Biodegradable Nanoparticles for Delivery of Therapeutics in CNS Infection

DeMarino, Catherine; Schwab, Angela; Pleet, Michelle L.; Mathiesen, Allison; Friedman, Joel M.; El‐Hage, Nazira; Kashanchi, Fatah

doi:10.1007/s11481-016-9692-7

Cited by 32 publications

(27 citation statements)

References 161 publications

(333 reference statements)

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“…Various therapeutic agents against AD have been established in the past few years, including therapies that promote inhibition of secretase activity, Aβ clearance from the brain, and protection of neurons to correct neuronal function; nanoparticulate systems have also been developed 17–20 . Recently, various nanoparticles have been used for drug delivery systems that transfer therapeutics to a specific region and ameliorate various neurodegenerative disorders to reduce neurotoxic effects in the brain 21,22 .…”

Section: Introductionmentioning

confidence: 99%

A novel kit for early diagnosis of Alzheimer’s disease using a fluorescent nanoparticle imaging

Park

Choi³

et al. 2019

Sci Rep

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease and chronic illness with long preclinical phases and a long clinical duration. Until recently, a lack of potential therapeutic agents against AD was the primary focus of research, which resulted in less effort directed towards developing useful diagnostic approaches. In this study, we developed a WO2002/088706 kit that is composed of fluorescent nanoparticles for the early detection of AD. We provided a fluorescent nanoparticle for detecting markers and a kit for the early diagnosis of AD. The kit consists of a probe molecule comprising an oligonucleotide capable of detecting one or more AD-specific microRNAs (miRNAs) and biomarkers related to AD. Through screening, we selected miR-106b, miR-146b, miR-181a, miR-200a, miR-34a, miR-124b, miR-153, miR-155, Aβ1-42 monomer (mAβ), Aβ1–42 oligomer (oAβ), UCHL1, NLRP3, Tau, STAT3, SORL1, Clusterin, APOE3, APOE4, Nogo-A, IL-13, and Visfatin to serve as AD- and inflammation-related markers. For detection of kit-binding properties, we checked the expression levels of amyloid beta (Aβ), tau protein, and inflammatory mediators in APP/PS/ApoE knockdown (KD) mice and a control group using co-localisation analysis conducted with a confocal microscope. Using a similar approach, we checked the expression levels of miRNAs in HT22 cells. Finally, we used the plasma from AD patients to confirm that our fluorescent nanoparticles and the WO2002/088706 kit will provide a possible early diagnosis to serve as an AD detector that can be further improved for future studies on targeting AD.

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Section: Introductionmentioning

confidence: 99%

A novel kit for early diagnosis of Alzheimer’s disease using a fluorescent nanoparticle imaging

Park

Choi³

et al. 2019

Sci Rep

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“…Compared to magnetic NPs, which have been extensively studied to deliver ART drugs to the brain, polymer-based NPs, such as the PLGA-based NPs we used, are easy to prepare, composed of FDA-approved nontoxic NPs, and do not require the application of an external magnetic field [37]. PLGA-based NPs have shown improved BBB penetration for delivering ART drugs [45], improved viral suppression, and reduced toxicity of ART drugs in brain macrophages [27,46]. However, to the best of our knowledge, this is the first report of a study using PLGA-based NPs to deliver ART drugs to microglia for HIV-1 suppression.…”

Section: Discussionmentioning

confidence: 99%

An Elvitegravir Nanoformulation Crosses the Blood–Brain Barrier and Suppresses HIV-1 Replication in Microglia

