Immune response elicited by an intranasally delivered HBsAg low-dose adsorbed to poly-ε-caprolactone based nanoparticles

Jesus, Sandra; Soares, Edna; Costa, João Panão; Borchard, Gerrit; Borges, Olga

doi:10.1016/j.ijpharm.2016.03.013

Cited by 41 publications

(16 citation statements)

References 41 publications

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“…The immunization schedule comprised a primary nasal immunization followed by two nasal boosts at Days 7 and 21. Therefore, in this study, we included two other established chitosan-based nano-delivery systems developed by our group, Chi-Al NPs [26] and Chi-PCL NPs [27], in order to compare adjuvanticity elicited by the new system.…”

Section: Resultsmentioning

confidence: 99%

“…Chitosan–aluminum nanoparticles (Chi-Al NPs) and chitosan–poly epsilon caprolactone (Chi-PCL) NPs used in the immunogenicity study were produced as previously described by our group [26,27]…”

Section: Methodsmentioning

confidence: 99%

“…Quantification of immunoglobulins was performed using a protocol optimized by our group [27,30]. The endpoint titers presented in the results represent the antilog of the last log2 dilution, for which the OD values were at least two-fold higher than that of the naive sample, equally diluted.…”

Section: Methodsmentioning

confidence: 99%

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Chitosan Plus Compound 48/80: Formulation and Preliminary Evaluation as a Hepatitis B Vaccine Adjuvant

et al. 2019

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Current vaccine research is mostly based on subunit antigens. Despite the better toxicity profile of these antigens they are often poorly immunogenic, so adjuvant association has been explored as a strategy to obtain a potent vaccine formulation. Recently, mast cell activators were recognized as a new class of vaccine adjuvants capable of potentiating mucosal and systemic immune responses. In this study, a co-adjuvanted delivery system was developed and characterized, combining the mast cell activator C48/80 with chitosan nanoparticles (Chi-C48/80 NPs), and the results were compared with plain chitosan nanoparticles. The adsorption of model antigens onto the NP surface as well as the biocompatibility of the system was not affected by the incorporation of C48/80 in the formulation. The stability of the nanoparticles was demonstrated by studying the variation of size and zeta potential at different times, and the ability to be internalized by antigen presenting cells was confirmed by confocal microscopy. Vaccination studies with hepatitis B surface antigen loaded Chi-C48/80 NPs validated the adjuvanticity of the delivery system, demonstrating for the first time a successful association between a mast cell activator and chitosan nanoparticles as a vaccine adjuvant for hepatitis B virus, applied to a nasal vaccination strategy.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Chitosan Plus Compound 48/80: Formulation and Preliminary Evaluation as a Hepatitis B Vaccine Adjuvant

et al. 2019

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“…Several in vitro models have been used to explore the interaction of xenobiotics with the airway epithelium. Human nasal septum epithelial cells RPMI2650 ATCC® CCL-30™ were used however these cells pile and fail to reach a complete confluence [26] , [27] . The 16HBE14o-human bronchial epithelial cell line are useful in the study of paracellular drug transport, since they form a pseudo-stratified monolayer and express TJ proteins [28] , [29] , [30] and have been established as a model system to investigate drug transport across the airway epithelium [31] .…”

Section: Introductionmentioning

confidence: 99%

Mechanisms allowing protein delivery in nasal mucosa using NPL nanoparticles

Bernocchi

Carpentier

Lantier

et al. 2016

Journal of Controlled Release

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The intranasal administration of proteins using nanoparticles is a promising approach for several applications, especially for mucosal vaccines. Delivery of protein within the epithelial barrier is a key point to elicit an immune response and nano-carrier has to show no toxicity. The aim of this work was to elucidate the interactions of cationic porous nanoparticles loaded with protein delivery for antigen delivery in the nose. We investigated the loading, the cellular delivery and the epithelial transcytosis of proteins associated to these nanoparticles containing an anionic lipid in their core (NPL). NPL were highly endocytosed by airway epithelial cells and significantly improved the protein delivery into the cell. In vitro transcytosis studies showed that NPL did not modify the in vitro epithelial permeability suggesting no toxicity of these carriers. Moreover protein and NPL did not translocate the epithelial barrier. In vivo studies demonstrated that NPL prolonged the nasal residence time of the protein and no NPL were found beyond the epithelial barrier in vivo, precluding a negative side effect. All together these results establish the NPL as a bio-eliminable and optimal vaccine carrier.

