Nanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin for intranasal administration: Formulation development and in vitro characterization

Pires, Patrícia C.; Peixoto, Diana; Teixeira, Isaura; Rodrigues, Márcio; Alves, Gilberto; Santos, Adriana O.

doi:10.1016/j.ejps.2019.105099

Cited by 23 publications

(16 citation statements)

References 24 publications

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“…Afterward, “intranasal drug delivery for neurodegenerative, neuropsychiatric, and other neurological disorders (cluster 1 and cluster 3)” have progressively gained importance around 2015, and some areas remain the hotpots until today, for example, “neuroinflammation (AAY = 2017.90) ( Rhea et al, 2020 ),” “mesenchymal stem cell (AAY = 2017.62)” ( Aguilera et al, 2021 ; Vaes et al, 2021 ), and “mild cognitive impairment (AAY = 2016.85) ( Craft et al, 2012 ).” Also, it needs to be noted that keywords in “cluster 2: the study of nasal drug delivery systems” had the largest AAY compared with other clusters, and the keywords of “nanocarriers (AAY = 2018.22) ( Rehman et al, 2019 ),” “nanostructured lipid carriers (AAY = 2018.11) ( Agbo et al, 2021 ),” “loaded chitosan nanoparticles (AAY = 2017.52) ( Zhao et al, 2017 ),” and “PLGA nanoparticles (2017.41) ( Nanaki et al, 2020 )” were mainly found in the early years. These results indicate that the research focus of this field has shifted from “cluster 4: pathways and mechanisms of intranasal delivery” to “cluster 2: the study of nasal drug delivery systems, especially the nanostructured and nano-sized carrier systems” ( Ali et al, 2010 ; Battaglia et al, 2018 ; Pires et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…Also, it needs to be noted that keywords in "cluster 2: the study of nasal drug delivery systems" had the largest AAY compared with other clusters, and the keywords of "nanocarriers (AAY 2018.22) (Rehman et al, 2019)," "nanostructured lipid carriers (AAY 2018.11) (Agbo et al, 2021)," "loaded chitosan nanoparticles (AAY 2017.52) (Zhao et al, 2017)," and "PLGA nanoparticles (2017.41) (Nanaki et al, 2020)" were mainly found in the early years. These results indicate that the research focus of this field has shifted from "cluster 4: pathways and mechanisms of intranasal delivery" to "cluster 2: the study of nasal drug delivery systems, especially the nanostructured and nano-sized carrier systems" (Ali et al, 2010;Battaglia et al, 2018;Pires et al, 2020).…”

Section: Analysis Of Changes In Research Hotspotsmentioning

confidence: 99%

“…In view of this, we conducted a scientometric analysis of studies on intranasal delivery research published from 1998 to 2020. The aims of this study were to identify the major players and their cooperation networks, including countries, academic groups, and individuals; to analyze research status and hotspots, especially the key study findings in this field; to summarize the main research themes and clusters, discuss the potentially valuable research directions, including drug delivery systems ( Ali et al, 2010 ; Battaglia et al, 2018 ; Pires et al, 2020 ) and the broad prospect of clinical application.…”

Section: Introductionmentioning

confidence: 99%

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Current State and Future Directions of Intranasal Delivery Route for Central Nervous System Disorders: A Scientometric and Visualization Analysis

Zhou

Wang

et al. 2021

Front. Pharmacol.

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Background: The management of various central nervous system (CNS) disorders has been challenging, due to highly compact blood-brain barrier (BBB) impedes the access of most pharmacological agents to the brain. Among multiple strategies proposed to circumvent this challenge, intranasal delivery route has sparked great interest for brain targeting in the past decades. The aim of this study was to apply scientometric method to estimate the current status and future trends of the field from a holistic perspective.Methods: All relevant publications during 1998–2020 were retrieved from the Web of Science Core Collection (SCIE, 1998-present). Two different scientometric software including VOS viewer and CiteSpace, and one online platform were used to conduct co-authorship, co-citation, and co-occurrence analysis of journals, countries, institutes, authors, references and keywords.Results: A total of 2,928 documents, including 2,456 original articles and 472 reviews, were retrieved. Our analysis revealed a significant increasing trend in the total number of scientific publications over the past 2 decades (R2 = 0.98). The United States dominated the field, reflecting in the largest amount of publications (971), the highest H-index (99), and extensive international collaboration. Jamia Hamdard contributed to most publications. Frey WH and Illum L were key researchers with the highest number of publications and citations, respectively. The International Journal of Pharmaceutics was the most influential academic journal, and Pharmacology/Pharmacy and Neurosciences/Neurology were the hottest research categories in this field. Based on keywords occurrence analysis, four main topics were identified, and the current research focus of this field has shifted from cluster 4 (pathways and mechanisms of intranasal delivery) to cluster 2 (the study of nasal drug delivery systems), especially the nanostructured and nano-sized carrier systems. Keywords burst detection revealed that the research focus on oxidative stress, drug delivery, neuroinflammation, nanostructured lipid carrier, and formulation deserves our continued attention.Conclusion: To the authors’ knowledge, this is the first scientometric analysis regarding intranasal delivery research. This study has demonstrated a comprehensive knowledge map, development landscape and future directions of intranasal delivery research, which provides a practical and valuable reference for scholars and policymakers in this field.

