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 |