Nanoparticulate peptide delivery exclusively to the brain produces tolerance free analgesia

Godfrey, Lisa; Iannitelli, Antonio; Garrett, Natalie; Moger, Julian; Imbert, Ian; King, Tamara; Porreca, Frank; Soundararajan, Ramesh; Lalatsa, Aikaterini; Schätzlein, Andreas; Uchegbu, Ijeoma F.

doi:10.1016/j.jconrel.2017.11.041

Cited by 63 publications

(69 citation statements)

References 42 publications

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“…Regarding the nose-to-brain delivery, various clinical and preclinical studies have been conducted to involve the use of drugs in solution and particulate dispersions [155][156][157]. Clinical studies have usually involved the use of a nasal drug delivery device, while most animal studies have been conducted in rodents.…”

Section: Formulations For Nose-to-brain Deliverymentioning

confidence: 99%

“…With conventional nasal solutions, very low drug transfer levels have been observed. Therefore, to address the low drug delivery problem, scientists are conducting experiments with nanoparticulate formulations like nanoemulsions, lipids, or polymer particles, which offer enhanced penetration and a longer residence time within the nasal cavity [156,[168][169][170][171][172][173][174][175][176] (Table 2). It has been found that 100 nm nanoemulsion particles penetrated the olfactory bulb and reached the brain to a small extent, whereas 900 nm particles could not penetrate the brain, which indicated that a particle size cut-off may be operational for the delivery of nanoformulations beyond the olfactory bulb [168].…”

Section: Nanoparticles For Nose-to-brain Deliverymentioning

confidence: 99%

“…The solution of a delta selective opioid agonist, leucine-5-enkephalin (LENK), initially failed to reach the rat brains in a considerable amount via the nasal route. However, the delivery was increased when LENK was formulated as an absorption-enhancing chitosan-based nanoparticle [156]. Compared to an intranasal dose of rivastigmine (a cholinesterase inhibitor used for the treatment of dementia) in solution, the emulsion form when administered intranasally led to a 5-fold increase in brain exposure [178].…”

Section: Nanoparticles For Nose-to-brain Deliverymentioning

confidence: 99%

“…From the commercial point of view, solution-based formulations exhibit a short half-life and are more prone to microbial contamination. Nanoformulations for nasal drug delivery can be further divided into solid lipid nanoparticles and nanoparticles prepared from chitosan derivatives or poly(l-lactide-co-glycolide), as described below [156,[180][181][182]. * The numbers refer to the numbered references in the text.…”

Section: Nanoparticles For Nose-to-brain Deliverymentioning

confidence: 99%

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Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

et al. 2020

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Although the global prevalence of neurological disorders such as Parkinson's disease, Alzheimer's disease, glioblastoma, epilepsy, and multiple sclerosis is steadily increasing, effective delivery of drug molecules in therapeutic quantities to the central nervous system (CNS) is still lacking. The blood brain barrier (BBB) is the major obstacle for the entry of drugs into the brain, as it comprises a tight layer of endothelial cells surrounded by astrocyte foot processes that limit drugs' entry. In recent times, intranasal drug delivery has emerged as a reliable method to bypass the BBB and treat neurological diseases. The intranasal route for drug delivery to the brain with both solution and particulate formulations has been demonstrated repeatedly in preclinical models, including in human trials. The key features determining the efficacy of drug delivery via the intranasal route include delivery to the olfactory area of the nares, a longer retention time at the nasal mucosal surface, enhanced penetration of the drugs through the nasal epithelia, and reduced drug metabolism in the nasal cavity. This review describes important neurological disorders, challenges in drug delivery to the disordered CNS, and new nasal delivery techniques designed to overcome these challenges and facilitate more efficient and targeted drug delivery. The potential for treatment possibilities with intranasal transfer of drugs will increase with the development of more effective formulations and delivery devices. Figure 1. Schematic demonstrating various transport systems that shuttle molecules across the BBB. Very small amount of water-soluble compounds cross through the tight junctions (paracellular), whereas lipid-soluble agents traverse via the transcellular lipophilic pathway. Selective transport systems exist for glucose, amino acids, nucleosides, and other substances, in addition to specific receptor-mediated endocytosis for certain proteins such as insulin and transferrin. (AZT = azathioprine). List of CNS Diseases Parkinson's Disease (PD)PD, occurring primarily in the substantia nigra, is the second-most common neurodegenerative disease, leading to the development of bradykinesia and tremors of cardinal motor functions ( Figure 2) [3]. PD models specifically show a decrease in dopamine transporters, which are responsible for dopamine uptake by dopaminergic neurons and progression of neuronal communications. Reduced Figure 1. Schematic demonstrating various transport systems that shuttle molecules across the BBB. Very small amount of water-soluble compounds cross through the tight junctions (paracellular), whereas lipid-soluble agents traverse via the transcellular lipophilic pathway. Selective transport systems exist for glucose, amino acids, nucleosides, and other substances, in addition to specific receptor-mediated endocytosis for certain proteins such as insulin and transferrin. (AZT = azathioprine). List of CNS Diseases Parkinson's Disease (PD)PD, occurring primarily in the substantia nigra, is the second-most common neuro...

