharmaceuticals, L.J. Zielstraweg 1, 9713 GX Groningen, The Netherlands.
FAU - Frijlink, Henderik W
AU  - Frijlink HW
AUID- ORCID: 0000-0001-7901-8198
AD  - Department of Pharmaceutical Technology and Biopharmacy, Groningen Research 
      Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV 
      Groningen, The Netherlands.
FAU - Hinrichs, Wouter L J
AU  - Hinrichs WLJ
AUID- ORCID: 0000-0002-1481-2769
AD  - Department of Pharmaceutical Technology and Biopharmacy, Groningen Research 
      Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV 
      Groningen, The Netherlands.
LA  - eng
GR  - InnoCore Pharmaceuticals/
PT  - Journal Article
DEP - 20211103
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC8625087
OTO - NOTNLM
OT  - controlled release
OT  - core-shell microspheres
OT  - delayed pulsatile release
OT  - microfluidics
OT  - poly(dl-lactide-co-glycolide)
OT  - single-injection vaccine
COIS- The authors declare no conflict of interest. InnoCore Pharmaceuticals had no role 
      in the design of the study; in the collection, analyses, or interpretation of 
      data; in the writing of the manuscript, and in the decision to publish the 
      results.
EDAT- 2021/11/28 06:00
MHDA- 2021/11/28 06:01
PMCR- 2021/11/03
CRDT- 2021/11/27 01:24
PHST- 2021/09/30 00:00 [received]
PHST- 2021/10/15 00:00 [revised]
PHST- 2021/10/28 00:00 [accepted]
PHST- 2021/11/27 01:24 [entrez]
PHST- 2021/11/28 06:00 [pubmed]
PHST- 2021/11/28 06:01 [medline]
PHST- 2021/11/03 00:00 [pmc-release]
AID - pharmaceutics13111854 [pii]
AID - pharmaceutics-13-01854 [pii]
AID - 10.3390/pharmaceutics13111854 [doi]
PST - epublish
SO  - Pharmaceutics. 2021 Nov 3;13(11):1854. doi: 10.3390/pharmaceutics13111854.