Advances and Challenges in Intranasal Delivery of Antipsychotic Agents Targeting the Central Nervous System

Pandey, Manisha; Jain, Nidhi; Kanoujia, Jovita; Hussain, Zahid; Gorain, Bapi

doi:10.3389/fphar.2022.865590

Cited by 16 publications

(8 citation statements)

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“…Intranasal administration for the treatment of diseases of the CNS is attractive because it allows the drug to be delivered directly to the brain, bypassing the blood-brain barrier. At the same time, neurotherapeutic drugs are delivered to the brain in significant concentrations with minimal exposure to systemic circulation [ 46 ]. The results of the cataleptogenic effect of Hal in the formulation with VC10, and the commercial formulation of Hal (as a control), with intranasal administration are shown in Figure 8 .…”

Section: Resultsmentioning

confidence: 99%

Cataleptogenic Effect of Haloperidol Formulated in Water-Soluble Calixarene-Based Nanoparticles

et al. 2023

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In this study, a water-soluble form of haloperidol was obtained by coaggregation with calix[4]resorcinol bearing viologen groups on the upper rim and decyl chains on the lower rim to form vesicular nanoparticles. The formation of nanoparticles is achieved by the spontaneous loading of haloperidol into the hydrophobic domains of aggregates based on this macrocycle. The mucoadhesive and thermosensitive properties of calix[4]resorcinol–haloperidol nanoparticles were established by UV-, fluorescence and CD spectroscopy data. Pharmacological studies have revealed low in vivo toxicity of pure calix[4]resorcinol (LD50 is 540 ± 75 mg/kg for mice and 510 ± 63 mg/kg for rats) and the absence of its effect on the motor activity and psycho-emotional state of mice, which opens up a possibility for its use in the design of effective drug delivery systems. Haloperidol formulated with calix[4]resorcinol exhibits a cataleptogenic effect in rats both when administered intranasally and intraperitoneally. The effect of the intranasal administration of haloperidol with macrocycle in the first 120 min is comparable to the effect of commercial haloperidol, but the duration of catalepsy was shorter by 2.9 and 2.3 times (p < 0.05) at 180 and 240 min, respectively, than that of the control. There was a statistically significant reduction in the cataleptogenic activity at 10 and 30 min after the intraperitoneal injection of haloperidol with calix[4]resorcinol, then there was an increase in the activity by 1.8 times (p < 0.05) at 60 min, and after 120, 180 and 240 min the effect of this haloperidol formulation was at the level of the control sample.

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Section: Resultsmentioning

confidence: 99%

Cataleptogenic Effect of Haloperidol Formulated in Water-Soluble Calixarene-Based Nanoparticles

et al. 2023

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“…It provides advantages such as ease and self-administration, suitability for long-term use, cost effectiveness, and ability for scale-up manufacturing [ 27 , 67 ]. However, after oral administration, drugs need to pass several GIT compartments with different characteristics in terms of pH, aqueous volume, and membrane structures [ 2 ]. In addition, drug solubilization within GIT is mandatory, since incomplete dissolution may lead to incomplete absorption, low bioavailability, and higher fluctuations in systemic concentration [ 9 ].…”

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

confidence: 99%

“…Even so, a percentage of the administered dose can reach the systemic circulation. However, due to other physicochemical characteristics such as high molecular weight, these molecules could be restricted in passing through the BBB, hardly achieving effective therapeutic concentrations in the brain [ 2 , 3 ]. Different types of lipidic nanosystems have been developed to overcome the disadvantages of oral administration of neurotherapeutics, SEDDS being one of those systems [ 13 , 22 ].…”

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

confidence: 99%

“…In fact, global statistics show that 50 million people suffer from epilepsy, 62 million from cerebrovascular diseases, 326 million from migraine, and 24 million from Alzheimer's disease and other dementias. For that reason, Pharmaceutics 2022, 14, 1487 2 of 28 neurological disorders are considered one of the biggest causes of disability and death worldwide [1,2]. Taking this into account, efforts in discovering and developing new and effective neuropharmaceuticals are made daily, even though most of the new entities fail to reach clinical trials [3].…”

Section: Introductionmentioning

confidence: 99%

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

2022

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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.

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“…A billion people worldwide may suffer from neurological illnesses, according to a 2020 World Health Organization (WHO) assessment [ 1 ]. Based on this fact, neurological illnesses are regarded as one of the leading causes of disability and fatalities globally [ 1 , 2 ]. Despite the fact that the majority of novel entities never make it to clinical trials, scientific efforts are continuous to find and create new and effective neuropharmaceuticals.…”

Section: Introductionmentioning

confidence: 99%

Brain Targeting by Intranasal Drug Delivery: Effect of Different Formulations of the Biflavone “Cupressuflavone” from Juniperus sabina L. on the Motor Activity of Rats

et al. 2023

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The polar fractions of the Juniperus species are rich in bioflavonoid contents. Phytochemical study of the polar fraction of Juniperus sabina aerial parts resulted in the isolation of cupressuflavone (CPF) as the major component in addition to another two bioflavonoids, amentoflavone and robustaflavone. Biflavonoids have various biological activities, such as antioxidant, anti-inflammatory, antibacterial, antiviral, hypoglycemic, neuroprotective, and antipsychotic effects. Previous studies have shown that the metabolism and elimination of biflavonoids in rats are fast, and their oral bioavailability is very low. One of the methods to improve the bioavailability of drugs is to alter the route of administration. Recently, nose-to-brain drug delivery has emerged as a reliable method to bypass the blood–brain barrier and treat neurological disorders. To find the most effective CPF formulation for reaching the brain, three different CPF formulations (A, B and C) were prepared as self-emulsifying drug delivery systems (SEDDS). The formulations were administered via the intranasal (IN) route and their effect on the spontaneous motor activity in addition to motor coordination and balance of rats was observed using the activity cage and rotarod, respectively. Moreover, pharmacokinetic investigation was used to determine the blood concentrations of the best formulation after 12 h. of the IN dose. The results showed that formulations B and C, but not A, decreased the locomotor activity and balance of rats. Formula C at IN dose of 5 mg/kg expressed the strongest effect on the tested animals.

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Advances and Challenges in Intranasal Delivery of Antipsychotic Agents Targeting the Central Nervous System

Cited by 16 publications

References 100 publications

Cataleptogenic Effect of Haloperidol Formulated in Water-Soluble Calixarene-Based Nanoparticles

Cataleptogenic Effect of Haloperidol Formulated in Water-Soluble Calixarene-Based Nanoparticles

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

Brain Targeting by Intranasal Drug Delivery: Effect of Different Formulations of the Biflavone “Cupressuflavone” from Juniperus sabina L. on the Motor Activity of Rats

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