Delivery of PLGA-Loaded Influenza Vaccine Microparticles Using Dissolving Microneedles Induces a Robust Immune Response

<b>Background:</b> Influenza virus is one of the major respiratory virus infections that is a global health concern. Although there are already approved vaccines, most are administered via the intramuscular route, which is usually painful, leading to vaccine hesitancy. To this end, explo...

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Main Authors: Emmanuel Adediran, Tanisha Arte, Dedeepya Pasupuleti, Sharon Vijayanand, Revanth Singh, Parth Patel, Mahek Gulani, Amarae Ferguson, Mohammad Uddin, Susu M. Zughaier, Martin J. D’Souza
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Language:English
Published: MDPI AG 2025-04-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/4/510
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author Emmanuel Adediran
Tanisha Arte
Dedeepya Pasupuleti
Sharon Vijayanand
Revanth Singh
Parth Patel
Mahek Gulani
Amarae Ferguson
Mohammad Uddin
Susu M. Zughaier
Martin J. D’Souza
author_facet Emmanuel Adediran
Tanisha Arte
Dedeepya Pasupuleti
Sharon Vijayanand
Revanth Singh
Parth Patel
Mahek Gulani
Amarae Ferguson
Mohammad Uddin
Susu M. Zughaier
Martin J. D’Souza
author_sort Emmanuel Adediran
collection DOAJ
description <b>Background:</b> Influenza virus is one of the major respiratory virus infections that is a global health concern. Although there are already approved vaccines, most are administered via the intramuscular route, which is usually painful, leading to vaccine hesitancy. To this end, exploring the non-invasive, transdermal vaccination route using dissolving microneedles would significantly improve vaccine compliance. Research on innovative vaccine delivery systems, such as antigen-loaded PLGA microparticles, has the potential to pave the way for a broader range of vaccine candidates. <b>Methods:</b> In this proof-of-concept study, a combination of the inactivated influenza A H1N1 virus and inactivated influenza A H3N2 virus were encapsulated in a biodegradable poly (lactic-co-glycolic acid) (PLGA) polymeric matrix within microparticles, which enhanced antigen presentation. The antigen PLGA microparticles were prepared separately using a double emulsion (<i>w</i>/<i>o</i>/<i>w</i>), lyophilized, and characterized. Next, the vaccine microparticles were assessed in vitro in dendritic cells (DC 2.4) for immunogenicity. To explore pain-free transdermal vaccination, the vaccine microparticles were loaded into dissolving microneedles and administered in mice (n = 5). <b>Results:</b> Our vaccination study demonstrated that the microneedle-based vaccine elicited strong humoral responses as demonstrated by high antigen-specific IgA, IgG, IgG1, and IgG2a antibodies in serum samples and IgA in lung supernatant. Further, the vaccine also elicited a strong cellular response as evidenced by high levels of CD4+ and CD8a+ T cells in lymphoid organs such as the lymph nodes and spleen. <b>Conclusion:</b> The delivery of influenza vaccine-loaded PLGA microparticles using microneedles would be beneficial to individuals experiencing needle-phobia, as well as the geriatric and pediatric population.
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spelling doaj-art-c7b73def2e4242e69fbf18419d3d9b242025-08-20T02:28:20ZengMDPI AGPharmaceutics1999-49232025-04-0117451010.3390/pharmaceutics17040510Delivery of PLGA-Loaded Influenza Vaccine Microparticles Using Dissolving Microneedles Induces a Robust Immune ResponseEmmanuel Adediran0Tanisha Arte1Dedeepya Pasupuleti2Sharon Vijayanand3Revanth Singh4Parth Patel5Mahek Gulani6Amarae Ferguson7Mohammad Uddin8Susu M. Zughaier9Martin J. D’Souza10Center for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACenter for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACenter for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACenter for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACenter for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACenter for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACenter for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACenter for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACenter for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USACollege of Medicine, QU Health, Qatar University, Doha P.O. Box 2713, QatarCenter for Drug Delivery Research, Vaccine Nanotechnology Laboratory, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA<b>Background:</b> Influenza virus is one of the major respiratory virus infections that is a global health concern. Although there are already approved vaccines, most are administered via the intramuscular route, which is usually painful, leading to vaccine hesitancy. To this end, exploring the non-invasive, transdermal vaccination route using dissolving microneedles would significantly improve vaccine compliance. Research on innovative vaccine delivery systems, such as antigen-loaded PLGA microparticles, has the potential to pave the way for a broader range of vaccine candidates. <b>Methods:</b> In this proof-of-concept study, a combination of the inactivated influenza A H1N1 virus and inactivated influenza A H3N2 virus were encapsulated in a biodegradable poly (lactic-co-glycolic acid) (PLGA) polymeric matrix within microparticles, which enhanced antigen presentation. The antigen PLGA microparticles were prepared separately using a double emulsion (<i>w</i>/<i>o</i>/<i>w</i>), lyophilized, and characterized. Next, the vaccine microparticles were assessed in vitro in dendritic cells (DC 2.4) for immunogenicity. To explore pain-free transdermal vaccination, the vaccine microparticles were loaded into dissolving microneedles and administered in mice (n = 5). <b>Results:</b> Our vaccination study demonstrated that the microneedle-based vaccine elicited strong humoral responses as demonstrated by high antigen-specific IgA, IgG, IgG1, and IgG2a antibodies in serum samples and IgA in lung supernatant. Further, the vaccine also elicited a strong cellular response as evidenced by high levels of CD4+ and CD8a+ T cells in lymphoid organs such as the lymph nodes and spleen. <b>Conclusion:</b> The delivery of influenza vaccine-loaded PLGA microparticles using microneedles would be beneficial to individuals experiencing needle-phobia, as well as the geriatric and pediatric population.https://www.mdpi.com/1999-4923/17/4/510microneedlesPLGAinfluenzamicroparticlespolymer
spellingShingle Emmanuel Adediran
Tanisha Arte
Dedeepya Pasupuleti
Sharon Vijayanand
Revanth Singh
Parth Patel
Mahek Gulani
Amarae Ferguson
Mohammad Uddin
Susu M. Zughaier
Martin J. D’Souza
Delivery of PLGA-Loaded Influenza Vaccine Microparticles Using Dissolving Microneedles Induces a Robust Immune Response
Pharmaceutics
microneedles
PLGA
influenza
microparticles
polymer
title Delivery of PLGA-Loaded Influenza Vaccine Microparticles Using Dissolving Microneedles Induces a Robust Immune Response
title_full Delivery of PLGA-Loaded Influenza Vaccine Microparticles Using Dissolving Microneedles Induces a Robust Immune Response
title_fullStr Delivery of PLGA-Loaded Influenza Vaccine Microparticles Using Dissolving Microneedles Induces a Robust Immune Response
title_full_unstemmed Delivery of PLGA-Loaded Influenza Vaccine Microparticles Using Dissolving Microneedles Induces a Robust Immune Response
title_short Delivery of PLGA-Loaded Influenza Vaccine Microparticles Using Dissolving Microneedles Induces a Robust Immune Response
title_sort delivery of plga loaded influenza vaccine microparticles using dissolving microneedles induces a robust immune response
topic microneedles
PLGA
influenza
microparticles
polymer
url https://www.mdpi.com/1999-4923/17/4/510
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