A study of rivastigmine liposomes for delivery into the brain through intranasal route

Karthik, A.; Subramanian, G.; Mallayasamy, Surulivelrajan; Averineni, Ranjith Kumar; Reddy, M. Sreenivasa; Udupa, N.

doi:10.2478/v10007-008-0014-3

Cited by 147 publications

(75 citation statements)

References 18 publications

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“…Often, efficient drug candidates in vitro were found to exert little impact on the outcome of neurodegenerative diseases in animal models or in clinical trials because of their inability to be adequately delivered across the blood-brain barrier. The identification of anatomical routes connecting the nasal passages, the brainstem and the spinal cord has paved the way for new treatment paradigms of CNS diseases by intranasal administration, using drug candidates such as peptides 53 or liposome-encapsulated molecules 54 .…”

Section: Discussionmentioning

confidence: 99%

A viral peptide that targets mitochondria protects against neuronal degeneration in models of Parkinson’s disease

et al. 2014

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Mitochondrial dysfunction is a common feature of many neurodegenerative disorders, notably Parkinson's disease. Consequently, agents that protect mitochondria have strong therapeutic potential. Here, we sought to divert the natural strategy used by Borna disease virus (BDV) to replicate in neurons without causing cell death. We show that the BDV X protein has strong axoprotective properties, thereby protecting neurons from degeneration both in tissue culture and in an animal model of Parkinson's disease, even when expressed alone outside of the viral context. We also show that intranasal administration of a cellpermeable peptide derived from the X protein is neuroprotective. We establish that both the X protein and the X-derived peptide act by buffering mitochondrial damage and inducing enhanced mitochondrial filamentation. Our results open the way to novel therapies for neurodegenerative diseases by targeting mitochondrial dynamics and thus preventing the earliest steps of neurodegenerative processes in axons.

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Section: Discussionmentioning

confidence: 99%

A viral peptide that targets mitochondria protects against neuronal degeneration in models of Parkinson’s disease

et al. 2014

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“…Szoka and Papahadjopoulos attributed the increase in entrapment to the increase in the internally captured volume which was synchronized with the increase in liposomal PS (Szoka & Papahadjopoulos, 1978). Similarly Arumugam et al (2008) prepared multilamellar liposomes by thin film hydration method containing soya lecithin and cholesterol in a 4:1 molar ratio. EE% of the developed formulation was found to be 80.0 ± 5.0% with a large PS of 10.0 ± 2.8 mm.…”

Section: Discussionmentioning

confidence: 99%

“…Three rabbits for each formulation per time point were used in the study, 18 rabbits total were used for each formulation. The groups received a dose of 1 mg/kg RHT (Arumugam et al, 2008). The rabbits were anesthetized by diethyl ether.…”

Section: Methodsmentioning

confidence: 99%

“…The resulting vesicles were sonicated for 10 minutes in an ultrasonic water bath to reduce their particle size (PS) (Woodbury et al, 2006;Jesorka & Orwar, 2008). The obtained dispersion was left to mature overnight at 4 C. Liposomal dispersion was then subjected to three freeze-thaw cycles, freezing at À4 C and then thawing at room temperature (Arumugam et al, 2008). The liposomal dispersion was stored at 4 C until analysis.…”

Section: Preparation Of Electrosteric Stealth (Ess) Liposomesmentioning

confidence: 99%

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Electrosteric stealth Rivastigmine loaded liposomes for brain targeting: preparation, characterization, ex vivo, bio-distribution and in vivo pharmacokinetic studies

et al. 2017

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Being one of the highly effective drugs in treatment of Alzheimer's disease, Rivastigmine brain targeting is highly demandable, therefore liposomal dispersion of Rivastigmine was prepared containing 2 mol% PEG-DSPE added to Lecithin, Didecyldimethyl ammonium bromide (DDAB), Tween 80 in 1:0.02:0.25 molar ratio. A major challenge during the preparation of liposomes is maintaining a stable formulation, therefore the aim of our study was to increase liposomal stability by addition of DDAB to give an electrostatic stability and PEG-DSPE to increase stability by steric hindrance, yielding what we called an electrosteric stealth (ESS) liposomes. A medium nano-sized liposome (478 ± 4.94 nm) with a nearly neutral zeta potential (ZP, À8 ± 0.2 mV) and an entrapment efficiency percentage of 48 ± 6.22 was prepared. Stability studies showed no major alteration after three months storage period concerning particle size, polydispersity index, ZP, entrapment efficiency and in vitro release study confirming the successful formation of a stable liposomes. No histopathological alteration was recorded for ESS liposomes of the sheep nasal mucosa. While ESS liposomes showed higher % of drug permeating through the sheep nasal mucosa (48.6%) than the drug solution (28.7%). On completing the in vivo pharmacokinetic studies of 36 rabbits showed 424.2% relative bioavailability of the mean plasma levels of the formula ESS compared to that of RHT intranasal solution and 486% relative bioavailability of the mean brain levels. KeywordsRivastigmine, pegylated liposomes, Tween 80, ex vivo permeation, in vivo pharmacokinetic studies History

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“…PBS (pH 6.4) was used as a dialyzing medium (Arumugam et al, 2008). Cellulose membranes were soaked for overnight into PBS at room temperature and then sandwiched between the receptor and donor compartment.…”

Section: Characterizationmentioning

confidence: 99%

Nose to brain microemulsion-based drug delivery system of rivastigmine: formulation and ex-vivo characterization

et al. 2014

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Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to irreversible loss of neurons, cognition and formation of abnormal protein aggregates. Rivastigmine, a reversible cholinesterase inhibitor used for the treatment of AD, undergoes extensive first-pass metabolism, thus limiting its absolute bioavailability to only 36% after 3-mg dose. Due to extreme aqueous solubility, rivastigmine shows poor penetration and lesser concentration in the brain thus requiring frequent oral dosing. This investigation was aimed to formulate microemulsion (ME) and mucoadhesive microemulsions (MMEs) of rivastigmine for nose to brain delivery and to compare percentage drug diffused for both systems using in-vitro and ex-vivo study. Rivastigmine-loaded ME and MMEs were prepared by titration method and characterized for drug content, globule size distribution, zeta potential, pH, viscosity and nasal ciliotoxicity study. Rivastigmine-loaded ME system containing 8% w/w Capmul MCM EP, 44% w/w Labrasol:Transcutol-P (1:1) and 48% w/w distilled water was formulated, whereas 0.3% w/ w chitosan (CH) and cetyl trimethyl ammonium bromide (as mucoadhesive agents) were used to formulate MMEs, respectively. ME and MMEs formulations were transparent with drug content, globule size and zeta potential in the range of 98.59% to 99.43%, 53.8 nm to 55.4 nm and À2.73 mV to 6.52 mV, respectively. MME containing 0.3% w/w CH followed Higuchi model (r 2 ¼ 0.9773) and showed highest diffusion coefficient. It was free from nasal ciliotoxicity and stable for three months. However, the potential of developed CH-based MME for nose to brain delivery of rivastigmine can only be established after in-vivo and biodistribution study.

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A study of rivastigmine liposomes for delivery into the brain through intranasal route

Cited by 147 publications

References 18 publications

A viral peptide that targets mitochondria protects against neuronal degeneration in models of Parkinson’s disease

A viral peptide that targets mitochondria protects against neuronal degeneration in models of Parkinson’s disease

Electrosteric stealth Rivastigmine loaded liposomes for brain targeting: preparation, characterization, ex vivo, bio-distribution and in vivo pharmacokinetic studies

Nose to brain microemulsion-based drug delivery system of rivastigmine: formulation and ex-vivo characterization

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