Nose-to-brain delivery of amisulpride-loaded lipid-based poloxamer-gellan gum nanoemulgel: In vitro and in vivo pharmacological studies

Gadhave, Dnyandev; Tupe, Shrikant; Tagalpallewar, Amol; Gorain, Bapi; Choudhury, Hira; Kokare, Chandrakant

doi:10.1016/j.ijpharm.2021.121050

Cited by 38 publications

(21 citation statements)

References 62 publications

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“…Figure 5 indicates that the administration of intranasal amisulpride nanoemulgel and nanoemulsion could lead to significant increase in brain concentration as compared to the brain kinetics following intravenous administration. Moreover, on evaluation of the pharmacokinetic profile, Cmax of the intranasal amisulpride-loaded in situ nanoemulgel was found to be 1.48 times higher than that of intranasal amisulpride-loaded nanoemulsion, which indicated that the conversion of nanoemulsion to nanoemulgel facilitated intranasal retention for prolonged absorption ( Gadhave et al, 2021 ). The importance and application of the gel in the delivery of therapeutics via the intranasal route have been discussed in the subsequent section.…”

Section: Recent Advancement Of Delivering Antipsychotics Using Intran...mentioning

confidence: 99%

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

et al. 2022

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Treatment of central nervous system (CNS) disorders is challenging using conventional delivery strategies and routes of administration because of the presence of the blood–brain barrier (BBB). This BBB restricts the permeation of most of the therapeutics targeting the brain because of its impervious characteristics. Thus, the challenges of delivering the therapeutic agents across the BBB to the brain overcoming the issue of insufficient entry of neurotherapeutics require immediate attention for recovering from the issues by the use of modern platforms of drug delivery and novel routes of administration. Therefore, the advancement of drug delivery tools and delivering these tools using the intranasal route of drug administration have shown the potential of circumventing the BBB, thereby delivering the therapeutics to the brain at a significant concentration with minimal exposure to systemic circulation. These novel strategies could lead to improved efficacy of antipsychotic agents using several advanced drug delivery tools while delivered via the intranasal route. This review emphasized the present challenges of delivering the neurotherapeutics to the brain using conventional routes of administration and overcoming the issues by exploring the intranasal route of drug administration to deliver the therapeutics circumventing the biological barrier of the brain. An overview of different problems with corresponding solutions in administering therapeutics via the intranasal route with special emphasis on advanced drug delivery systems targeting to deliver CNS therapeutics has been focused. Furthermore, preclinical and clinical advancements on the delivery of antipsychotics using this intranasal route have also been emphasized.

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Section: Recent Advancement Of Delivering Antipsychotics Using Intran...mentioning

confidence: 99%

“… Mean (A) blood, (B) brain concentration-time curve for amisulpride nanogel (AMS-NG) (intranasal), amisulpride nanoemulsion (AMS-NE) (intranasal), and AMS-NE (intravenous) ( Gadhave et al, 2021 ). …”

Section: Recent Advancement Of Delivering Antipsychotics Using Intran...mentioning

confidence: 99%

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

et al. 2022

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“…Moreover, it has low aqueous solubility (predicted to be 0.293 mg/mL), which is also pH dependent, resulting in high solubility in the stomach (low pH) but poor solubility in the intestinal medium (higher pH), which could cause drug precipitation when reaching the intestine after oral administration [ 32 , 52 ]. Moreover, albeit selective, there have been reports of cardiovascular (prolongation of QT interval, bradycardia, hypotension), neuropsychiatric (sedation, seizures) and endocrine (increased prolactin levels) adverse events, as well as hematological toxicity with prolonged therapy (agranulocytosis or leukopenia) [ 33 , 52 ]. To solve some of these problems, Gamal et al [ 32 ] decided to develop an oral SNEDDS, made of Capryol™ 90 (propylene glycol monocaprylate (type II)), Cremophor ® RH40 (polyoxyl 40 hydrogenated castor oil) and Transcutol ® HP (diethylene glycol monoethyl ether), with varying proportions (detailed quantities in Table 7 ).…”

Section: Nanometric Emulsions Containing Antipsychotic Drugsmentioning

confidence: 99%

“…Gadhave et al [ 33 ] also developed amisulpride formulations, but for intranasal delivery. The developed nanoemulsions had Maisine ® CC (glyceryl monolinoleate), Labrasol ® (polyethylene glycol-8 caprylic/capric glycerides), Transcutol ® HP (diethylene glycol monoethyl ether) and water in their composition (concentration of each component in Table 7 ).…”

