Login Register Cart 0
Generic placeholder image

Pharmaceutical Nanotechnology

Editor-in-Chief

ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Unravelling Micro and Nano Vesicular System in Intranasal Drug Delivery for Epilepsy

Author(s): Sagar Salave, Dhwani Rana, Rupali Pardhe, Prajakta Bule and Derajram Benival*

Volume 10, Issue 3, 2022

Published on: 09 June, 2022

Page: [182 - 193] Pages: 12

DOI: 10.2174/2211738510666220426115340

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Epilepsy is one of the major neurological disorders, affecting about 50 million people globally. Oral, intravenous and rectal delivery systems are available for the management of epileptic seizures. However, intranasal delivery serves as beneficial for delivering antiepileptic drugs owing to the advantages it offers.

Objective: Various approaches have been developed over the years aiming to attain either a safer or faster brain delivery; a nasal delivery system proposes significant outcomes. The noninvasiveness and high vascularity contribute to the high permeability of the nasal mucosa, allowing rapid drug absorption. This review highlights some promising novel approaches to efficiently deliver anti-epileptic drugs by employing the nasal route.

Methods: The method includes a collection of data from different search engines like PubMed, ScienceDirect and SciFinder for obtaining appropriate and relevant literature regarding epilepsy, intranasal delivery of anti-epileptic agents, and novel therapeutics.

Results: The present review underlines the majority of work related to intranasal delivery in the treatment of epilepsy, aiming to draw the attention of the researchers towards the easiest and most efficient ways of formulation for the delivery of anti-epileptics during seizures.

Conclusion: This review intends to provide an understanding of the delivery aspects of antiepileptic drugs, the benefits of intranasal delivery and the novel approaches employed for the treatment of epilepsy.

Keywords: Epilepsy, intranasal, nanomedicines, nanoparticles, drug delivery, nasal route.