Gong

Zhi

Nagesh

et al. 2020

Viruses

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Even with an efficient combination of antiretroviral therapy (ART), which significantly decreases viral load in human immunodeficiency virus type 1 (HIV-1)-positive individuals, the occurrence of HIV-1-associated neurocognitive disorders (HAND) still exists. Microglia have been shown to have a significant role in HIV-1 replication in the brain and in subsequent HAND pathogenesis. However, due to the limited ability of ART drugs to cross the blood–brain barrier (BBB) after systemic administration, in addition to efflux transporter expression on microglia, the efficacy of ART drugs for viral suppression in microglia is suboptimal. Previously, we developed novel poly (lactic-co-glycolic acid) (PLGA)-based elvitegravir nanoparticles (PLGA-EVG NPs), which showed improved BBB penetration in vitro and improved viral suppression in HIV-1-infected primary macrophages, after crossing an in vitro BBB model. Our objective in the current study was to evaluate the efficacy of our PLGA-EVG NPs in an important central nervous system (CNS) HIV-1 reservoir, i.e., microglia. In this study, we evaluated the cyto-compatibility of the PLGA-EVG NPs in microglia, using an XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) assay and cellular morphology observation. We also studied the endocytosis pathway and the subcellular localization of PLGA NPs in microglia, using various endocytosis inhibitors and subcellular localization markers. We determined the ability of PLGA-EVG NPs to suppress HIV-1 replication in microglia, after crossing an in vitro BBB model. We also studied the drug levels in mouse plasma and brain tissue, using immunodeficient NOD scid gamma (NSG) mice, and performed a pilot study, to evaluate the efficacy of PLGA-EVG NPs on viral suppression in the CNS, using an HIV-1 encephalitic (HIVE) mouse model. From our results, the PLGA-EVG NPs showed ~100% biocompatibility with microglia, as compared to control cells. The internalization of PLGA NPs in microglia occurred through caveolae-/clathrin-mediated endocytosis. PLGA NPs can also escape from endo-lysosomal compartments and deliver the therapeutics to cells efficiently. More importantly, the PLGA-EVG NPs were able to show ~25% more viral suppression in HIV-1-infected human-monocyte-derived microglia-like cells after crossing the in vitro BBB compared to the EVG native drug, without altering BBB integrity. PLGA-EVG NPs also showed a ~two-fold higher level in mouse brain and a trend of decreasing CNS HIV-1 viral load in HIV-1-infected mice. Overall, these results help us to create a safe and efficient drug delivery method to target HIV-1 reservoirs in the CNS, for potential clinical use.

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“…292 HIV is able to establish latency in the brain where there is no exposure to ARV drugs. 291 Replication in this compartment can lead to several neurological disorders. 293 Nanocarriers have been successfully developed, which are capable of overcoming these barriers to achieve both targeted and specific delivery.…”

Section: Limitations Of Nanoparticles As Therapeuticsmentioning

confidence: 99%

The role of nanotechnology in the treatment of viral infections

Singh

Kruger

Maguire

et al. 2017

Therapeutic Advances in Infection

264

248

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Infectious diseases are the leading cause of mortality worldwide, with viruses in particular making global impact on healthcare and socioeconomic development. In addition, the rapid development of drug resistance to currently available therapies and adverse side effects due to prolonged use is a serious public health concern. The development of novel treatment strategies is therefore required. The interaction of nanostructures with microorganisms is fast-revolutionizing the biomedical field by offering advantages in both diagnostic and therapeutic applications. Nanoparticles offer unique physical properties that have associated benefits for drug delivery. These are predominantly due to the particle size (which affects bioavailability and circulation time), large surface area to volume ratio (enhanced solubility compared to larger particles), tunable surface charge of the particle with the possibility of encapsulation, and large drug payloads that can be accommodated. These properties, which are unlike bulk materials of the same compositions, make nanoparticulate drug delivery systems ideal candidates to explore in order to achieve and/or improve therapeutic effects. This review presents a broad overview of the application of nanosized materials for the treatment of common viral infections.

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Biodegradable Nanoparticles for Delivery of Therapeutics in CNS Infection

Cited by 32 publications

References 161 publications

A novel kit for early diagnosis of Alzheimer’s disease using a fluorescent nanoparticle imaging

A novel kit for early diagnosis of Alzheimer’s disease using a fluorescent nanoparticle imaging

An Elvitegravir Nanoformulation Crosses the Blood–Brain Barrier and Suppresses HIV-1 Replication in Microglia

The role of nanotechnology in the treatment of viral infections

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