Microemulsion-Based Media in Nose-to-Brain Drug Delivery

Nose-to-brain drug delivery has recently attracted enormous attention as an alternative to other delivery routes, including the most popular oral one. Due to the unique anatomical features of the nasal cavity, drugs administered intranasally can be delivered directly to the central nervous system. The most important advantage of this approach is the ability to avoid the blood–brain barrier surrounding the brain and blocking the entry of exogenous substances to the central nervous system.

Moreover, selective brain targeting could possibly avoid peripheral side effects of pharmacotherapy. The challenges associated with nose-to-brain drug delivery are mostly due to the small volume of the nasal cavity and insufficient drug absorption from nasal mucosa. These issues could be minimized by using a properly designed drug carrier. Microemulsions as potential drug delivery systems offer good solubilizing properties and the ability to enhance drug permeation through biological membranes. The aim of this review is to summarize the current status of the research focused on microemulsion-based systems for nose-to-brain delivery with special attention to the most extensively investigated neurological and psychiatric conditions, such as neurodegenerative diseases, epilepsy, and schizophrenia.

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or continue reading here: Froelich, A.; Osmałek, T.; Jadach, B.; Puri, V.; Michniak-Kohn, B. Microemulsion-Based Media in Nose-to-Brain Drug Delivery. Pharmaceutics 2021, 13, 201. https://doi.org/10.3390/pharmaceutics13020201

Microemulsion-based systems investigated in nose-to-brain delivery in neurodegenerative diseases

Active Component	Microemulsion Components	Drug Release/Permeation Assessment	General Conclusions
rivastigmine hydrogen tartrate	Capmul® MCM EP, Labrasol®, Transcutol® P, water, chitosan, cetyltrimethylammonium bromide	in vitro: Franz cells, cellulose acetate membrane (m.w. cut-off 12,000–14,000) ex vivo: Franz cells, goat nasal mucosa	chitosan-based microemulsion showed improved ex vivo permeation
rivastigmine hydrogen tartrate	Capmul® MCM EP, Labrasol®, Transcutol® P, water, chitosan	in vitro: Franz cells, cellulose acetate membrane in vivo: male Sprague-Dawley rats, blood and brain concentration, gamma scintigraphy visualization	addition of chitosan contributed to higher brain concentration of the drug
rivastigmine hydrogen tartrate	Capmul® MCM EP, Labrasol®, Transcutol® P, water, butter oil, fish oil	in vitro: evaluation of the protective role of ME against Amyloid Beta (1–42) oligomer induced toxicity in IMR 32 cell line	fish oil and butter oil acted as penetration enhancers through nasal mucosa, no protection in IMR 32 cell line
galantamine hydrochloride	Capmul® MCM EP, Labrasol®, Transcutol® P, water, butter oil, fish oil	ex vivo: Franz cells, goat nasal mucosa	enhancement of permeation by addition of fish and butter oils
donepezil hydrochloride	Capmul® MCM EP, Tween® 20, Transcutol® EP, water, butter oil, omega-3 fish oil	ex vivo: Franz cells, goat nasal mucosa in vitro: cell permeability studies on bEnd.3 mouse cerebral microvascular endothelial cell line	fish oil induced higher bioavailability than butter oil
tacrine	Labrafil® M 1944 CS, Cremophor®RH 40, Transcutol® P, water	in vivo: male C57BL/6 mice, intranasal administration, ventral mid brain and striatum drug concentration, behavioral tests	in scopolamine-induced amnesia model in mice the fastest recovery was reached for microemulsions
donepezil hydrochloride	castor oil, Labrasol®, Transcutol® P, propylene glycol	in vitro: Franz cells, dialysis membrane (pore size 12–14 kDa) ex vivo: Franz cells, porcine nasal mucosa	more than 32% of the drug retained in porcine nasal mucosa
huperzine A	1,2-propanediol, castor oil Cremophor® RH40, water, Pluronic F68, chitosan	in vitro: Franz cells, dialysis membrane (m.w. cut-off 6000–8000 U) in vivo: male Sprague-Dawley rats, microdialysis assay	after nasal administration both the plasma and brain concentration profiles showed the evidence of sustained and prolonged release, also higher bioavailability was observed
morin hydrate	Capmul® MCM, Cremophor® EL, PEG-400, water	in vitro: Franz cells, cellulose membranę behavioral tests	significant memory improvement in rats with streptozotocin-induced dementia
vinpocetine, piracetam	Tween® 20, oleic acid, ethanol, water, soybean lecithin—Epikuron® 200	in vivo: male Wistar rats, brain drug concentration determination, behavioral tests	increase of both pharmaceutical and pharmacological properties due to application of nanocarriers
ibuprofen	Capmul® MCM, Accenon® CC, Transcutol®, water, polycarbophil	in vitro: Franz cells with sheep mucosa in vivo: male C57BL/6 mice, striatal dopamine concentrations, behavioral tests, nasal cilitoxicity	increased dopamine levels and better motor activity due to application of ibuprofen-loaded microemulsion, no toxicity

Microemulsion-based systems investigated in nose-to-brain delivery in epilepsy

Active Component	Microemulsion Components	Drug release/Permeation Assessment	General Conclusions
clobazam	Capmul® MCM, Acconan® C6, Tween® 20, water, Carbopol 940P	ex vivo animal mucosa, in vivo gamma-scintigraphy, pharmacodynamic tests	better efficacy of mucoadhesive formulationintranasal system
lorazepam	Capmul® MCM, Nikkol PBC-34, Transcutol® P, water, gellan gum, Carbopol®	ex vivo goat nasal mucosa, pharmacodynamic tests (including behavioral ones)	faster and longer duration of action than the marketed product; better results for mucoadhesive formulation
diazepam	oleic acid, Tween® 80, propylene glycol, water, chitosan	in vivo pharmacokinetic studies, behavioral tests	enhanced brain delivery in microemulsion systems; better performance of mucoadhesive product
carbamazepine	oleic acid, Tween® 80, propylene glycol or Transcutol®, water	ex vivo sheep nasal mucosa, in vivo pharmacokinetic studies, induced convulsions in mice	seizure time reduction similar to intraperitoneal drug solution; higher drug concentration in brain tissue for Transcutol®-based microemulsion
carbamazepine	Labrafil® M1944, Cremophor®RH40, Transcutol®, water, polycarbophil	ex vivo sheep nasal mucosa, pharmacokinetic studies, gamma scintigraphy	no significant differences between microemulsion-based systems and drug solution in ex vivo study; higher concentrations in brain obtained for microemulsions; selective accumulation in brain
phenytoin	Capmul® MCM, Labrasol®, Transcutol®, water	in vivo pharmacokinetic studies, gamma scintigraphy, induced convulsions in mice	better selectivity towards brain compared to intraperitoneal administration; faster recovery after epileptic seizure