Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson&amp;rsquo;s disease treatment

Bi, Chenchen; Wang, Aiping; Chu, Yongchao; Li, Sha; Mu, Hongjie; Liu, Wanhui; Wu, Zimei; Sun, Kaoxiang; Li, Youxin

doi:10.2147/ijn.s120939

Cited by 154 publications

(79 citation statements)

References 24 publications

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“…41 PLGA is a potential vehicle candidate for the sustained release of proteins that show promise as treatments for cardiac diseases. [42][43][44][45] Moreover, PEG is effective in preventing NP phagocytosis by …”

Section: Discussionmentioning

confidence: 99%

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Spatiotemporal delivery of nanoformulated liraglutide for cardiac regeneration after myocardial infarction

Qi¹,

Lü

Li³

et al. 2017

IJN

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The local, intramyocardial injection of proteins into the infarcted heart is an attractive option to initiate cardiac regeneration after myocardial infarction (MI). Liraglutide, which was developed as a treatment for type 2 diabetes, has been implicated as one of the most promising protein candidates in cardiac regeneration. A significant challenge to the therapeutic use of this protein is its short half-life in vivo. In this study, we evaluated the therapeutic effects and long-term retention of liraglutide loaded in poly(lactic- co -glycolic acid)–poly(ethylene glycol) (PLGA–PEG) nanoparticles (NP-liraglutide) on experimental MI. PLGA–PEG nanoparticles (NPs) have been shown to efficiently load liraglutide and release bioactive liraglutide in a sustained manner. For in vitro test, the released liraglutide retained bioactivity, as measured by its ability to activate liraglutide signaling pathways. Next, we compared the effects of an intramyocardial injection of saline, empty NPs, free liraglutide and NP-liraglutide in a rat model of MI. NPs were detected in the myocardium for up to 4 weeks. More importantly, an intramyocardial injection of NP-liraglutide was sufficient to improve cardiac function ( P <0.05), attenuate the infarct size ( P <0.05), preserve wall thickness ( P <0.05), promote angiogenesis ( P <0.05) and prevent cardiomyocyte apoptosis ( P <0.05) at 4 weeks after injection without affecting glucose levels. The local, controlled, intramyocardial delivery of NP-liraglutide represents an effective and promising strategy for the treatment of MI.

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Section: Discussionmentioning

confidence: 99%

“…44,[46][47][48] Liraglutide can benefit from the advantages offered by the PLGA-PEG delivery system to overcome the short half-life challenges of protein therapy.…”

mentioning

confidence: 99%

Spatiotemporal delivery of nanoformulated liraglutide for cardiac regeneration after myocardial infarction

Qi¹,

Lü

Li³

et al. 2017

IJN

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“…According to the expected constraint in the range of independent variables, the minimum and maximum constraint conditions of particle diameter and EE were selected, respectively. 20 The optimal formulation (A =6.13 mg/mL, B =12.98%, C =1.00 mg/100 mL, predicted response to Y 1 =78.78%, and Y 2 =120.94 nm) was selected by the desired factors. The response of the optimized recipe Y 1 (77.0%±3.9%) and Y 2 (125.4±9.1 nm) values was consistent with the predicted values generated by RSM, and the results confirmed the effectiveness of the RSM model.…”

Section: Bmentioning

confidence: 99%

“…[15][16][17] These findings suggest that Lf is a suitable ligand to mediate enhanced nose-to-brain delivery of formulations after intranasal administration. [18][19][20] Huperzine A (HupA) is a reversible inhibitor of acetylcholinesterase (AChE) in a club moss (Huperzia serrata), which enhances memory in behavioral animal models. [21][22][23] Studies have shown that HupA exerts multiple neuroprotective effects in addition to inhibition of AChE.…”

Section: Introductionmentioning

confidence: 99%

“…18,20 Figure 6A shows that PLGA, TMC, and Lf-TMC NPs were nontoxic to 16HBE cells at low nanocarrier concentrations. However, exposure to a higher concentration (20 mg/mL) of TMC and Lf-TMC NPs for 24 h resulted in a significant decrease (p,0.05) in cell viability compared with the control group, indicating that TMC-modified NPs exhibited cytotoxicity at a high concentration.…”

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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

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229

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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Intranasal Delivery of Functionalized Polymeric Nanomaterials to the Brain

Zha

Wong

All

2022

Adv Healthcare Materials

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Intravenous delivery of nanomaterials containing therapeutic agents and various cargos for treating neurological disorders is often constrained by low delivery efficacy due to difficulties in passing the blood-brain barrier (BBB). Nanoparticles (NPs) administered intranasally can move along olfactory and trigeminal nerves so that they do not need to pass through the BBB, allowing non-invasive, direct access to selective neural pathways within the brain. Hence, intranasal (IN) administration of NPs can effectively deliver drugs and genes into targeted regions of the brain, holding potential for efficacious disease treatment in the central nervous system (CNS). In this review, current methods for delivering conjugated NPs to the brain are primarily discussed. Distinctive potential mechanisms of therapeutic nanocomposites delivered via IN pathways to the brain are then discussed. Recent progress in developing functional NPs for applications in multimodal bioimaging, drug delivery, diagnostics, and therapeutics is also reviewed. This review is then concluded by discussing existing challenges, new directions, and future perspectives in IN delivery of nanomaterials.

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Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment

Cited by 154 publications

References 24 publications

Spatiotemporal delivery of nanoformulated liraglutide for cardiac regeneration after myocardial infarction

Spatiotemporal delivery of nanoformulated liraglutide for cardiac regeneration after myocardial infarction

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 Functionalized Polymeric Nanomaterials to the Brain

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Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson&rsquo;s disease treatment

Cited by 154 publications

References 24 publications

Spatiotemporal delivery of nanoformulated liraglutide for cardiac regeneration after myocardial infarction

Spatiotemporal delivery of nanoformulated liraglutide for cardiac regeneration after myocardial infarction

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 Functionalized Polymeric Nanomaterials to the Brain

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Product

Resources

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Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson’s disease treatment

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