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“…81 Other polymers investigated include pullulan, a naturally occurring polysaccharide copolymer made up of maltotriose subunits from fungus; 82 pectin, a naturally occurring polysaccharide found in fruits; and the biodegradable synthetic polymer polycaprolactone. 83 Liposomes are nano-or micrometre sized particles made up of one or more lipid bilayers, which have the ability to incorporate antigen at their surface or inside the aqueous core. There are numerous examples of coated and un-coated liposomal formulations used to deliver vaccine intranasally in a range of formats.…”

Section: Formulation Approachesmentioning

confidence: 99%

Current prospects and future challenges for nasal vaccine delivery

Yusuf

Kett

2016

Human Vaccines & Immunotherapeutics

124

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Nasal delivery offers many benefits over traditional approaches to vaccine administration. These include ease of administration without needles that reduces issues associated with needlestick injuries and disposal. Additionally, this route offers easy access to a key part of the immune system that can stimulate other mucosal sites throughout the body. Increased acceptance of nasal vaccine products in both adults and children has led to a burgeoning pipeline of nasal delivery technology. Key challenges and opportunities for the future will include translating in vivo data to clinical outcomes. Particular focus should be brought to designing delivery strategies that take into account the broad range of diseases, populations and healthcare delivery settings that stand to benefit from this unique mucosal route. In this review the current state of the art in nasal vaccine delivery will be described along with future prospects. A brief introduction to the anatomy and physiology of the nasal cavity will highlight the advantages and disadvantages of the route. Encapsulation and presentation methods along with particular formulation considerations for the nasal route will also be discussed.There are many mucosal routes which have been regarded as potential sites for vaccine delivery such as oral, nasal, pulmonary, conjunctival, rectal and vaginal mucosa. However, for practical and cultural reasons researchers have tended to focus only on oral, nasal, and pulmonary administration. 1 Needlefree vaccines offer many advantages over traditional vaccination approaches including convenience, cost, ease of administration and disposal.There are several needle free methods of vaccination such as transdermal delivery and mucosal delivery. 2,3 Mucosal immunization has been successfully used in human vaccination. The human mucosal immune system is large and specialized in performing inspection for foreign antigens to protect the surfaces themselves and of course human body interior. Since most infections affect or start from mucosal surfaces, using a mucosal route of vaccination is of great interest and provides a rational reason to induce a protective immune response. 3 Nasal delivery of vaccine offers an easily accessible route to the immune system.The nose has the function of olfactory detection (sense of smell) and also filtration, humidification and temperature control of air as it enters the respiratory system. Moving from front to back the areas of the nasal cavity are the nasal vestibule, the respiratory region, and the olfactory region. The nasal cavity is divided by the septum to form the left and right nares, which lead into the left and right choana before opening onto the nasopharynx at the top of the throat. The turbinates bound the nasal walls and are responsible for air conditioning and the large mucosal surface area of the nasal cavity. The nose is also the main port of entry for many pathogens. The first barrier to foreign bodies is hair at the entrance to the nares, the nostrils, which successfully keeps ou...

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Immune response elicited by an intranasally delivered HBsAg low-dose adsorbed to poly-ε-caprolactone based nanoparticles

Cited by 41 publications

References 41 publications

Chitosan Plus Compound 48/80: Formulation and Preliminary Evaluation as a Hepatitis B Vaccine Adjuvant

Chitosan Plus Compound 48/80: Formulation and Preliminary Evaluation as a Hepatitis B Vaccine Adjuvant

Mechanisms allowing protein delivery in nasal mucosa using NPL nanoparticles

Current prospects and future challenges for nasal vaccine delivery

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