Intranasal delivery of lipid-based nanosystems as a promising approach for brain targeting of the new-generation antiepileptic drug perampanel

Meirinho, Sara; Rodrigues, Márcio; Ferreira, Catarina L.; Oliveira, Rui Caetano; Fortuna, Ana; Santos, Adriana O.; Falcão, Amílcar; Falcão, Amı́lcar

doi:10.1016/j.ijpharm.2022.121853

Cited by 5 publications

(13 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Considering that the pH range of nasal mucosa is between 5 and 6.5 [ 10 ], to avoid nasal irritation and local toxicity, after self-emulsification, the pH of the formed emulsions should be within this interval. Of the studies revised here that developed SEDDS for nose-to-brain targeting, only Meirinho et al [ 28 ], Chen et al [ 30 ], and Nagaraja et al [ 5 ] investigated the final pH of, respectively, SMEDDS loaded with perampanel, the temperature and pH-responsive in situ gel containing SMEDDS loaded with huperzine A, and naringin in situ gelling SNEDDS, being all within acceptable values ( Table 1 ). The morphology and percentage of transmittance can also be examined to explore the shape and the clearness of SEDDS after suitable dilutions [ 7 , 8 ].…”

Section: Sedds Development For Delivery Of Neurotherapeutics Agents T...mentioning

confidence: 95%

“…In vitro dissolution assays are also very important, particularly for SEDDS loaded with poorly water-soluble drugs. These assays are able to predict drug dissolution/release rate and extent in the nasal cavity or GIT after SEDDS administration [ 28 ]. Formulation composition and its characteristics (e.g., particle size and viscosity) can have a high impact on dissolution.…”

Section: Sedds Development For Delivery Of Neurotherapeutics Agents T...mentioning

confidence: 99%

“…Another suitable alternative to predict in vitro drug release from a formulation are the horizontal Ussing chambers using synthetic membranes as barriers [ 58 ]. An example that employed horizontal Ussing chambers is reported by Meirinho et al [ 28 ], who studied perampanel release from a SMEDDS formulated for nose-to-brain delivery. The authors were able to predict perampanel release percentage and rate after 4 h of assay and compare it with perampanel release from a Transcutol HP solution used as a positive release control [ 28 ].…”

Section: Sedds Development For Delivery Of Neurotherapeutics Agents T...mentioning

confidence: 99%

“…An example that employed horizontal Ussing chambers is reported by Meirinho et al [ 28 ], who studied perampanel release from a SMEDDS formulated for nose-to-brain delivery. The authors were able to predict perampanel release percentage and rate after 4 h of assay and compare it with perampanel release from a Transcutol HP solution used as a positive release control [ 28 ]. Even so, few studies describe the use of this approach for the prediction of drug dissolution and release.…”

Section: Sedds Development For Delivery Of Neurotherapeutics Agents T...mentioning

confidence: 99%

“…Although derived microemulsions (and some nanoemulsions) have been extensively tested [ 10 ], up to date, and as far as we know, there are only six works in the scientific literature that developed SEDDS for nose-to-brain delivery [ 4 , 5 , 28 ]. However, after balancing the pros and cons of oral and IN routes, the increasing interest in the IN route for treating CNS disorders is undeniable.…”

Section: Intranasal Administration As An Alternative To the Oral Rout...mentioning

confidence: 99%

See 4 more Smart Citations

Self-Emulsifying Drug Delivery Systems: An Alternative Approach to Improve Brain Bioavailability of Poorly Water-Soluble Drugs through Intranasal Administration