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Section: Formulations For Nose-to-brain Deliverymentioning

confidence: 99%

Section: Nanoparticles For Nose-to-brain Deliverymentioning

confidence: 99%

Section: Nanoparticles For Nose-to-brain Deliverymentioning

confidence: 99%

Section: Nanoparticles For Nose-to-brain Deliverymentioning

confidence: 99%

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Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

et al. 2020

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“…GCPQ consists of a glucosamine sugar backbone where, a fraction of the amine groups have been functionalised with either a long chained hydrophobic pendant group or a quaternary ammonium cation. Functionalisation in this way creates an amphiphilic polymer which self assembles into nanoparticles [35] and which enables drugs to cross biological barriers to produce formulations with a number of differentiating features [36][37][38]. The cationic polymer binds to the anionic surface of the precipitated SPIONs to form stable nano-sized clusters.…”

Section: Introductionmentioning

confidence: 99%

Facile aqueous, room temperature preparation of high transverse relaxivity clustered iron oxide nanoparticles

Hobson¹,

Weng²,

Thanh

et al. 2019

Colloids and Surfaces A: Physicochemical and Engineering Aspect

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Chitosan T2-weighted Colloid Relaxivity A B S T R A C TClustering superparamagnetic iron oxide nanoparticles (SPIONs) is one method of providing the biomedical benefits of larger SPIONs [e.g. superior T2 weighted magnetic resonance imaging (MRI) contrast] without increasing particle size. The work presented herein, describes the facile synthesis of clustered SPIONs that are suitable for MRI applications, by using a chitosan based polymer: N-palmitoyl-N-monomethyl-N-N-dimethyl-N-N-N-trimethyl-6-O-glycolchitosan (GCPQ) and aqueous nanoprecipitation followed by probe sonication, in the absence of organic solvents or elevated temperatures. The resulting clustered SPIONs consist of individual 8 nm iron oxide nanoparticles clustered into a 150 nm particle with a positive zeta potential (+23 mV) at neutral pH. X-ray diffraction confirms the presence of crystalline magnetic iron oxide, while magnetometer experiments show the clustered SPIONs are superparamagnetic giving an overall M s of 63.5 ± 1.3 emu g −1 . Relaxometry analyses revealed that the clustered SPIONs (inclusive of coatings) had a high r 2 value of 294.8 mM −1 s −1 and an r 2 /r 1 of 21.1 making the clustered SPIONs suitable for T2 weighted (negative) MRI contrast imaging applications. The resulting clustered SPIONs demonstrate that highly sensitive T2 contrast agents may be produced in mild room temperature conditions, without the need for organic solvents or low molecular weight surfactants.

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Smart Gold Nanostructures for Light Mediated Cancer Theranostics: Combining Optical Diagnostics with Photothermal Therapy

et al. 2020

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Nanotheranostics, which combines optical multiplexed disease detection with therapeutic monitoring in a single modality, has the potential to propel the field of nanomedicine toward genuine personalized medicine. Currently employed mainstream modalities using gold nanoparticles (AuNPs) in diagnosis and treatment are limited by a lack of specificity and potential issues associated with systemic toxicity. Light‐mediated nanotheranostics offers a relatively non‐invasive alternative for cancer diagnosis and treatment by using AuNPs of specific shapes and sizes that absorb near infrared (NIR) light, inducing plasmon resonance for enhanced tumor detection and generating localized heat for tumor ablation. Over the last decade, significant progress has been made in the field of nanotheranostics, however the main biological and translational barriers to nanotheranostics leading to a new paradigm in anti‐cancer nanomedicine stem from the molecular complexities of cancer and an incomplete mechanistic understanding of utilization of Au‐NPs in living systems. This work provides a comprehensive overview on the biological, physical and translational barriers facing the development of nanotheranostics. It will also summarise the recent advances in engineering specific AuNPs, their unique characteristics and, importantly, tunability to achieve the desired optical/photothermal properties.

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Nanoparticulate peptide delivery exclusively to the brain produces tolerance free analgesia

Cited by 63 publications

References 42 publications

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

Facile aqueous, room temperature preparation of high transverse relaxivity clustered iron oxide nanoparticles

Smart Gold Nanostructures for Light Mediated Cancer Theranostics: Combining Optical Diagnostics with Photothermal Therapy

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