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Section: Resultsmentioning

confidence: 99%

Section: Analysis Of Changes In Research Hotspotsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Current State and Future Directions of Intranasal Delivery Route for Central Nervous System Disorders: A Scientometric and Visualization Analysis

Zhou

Wang

et al. 2021

Front. Pharmacol.

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“…Similar results have been reported in other studies. For example, Fatouh et al [14] observed a slight increase in the particle size of agomelatine-loaded SLN (167.7 ± 0.42 nm) after incorporation in an in situ gel (175.75 ± 1.10 nm), and Pires et al [16] verified an increase in the droplet size of a fosphenytoin-loaded nanoemulsion (216.4 ± 10.5 nm) after incorporation in a thermosensitive gel (219.7 ± 26.8 nm).…”

Section: Particle Size Pdi and Zpmentioning

confidence: 99%

Thermosensitive Nasal In Situ Gels of Lipid-Based Nanosystems to Improve the Treatment of Alzheimer’s Disease

Cunha

Forbes

Lobo

et al. 2020

The 1st International Electronic Conference on Pharmaceutics

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Thermosensitive in situ gels are promising formulations for the management of Alzheimer’s disease (AD), since they increase the residence time of lipid-based nanosystems in the nasal cavity, improving drug therapeutic efficacy. The purpose of this study is to prepare thermosensitive in situ gels with anticholinesterase inhibitor (RVG)-loaded nanostructured lipid carriers (NLC) and nanoemulsions to improve the residence time of the formulations in the nasal cavity. Different concentrations of thermosensitive polymers were added to the RVG-loaded NLC and to the RVG-loaded nanoemulsion to optimize the gelation temperature of the in situ gels; concentrations of 17% (%, w/w) of Kolliphor® P407 and 0.3% (%, w/w) of MethocelTM K4M were selected. The in situ gels of the RVG-loaded NLC and RVG-loaded nanoemulsion had a particle size, PDI, ZP, and pH of, respectively: 141.70 ± 0.40 nm and 146.10 ± 1.73 nm; 0.45 ± 0.00 and 0.43 ± 0.02; −4.06 ± 1.03 mV and −4.09 ± 0.71 mV, 6.60 ± 0.01 and 7.00 ± 0.02. In addition, these in situ gels showed a non-Newtonian plastic behavior, and the texture parameters presented desirable values for nasal administration. From these results, we concluded that the developed in situ gels can be used to improve the treatment of AD through the nose-to-brain route.

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“…A fast drug release was achieved from nanoemulsion with 60% of fosphenytoin, which has the potential to treat acute pain episodes, while nanoemulsion with 90% fosphenytoin and in situ fosphenytoin-loaded nanoemulsion hydrogel exhibited a prolonged drug release, showing potential for the management of nasal wound healing, inflammatory reactions, and tissue remodelling. 112 Ahmad et al developed a naringenin-loaded nanoemulsion and an in situ-based nanoemulsion hydrogel for nose-to-brain delivery to improve drug bioavailability. Naringenin is a flavonoid compound with potential for the management of AD due to its anti-inflammatory and antioxidative effects.…”

Section: Current Strategies To Improve the Treatment Of Alzheimer’s Diseasementioning

confidence: 99%

Improving Drug Delivery for Alzheimer’s Disease Through Nose-to-Brain Delivery Using Nanoemulsions, Nanostructured Lipid Carriers (NLC) and in situ Hydrogels

Cunha¹,

Forbes²,

Lobo³

et al. 2021

IJN

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Current treatments for Alzheimer’s disease (AD) attenuate the progression of symptoms and aim to improve the patient’s quality of life. Licensed medicines are mostly for oral administration and are limited by the difficulty in crossing the blood–brain barrier (BBB). Here in, the nasal route has been explored as an alternative pathway that allows drugs to be directly delivered to the brain via the nasal cavity. However, clearance mechanisms in the nasal cavity impair the delivery of drugs to the brain and limit their bioavailability. To optimize nose-to-brain delivery, formulations of lipid-based nanosystems, namely nanoemulsions and nanostructured lipid carriers (NLC), formulated in situ gelling hydrogels have been proposed as approaches for nose-to-brain delivery. These formulations possess characteristics that facilitate drug transport directly to the brain, minimizing side effects and maximizing therapeutic benefits. It has been recommended that the manufacture of these drug delivery systems follows the quality by design (QbD) approach based on nasal administration requirements. This review provides an insight into the current knowledge of the AD, highlighting the need for an effective drug delivery to the brain. Considering the mounting interest in the use of nanoemulsions and NLC for nose-to-brain delivery, a description of drug transport pathways in the nasal cavity and the application of these nanosystems and their in situ hydrogels through the intranasal route are presented. Relevant preclinical studies are summarised, and the future prospects for the use of lipid-based nanosystems in the treatment of AD are emphasized.

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Nanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin for intranasal administration: Formulation development and in vitro characterization

Cited by 23 publications

References 24 publications

Current State and Future Directions of Intranasal Delivery Route for Central Nervous System Disorders: A Scientometric and Visualization Analysis

Current State and Future Directions of Intranasal Delivery Route for Central Nervous System Disorders: A Scientometric and Visualization Analysis

Thermosensitive Nasal In Situ Gels of Lipid-Based Nanosystems to Improve the Treatment of Alzheimer’s Disease

Improving Drug Delivery for Alzheimer’s Disease Through Nose-to-Brain Delivery Using Nanoemulsions, Nanostructured Lipid Carriers (NLC) and in situ Hydrogels

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