Nose-to-brain drug delivery mediated by polymeric nanoparticles: influence of PEG surface coating

Oliveira, Edilson Ribeiro de; Santos, Lílian Cristina Rosa; Salomão, Mariana Arraes; Nascimento, Thaís Leite; Oliveira, Gerlon de Almeida Ribeiro; Lião, Luciano M.; Lima, Eliana Martins

doi:10.1007/s13346-020-00816-2

Cited by 33 publications

(14 citation statements)

References 57 publications

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“…However, the complexity of the nasal anatomy and physiology can pose a remarkable challenge in achieving the delivery of intranasally administered drugs to the brain. The use of nanomedicine is a promising approach for the nose-to-brain transport of therapeutics across the nasal mucosa (Mistry et al, 2009;Ahmad et al, 2017;Junior et al, 2020). However, the delivery of therapeutically relevant amounts of drugs exploiting the nasal route is strongly dependent on the availability of efficient nanoparticulate drug carriers (Mistry et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Properties of Statin-Loaded Biodegradable Lecithin/Chitosan Nanoparticles: A Step Toward Nose-to-Brain Treatment of Neurodegenerative Diseases

et al. 2021

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Nasal delivery has been indicated as one of the most interesting alternative routes for the brain delivery of neuroprotective drugs. Nanocarriers have emerged as a promising strategy for the delivery of neurotherapeutics across the nasal epithelia. In this work, hybrid lecithin/chitosan nanoparticles (LCNs) were proposed as a drug delivery platform for the nasal administration of simvastatin (SVT) for the treatment of neuroinflammatory diseases. The impact of SVT nanoencapsulation on its transport across the nasal epithelium was investigated, as well as the efficacy of SVT-LCNs in suppressing cytokines release in a cellular model of neuroinflammation. Drug release studies were performed in simulated nasal fluids to investigate SVT release from the nanoparticles under conditions mimicking the physiological environment present in the nasal cavity. It was observed that interaction of nanoparticles with a simulated nasal mucus decreased nanoparticle drug release and/or slowed drug diffusion. On the other hand, it was demonstrated that two antibacterial enzymes commonly present in the nasal secretions, lysozyme and phospholipase A2, promoted drug release from the nanocarrier. Indeed, an enzyme-triggered drug release was observed even in the presence of mucus, with a 5-fold increase in drug release from LCNs. Moreover, chitosan-coated nanoparticles enhanced SVT permeation across a human cell model of the nasal epithelium (×11). The nanoformulation pharmacological activity was assessed using an accepted model of microglia, obtained by activating the human macrophage cell line THP-1 with the Escherichia coli–derived lipopolysaccharide (LPS) as the pro-inflammatory stimulus. SVT-LCNs were demonstrated to suppress the pro-inflammatory signaling more efficiently than the simple drug solution (−75% for IL-6 and −27% for TNF-α vs. −47% and −15% at 10 µM concentration for SVT-LCNs and SVT solution, respectively). Moreover, neither cellular toxicity nor pro-inflammatory responses were evidenced for the treatment with the blank nanoparticles even after 36 h of incubation, indicating a good biocompatibility of the nanomedicine components in vitro. Due to their biocompatibility and ability to promote drug release and absorption at the biointerface, hybrid LCNs appear to be an ideal carrier for achieving nose-to-brain delivery of poorly water-soluble drugs such as SVT.

