Antigen-conjugated N-trimethylaminoethylmethacrylate Chitosan Nanoparticles Induce Strong Immune Responses After Nasal Administration

Li, Qingfeng; Zheng, Xiaoyao; Zhang, Chi; Shao, Xia; Zhang, Xi; Zhang, Qizhi; Jiang, Xinguo

doi:10.1007/s11095-014-1441-0

Cited by 21 publications

(21 citation statements)

References 33 publications

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“…35 The degree of quaternization of TMC was 27.9%, which was similar to a previous study. 34 Content analysis by HPLC showed that the incorporation efficiency of Mal with TMC was 11.3%±2.5%.…”

Section: In Vivo Imagingsupporting

confidence: 90%

“…Mal-TMC was synthesized via the reaction of TMC and SMP. 35 In brief, TMC was dissolved in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer. A solution of SMP in dimethyl sulfoxide (DMSO) was added dropwise to the HEPES solution, and the mixture was stirred at room temperature for 8 h. After dialyzing against deionized water for 24 h, the reaction product (Mal-TMC) was collected by lyophilization.…”

Section: Synthesis and Characterization Of The Conjugated Polymersmentioning

confidence: 99%

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Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease

Meng¹,

Wang²,

Hua³

et al. 2018

IJN

239

101

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Background Safe and effective delivery of therapeutic drugs to the brain is important for successful therapy of Alzheimer’s disease (AD). Purpose To develop Huperzine A (HupA)-loaded, mucoadhesive and targeted polylactide-co-glycoside (PLGA) nanoparticles (NPs) with surface modification by lactoferrin (Lf)-conjugated N-trimethylated chitosan (TMC) (HupA Lf-TMC NPs) for efficient intranasal delivery of HupA to the brain for AD treatment. Methods HupA Lf-TMC NPs were prepared using the emulsion–solvent evaporation method and optimized using the Box–Behnken design. The particle size, zeta potential, drug entrapment efficiency, adhesion and in vitro release behavior were investigated. The cellular uptake was investigated by fluorescence microscopy and flow cytometry. MTT assay was used to evaluate the cytotoxicity of the NPs. In vivo imaging system was used to investigate brain targeting effect of NPs after intranasal administration. The biodistribution of Hup-A NPs after intranasal administration was determined by liquid chromatography–tandem mass spectrometry. Results Optimized HupA Lf-TMC NPs had a particle size of 153.2±13.7 nm, polydispersity index of 0.229±0.078, zeta potential of +35.6±5.2 mV, drug entrapment efficiency of 73.8%±5.7%, and sustained release in vitro over a 48 h period. Adsorption of mucin onto Lf-TMC NPs was 86.9%±1.8%, which was significantly higher than that onto PLGA NPs (32.1%±2.5%). HupA Lf-TMC NPs showed lower toxicity in the 16HBE cell line compared with HupA solution. Qualitative and quantitative cellular uptake experiments indicated that accumulation of Lf-TMC NPs was higher than nontargeted analogs in 16HBE and SH-SY5Y cells. In vivo imaging results showed that Lf-TMC NPs exhibited a higher fluorescence intensity in the brain and a longer residence time than nontargeted NPs. After intranasal administration, Lf-TMC NPs facilitated the distribution of HupA in the brain, and the values of the drug targeting index in the mouse olfactory bulb, cerebrum (with hippocampus removal), cerebellum, and hippocampus were about 2.0, 1.6, 1.9, and 1.9, respectively. Conclusion Lf-TMC NPs have good sustained-release effect, adhesion and targeting ability, and have a broad application prospect as a nasal drug delivery carrier.

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Section: In Vivo Imagingsupporting

confidence: 90%

Section: Synthesis and Characterization Of The Conjugated Polymersmentioning

confidence: 99%

Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease

Meng¹,

Wang²,

Hua³

et al. 2018

IJN

239

101

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“…The nasal-associated lymphoid tissue allows the passage of TMC NPs conjugated proteins across it in addition to the increased immune response, upon nasal vaccination. 68 The TMC NPs encapsulating OVA were able to increase the residence time of protein in the nasal epithelium and gave a high anti-OVA IgG as well as sIgA titer. These NPs were able to release the protein faster than the poly(lactic-co-glycolic acid) (PLGA) or PLGA/TMC NPs.…”

