Pluronic P85-coated poly(butylcyanoacrylate) nanoparticles overcome phenytoin resistance in P-glycoprotein overexpressing rats with lithium-pilocarpine-induced chronic temporal lobe epilepsy

Fang, Ziyan; Chen, Shuda; Qin, Jiaming; Bao, Chao; Ni, Guanzhong; Chen, Ziyi; Zhou, Jueqian; Li, Ze; Ning, Yuping; Wu, Chuanbin; Zhou, Liemin

doi:10.1016/j.biomaterials.2016.04.021

Cited by 46 publications

(39 citation statements)

References 60 publications

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“…This approach has been shown to be efficient for the preparation of a PEG-shell on the surface of hydrophobic NPs. 22,26,[46][47][48][49] However, it remains unclear how stable is this non-covalent hydrophobic shell in biological media. Recently, we showed that PF-68 coated polymeric NPs loaded with large drug molecule provided pharmacological effects on central nervous system (CNS) upon intravenous (iv) injection to rodents with brain trauma, 50 however the mechanism of its action is still debatable and controversial.…”

Section: Meaningful Monitoring Of the Behavior Of Single Nps In Vivo mentioning

confidence: 99%

Ultrabright Fluorescent Polymeric Nanoparticles with a Stealth Pluronic Shell for Live Tracking in the Mouse Brain

Khalin¹,

Heimburger

Melnychuk

et al. 2020

ACS Nano

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The inability to visualize single organic nanoparticles (NPs) in vivo is an unsolved issue in the field of nanomedicine. To enable high single particle fluorescence, we loaded polymer poly(methyl methacrylate)-sulfonate (PMMA-SO3H) NPs with octadecyl rhodamine B together with hydrophobic counter-ions as a fluorophore insulator to prevent aggregation-induced quenching. To create NPs with stealth properties we used the amphiphilic block copolymers pluronic F-127 and F-68. Fluorescence correlation spectroscopy (FCS) and Förster resonance energy transfer (FRET) showed that pluronics remain at the NP surface after dialysis (density: one amphiphile per 5.5 nm 2) and protected NPs from degradation by serum proteins and surfactants. Single particle brightness was increased 150-fold as compared to commercially available preparations by increasing dye loading to 20 wt% and optimizing particle size. Added to primary cultured neurons, these NPs were stable and interacted with dendrites and axons. After intravenous injection in mice, NPs could be tracked in cerebral vessels for at least 1h by in vivo two-photon microscopy. Following brain injury or neuroinflammation, NPs extravasated from meningeal vessels, were taken up by meningeal macrophages, and entered the brain parenchyma. In summary, we developed biocompatible NPs suitable for drug delivery with in vitro and in vivo stealth properties and extremely bright fluorescence. Thus, individual NPs could be tracked in mouse brain and their dynamics visualized with subcellular resolution. Using superbright NPs may thus open new avenues for the investigation of NPs in living organisms.

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Section: Meaningful Monitoring Of the Behavior Of Single Nps In Vivo mentioning

confidence: 99%

Ultrabright Fluorescent Polymeric Nanoparticles with a Stealth Pluronic Shell for Live Tracking in the Mouse Brain

Khalin¹,

Heimburger

Melnychuk

et al. 2020

ACS Nano

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“…3 The increasing expressions of P-gp promote tumor cell ability to efflux a wide range of cytotoxic agents, which leads to treatment failure. 4 Polymeric nano-carriers (NCs) have been reported as promising carriers of many anticancer drugs, 5,6 due to their function as sustained, controlled and targeted drug delivery systems. [7][8][9][10] By modifying the size and the surface charge, we designed a type of dextran-based nanogel with high biocompatibility and biosafety, which can be retained for a long time in lymph nodes.…”