2022

Self Cite

View full text Add to dashboard Cite

Efforts in discovering new and effective neurotherapeutics are made daily, although most fail to reach clinical trials. The main reason is their poor bioavailability, related to poor aqueous solubility, limited permeability through biological membranes, and the hepatic first-pass metabolism. Nevertheless, crossing the blood–brain barrier is the major drawback associated with brain drug delivery. To overcome it, intranasal administration has become more attractive, in some cases even surpassing the oral route. The unique anatomical features of the nasal cavity allow partial direct drug delivery to the brain, circumventing the blood–brain barrier. Systemic absorption through the nasal cavity also avoids the hepatic first-pass metabolism, increasing the systemic bioavailability of highly metabolized entities. Nevertheless, most neurotherapeutics present physicochemical characteristics that require them to be formulated in lipidic nanosystems as self-emulsifying drug delivery systems (SEDDS). These are isotropic mixtures of oils, surfactants, and co-surfactants that, after aqueous dilution, generate micro or nanoemulsions loading high concentrations of lipophilic drugs. SEDDS should overcome drug precipitation in absorption sites, increase their permeation through absorptive membranes, and enhance the stability of labile drugs against enzymatic activity. Thus, combining the advantages of SEDDS and those of the intranasal route for brain delivery, an increase in drugs’ brain targeting and bioavailability could be expected. This review deeply characterizes SEDDS as a lipidic nanosystem, gathering important information regarding the mechanisms associated with the intranasal delivery of drugs loaded in SEDDS. In the end, in vivo results after SEDDS intranasal or oral administration are discussed, globally revealing their efficacy in comparison with common solutions or suspensions.

show abstract

Section: Sedds Development For Delivery Of Neurotherapeutics Agents T...mentioning

confidence: 95%

Section: Sedds Development For Delivery Of Neurotherapeutics Agents T...mentioning

confidence: 99%

Section: Sedds Development For Delivery Of Neurotherapeutics Agents T...mentioning

confidence: 99%

Section: Sedds Development For Delivery Of Neurotherapeutics Agents T...mentioning

confidence: 99%

Section: Intranasal Administration As An Alternative To the Oral Rout...mentioning

confidence: 99%

See 3 more Smart Citations

Self-Emulsifying Drug Delivery Systems: An Alternative Approach to Improve Brain Bioavailability of Poorly Water-Soluble Drugs through Intranasal Administration

2022

Self Cite

View full text Add to dashboard Cite

show abstract

Nose-to-brain delivery of perampanel formulated in a self-microemulsifying drug delivery system improves anticonvulsant and anxiolytic activity in mice

Meirinho

Rodrigues

Santos

et al. 2023

International Journal of Pharmaceutics

View full text Add to dashboard Cite

Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures

Zhang,

Zuo,

et al. 2024

J Nanobiotechnol

View full text Add to dashboard Cite

Improving the efficiency of antiseizure medication entering the brain is the key to reducing its peripheral toxicity. A combination of intranasal administration and nanomedicine presents a practical approach for treating epileptic seizures via bypassing the blood-brain barrier. In this study, phenytoin (PHT) loaded layered double hydroxide nanoparticles (BSA-LDHs-PHT) were fabricated via a coprecipitation − hydrothermal method for epileptic seizure control. In this study, we expound on the preparation method and characterization of BSA-LDHs-PHT. In-vitro drug release experiment shows both rapid and continuous drug release from BSA-LDHs-PHT, which is crucial for acute seizure control and chronic epilepsy therapy. In-vivo biodistribution assays after intranasal administration indicate excellent brain targeting ability of BSA-LDHs. Compared to BSA-Cyanine5.5, BSA-LDHs-Cyanine5.5 were associated with a higher brain/peripheral ratio across all tested time points. Following intranasal delivery with small doses of BSA-LDHs-PHT, the latency of seizures in the pentylenetetrazole-induced mouse models was effectively improved. Collectively, the present study successfully designed and applied BSA-LDHs-PHT as a promising strategy for treating epileptic seizures with an enhanced therapeutic effect.

show abstract

Intranasal delivery of lipid-based nanosystems as a promising approach for brain targeting of the new-generation antiepileptic drug perampanel

Cited by 5 publications

References 47 publications

Self-Emulsifying Drug Delivery Systems: An Alternative Approach to Improve Brain Bioavailability of Poorly Water-Soluble Drugs through Intranasal Administration

Self-Emulsifying Drug Delivery Systems: An Alternative Approach to Improve Brain Bioavailability of Poorly Water-Soluble Drugs through Intranasal Administration

Nose-to-brain delivery of perampanel formulated in a self-microemulsifying drug delivery system improves anticonvulsant and anxiolytic activity in mice

Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures

Contact Info

Product

Resources

About