Section: Nanometric Emulsions Containing Antipsychotic Drugsmentioning

confidence: 99%

Antipsychotics-Loaded Nanometric Emulsions for Brain Delivery

2022

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Antipsychotic drugs have numerous disabling side effects, and many are lipophilic, making them hard to formulate at high strength. Incorporating them into nanometric emulsions can increase their solubility, protect them from degradation, and increase their brain delivery, being a promising strategy to overcome the current treatment gap. A thorough review was performed to assess the true potential of these formulations for antipsychotic drugs brain delivery. Intranasal administration was preferred when compared to oral or intravenous administration, since it allowed for direct brain drug transport and reduced systemic drug distribution, having increased efficacy and safety. Moreover, the developed systems increased antipsychotic drug solubility up to 4796 times (when compared to water), which is quite substantial. In the in vivo experiments, nanometric emulsions performed better than drug solutions or suspensions, leading to improved brain drug targeting, mainly due to these formulation’s excipients (surfactants and cosolvents) permeation enhancing capability, added to a small droplet size, which leaves a large surface area available for drug absorption to occur. Thus, even if it is difficult to conclude on which formulation composition leads to a best performance (high number of variables), overall nanometric emulsions have proven to be promising strategies to improve brain bioavailability of antipsychotic drugs.

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“…Enhanced in vivo bioavailability of EH from the prepared nasal emulsomes can be correlated to the in vitro enhancement of drug permeation through the nasal mucosa. This enhancement is related to high mucoadhesive effect of TMC, which leads to longer residence time with lower mucociliary clearance enabling the emulsomes particles to remain attached to the nasal mucosa, resulting in improved drug permeation [57]. In addition, it was reported that only positively charged chitosan can trigger the opening of tight junctions and thereby facilitate the paracellular transport [58].…”

Section: In Vivo Biodistribution Studymentioning

confidence: 99%

Assessment of Nasal-Brain-Targeting Efficiency of New Developed Mucoadhesive Emulsomes Encapsulating an Anti-Migraine Drug for Effective Treatment of One of the Major Psychiatric Disorders Symptoms

et al. 2022

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Migraine is one of the major symptoms of many psychiatric and mental disorders like depression and anxiety. Eletriptan Hydrobromide (EH) is a well-tolerated drug in migraine treatment, but suffers from low oral bioavailability and low brain targeting after oral delivery. New nasal mucoadhesive EH-emulsomes development could be a new means to direct the drug from the nose-to-brain to achieve rapid onset of action and high drug concentration in the brain for acute migraine treatment. Eletriptan mucoadhesive emulsomes formulations were prepared using thin-film hydration method and 23 full factorial design was adopted to study different formulation factors’ effect on the emulsomes characters. The emulsomes were characterized for entrapment efficiency (EE%), zeta potential (ZP), particle size (PS), morphology, and ex-vivo permeation through the nasal mucosa. The selected formula was evaluated in mice for its in-vivo bio-distribution in comparison with EH intranasal and intravenous solutions. Drug targeting efficacy (DTE%) and nose-to-brain direct transport percentage (DTP%) were calculated. The optimization formulation showed a nanoparticle size of 177.01 nm, EE 79.44%, and ZP = 32.12 ± 3.28 mV. In addition, in-vitro permeability studies revealed enhanced drug permeability with suitable mean residence time up to 120 ± 13 min. EH-emulsomes were stable under different storage conditions for three months. In vivo examination and pharmacokinetic drug targeting parameters revealed EH transport to the CNS after EH nanoparticle nasal administration. Histopathology study showed no ciliotoxic effect on the nasal mucosa. From the results, it can be confirmed that the emulsomes formulation of EH proved safe direct nose-to-brain transport of EH after nasal administration of EH emulsomes.

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Nose-to-brain delivery of amisulpride-loaded lipid-based poloxamer-gellan gum nanoemulgel: In vitro and in vivo pharmacological studies

Cited by 38 publications

References 62 publications

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

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

Antipsychotics-Loaded Nanometric Emulsions for Brain Delivery

Assessment of Nasal-Brain-Targeting Efficiency of New Developed Mucoadhesive Emulsomes Encapsulating an Anti-Migraine Drug for Effective Treatment of One of the Major Psychiatric Disorders Symptoms

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