Section: Introductionmentioning

confidence: 99%

Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity

Fang¹,

Wang²,

Dou³

et al. 2018

IJN

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PurposeCardiac side effects of doxorubicin (Dox) have limited its clinical application. The aim of this study was to explore new Dox-loaded dextran-based nano-carriers (NCs) in efficiently targeting tumor growth with less cardiac toxicity.MethodsInspired by recent reports that polymeric NCs could function as sustained, controlled and targeted drug delivery systems, we developed Dox-loaded NCs which displayed a 2-fold release ratio of Dox in the mimic tumor site condition (pH 5.0 with 10 mM glutathione, GSH) as much as that in systemic circulation condition (pH 7.4).ResultsLymphoma cells treated with Dox-NCs had significantly higher intracellular Dox concentrations and more apoptotic induction, with lower P-gp expression, when compared with those treated with Dox alone. The identified mechanism of action, apoptosis, was triggered through survivin reduction and caspase-3 activation. Even in the Dox-resistant cells, Dox-NCs could significantly inhibit cell growth and induce apoptosis. In murine lymphoma xenograft models, Dox-NCs also remarkably significantly retarded tumor growth, assessed by murine weight, and demonstrated less cytotoxicity. Noticeably, apoptotic myocardial cells were decreased in the Dox-NCs-treated group, when compared with the control group, which was consistent with low intracellular Dox concentration in the cardiac cell line H9C2.ConclusionDox-NCs showed an anti-lymphoma effect with reduced cardiac toxicity in both in vivo and in vitro models and, therefore, could be a potential therapeutic agent in the treatment of lymphoma.

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“…Antiepileptic drugs for the treatment of seizures are accompanied by adverse effects, such as cognitive impairment, microcephaly, and congenital disabilities. The cause of the adverse effects of antiepileptic drugs is unknown (Fang et al, 2016;Landmark and Patsalos, 2010;Ye et al, 2018). PHT is a common antiepileptic drug, but its therapeutic spectrum is narrow (Appleton and Gill, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have shown that PHT not only has antiepileptic properties but also may induce neuronal apoptosis and thus damage the nervous system (Kaushal et al, 2016). Long-term use or an overdose of PHT may cause irreversible cerebellar atrophy (Fang et al, 2016;Singh et al, 2019;Ye et al, 2018). Therefore, preventing neuronal apoptosis is essential for the treatment of epilepsy.…”

Section: Introductionmentioning

confidence: 99%

Dl-3-n-butylphthalide inhibits phenytoin-induced neuronal apoptosis in rat hippocampus and cerebellum

Chen

Liu

Wang

et al. 2019

Journal of Integrative Neuroscience

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Rats were divided into six groups: sham/control, Dl-3-n-butylphthalide, P1 (low phenytoin, 100 mg/kg), P2 (high phenytoin, 200 mg/kg), NP1 (Dl-3-n-butylphthalide 80 mg/kg, phenytoin 100 mg/kg), NP2 (Dl-3-nbutylphthalide 80 mg/kg, phenytoin 200 mg/kg). Hematoxylin/eosin and Nissl staining showed that, compared to the sham/control group, the Dl-3-n-butylphthalide group had no obvious hippocampal and cerebellar neuron loss, but there was a significant neuron loss in the P1 and P2 groups (P < 0.05), which was more obvious in the P2 group (P < 0.05). The positive expression of Bax and Bcl-2 proteins in hippocampal and cerebellar neurons was not significantly different between sham and Dl-3-nbutylphthalide groups; however, compared to sham, Bax expression was significantly increased and Bcl-2 was significantly decreased in the hippocampal and cerebellar neurons of rats in both P1 and P2 groups (P < 0.05), being more obvious in the P2 group (P < 0.05). Furthermore, the administration of Dl-3-n-butylphthalide attenuated the deleterious effects of phenytoin (P < 0.05). Our results indicate that phenytoin causes apoptosis of hippocampal and cerebellar neurons in rats in a dose-dependent manner, with the effect of a higher dose being more obvious, whereas, Dl-3-n-butylphthalide inhibits the phenytoininduced apoptosis of neurons and has a neuroprotective role.

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Pluronic P85-coated poly(butylcyanoacrylate) nanoparticles overcome phenytoin resistance in P-glycoprotein overexpressing rats with lithium-pilocarpine-induced chronic temporal lobe epilepsy

Cited by 46 publications

References 60 publications

Ultrabright Fluorescent Polymeric Nanoparticles with a Stealth Pluronic Shell for Live Tracking in the Mouse Brain

Ultrabright Fluorescent Polymeric Nanoparticles with a Stealth Pluronic Shell for Live Tracking in the Mouse Brain

Doxorubicin-loaded dextran-based nano-carriers for highly efficient inhibition of lymphoma cell growth and synchronous reduction of cardiac toxicity

Dl-3-n-butylphthalide inhibits phenytoin-induced neuronal apoptosis in rat hippocampus and cerebellum

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