Microemulsion-Based Media in Nose-to-Brain Drug Delivery
Abstract
:1. Introduction
2. Microemulsions: Structure, Properties, and Applications
2.1. Definition and Structure
2.2. Formation Process and Microemulsion Stability
2.3. Classification of Microemulsions
- Water-in-oil (W/O) with water as the dispersed phase and oil as the continuous one,
- Oil-in-water (O/W) with oil as the dispersed phase and water as the continuous one,
- Bicontinuous with water and oil forming interpenetrating three-dimensional domains without the possibility to discern internal and external phases.
2.4. Applications
3. Nasal Cavity as Drug Administration Site
3.1. Anatomy and Physiology of Nasal Cavity
3.2. Drug Delivery Pathways
3.2.1. Olfactory Pathway
3.2.2. Trigeminal Nerve Pathway
4. Transnasal Formulations in Brain Targeting
4.1. Neurodegenerative Disorders
4.2. Epilepsy
4.3. Schizophrenia
4.4. Other Applications
5. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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Active Component | Microemulsion Components | Drug Release/Permeation Assessment | General Conclusions | References |
---|---|---|---|---|
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 | [136] |
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 | [42] |
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 | [137] |
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 | [138] |
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 | [139] |
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 | [140] |
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 | [141] |
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 | [142] |
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 | [143] |
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 | [144] |
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 | [145] |
Active Component | Microemulsion Components | Drug release/Permeation Assessment | General Conclusions | References |
---|---|---|---|---|
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 | [146] |
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 | [152] |
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 | [153] |
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 | [154,155] |
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 | [156,157] |
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 | [159] |
Active Component | Microemulsion Components | Drug Release/Permeation Assessment | General Conclusions | References |
---|---|---|---|---|
olanzapine | oleic acid, Kolliphor® RH40, Transcutol®, water, polycarbophil | in vivo pharmacokinetic studies; pharmacodynamic tests; gamma scintigraphy | higher concentration in brain compared to intravenous microemulsion and intranasal solution; no peripheral distribution | [165] |
olanzapine | Labrafil® M1944CS, Cremophor® RH40, ethanol, water, HPMC K4M, poloxamer 407 | ex vivo sheep nasal mucosa; in vivo studies; gamma scintigraphy | higher permeation rate compared to NLC; lower drug concentrations in brain compared to NLC; less selective drug delivery than NLC; nasal mucosa irritation | [167] |
quetiapine | Capmul® MCM EP, Tween® 80, Transcutol® P, water, chitosan | ex vivo nasal and intestinal mucosa; in vivo pharmacokinetic studies | the highest permeation rate ex vivo and the highest drug level in brain in vivo was observed for chitosan-loaded microemulsion | [160] |
quetiapine | Capmul® MCM EP, Tween® 80, Transcutol® P, water, butter oil | ex vivo goat nasal mucosa; in vivo pharmacokinetic studies | the highest permeation rate ex vivo and drug levels in plasma were observed for butter oil-enriched microemulsion | [169] |
paliperidone | oleic acid, Cremophor® RH40, Transcutol®, water, polycarbophil | behavioral studies, pharmacokinetic in vivo studies, gamma scintigraphy | mucoadhesive microemulsion exhibited the best performance in behavioral studies and the better selectivity than intravenous formulation | [170] |
paliperidone | oleic acid, Cremophor® RH40, Labrasol®, Transcutol®, water, polycarbophil | ex vivo sheep mucosa | no significant differences between microemulsion, mucoadhesive microemulsions and drug solution | [171] |
risperidone | oleic acid, Cremophor® RH40, Labrasol®, Transcutol®, water, polycarbophil | ex vivo sheep mucosa | no significant differences between microemulsion, mucoadhesive microemulsions and drug solution | [172] |
asenapine | Capmul MCM, Tween 80, propylene glycol, water, polycarbophil | drug release with synthetic membrane, drug permeation with excised animal mucosa | no significant differences between samples with different composition in drug release study; permeation through nasal mucosa was faster for mucoadhesive formulation | [173] |
sulpiride | glyceryl monooleate/Labrafil, different surfactants and co-surfactants | drug release with synthetic membranes; drug permeation through sheep nasal mucosa; behavioral tests | the differences in drug release were related to drug solubility; the same results in behavioral tests obtained for microemulsions and intravenous formulation | [174] |
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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
Froelich A, Osmałek T, Jadach B, Puri V, Michniak-Kohn B. Microemulsion-Based Media in Nose-to-Brain Drug Delivery. Pharmaceutics. 2021; 13(2):201. https://doi.org/10.3390/pharmaceutics13020201
Chicago/Turabian StyleFroelich, Anna, Tomasz Osmałek, Barbara Jadach, Vinam Puri, and Bozena Michniak-Kohn. 2021. "Microemulsion-Based Media in Nose-to-Brain Drug Delivery" Pharmaceutics 13, no. 2: 201. https://doi.org/10.3390/pharmaceutics13020201