Nose-to-brain delivery of antipsychotics using nanotechnology: a review

Tan, Madeleine S. A.; Parekh, Harendra S.; Pandey, Preeti; Siskind, Dan; Falconer, James R.

doi:10.1080/17425247.2020.1762563

Cited by 51 publications

(51 citation statements)

References 105 publications

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“…They facilitate a more targeted and efficient brain delivery and reduce side effects at the same time [223]. The advantage of using nanotechnology-based drug delivery systems has been shown for different CNS indications, such as epilepsy, psychosis-related disorders and glioma [152,[223][224][225][226][227].…”

Section: Systemic and Cns Side Effectsmentioning

confidence: 99%

Intranasal drug delivery: opportunities and toxicologic challenges during drug development

Keller

Merkel

Popp

2021

Drug Deliv. and Transl. Res.

300

178

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Over the past 10 years, the interest in intranasal drug delivery in pharmaceutical R&D has increased. This review article summarises information on intranasal administration for local and systemic delivery, as well as for CNS indications. Nasal delivery offers many advantages over standard systemic delivery systems, such as its non-invasive character, a fast onset of action and in many cases reduced side effects due to a more targeted delivery. There are still formulation limitations and toxicological aspects to be optimised. Intranasal drug delivery in the field of drug development is an interesting delivery route for the treatment of neurological disorders. Systemic approaches often fail to efficiently supply the CNS with drugs. This review paper describes the anatomical, histological and physiological basis and summarises currently approved drugs for administration via intranasal delivery. Further, the review focuses on toxicological considerations of intranasally applied compounds and discusses formulation aspects that need to be considered for drug development. Graphical abstract

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Section: Systemic and Cns Side Effectsmentioning

confidence: 99%

Intranasal drug delivery: opportunities and toxicologic challenges during drug development

Keller

Merkel

Popp

2021

Drug Deliv. and Transl. Res.

300

178

View full text Add to dashboard Cite

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“…It is noteworthy that currently applied antipsychotic drugs have numerous drawbacks related to their severe side effects including weight gain, sedation, extrapyramidal and other effects. The adverse drug reactions accompanying the therapy may contribute to the reduction of patient compliance [163]. Nose-to-brain formulations can be an interesting alternative to oral therapy, providing direct transport of the active ingredient to the brain tissue.…”

Section: Schizophreniamentioning

confidence: 99%

Microemulsion-Based Media in Nose-to-Brain Drug Delivery

et al. 2021

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Nose-to-brain drug delivery has recently attracted enormous attention as an alternative to other delivery routes, including the most popular oral one. Due to the unique anatomical features of the nasal cavity, drugs administered intranasally can be delivered directly to the central nervous system. The most important advantage of this approach is the ability to avoid the blood–brain barrier surrounding the brain and blocking the entry of exogenous substances to the central nervous system. Moreover, selective brain targeting could possibly avoid peripheral side effects of pharmacotherapy. The challenges associated with nose-to-brain drug delivery are mostly due to the small volume of the nasal cavity and insufficient drug absorption from nasal mucosa. These issues could be minimized by using a properly designed drug carrier. Microemulsions as potential drug delivery systems offer good solubilizing properties and the ability to enhance drug permeation through biological membranes. The aim of this review is to summarize the current status of the research focused on microemulsion-based systems for nose-to-brain delivery with special attention to the most extensively investigated neurological and psychiatric conditions, such as neurodegenerative diseases, epilepsy, and schizophrenia.

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“…The anatomical and physiological characteristics of the different regions of the nasal cavity are summarized in Table 1 and the location of each region is shown in Figure 1 [ 12 , 13 , 14 ].…”

Section: Nasal Routementioning

confidence: 99%

“…Some factors of the nasal formulations can interfere with drug absorption and should be considered. For instance, these formulations should be isotonic (i.e., osmolality between 280 mOsm/Kg and 310 mOsm/Kg) and have a pH close to that of the nasal cavity (5.0–6.8), to avoid discomfort, mucosal irritation and/or damage to the cilia, after administration [ 13 , 19 ]. In addition, the drug excipients used should be compatible with the nasal mucosa to avoid irritation and toxicity [ 20 , 21 ].…”

Section: Nasal Routementioning

confidence: 99%

“…Nonetheless, it is important to keep in mind that after intranasal administration, part of the drug is absorbed into the systemic circulation and reaches the brain through the BBB [ 3 ]. In addition, the use of lipid nanoparticles, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), to promote the targeting of drugs to the brain after intranasal administration, has been suggested as a promising alternative to the conventional treatments of brain disorders [ 1 , 3 , 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

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In Vitro Studies on Nasal Formulations of Nanostructured Lipid Carriers (NLC) and Solid Lipid Nanoparticles (SLN)

et al. 2021

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The nasal route has been used for many years for the local treatment of nasal diseases. More recently, this route has been gaining momentum, due to the possibility of targeting the central nervous system (CNS) from the nasal cavity, avoiding the blood−brain barrier (BBB). In this area, the use of lipid nanoparticles, such as nanostructured lipid carriers (NLC) and solid lipid nanoparticles (SLN), in nasal formulations has shown promising outcomes on a wide array of indications such as brain diseases, including epilepsy, multiple sclerosis, Alzheimer’s disease, Parkinson’s disease and gliomas. Herein, the state of the art of the most recent literature available on in vitro studies with nasal formulations of lipid nanoparticles is discussed. Specific in vitro cell culture models are needed to assess the cytotoxicity of nasal formulations and to explore the underlying mechanism(s) of drug transport and absorption across the nasal mucosa. In addition, different studies with 3D nasal casts are reported, showing their ability to predict the drug deposition in the nasal cavity and evaluating the factors that interfere in this process, such as nasal cavity area, type of administration device and angle of application, inspiratory flow, presence of mucoadhesive agents, among others. Notwithstanding, they do not preclude the use of confirmatory in vivo studies, a significant impact on the 3R (replacement, reduction and refinement) principle within the scope of animal experiments is expected. The use of 3D nasal casts to test nasal formulations of lipid nanoparticles is still totally unexplored, to the authors best knowledge, thus constituting a wide open field of research.

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Nose-to-brain delivery of antipsychotics using nanotechnology: a review

Cited by 51 publications

References 105 publications

Intranasal drug delivery: opportunities and toxicologic challenges during drug development

Intranasal drug delivery: opportunities and toxicologic challenges during drug development

Microemulsion-Based Media in Nose-to-Brain Drug Delivery

In Vitro Studies on Nasal Formulations of Nanostructured Lipid Carriers (NLC) and Solid Lipid Nanoparticles (SLN)

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