Identifying lipidic emulsomes for improved oxcarbazepine brain targeting: In vitro and rat in vivo studies

El-Zaafarany, Ghada M.; Soliman, Mahmoud E.; Mansour, Samar; Awad, Gehanne A.S.

doi:10.1016/j.ijpharm.2016.02.038

Cited by 61 publications

(67 citation statements)

References 55 publications

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“…In what concerns the oral and oromucosal routes, the limitations are related with altered physiological states of individuals (such as nausea and vomiting, or the hypersalivation and inability to swallow that happen during an epileptic seizure) [3,4,[9][10][11], large intersubject absorption rate variability, slow onset of action, drug-drug and drug-food interactions and cytochrome P450 induction [8,10,[12][13][14][15][16][17]. Moreover, IN delivery offers the possibility of avoiding hepatic first pass metabolism and can reduce drug distribution to non-targeted sites, thereby minimizing systemic adverse effects [8,[18][19][20][21][22][23][24].…”

Section: Fig 1 Schematic Representation Of Intranasal (In) Deliverymentioning

confidence: 99%

“…General advantages include rapid uptake, absence of burst effect and good tolerability. Stated advantages over polymeric nanoparticles comprise avoidance of the use of organic solvents in production, and over SLN higher drug loading, smaller particle size and no drug leakage or expulsion during storage, with improved long-term stability [18,21,44,60,62,68].…”

Section: Delivery Nanosystemsmentioning

confidence: 99%

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Nanosystems in nose-to-brain drug delivery: A review of non-clinical brain targeting studies

Pires

Santos

2018

Journal of Controlled Release

148

135

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The treatment of neurodegenerative and psychiatric disorders remains a challenge in medical research. Several strategies have been developed over the years, either to overcome the blood-brain barrier or to achieve a safer or faster brain delivery, one of them being intranasal (IN) administration. The possibility of direct nose-to-brain transport offers enhanced targeting and reduced systemic side effects. Nevertheless, labile, low soluble, low permeant and/or less potent drugs might need a formulation other than the common solutions or suspensions. For that, the formulation of nanosystems is considered to be a promising approach, since it can protect drugs from chemical and/or metabolic degradation, enhance their solubility, or offer transport through biological membranes. However, the understanding of the factors promoting efficient brain targeting when using nanosystems through the nasal route is currently patchy and incomplete. The main purpose of the present review was to evaluate the association between brain delivery efficacy (in terms of brain targeting, brain bioavailability and time to reach the brain) and nanosystem type. For that, we performed a systematic bibliographic search and analysis. Furthermore, study designs, nanosystem properties, and reporting quality were also analyzed and discussed. It was found a high heterogeneity in how pre-clinical brain targeting studies have been conducted, analyzed and reported in scientific literature, which surely originates a significant degree of bias and data dispersion. This review attempts to provide some systematization recommendations, which may be useful for researchers entering the field, and assist in increasing the uniformity of future reports. The analysis of literature data confirmed that there is evidence of the advantage of the IN route (when compared to the intravenous route) and in using carrier nanosystems (when compared to IN solutions) for brain delivery of a large set of drugs. Among the most represented nanosystem classes, microemulsions had some of the lowest pharmacokinetic ratios values, while polymeric micelles had some of the best. Nevertheless, brain targeting efficacy comparisons between nanosystem groups had little statistical significance, and the superiority of the polymeric micelles group disappeared when nanosystems were compared to the respective IN drug solutions. In fact, some drugs reached the brain so efficiently, even as drug solutions, that further benefit from formulating them into nanosystems became less evident.

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Section: Fig 1 Schematic Representation Of Intranasal (In) Deliverymentioning

confidence: 99%

Section: Delivery Nanosystemsmentioning

confidence: 99%

Nanosystems in nose-to-brain drug delivery: A review of non-clinical brain targeting studies

Pires

Santos

2018

Journal of Controlled Release

148

135

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“…An optimised emulsome formulation (TO17-TW) was chosen from previous studies comprising a 3:1 ratio of PC:TG (TG ~ Triolein), a total lipid content of 30 mg and coated with Tween 80 [36,37]. The emulsomes were prepared and characterized as a lipid mixture of PC and TO, as previously described [39,40]. Briefly, 10 mgs OX were introduced into a clean, dry round bottom flask, dissolved in chloroform, and then mixed with 30 mg lipid mixture composed of PC:TG (3:1).…”

Section: Methodsmentioning

confidence: 99%

“…The formed dispersion was sonicated for 1 min (Bath sonicator model 275T, Crest Ultrasonics Carp, Trenton, NJ, USA), then extruded through 450 nm cellulose nitrate membranes, and stored at 4 °C. The size of the emulsomes has previously been found to be in the order of 101.5 ± 2.9 nm [40].…”

Section: Methodsmentioning

confidence: 99%

A Tailored Thermosensitive PLGA-PEG-PLGA/Emulsomes Composite for Enhanced Oxcarbazepine Brain Delivery via the Nasal Route

et al. 2018

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The use of nanocarrier delivery systems for direct nose to brain drug delivery shows promise for achieving increased brain drug levels as compared to simple solution systems. An example of such nanocarriers is emulsomes formed from lipid cores surrounded and stabilised by a corona of phospholipids (PC) and a coating of Tween 80, which combines the properties of both liposomes and emulsions. Oxcarbazepine (OX), an antiepileptic drug, was entrapped in emulsomes and then localized in a poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymer thermogel. The incorporation of OX emulsomes in thermogels retarded drug release and increased its residence time (MRT) in rats. The OX-emulsome and the OX-emulsome-thermogel formulations showed in vitro sustained drug release of 81.1 and 53.5%, respectively, over a period of 24 h. The pharmacokinetic studies in rats showed transport of OX to the systemic circulation after nasal administration with a higher uptake in the brain tissue in case of OX-emulsomes and highest MRT for OX-emulsomal-thermogels as compared to the IN OX-emulsomes, OX-solution and Trileptal® suspension. Histopathological examination of nasal tissues showed a mild vascular congestion and moderate inflammatory changes around congested vessels compared to saline control, but lower toxic effect than that reported in case of the drug solution.

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“…The formulation loaded into upper donor compartment is separated from the receptor medium present in the lower compartment by a semipermeable membrane. Franz-diffusion cell was used to assess the drug release properties from numerous formulations aimed for nasal application, such as thermoresponsive soluble gels [55], ion activated in situ gels [56], microparticles [57], nanostructured lipid carriers [58], gel containing microspheres [59], lipidic emulsomes [60], in situ gelling microemulsions [61] and solid lipid nanoparticles [62]. This method is advantageous over other compendial and non-compendial membrane diffusion methods particularly in case of dry powders as it allows them to hydrate slowly, and gel eventually, in humid environment conditions designed to be similar to those encountered in the nasal cavity [63].…”

Section: Membrane Diffusion Methodsmentioning

confidence: 99%

In vitro dissolution/release methods for mucosal delivery systems

et al. 2017

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Identifying lipidic emulsomes for improved oxcarbazepine brain targeting: In vitro and rat in vivo studies

Cited by 61 publications

References 55 publications

Nanosystems in nose-to-brain drug delivery: A review of non-clinical brain targeting studies

Nanosystems in nose-to-brain drug delivery: A review of non-clinical brain targeting studies

A Tailored Thermosensitive PLGA-PEG-PLGA/Emulsomes Composite for Enhanced Oxcarbazepine Brain Delivery via the Nasal Route

In vitro dissolution/release methods for mucosal delivery systems

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