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Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Properties of Statin-Loaded Biodegradable Lecithin/Chitosan Nanoparticles: A Step Toward Nose-to-Brain Treatment of Neurodegenerative Diseases

et al. 2021

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“…Explanation for the lack of concentration dependence was not provided. Similarly, 5% PEGylation of ~110 nm polycaprolactone NPs increased brain fluorescence more than 0% or 10% PEGylation, attributed to its lower hydrophilicity and greater negative zeta potential (−20 mV) than 10% PEGylation (−9 mV) (de Oliveira Junior et al, 2020). Fifteen nanometer PEG‐coated quantum dots (−9 mV) were not taken up by bovine olfactory explants whereas 13 nm carboxylate‐coated quantum dots (−18 mV) were (Bejgum & Donovan, 2021) taken up by bovine olfactory explants.…”

Section: Nanoscale Physicochemical Properties Affect Olfactory Epithe...mentioning

confidence: 98%

“…Based on typical rat brain weight (1.75 g) this would equate to ~0.15% of the dose. Brain delivery, determined in live mice by fluorescence tomography, was estimated to be 4% 1 h after i.n. instillation of 5% PEGylated ~110 nm polycaprolactone NPs (de Oliveira Junior et al, 2020). Rat cerebrum, cerebellum, and olfactory bulb coumarin concentration peaked at ~1050, 1300, and 1050 pg/g 1 h after i.n.…”

Section: Direct Nose‐to‐brain Nanomedicine Delivery Is Not Efficientmentioning

confidence: 99%

Direct nose to the brain nanomedicine delivery presents a formidable challenge

Yokel

2021

WIREs Nanomed Nanobiotechnol

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This advanced review describes the anatomical and physiological barriers and mechanisms impacting nanomedicine translocation from the nasal cavity directly to the brain. There are significant physiological and anatomical differences in the nasal cavity, olfactory area, and airflow reaching the olfactory epithelium between humans and experimentally studied species that should be considered when extrapolating experimental results to humans. Mucus, transporters, and tight junction proteins present barriers to material translocation across the olfactory epithelium. Uptake of nanoparticles through the olfactory mucosa and translocation to the brain can be intracellular via cranial nerves (intraneuronal) or other cells of the olfactory epithelium, or extracellular along cranial nerve pathways (perineural) and surrounding blood vessels (perivascular, the glymphatic system). Transport rates vary greatly among the nose to brain pathways. Nanomedicine physicochemical properties (size, surface charge, surface coating, and particle stability) can affect uptake efficiency, which is usually less than 5%. Incorporation of therapeutic agents in nanoparticles has been shown to produce pharmacokinetic and pharmacodynamic benefits. Assessment of adverse effects has included olfactory mucosa toxicity, ciliotoxicity, and olfactory bulb and brain neurotoxicity. The results have generally suggested the investigated nanomedicines do not present significant toxicity. Research needs to advance the understanding of nanomedicine translocation and its drug cargo after intranasal administration is presented. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials

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“…However, it was merely the tip of the clinical application iceberg. The nanoparticle drug delivery system (Nano-DDS), including polymeric micelles, 123 liposomes, 124 polymeric nanoparticles, 125 and crystalline metals, 126 has been characterized as nearly nontoxic and stable when carrying biomolecules within tissues and has become a central strategy in contemporary cardiovascular medicine. 127 Different dosing methods also affected the delivery efficiency of Nano-DDS, among which the biodegradable molecules still depended on the in situ injection ( Figure 4 ).…”

Section: Nanomaterials For Micro-rna and Stem Cell Deliverymentioning

confidence: 99%

New diagnostic and therapeutic strategies for myocardial infarction via nanomaterials

Shi

Huang

et al. 2022

eBioMedicine

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Nose-to-brain drug delivery mediated by polymeric nanoparticles: influence of PEG surface coating

Cited by 33 publications

References 57 publications

Anti-Inflammatory Properties of Statin-Loaded Biodegradable Lecithin/Chitosan Nanoparticles: A Step Toward Nose-to-Brain Treatment of Neurodegenerative Diseases

Anti-Inflammatory Properties of Statin-Loaded Biodegradable Lecithin/Chitosan Nanoparticles: A Step Toward Nose-to-Brain Treatment of Neurodegenerative Diseases

Direct nose to the brain nanomedicine delivery presents a formidable challenge

New diagnostic and therapeutic strategies for myocardial infarction via nanomaterials

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