Brain targeted rivastigmine mucoadhesive thermosensitive In situ gel: Optimization, in vitro evaluation, radiolabeling, in vivo pharmacokinetics and biodistribution

Abouhussein, Dalia M N; Khattab, Abeer; Bayoumi, N. A.; Mahmoud, Ashgan F.; Sakr, Tamer M.

doi:10.1016/j.jddst.2017.09.021

Cited by 79 publications

(40 citation statements)

References 64 publications

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“…For this reason, poloxamer hydrogels were used as potential formulations that are able to promote the “nose to brain” delivery of many active compounds (i.e., levodopa, selegiline, anti-Parkinson’s drugs, etc.) thanks to their peculiar mucoadhesive features that are previously described [ 109 , 154 , 155 , 156 , 157 , 158 , 159 , 160 ].…”

Section: Poloxamer 407-based Mucoadhesive Formulationsmentioning

confidence: 99%

Mucosal Applications of Poloxamer 407-Based Hydrogels: An Overview

et al. 2018

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Poloxamer 407, also known by the trademark Pluronic® F127, is a water-soluble, non-ionic triblock copolymer that is made up of a hydrophobic residue of polyoxypropylene (POP) between the two hydrophilic units of polyoxyethylene (POE). Poloxamer 407-based hydrogels exhibit an interesting reversible thermal characteristic. That is, they are liquid at room temperature, but they assume a gel form when administered at body temperature, which makes them attractive candidates as pharmaceutical drug carriers. These systems have been widely investigated in the development of mucoadhesive formulations because they do not irritate the mucosal membranes. Based on these mucoadhesive properties, a simple administration into a specific compartment should maintain the required drug concentration in situ for a prolonged period of time, decreasing the necessary dosages and side effects. Their main limitations are their modest mechanical strength and, notwithstanding their bioadhesive properties, their tendency to succumb to rapid elimination in physiological media. Various technological approaches have been investigated in the attempt to modulate these properties. This review focuses on the application of poloxamer 407-based hydrogels for mucosal drug delivery with particular attention being paid to the latest published works.

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Section: Poloxamer 407-based Mucoadhesive Formulationsmentioning

confidence: 99%

Mucosal Applications of Poloxamer 407-Based Hydrogels: An Overview

et al. 2018

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“…In situ gel loaded with rivastigmine tartarate for administration via intranasal route was reported by Abouhussein et al [96]. The gels were prepared from HPMC (hydroxypropyl methylcellulose), Carbopol 934, NaCMC (sodium salt of carboxymethylcellulose), Chitosan, and pluronic F127.…”

Section: In Situ Gelmentioning

confidence: 99%

“…This could be due to the high drug permeation from the in situ gel observed in the ex vivo permeation study. The drug distribution in the vital organs, such as the liver and the kidney, was high after the administration of the drug solution indicating that the in situ gel has the capability to reduce the systemic drug distribution to vital organs resulting in drug targeting to the brain and hence, reduced side effects [96]. An intranasal thermosensitive gel loaded with rasagiline mesylate (RM), a drug used for the treatment of Parkinson's disease, was developed from poloxamer 407, carbopol 934 P, poloxamer 188, and chitosan.…”

Section: In Situ Gelmentioning

confidence: 99%

Chitosan-Based Nanocarriers for Nose to Brain Delivery

Aderibigbe

Naki

2019

Applied Sciences

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In the treatment of brain diseases, most potent drugs that have been developed exhibit poor therapeutic outcomes resulting from the inability of a therapeutic amount of the drug to reach the brain. These drugs do not exhibit targeted drug delivery mechanisms, resulting in a high concentration of the drugs in vital organs leading to drug toxicity. Chitosan (CS) is a natural-based polymer. It has unique properties such as good biodegradability, biocompatibility, mucoadhesive properties, and it has been approved for biomedical applications. It has been used to develop nanocarriers for brain targeting via intranasal administration. Nanocarriers such as nanoparticles, in situ gels, nanoemulsions, and liposomes have been developed. In vitro and in vivo studies revealed that these nanocarriers exhibited enhanced drug uptake to the brain with reduced side effects resulting from the prolonged contact time of the nanocarriers with the nasal mucosa, the surface charge of the nanocarriers, the nano size of the nanocarriers, and their capability to stretch the tight junctions within the nasal mucosa. The aforementioned unique properties make chitosan a potential material for the development of nanocarriers for targeted drug delivery to the brain. This review will focus on chitosan-based carriers for brain targeting.