« Previous Next »
Graphical Abstract

[1]
Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017; 58(4): 522-30.
[http://dx.doi.org/10.1111/epi.13670] [PMID: 28276060]
[2]
Dupuis N, Auvin S. Inflammation and epilepsy in the developing brain: Clinical and experimental evidence. CNS Neurosci Ther 2015; 21(2): 141-51.
[http://dx.doi.org/10.1111/cns.12371] [PMID: 25604829]
[3]
Hon KL, Leung AKC, Torres AR. Febrile infection-related epilepsy syndrome (FIRES): An overview of treatment and recent patents. Recent Pat Inflamm Allergy Drug Discov 2018; 12(2): 128-35.
[http://dx.doi.org/10.2174/1872213X12666180508122450] [PMID: 29745347]
[4]
Schmidt D. Drug treatment of epilepsy: Options and limitations. Epilepsy Behav 2009; 15(1): 56-65.
[http://dx.doi.org/10.1016/j.yebeh.2009.02.030] [PMID: 19236951]
[5]
Fisher RS, Ho J. Potential new methods for antiepileptic drug delivery. CNS Drugs 2002; 16(9): 579-93.
[http://dx.doi.org/10.2165/00023210-200216090-00001] [PMID: 12153331]
[6]
Mula M. New non-intravenous routes for benzodiazepines in epilepsy: A clinician perspective. CNS Drugs 2017; 31(1): 11-7.
[http://dx.doi.org/10.1007/s40263-016-0398-4] [PMID: 27943132]
[7]
Faber WM. The nasal mucosa and the subarachnoid space. Am J Anat 1937; 62(1): 121-48.
[http://dx.doi.org/10.1002/aja.1000620106]
[8]
Musumeci T, Serapide MF, Pellitteri R, et al. Oxcarbazepine free or loaded PLGA nanoparticles as effective intranasal approach to control epileptic seizures in rodents. Eur J Pharm Biopharm 2018; 133: 309-20.
[http://dx.doi.org/10.1016/j.ejpb.2018.11.002] [PMID: 30399400]
[9]
Trinka E, Höfler J, Leitinger M, Brigo F. Pharmacotherapy for status epilepticus. Drugs 2015; 75(13): 1499-521.
[http://dx.doi.org/10.1007/s40265-015-0454-2] [PMID: 26310189]
[10]
Alexander A, Saraf S. Nose-to-brain drug delivery approach: A key to easily accessing the brain for the treatment of Alzheimer’s disease. Neural Regen Res 2018; 13(12): 2102-4.
[http://dx.doi.org/10.4103/1673-5374.241458] [PMID: 30323136]
[11]
Sahay G, Alakhova DY, Kabanov AV. Endocytosis of nanomedicines. J Control Release 2010; 145(3): 182-95.
[http://dx.doi.org/10.1016/j.jconrel.2010.01.036] [PMID: 20226220]
[12]
Crowe TP, Greenlee MHW, Kanthasamy AG, Hsu WH. Mechanism of intranasal drug delivery directly to the brain. Life Sci 2018; 195: 44-52.
[http://dx.doi.org/10.1016/j.lfs.2017.12.025] [PMID: 29277310]
[13]
Djupesland PG. Nasal drug delivery devices: Characteristics and performance in a clinical perspective-a review. Drug Deliv Transl Res 2013; 3(1): 42-62.
[http://dx.doi.org/10.1007/s13346-012-0108-9] [PMID: 23316447]
[14]
Moinuddin S, Hasan Razvi S, Fazil M, Mustaneer Akmal M, Syed Moinuddin C, Shanawaz Uddin M, et al. Nasal drug delivery system: A innovative approach. Pharma Innov J 2019; 8(3): 169-77.
[15]
Dahl R, Mygind N. Anatomy, physiology and function of the nasal cavities in health and disease. Adv Drug Deliv Rev 1998; 29(1-2): 3-12.
[http://dx.doi.org/10.1016/S0169-409X(97)00058-6] [PMID: 10837577]
[16]
Kushwaha SKS, Keshari RK, Rai AK. Advances in nasal trans-mucosal drug delivery. J Appl Pharm Sci 2011; 1(7): 21-8.
[17]
Sabale AS, Kulkarni AD, Sabale AS. Nasal in situ gel: Novel approach for nasal drug delivery. J Drug Deliv Ther 2020; 10(2-s): 183-97.
[http://dx.doi.org/10.22270/jddt.v10i2-s.4029]
[18]
Upadhyay S, Parikh A, Joshi P, Upadhyay UM, Chotai NP. Intranasal drug delivery system- A glimpse to become maestro. J Appl Pharm Sci 2011; 1(3): 34-44.
[19]
Illum L. Nasal drug delivery - recent developments and future prospects. J Control Release 2012; 161(2): 254-63.
[http://dx.doi.org/10.1016/j.jconrel.2012.01.024] [PMID: 22300620]
[20]
Cornett EM, Amarasinghe SN, Angelette A, et al. VALTOCO® (Diazepam Nasal Spray) for the Acute Treatment of Intermittent Stereotypic Episodes of Frequent Seizure Activity. Neurol Int 2021; 13(1): 64-78.
[http://dx.doi.org/10.3390/neurolint13010007] [PMID: 33670456]
[21]
Rabinowicz AL, Carrazana E, Maggio ET. Improvement of intranasal drug delivery with intravail® alkylsaccharide excipient as a mucosal absorption enhancer aiding in the treatment of conditions of the central nervous system. Drugs R D 2021; 21(4): 361-9.
[http://dx.doi.org/10.1007/s40268-021-00360-5] [PMID: 34435339]
[22]
Maggio ET, Pillion DJ. High efficiency intranasal drug delivery using Intravail® alkylsaccharide absorption enhancers. Drug Deliv Transl Res 2013; 3(1): 16-25.
[http://dx.doi.org/10.1007/s13346-012-0069-z] [PMID: 25787864]
[23]
NAYZILAM® (midazolam) nasal spray. Label. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211321s000lbl.pdf
[24]
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.
[http://dx.doi.org/10.3390/pharmaceutics13020201] [PMID: 33540856]
[25]
Botner S, Sintov AC. Intranasal delivery of two benzodiazepines, midazolam and diazepam, by a microemulsion system. Pharmacol Pharm 2011; 02(03): 180-8.
[26]
Acharya SP, Pundarikakshudu K, Panchal A, Lalwani A. Development of carbamazepine transnasal microemulsion for treatment of epilepsy. Drug Deliv Transl Res 2013; 3(3): 252-9.
[http://dx.doi.org/10.1007/s13346-012-0126-7] [PMID: 25788134]
[27]
