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Sustained release system from PLGA particles co-encapsulated with inactivated influenza virus with natural killer T cell agonist α-galactosylceramide.
- Source :
-
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2024 Aug; Vol. 201, pp. 114365. Date of Electronic Publication: 2024 Jun 12. - Publication Year :
- 2024
-
Abstract
- Vaccines against influenza and many other infectious diseases require multiple boosters in addition to the primary dose to improve efficacy, but this approach is not ideal for compliance. The multiple doses could potentially be replaced by sustained or pulsatile release of antigens encapsulated in degradable microparticles (MPs). The efficacy of a vaccine is improved by adding an adjuvant, which can be co-delivered from the particles to enhance immunogenicity. Here, we developed degradable poly-lactic-co-glycolic acid (PLGA) (7-17 kDa) MPs capable of sustained release of ultraviolet killed influenza virus (A/PR/8/34) (kPR8) vaccine and the natural killer T (NKT) cell agonist alpha-galactosylceramide (α-GalCer) and tested their effectiveness at providing long-term protection against influenza virus infection in mice. Multiple formulations were developed for encapsulating the virus and adjuvant separately, and in combination. The MPs exhibited sustained release of both the virus and the adjuvant lasting more than a month. Co-encapsulation significantly increased the encapsulation efficiency (EE) of the vaccine but reduced the release duration. On the other hand, co-encapsulation led to a reduction in EE for the α-GalCer and a change in release profile to a higher initial burst followed by a linear release compared to a low initial burst and slower linear release. The α-GalCer also had considerably longer release duration compared to the vaccine. Mice injected with particle formulations co-encapsulating kPR8 and α-GalCer were protected from a lethal influenza virus infection 30 weeks after vaccination. This study demonstrates that PLGA MP based vaccines are promising for providing effective vaccination and possibly for replacing multiple doses with a single injection.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Mice
Female
Mice, Inbred BALB C
Adjuvants, Immunologic administration & dosage
Adjuvants, Immunologic pharmacology
Mice, Inbred C57BL
Vaccines, Inactivated immunology
Vaccines, Inactivated administration & dosage
Galactosylceramides administration & dosage
Galactosylceramides immunology
Galactosylceramides chemistry
Polylactic Acid-Polyglycolic Acid Copolymer chemistry
Influenza Vaccines immunology
Influenza Vaccines administration & dosage
Influenza Vaccines chemistry
Delayed-Action Preparations
Natural Killer T-Cells immunology
Natural Killer T-Cells drug effects
Orthomyxoviridae Infections prevention & control
Orthomyxoviridae Infections immunology
Orthomyxoviridae Infections virology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-3441
- Volume :
- 201
- Database :
- MEDLINE
- Journal :
- European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
- Publication Type :
- Academic Journal
- Accession number :
- 38876362
- Full Text :
- https://doi.org/10.1016/j.ejpb.2024.114365