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“…In vivo biodistribution studies were carried out in mice using a radiolabeling technique to study the ability of the developed BA-loaded-LA-modified-CL-NPs to target the liver in comparison to BA-loaded-LA-free-CL-NPs, and BA solution in TPP as a control following oral administration of equal doses. Direct radiolabelling method was applied to radiolabel BA with 99m Tc under reductive conditions using stannous chloride (SnCl 2 ) as a reducing agent [60]. The individual effect of different labelling conditions on the efficiency of the radiolabelling technique were first explored and optimized to maximize the percentage radiochemical yield (% RCY) of 99m Tc-BA complex.…”

Section: In Vivo Studiesmentioning

confidence: 99%

Nanoparticle-Mediated Dual Targeting: An Approach for Enhanced Baicalin Delivery to the Liver

et al. 2020

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In this study, water-soluble chitosan lactate (CL) was reacted with lactobionic acid (LA), a disaccharide with remarkable affinity to hepatic asialoglycoprotein (ASGP) receptors, to form dual liver-targeting LA-modified-CL polymer for site-specific drug delivery to the liver. The synthesized polymer was used to encapsulate baicalin (BA), a promising bioactive flavonoid with pH-dependent solubility, into ultrahigh drug-loaded nanoparticles (NPs) via the ionic gelation method. The successful chemical conjugation of LA with CL was tested and the formulated drug-loaded LA-modified-CL-NPs were assessed in terms of particle size (PS), encapsulation efficiency (EE) and zeta potential (ZP) using full factorial design. The in vivo biodistribution and pharmacokinetics of the designed NPs were assessed using 99mTc-radiolabeled BA following oral administration to mice and results were compared to 99mTc-BA-loaded-LA-free-NPs and 99mTc-BA solution as controls. Results showed that the chemical modification of CL with LA was successfully achieved and the method of preparation of the optimized NPs was very efficient in encapsulating BA into nearly spherical particles with an extremely high EE exceeding 90%. The optimized BA-loaded-LA-modified-CL-NPs showed an average PS of 490 nm, EE of 93.7% and ZP of 48.1 mV. Oral administration of 99mTc-BA-loaded-LA-modified-CL-NPs showed a remarkable increase in BA delivery to the liver over 99mTc-BA-loaded-LA-free-CL-NPs and 99mTc-BA oral solution. The mean area under the curve (AUC0–24) estimates from liver data were determined to be 11-fold and 26-fold higher from 99mTc-BA-loaded-LA-modified-CL-NPs relative to 99mTc-BA-loaded-LA-free-CL-NPs and 99mTc-BA solution respectively. In conclusion, the outcome of this study highlights the great potential of using LA-modified-CL-NPs for the ultrahigh encapsulation of therapeutic molecules with pH-dependent/poor water-solubility and for targeting the liver.

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Brain targeted rivastigmine mucoadhesive thermosensitive In situ gel: Optimization, in vitro evaluation, radiolabeling, in vivo pharmacokinetics and biodistribution

Cited by 79 publications

References 64 publications

Mucosal Applications of Poloxamer 407-Based Hydrogels: An Overview

Mucosal Applications of Poloxamer 407-Based Hydrogels: An Overview

Chitosan-Based Nanocarriers for Nose to Brain Delivery

Nanoparticle-Mediated Dual Targeting: An Approach for Enhanced Baicalin Delivery to the Liver

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