Preparation and characterization of biodegradable nanoparticles based on poly(γ-glutamic acid) with l-phenylalanine as a protein carrier

Akagi, Takami; Kaneko, Tatsuo; Kida, Toshiyuki; Akashi, Mitsuru

doi:10.1016/j.jconrel.2005.08.003

Cited by 187 publications

(118 citation statements)

References 42 publications

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“…The synthetic procedures for ␥-PGA NPs and OVA-carrying ␥-PGA NPs (OVA-NPs) have been described in our previous report (28). FITC-labeled ␥-PGA NPs (FITC-NPs) were synthesized as follows.…”

Section: Nanoparticlesmentioning

confidence: 99%

Targeting of Antigen to Dendritic Cells with Poly(γ-Glutamic Acid) Nanoparticles Induces Antigen-Specific Humoral and Cellular Immunity

Uto

Wang

Sato

et al. 2007

The Journal of Immunology

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153

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Nanoparticles are considered to be efficient tools for inducing potent immune responses by an Ag carrier. In this study, we examined the effect of Ag-carrying biodegradable poly(γ-glutamic acid) (γ-PGA) nanoparticles (NPs) on the induction of immune responses in mice. The NPs were efficiently taken up by dendritic cells (DCs) and subsequently localized in the lysosomal compartments. γ-PGA NPs strongly induced cytokine production, up-regulation of costimulatory molecules, and the enhancement of T cell stimulatory capacity in DCs. These maturational changes of DCs involved the MyD88-mediated NF-κB signaling pathway. In vivo, γ-PGA NPs were preferentially internalized by APCs (DCs and macrophages) and induced the production of IL-12p40 and IL-6. The immunization of mice with OVA-carrying NPs induced Ag-specific CTL activity and Ag-specific production of IFN-γ in splenocytes as well as potent production of Ag-specific IgG1 and IgG2a Abs in serum. Furthermore, immunization with NPs carrying a CD8+ T cell epitope peptide of Listeria monocytogenes significantly protected the infected mice from death. These results suggest that Ag-carrying γ-PGA NPs are capable of inducing strong cellular and humoral immune responses and might be potentially useful as effective vaccine adjuvants for the therapy of infectious diseases.

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Section: Nanoparticlesmentioning

confidence: 99%

Targeting of Antigen to Dendritic Cells with Poly(γ-Glutamic Acid) Nanoparticles Induces Antigen-Specific Humoral and Cellular Immunity

Uto

Wang

Sato

et al. 2007

The Journal of Immunology

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201

153

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“…The γ-PGA-l-PAE-TP (PPT) biopolymer was synthesized by modifying the Akaga method. 29 Briefly, 6.24 g of l-PAE was grafted to 4 g small-molecular-weight γ-PGA through amidation with the catalyst 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide for 24 hours at room temperature to form the l-PAE-γ-PGA complex (PP). The PPT complex was produced by mixing 5 mg of TP with 20 mg of PP dimethyl sulfoxide solution, which was dropped into ultrapure water to develop a translucent liquid, under magnetic stirrers with a rotating speed of 60 rpm, following ultracentrifugation to remove the free TP.…”