Section: Route Of Administrationmentioning

confidence: 97%

Novel application of trimethyl chitosan as an adjuvant in vaccine delivery

Malik

Gupta

et al. 2018

IJN

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The application of natural carbohydrate polysaccharides for antigen delivery and its adjuvanation potential has garnered interest in the scientific community in the recent years. These biomaterials are considered favorable candidates for adjuvant development due to their desirable properties like enormous bioavailability, non-toxicity, biodegradability, stability, affordability, and immunostimulating ability. Chitosan is the one such extensively studied natural polymer which has been appreciated for its excellent applications in pharmaceuticals. Trimethyl chitosan (TMC), a derivative of chitosan, possesses these properties. In addition it has the properties of high aqueous solubility, high charge density, mucoadhesive, permeation enhancing (ability to cross tight junction), and stability over a range of ionic conditions which makes the spectrum of its applicability much broader. It has also been seen to perform analogously to alum, complete Freund’s adjuvant, incomplete Freund’s adjuvant, and cyclic guanosine monophosphate adjuvanation, which justifies its role as a potent adjuvant. Although many review articles detailing the applications of chitosan in vaccine delivery are available, a comprehensive review of the applications of TMC as an adjuvant is not available to date. This article provides a comprehensive overview of structural and chemical properties of TMC which affect its adjuvant characteristics; the efficacy of various delivery routes for TMC antigen combination; and the recent advances in the elucidation of its mechanism of action.

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“…This is because, for classic lymphatic vessels, nanoparticles can be passively targeted to LNs through free diffusion to the lymphatics and draining LNs, [5] or through ingestion by dendritic cells (DCs) or macrophages, [6,7] which then carry the particles to LNs. [8] And for meningeal lymphatic vessels, because they are formed by monolayer endothelial cells, which have no peripheral cells and are loosely bound to provide gaps. [9] Therefore, we suspected that nanoparticle drugs in the brain may be transported out of the brain by passing through the meningeal lymphatic vessels in addition to being absorbed into the blood by vascular transporters and arachnoid granulations.…”

Section: Introductionmentioning

confidence: 99%

Lymphatic clearance is the main drainage route of lamotrigine-loaded micelles following delivery to the brain

Yan

Ren

Zhu

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives This study aimed to investigate the clearance pathways of lamotrigine (LTG)‐loaded micelles by intranasal administration and intracerebral injection in the brain and whether nanoparticles can induce the inflammation promoted by interleukin‐6 (IL‐6), accelerating the phagocytosis of drug particles in the brain and drainage through lymphatics. Methods The drug concentrations in the deep cervical lymph node, superficial cervical lymph node, brain tissues and jugular vein, the pharmacokinetic parameters, and the concentrations of IL‐6 in deep cervical lymph node and brain tissues were investigated following UPLC/MS, DAS3.0, ELISA statistically analysed. Key findings The AUC0–t of deep cervical lymph node after intranasal and intracerebral injection was 1.93, 2.77, 1.34 times and 3.06, 16.4, 3.34 times higher compared with the superficial cervical lymph node, jugular vein and brain tissue, respectively. After intranasal administration of lamotrigine‐loaded micelles for 30 min, the IL‐6 concentrations in deep cervical lymph node and brain tissue were significantly increased (P < 0.05). Conclusions These results suggested that lamotrigine micelles were primarily cleared from the brain by lymphatics rather than blood clearance. Also, the nanoparticle induced the increase in IL‐6 level after entering the brain suggested that nanoparticles might induce the inflammation promoted by IL‐6 in the brain, accelerating the clearance of drug particles in the brain and drainage through lymphatics.

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Antigen-conjugated N-trimethylaminoethylmethacrylate Chitosan Nanoparticles Induce Strong Immune Responses After Nasal Administration

Abstract: The present study demonstrated that the conjugation of TMC nanoparticles with antigens is an effective strategy for nasal vaccination.

Cited by 21 publications

References 33 publications

Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease

Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease

Novel application of trimethyl chitosan as an adjuvant in vaccine delivery

Lymphatic clearance is the main drainage route of lamotrigine-loaded micelles following delivery to the brain

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Antigen-conjugated N-trimethylaminoethylmethacrylate Chitosan Nanoparticles Induce Strong Immune Responses After Nasal Administration

Abstract: The present study demonstrated that the conjugation of TMC nanoparticles with antigens is an effective strategy for nasal vaccination.

Cited by 21 publications

References 33 publications

Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer&rsquo;s disease

Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer&rsquo;s disease

Novel application of trimethyl chitosan as an adjuvant in vaccine delivery

Lymphatic clearance is the main drainage route of lamotrigine-loaded micelles following delivery to the brain

Contact Info

Product

Resources

About

Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease

Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease