Optimization of rivastigmine nanoemulsion for enhanced brain delivery: in-vivo and toxicity evaluation

Haider, Md. Faheem; Khan, Saba; Gaba, Bharti; Alam, Tausif; Baboota, Sanjula; Ali, Javed; Ali, Asgar

doi:10.1016/j.molliq.2018.01.123

Cited by 44 publications

(16 citation statements)

References 37 publications

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“…The appearance of the cilia and the epithelial layer was intact. These results are in congruence with the findings of many other related studies reporting that drug-loaded micro/nanoemulsions are not ciliotoxic and safe for intranasal administration (Haider et al, 2018 ; Kia’I and Bajaj, 2019 ).…”

Section: Resultssupporting

confidence: 92%

Repurposing ibuprofen-loaded microemulsion for the management of Alzheimer’s disease: evidence of potential intranasal brain targeting

et al. 2021

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Studies have shown the use of non-steroidal anti-inflammatory drugs, such as ibuprofen could reduce the risk of Alzheimer’s disease. The drug-repurposing strategy offers a bright opportunity for these patients. Intranasal administration through the olfactory pathway provides noninvasive and direct drug delivery to the target brain. A novel ibuprofen microemulsion was prepared, characterized and assessed the brain uptake in rats. The solubility of ibuprofen in various oils, surfactants, co-surfactants, and different ratios of surfactant/co-surfactant mixtures was screened and the phase diagrams were constructed. The colloidal particle size was 166.3 ± 2.55 nm and the zeta potential was −22.7 mV. Conductivity and dilution test identified an O/W type microemulsion with pH 4.09 ± 0.08. The rheological study showed a Newtonian flow behavior with cP 10.633 ± 0.603 (mPa⋅s). A steady drug release and linear permeation profiles were observed and showed a 90% permeation rate from the released drug. Ibuprofen microemulsion showed excellent stability in 3-months accelerated storage conditions, heating-cooling and freeze-thaw cycles, accelerated centrifugation, and 6- and 12-months long-term storage conditions. In vivo studies in rats further demonstrated a 4-fold higher brain uptake of ibuprofen from the microemulsion compared to the reference solution and nearly 4-fold and 10-fold higher compared to the intravenous and oral administrations. This study provides an exciting repurposing strategy and new administration route for the treatment of Alzheimer’s disease.

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Section: Resultssupporting

confidence: 92%

Repurposing ibuprofen-loaded microemulsion for the management of Alzheimer’s disease: evidence of potential intranasal brain targeting

et al. 2021

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“…5 Amongst these approaches, non-invasive nose to brain pathways of dosage forms can deliver the therapeutics rapidly and directly to the brain, and thus intranasal administration has emerged as a potential delivery approach for delivering therapeutics to the CNS. 6,7 The nasal cavity consists of a highly vascularized surface area (150e200 cm 2 ), which supports direct delivery of therapeutics to the brain via olfactory and trigeminal pathways, 8 representing a reliable and practical method for brain targeting of therapeutics without inducing systemic toxic effects. However, direct nose to brain transport through intranasal administration is influenced by two major factors, such as nasal mucociliary clearance and permeability across nasal mucosa.…”

Section: Introductionmentioning

confidence: 99%

Antipsychotic Potential and Safety Profile of TPGS-Based Mucoadhesive Aripiprazole Nanoemulsion: Development and Optimization for Nose-To-Brain Delivery