Section: Preparation Of Pptmentioning

confidence: 99%

Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo

Zhang

Wang

et al. 2016

IJN

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Triptolide (TP) displays a strong immunosuppression function in immune-mediated diseases, especially in the treatment of rheumatoid arthritis. However, in addition to its medical and health-related functions, TP also exhibits diverse pharmacological side effects, for instance, liver and kidney toxicity and myelosuppression. In order to reduce the side effects, a nano drug carrier system (γ-PGA- l -PAE-TP [PPT]), in which TP was loaded by a poly-γ-glutamic acid-grafted l -phenylalanine ethylester copolymer, was developed. PPT was characterized by photon scattering correlation spectroscopy and transmission electron microscopy, which demonstrated that the average diameter of the drug carrier system is 98±15 nm, the polydispersity index is 0.18, the zeta potential is −35 mV, and the TP encapsulation efficiency is 48.6% with a controlled release manner. The methylthiazolyldiphenyl-tetrazolium bromide assay and flow cytometry revealed that PPT could decrease toxicity and apoptosis induced by free TP on RAW264.7 cells, respectively. The detection of reactive oxygen species showed that PPT could decrease the cellular reactive oxygen species induced by TP. Compared with the free TP-treated group, PPT improved the survival rate of the mice ( P <0.01) and had no side effects or toxic effects on the thymus index ( P >0.05) and spleen index ( P >0.05). The blood biochemical indexes revealed that PPT did not cause much damage to the kidney (blood urea nitrogen and creatinine), liver (serum alanine aminotransferase and aspartate aminotransferase), or blood cells ( P >0.05). Meanwhile, hematoxylin and eosin staining and terminal-deoxynucleotidyl transferase dUTP nick-end labeling staining indicated that PPT reduced the damage of free TP on the liver, kidney, and spleen. Our results demonstrated that PPT reduced free TP toxicity in vitro and in vivo and that it is a promising fundamental drug delivery system for rheumatoid arthritis treatment.

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“…16 The copolymer consisted γ-PGA as the hydrophilic group and l-PAE (H) as hydrophobic side chain. 17,18 To form the copolymer (PH) of PGA and l-PAE, 3.12 g l-PAE was conjugated to 2 g small molecular weight (30 kDa) γ-PGA by amide reaction under the catalyst EDCI for 24 h at room temperature.…”

Section: Preparation Of Phromentioning

confidence: 99%

Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

Shen¹,

Zhao²,

Wang³

et al. 2017

IJN

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Diabetic cerebral infarction is with poorer prognosis and high rates of mortality. Ginsenoside Rg1 (Rg1) has a wide variety of therapeutic values for central nervous system (CNS) diseases for the neuron protective effects. However, the blood–brain barrier (BBB) restricts Rg1 in reaching the CNS. In this study, we investigated the therapeutic effects of Rg1 nanoparticle (PHRO, fabricated with γ-PGA, L-PAE (H), Rg1, and OX26 antibody), targeting transferrin receptor, on the diabetes rats complicated with diabetic cerebral infarction in vitro and in vivo. Dynamic light scattering analysis shows the average particle size of PHRO was 79±18 nm and the polydispersity index =0.18. The transmission electron microscope images showed that all NPs were spherical in shape with diameters of 89±23 nm. PHRO released Rg1 with sustained release manner and could promote the migration of cerebrovascular endothelial cells and tube formation and even penetrated the BBB in vitro. PHRO could penetrate the BBB with high concentration in brain tissue to reduce the cerebral infarction volume and promote neuronal recovery in vivo. PHRO was promising to be a clinical treatment of diabetes mellitus with cerebral infarction.

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Preparation and characterization of biodegradable nanoparticles based on poly(γ-glutamic acid) with l-phenylalanine as a protein carrier

Cited by 187 publications

References 42 publications

Targeting of Antigen to Dendritic Cells with Poly(γ-Glutamic Acid) Nanoparticles Induces Antigen-Specific Humoral and Cellular Immunity

Targeting of Antigen to Dendritic Cells with Poly(γ-Glutamic Acid) Nanoparticles Induces Antigen-Specific Humoral and Cellular Immunity

Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo

Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

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Preparation and characterization of biodegradable nanoparticles based on poly(γ-glutamic acid) with l-phenylalanine as a protein carrier

Cited by 187 publications

References 42 publications

Targeting of Antigen to Dendritic Cells with Poly(γ-Glutamic Acid) Nanoparticles Induces Antigen-Specific Humoral and Cellular Immunity

Targeting of Antigen to Dendritic Cells with Poly(γ-Glutamic Acid) Nanoparticles Induces Antigen-Specific Humoral and Cellular Immunity

Fabrication of novel vesicles of triptolide for antirheumatoid activity with reduced toxicity in vitro and in vivo

Ginsenoside Rg1 nanoparticle penetrating the blood&ndash;brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction

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Product

Resources

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Ginsenoside Rg1 nanoparticle penetrating the blood–brain barrier to improve the cerebral function of diabetic rats complicated with cerebral infarction