Development of PLGA nanoparticle loaded dissolving microneedles and comparison with hollow microneedles in intradermal vaccine delivery

Mönkäre, Juha; Pontier, Maria; Kampen, Eveline E.M. van; Du, Guangsheng; Leone, Marialucrezia; Romeijn, Stefan; Nejadnik, M. Reza; O’Mahony, Conor; Slütter, Bram; Bouwstra, Joke A.

doi:10.1016/j.ejpb.2018.05.031

Cited by 72 publications

(35 citation statements)

References 38 publications

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“…The antigen association in the shell of nanocapsules allows a fast recognition by immunocompetent cells and therefore it is expected that it would trigger an efficient immune response. Other nanoformulations have shown similar or lower OVA loading efficiency in comparison to our CSNCs [ 40 , 41 ].…”

Section: Resultsmentioning

confidence: 67%

Lower-Sized Chitosan Nanocapsules for Transcutaneous Antigen Delivery

2018

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Transcutaneous vaccination has several advantages including having a noninvasive route and needle-free administration; nonetheless developing an effective transdermal formulation has not been an easy task because skin physiology, particularly the stratum corneum, does not allow antigen penetration. Size is a crucial parameter for successful active molecule administration through the skin. Here we report a new core-shell structure rationally developed for transcutaneous antigen delivery. The resulting multifunctional carrier has an oily core with immune adjuvant properties and a polymeric corona made of chitosan. This system has a size of around 100 nm and a positive zeta potential. The new formulation is stable in storage and physiological conditions. Ovalbumin (OVA) was used as the antigen model and the developed nanocapsules show high association efficiency (75%). Chitosan nanocapsules have high interaction with the immune system which was demonstrated by complement activation and also did not affect cell viability in the macrophage cell line. Finally, ex vivo studies using a pig skin model show that OVA associated to the chitosan nanocapsules developed in this study penetrated and were retained better than OVA in solution. Thus, the physicochemical properties and their adequate characteristics make this carrier an excellent platform for transcutaneous antigen delivery.

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Section: Resultsmentioning

confidence: 67%

Lower-Sized Chitosan Nanocapsules for Transcutaneous Antigen Delivery

2018

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“…Particle based antigen carriers can also serve as a depot for controlled release of antigen, thereby increasing the availability of antigen to the immune cells [42,43]. In addition, particle-based adjuvants possess the ability to modulate the type of induced immune responses when used alone or in combination with other immune-stimulatory compounds [44]. Particulates can protect the integrity of antigens against degradation until delivered to the immune cells as antigens must be protected from the harsh acidic conditions of the stomach and enzymatic degradation in the GI tract [45,46].…”

Section: Particulate Vaccinesmentioning

confidence: 99%

“…Monkare et al have developed a PLGA nanoparticle-based microneedle for vaccine delivery [44]. The hyaluronan (HA)-based dissolving microneedles (MNs) are loaded with PLGA nanoparticles (NPs) co-encapsulating ovalbumin (OVA) and poly(I:C) for intradermal immunization.…”

Section: Particulate Vaccinesmentioning

confidence: 99%

“…The hyaluronan (HA)-based dissolving microneedles (MNs) are loaded with PLGA nanoparticles (NPs) co-encapsulating ovalbumin (OVA) and poly(I:C) for intradermal immunization. The NP:HA ratio used for the preparation of dissolving MNs appeared to be critical for the quality of MNs and their dissolution in ex vivo human skin [44]. Results revealed that HA-based dissolving MNs loaded with PLGA NPs were developed for minimally invasive intradermal vaccination.…”

Section: Particulate Vaccinesmentioning

confidence: 99%

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Overview and Future Potential of Fast Dissolving Buccal Films as Drug Delivery System for Vaccines

