Protamine nanoparticles with CpG-oligodeoxynucleotide prevent an allergen-induced Th2-response in BALB/c mice

Allergen-specific immunotherapy is the only curative approach for the treatment of allergies. There is an urgent need for improved therapies, which increase both, efficacy and patient compliance. Novel routes of immunization and the use of more advanced vaccine platforms have gained heightened interest in this field. Areas covered: The current status of allergen-specific immunotherapy is summarized and novel routes of immunization and their challenges in the clinics are critically discussed. The use of nanoparticles as novel delivery system for allergy vaccines is comprehensively reviewed. Specifically, the advantages of silica nanoparticles as vaccine carriers and adjuvants are summarized. Expert opinion: Future allergen-specific immunotherapy will combine engineered hypoallergenic vaccines with novel routes of administration, such as the skin. Due to their biodegradability, and the easiness to introduce surface modifications, silica nanoparticles are promising candidates for tailor-made vaccines. By covalently linking allergens and polysaccharides to silica nanoparticles, a versatile vaccination platform can be designed to specifically target antigen-presenting cells, render the formulation hypoallergenic, and introduce immunomodulatory functions. Combining potent skin vaccination methods, such as fractional laser ablation, with nanoparticle-based vaccines addresses all the requirements for safe and efficient therapy of allergic diseases.

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“…Following subcutaneous injection, a favorable TH1-biased response could be shown in a mouse model of allergy54 .…”

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confidence: 99%

Potential of nanoparticles for allergen-specific immunotherapy – use of silica nanoparticles as vaccination platform

Scheiblhofer

Machado

Feinle

et al. 2016

Expert Opinion on Drug Delivery

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“…In healthy mice, NPs induced a strong humoral and cellular response with a Th-1 profile In asthmatic mice, NPs led to a reduction of symptoms and a significant decrease in the level of inflammatory cytokines in BALF future science group Nanoparticle based-immunotherapy against allergy Review them [25]. Size has a significant influence on the cellular uptake and type of immune responses induced in the gut as well [61].…”

Section: Oralmentioning

confidence: 97%

“…NPs induced in mice strong mixed Th1/ Th2-type immune response [25] Protamin-based NPs Ara h2 extracted from raw peanuts sc.…”

Section: Extract Of Pollen Frommentioning

confidence: 99%

Nanoparticle Based-immunotherapy Against Allergy

et al. 2014

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Allergic diseases are one of the most prevalent diseases, reaching epidemic proportions in developed countries. An allergic reaction occurs after contact with an environmental protein, such as inhalants allergens (pollen, animal dander, house dust mites), or food proteins. This response is known as part of the type 2 immunity that is counterbalanced by Type 1 immunity and Tregs. Widely used allergen-specific immunotherapy (IT) is a long term treatment to induce such switch from Th2 to Th1 response. However, conventional IT requires multiple allergen injections over a long period of time and is not free of risk of producing allergic reactions. As a consequence, new safer and faster immunotherapeutic methods are required. This review deals with allergen IT using nanoparticles as allergen delivery system that will allow a different way of administration, reduce dose and diminish allergen exposure to IgE bound to mast cells or basophils.

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“…Peptides were initially added to proticle formulations in order to increase the stability under physiological conditions [24]. This aspect was further developed and proticles could already be used as drug delivery system for several peptides [25, 26]. Proticle research addressed issues like drug-targeting [27], vaccination [26] as well as depot-effects [25], and was recently reviewed in detail [28].…”

Section: Introductionmentioning

confidence: 99%

Manufacturing of a Secretoneurin Drug Delivery System with Self-Assembled Protamine Nanoparticles by Titration

et al. 2016

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Since therapeutic peptides and oligonucleotides are gathering interests as active pharmaceutical ingredients (APIs), nanoparticulate drug delivery systems are becoming of great importance. Thereby, the possibility to design drug delivery systems according to the therapeutic needs of APIs enhances clinical implementation. Over the last years, the focus of our group was laid on protamine-oligonucleotide-nanoparticles (so called proticles), however, the possibility to modify the size, zeta potential or loading efficiencies was limited. Therefore, at the present study we integrated a stepwise addition of protamine (titration) into the formation process of proticles loaded with the angiogenic neuropeptide secretoneurin (SN). A particle size around 130 nm was determined when proticles were assembled by the commonly used protamine addition at once. Through application of the protamine titration process it was possible to modify and adjust the particle size between approx. 120 and 1200 nm (dependent on mass ratio) without influencing the SN loading capacity. Dynamic light scattering pointed out that the difference in particle size was most probably the result of a secondary aggregation. Initially-formed particles of early stages in the titration process aggregated towards bigger assemblies. Atomic-force-microscopy images also revealed differences in morphology along with different particle size. In contrast, the SN loading was only influenced by the applied mass ratio, where a slight saturation effect was observable. Up to 65% of deployed SN could be imbedded into the proticle matrix. An in-vivo biodistribution study (i.m.) showed a retarded distribution of SN from the site of injection after the application of a SN-proticle formulation. Further, it was demonstrated that SN loaded proticles can be successfully freeze-dried and resuspended afterwards. To conclude, the integration of the protamine titration process offers new possibilities for the formulation of proticles in order to address key parameters of drug delivery systems as size, API loading or modified drug release.

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Protamine nanoparticles with CpG-oligodeoxynucleotide prevent an allergen-induced Th2-response in BALB/c mice

Cited by 57 publications

References 30 publications

Potential of nanoparticles for allergen-specific immunotherapy – use of silica nanoparticles as vaccination platform

Potential of nanoparticles for allergen-specific immunotherapy – use of silica nanoparticles as vaccination platform

Nanoparticle Based-immunotherapy Against Allergy

Manufacturing of a Secretoneurin Drug Delivery System with Self-Assembled Protamine Nanoparticles by Titration

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