Nano-enabled delivery of diverse payloads across complex biological barriers

Ross, Kathleen A.; Brenza, Timothy M.; Binnebose, Andrea M.; Phanse, Yashdeep; Kanthasamy, Anumantha G.; Gendelman, Howard E.; Salem, Aliasger K.; Bartholomay, Lyric C.; Bellaire, Bryan H.; Narasimhan, Balaji

doi:10.1016/j.jconrel.2015.08.039

Cited by 61 publications

(45 citation statements)

References 185 publications

(227 reference statements)

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“…By combining the ability to cross highly selective biological barriers with intracellular targeting, nano-carriers can deliver diverse payloads to organelles with reduced toxicity and increased bioavailability (12). Biodegradable nanomaterials have been extensively evaluated for drug delivery across the BBB (13).…”

Section: Introductionmentioning

confidence: 99%

Neuronal protection against oxidative insult by polyanhydride nanoparticle-based mitochondria-targeted antioxidant therapy

Brenza

Ghaisas

Ramirez

et al. 2017

Nanomedicine: Nanotechnology, Biology and Medicine

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A progressive loss of neuronal structure and function is a signature of many neurodegenerative conditions including chronic traumatic encephalopathy, Parkinson’s, Huntington’s and Alzheimer’s diseases. Mitochondrial dysfunction and oxidative and nitrative stress have been implicated as key pathological mechanisms underlying the neurodegenerative processes. However, current therapeutic approaches targeting oxidative damage are ineffective in preventing the progression of neurodegeneration. Mitochondria-targeted antioxidants were recently shown to alleviate oxidative damage. In this work, we investigated the delivery of biodegradable polyanhydride nanoparticles containing the mitochondria-targeted antioxidant apocynin to neuronal cells and the ability of the nano-formulation to protect cells against oxidative stress. The nano-formulated mitochondria-targeted apocynin provided excellent protection against oxidative stress-induced mitochondrial dysfunction and neuronal damage in a dopaminergic neuronal cell line, mouse primary cortical neurons, and a human mesencephalic cell line. Collectively, our results demonstrate that nano-formulated mitochondria-targeted apocynin may offer improved efficacy of mitochondria-targeted antioxidants to treat neurodegenerative disease.

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Section: Introductionmentioning

confidence: 99%

Neuronal protection against oxidative insult by polyanhydride nanoparticle-based mitochondria-targeted antioxidant therapy

Brenza

Ghaisas

Ramirez

et al. 2017

Nanomedicine: Nanotechnology, Biology and Medicine

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“…Nanoparticulate systems have been studied extensively to facilitate drug delivery across tough-to-penetrate biological barriers, most of which express efflux transporters. (4, 7, 8). Depending on their size and composition, nanoparticles interact with cellular membranes to enter the cells via clathrin and caveolin dependent or independent endocytotic and pinocytotic processes (9).…”

Section: Introductionmentioning

confidence: 99%

Mathematical Modeling and Experimental Validation of Nanoemulsion-Based Drug Transport across Cellular Barriers

2017

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Purpose Nanoemulsions have shown potential in delivering drug across epithelial and endothelial cell barriers, which express efflux transporters. However, their transport mechanisms are not entirely understood. Our goal was to investigate the cellular permeability of nanoemulsion-encapsulated drugs and apply mathematical modeling to elucidate transport mechanisms and sensitive nanoemulsion attributes. Methods Transport studies were performed in Caco-2 cells, using fish oil nanoemulsions and a model substrate, rhodamine-123. Permeability data was modeled using a semi-mechanistic approach, capturing the following cellular processes: endocytotic uptake of the nanoemulsion, release of rhodamine-123 from the nanoemulsion, efflux and passive permeability of rhodamine-123 in aqueous solution. Results Nanoemulsions not only improved the permeability of rhodamine-123, but were also less sensitive to efflux transporters. The model captured bidirectional permeability results and identified sensitive processes, such as the release of the nanoemulsion-encapsulated drug and cellular uptake of the nanoemulsion. Conclusions Mathematical description of cellular processes, improved our understanding of transport mechanisms, such as nanoemulsions don’t inhibit efflux to improve drug permeability. Instead, their endocytotic uptake, results in higher intracellular drug concentrations, thereby increasing the concentration gradient and transcellular permeability across biological barriers. Modeling results indicated optimizing nanoemulsion attributes like the droplet size and intracellular drug release rate, may further improve drug permeability.

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“…Many nanoencapsulation strategies aim to improve penetration through physiological pulmonary, nasal, orogastric, intestinal [103], transdermal, and blood-brain barriers [104], along with pathological obstructions such as mucus [105], desmoplastic tissue [102], and microbial biofilm [106]. In vitro NP imaging and particle tracking has been useful for quantifying the effect of physicochemical NP properties, including charge and PEGylation, on effective transport through biofilm [106], cystic-fibrosis sputum [107], and ECM [108].…”

Section: Discovering Np Action By High Resolution Ivm Imagingmentioning

confidence: 99%

Imaging the pharmacology of nanomaterials by intravital microscopy: Toward understanding their biological behavior

Miller

Weissleder

2017

Advanced Drug Delivery Reviews

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Therapeutic nanoparticles (NPs) can deliver cytotoxic chemotherapeutics and other drugs more safely and efficiently to patients; furthermore, selective delivery to target tissues can theoretically be accomplished actively through coating NPs with molecular ligands, and passively through exploiting physiological “enhanced permeability and retention” features. However, clinical trial results have been mixed in showing improved efficacy with drug nano-encapsulation, largely due to heterogeneous NP accumulation at target sites across patients. Thus, a clear need exists to better understand why many NP strategies fail in vivo and not result in significantly improved tumor uptake or therapeutic response. Multicolor in vivo confocal fluorescence imaging (intravital microscopy; IVM) enables integrated pharmacokinetic and pharmacodynamic (PK/PD) measurement at the single-cell level, and has helped answer key questions regarding the biological mechanisms of in vivo NP behavior. This review summarizes progress to date and also describes useful technical strategies for successful IVM experimentation.

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Nano-enabled delivery of diverse payloads across complex biological barriers

Cited by 61 publications

References 185 publications

Neuronal protection against oxidative insult by polyanhydride nanoparticle-based mitochondria-targeted antioxidant therapy

Neuronal protection against oxidative insult by polyanhydride nanoparticle-based mitochondria-targeted antioxidant therapy

Mathematical Modeling and Experimental Validation of Nanoemulsion-Based Drug Transport across Cellular Barriers

Imaging the pharmacology of nanomaterials by intravital microscopy: Toward understanding their biological behavior

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