et al. 2019

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Vaccination is considered one of the most successful public health interventions of the modern era. Vaccines are categorized based on the antigen used, delivery system and the route of administration. Traditional vaccines are produced from the dead, attenuated or inactivated pathogens that cause disease. However, newly developed vaccines are DNA based, liposome based, and virus like particle (VLP) based which are more effective and specific to some malignant diseases. The delivery system of vaccines has been advanced along with time as well. New delivery systems such as nanoparticles, liposomes, or cells (for DNA) has been proven to develop a more efficient vaccine. Most vaccines are administered via intramuscular (IM), subcutaneous (SQ) or oral (PO) route. However, these routes of administration have limitations and side effects. An alternative route could be oral cavity administration such as buccal or sublingual administration using film dosage form as delivery vehicle. In this article, we thoroughly reviewed the possibility of developing a quickly soluble film-based delivery system for vaccine administration. We reviewed the different types of new vaccines and vaccine formulations such as VLP based, liposome, bilosome, particulate, and summarized their suitability for use in a film dosage form. Quickly soluble film dosage form is the most optimized form of buccal administration. A film dosage form applied in the buccal cavity has several advantages: they can avoid first pass effect, they are easy to administer and prepare, and they are more cost effective. Since there is no first pass effect, only a small quantity of the vaccine is needed. Vaccines in their original form or in a nano or microparticulate form can be used in a film. The film can also be developed in multilayers to protect the vaccine from degradation by saliva or swallowing. Films are easy to prepare, administer, and can be used for systemic and local action. In addition, most of the current vaccines use mostly the parenteral route of administration, which has some major drawbacks such as poor induction of mucosal immunity, less patient compliant, less potent, high cost and cumbersome production process. Sublingual and buccal vaccine delivery can be good alternatives as they are easier to prepare and safer than parenteral administration routes. The buccal and sublingual administration have the advantage to produce both systemic and mucosal immunity.

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“…Given to BALB/c mice, the multiple adjuvant-constituted PLGA NPs loaded with Ags induced robust and efficient immune responses, as confirmed by evaluation of vivo cytokine (IFN-γ, IL-4, and IL-1β) secretion and antibody (IgG1 and IgG2a) production, demonstrating using a combination of adjuvants in a context-dependent manner may a feasible strategy for engineering a potent PLGA-based VADS. To make subunit vaccines suitable for immunization via skin, which is an attractive but also very challenging immunization site due to the presence of affluent APCs while difficulty of administration, recently, Bouwstra's group fabricated the hyaluronan (HA)-based dissolving microneedles (MNs) entrapped with PLGA NPs which co-encapsulated ovalbumin (OVA) as an Ag and poly(I:C) as an adjuvant for intradermal immunization [56]. Further investigation indicated that the immunogenicity of the PLGA NPs after administration of dissolving MNs was compared with that of hollow MN-delivered PLGA NPs in mice, while immunization with free Ag in dissolving MNs resulted in equally strong immune responses compared to delivery by hollow MNs.…”

Section: Plga Npsmentioning

confidence: 99%

Polymeric Nanoparticles Engineered as a Vaccine Adjuvant-Delivery System

Liu¹,

Wu²,

Liu³

et al. 2018

Immunization - Vaccine Adjuvant Delivery System and Strategies

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Global immunization saves millions of human lives each year through using vaccines, which include whole microbe-based products and the subunit ones formulated with just the components of antigens able to stimulate immune system to establish specific immunity against diseases. Subunit vaccines show numerous advantages, such as defined components, high safety profile, and production without the use of dangerous pathogens, but also limited capacity in eliciting immunity due to the lack of other components than antigens, including the immunostimulatory elements of pathogenassociated molecular patterns which are able to activate the innate immunoreponses.Recently, nanoparticles (NPs) formulated with polymeric materials, such as poly(lacticco-glycolic acid), viral proteins, chitosan, hyaluronic acid, and polystyrene, with some bearing intrinsic adjuvanticity, are widely employed as vaccine adjuvant-delivery systems (VADSs) and show great potential in developing subunit vaccines. Particularly, the polymeric NPs engineered with functional materials possess many features, such as targeting delivery, lysosome escape, anti-damaging protection, and ability to guide immune reactions toward a Th1 (T helper type 1) and Th2 pathway, which are crucial for establishing humoral and cellular immunity. This chapter describes polymeric NP-based VADSs designed for developing subunit vaccines able to elicit Ag-specific immunity at both systemic and mucosal levels via different vaccination routes.

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Development of PLGA nanoparticle loaded dissolving microneedles and comparison with hollow microneedles in intradermal vaccine delivery

Cited by 72 publications

References 38 publications

Lower-Sized Chitosan Nanocapsules for Transcutaneous Antigen Delivery

Lower-Sized Chitosan Nanocapsules for Transcutaneous Antigen Delivery

Overview and Future Potential of Fast Dissolving Buccal Films as Drug Delivery System for Vaccines

Polymeric Nanoparticles Engineered as a Vaccine Adjuvant-Delivery System

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