Kumbhar

Kokare

Shrivastava

et al. 2021

Journal of Pharmaceutical Sciences

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Delivering therapeutics to the brain using conventional dosage forms is always a challenge, thus the present study was aimed to formulate mucoadhesive nanoemulsion (MNE) of aripiprazole (ARP) for intranasal delivery to transport the drug directly to the brain. Therefore, a TPGS based ARP-MNE was formulated and optimized using the Box-Behnken statistical design. The improved in vitro release profile of the formulation was in agreement to enhanced ex vivo permeation through sheep mucous membranes with a maximum rate of permeation co-efficient (62.87 cm h À1 Â 10 3 ) and flux (31.43 mg cm À2 .h À1 ). The pharmacokinetic profile following single-dose administration showed the maximum concentration of drug in the brain (C max ) of 15.19 ± 2.51 mg mL À1 and T max of 1 h in animals with ARP-MNE as compared to 10.57 ± 1.88 mg mL À1 and 1 h, and 2.52 ± 0.38 mg mL À1 and 3 h upon intranasal and intravenous administration of ARP-NE, respectively. Further, higher values of % drug targeting efficiency (96.9%) and % drug targeting potential (89.73%) of ARP-MNE through intranasal administration were investigated. The studies in Wistar rats showed no existence of extrapyramidal symptoms through the catalepsy test and forelimb retraction results. No ex vivo ciliotoxicity on nasal mucosa reflects the safety of the components and delivery tool. Further, findings on locomotor activity and hind-limb retraction test in ARP-MNE treated animals established its antipsychotic efficacy. Thus, it can be inferred that the developed ARP-MNE could effectively be explored as brain delivery cargo in the effective treatment of schizophrenia without producing any toxic manifestation.

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“…From the previous studies, the effect of vitamin E in conjunction with an additional antioxidant was established for neurodegenerative disorder like Alzheimer's disease [20]. Also, intranasal route for the effective brain delivery was also investigated and proven to be beneficial [20, 21]. Hence, main aim of the present work is to develop a vitamin E loaded NRG NE to be given via intranasal route for the direct and effective brain delivery for PD.…”

Section: Introductionmentioning

confidence: 99%

Vitamin E Loaded Naringenin Nanoemulsion via Intranasal Delivery for the Management of Oxidative Stress in a 6-OHDA Parkinson’s Disease Model

Gaba

Khan

Haider

et al. 2019

BioMed Research International

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137

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Purpose. The present study is an attempt to develop a vitamin E loaded naringenin (NRG) Nanoemulsion (NE) for direct nose-to-brain delivery for better management of Parkinson's disease (PD). Methods. The optimized NE was evaluated for efficacy in PD using multiple behavioral studies (including narrow beam test, muscular coordination test, grip strength test, forced swimming test, and akinesia test) in a rat model. Optimized formulation was evaluated for droplet size, polydispersity index (PDI), refractive index, transmittance, zeta potential, and viscosity. Results. Optimized NE had a droplet size of 38.70 ± 3.11nm, PDI of 0.14 ± 0.0024, refractive index of 1.43 ± 0.01, transmittance of 98.12 ± 0.07 %, zeta potential of − 27.4 ± 0.14 mV, and viscosity of 19.67 ± 0.25 Pa s. Behavioral studies showed that 6-OHDA induced PD in rats were successfully reversed when administered with NRG NE intranasally along with the levodopa. While the levels of GSH and SOD were significantly higher, levels of MDA were significantly lower in the group treated with NRG NE via intranasal route along with levodopa. Conclusion. Encouraging results from current study provide evidence for possible efficacy of a novel noninvasive intranasal delivery system of NRG for management of PD related symptoms.

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Optimization of rivastigmine nanoemulsion for enhanced brain delivery: in-vivo and toxicity evaluation

Cited by 44 publications

References 37 publications

Repurposing ibuprofen-loaded microemulsion for the management of Alzheimer’s disease: evidence of potential intranasal brain targeting

Repurposing ibuprofen-loaded microemulsion for the management of Alzheimer’s disease: evidence of potential intranasal brain targeting

Antipsychotic Potential and Safety Profile of TPGS-Based Mucoadhesive Aripiprazole Nanoemulsion: Development and Optimization for Nose-To-Brain Delivery

Vitamin E Loaded Naringenin Nanoemulsion via Intranasal Delivery for the Management of Oxidative Stress in a 6-OHDA Parkinson’s Disease Model

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