Porecha S, Pundarikakshudu AK, Upadhyay P. Development of phenytoin intranasal microemulsion for treatment of epilepsy. J Pharm Investig 2015; 45(4): 375-84.
[http://dx.doi.org/10.1007/s40005-015-0190-3]
[28]
Kaur P, Kim K. Pharmacokinetics and brain uptake of diazepam after intravenous and intranasal administration in rats and rabbits. Int J Pharm 2008; 364(1): 27-35.
[http://dx.doi.org/10.1016/j.ijpharm.2008.07.030] [PMID: 18760341]
[29]
Shende AJ, Patil RR, Devarajan PV. Microemulsion of lamotrigine for nasal delivery. Indian J Pharm Sci 2007; 69(5): 721.
[30]
Patel TB, Soni TG, Suhagia BN. Preparation and characterization of oxcarbazepine microemulsion. Egyptian Pharma J 2016; 15(3): 173.
[http://dx.doi.org/10.4103/1687-4315.197586]
[31]
Kumar A, Naik PK, Pradhan D, Ghosh G, Rath G. Mucoadhesive formulations: Innovations, merits, drawbacks, and future outlook. Pharm Dev Technol 2020; 25(7): 797-814.
[http://dx.doi.org/10.1080/10837450.2020.1753771] [PMID: 32267180]
[32]
AK TI, Shahi SR, Thube MW, et al. Spray dried nasal mucoadhesive microspheres of carbamazepine: Preparation and in-vitro/ex-vivo. evaluation. Res Pharmaceutica 2011; 1(2): 23-32.
[33]
Makwana SB, Patel VA, Parmar SJ. Development and characterization of in-situ gel for ophthalmic formulation containing ciprofloxacin hydrochloride. Results Pharma Sci 2015; 6: 1-6.
[http://dx.doi.org/10.1016/j.rinphs.2015.06.001] [PMID: 26949596]
[34]
Paul A, Fathima KM, Nair SC. Intra nasal in situ gelling system of lamotrigine using ion activated mucoadhesive polymer. Open Med Chem J 2017; 11: 222-44.
[http://dx.doi.org/10.2174/1874104501711010222] [PMID: 29399211]
[35]
Li Y, Han J, Zhang GGZ, Grant DJW, Suryanarayanan R. In situ dehydration of carbamazepine dihydrate: A novel technique to prepare amorphous anhydrous carbamazepine 2000; 5: pp. (2)257-66.
[http://dx.doi.org/10.1081/PDT-100100540]
[36]
Basu S, Bandyopadhyay AK. Development and characterization of mucoadhesive in situ nasal gel of midazolam prepared with Ficus carica mucilage. AAPS PharmSciTech 2010; 11(3): 1223-31.
[http://dx.doi.org/10.1208/s12249-010-9477-x] [PMID: 20683687]
[37]
Basu S, Bandyopadhyay AK. Characterization of mucoadhesive nasal gels containing midazolam hydrochloride prepared from Linum usitatissimum L. mucilage. Braz J Pharm Sci 2011; 47(4): 817-23.
[http://dx.doi.org/10.1590/S1984-82502011000400019]
[38]
Deshkar SS, Jadhav MS, Shirolkar SV. Development of carbamazepine nanostructured lipid carrier loaded thermosensitive gel for intranasal delivery. Adv Pharm Bull 2021; 11(1): 150-62.
[http://dx.doi.org/10.34172/apb.2021.016] [PMID: 33747862]
[39]
Rana D, Salave S, Longare S, Agarwal R, Kalia K, Benival D. Nanotherapeutics in tumour microenvironment for cancer therapy, nanosci. Nanotechnology-Asia 2021; 1(12): e080921196283.
[40]
Brown S, Kumar S, Sharma B. Intra-articular targeting of nanomaterials for the treatment of osteoarthritis. Acta Biomater 2019; 93: 239-57.
[http://dx.doi.org/10.1016/j.actbio.2019.03.010] [PMID: 30862551]
[41]
Salave S, Rana D, Benival D. Peptide functionalised nanocarriers for bone specific delivery of PTH (1-34) in osteoporosis. Current Nanomedicine 2021; 11(3): 142-8.
[42]
He X, Xue J, Shi L, et al. Recent antioxidative nanomaterials toward wound dressing and disease treatment via ROS scavenging. Materials Today Nano 2022; 17: 100149.
[http://dx.doi.org/10.1016/j.mtnano.2021.100149]
[43]
Liang G, Wang H, Shi H, et al. Recent progress in the development of upconversion nanomaterials in bioimaging and disease treatment. J Nanobiotechnology 2020; 18(1): 1-22.
[http://dx.doi.org/10.1186/s12951-019-0560-5] [PMID: 31898555]
[44]
Sims CM, Hanna SK, Heller DA, et al. Redox-active nanomaterials for nanomedicine applications. Nanoscale 2017; 9(40): 15226-51.
[http://dx.doi.org/10.1039/C7NR05429G] [PMID: 28991962]
[45]
Xu K, Liang ZC, Ding X, et al. Nanomaterials in the prevention, diagnosis, and treatment of mycobacterium tuberculosis infections. Adv Healthc Mater 2018; 7(1): 1700509.
[http://dx.doi.org/10.1002/adhm.201700509] [PMID: 28941042]
[46]
Zinatloo-Ajabshir S, Mousavi-Kamazani M. Recent advances in nanostructured Sn− Ln mixed-metal oxides as sunlight-activated nanophotocatalyst for high-efficient removal of environmental pollutants. Ceram Int 2021; 47(17): 23702-24.
[http://dx.doi.org/10.1016/j.ceramint.2021.05.155]
[47]
Mahdavi K, Zinatloo-Ajabshir S, Yousif QA, Salavati-Niasari M. Enhanced photocatalytic degradation of toxic contaminants using Dy2O3-SiO2 ceramic nanostructured materials fabricated by a new, simple and rapid sonochemical approach. Ultrason Sonochem 2022; 82: 105892.
[http://dx.doi.org/10.1016/j.ultsonch.2021.105892] [PMID: 34959201]
[48]
Pal SL, Jana U, Manna PK, Mohanta GP, Manavalan R. Nanoparticle: An overview of preparation and characterization. J Appl Pharm Sci 2011; 1(6): 228-34.
[49]
Zinaltoo AS, Taheri QN. Inverse miniemulsion method for synthesis of gelatin nanoparticles in presence of CDI/NHS as a non-toxic cross-linking system. J Nanostructures 2014; 3(4): 267-75.
[50]
Zinaltoo AS, Taheri QN. Effect of some synthetic parameters on size and polydispersity index of gelatin nanoparticles cross-linked by CDI/NHS system. J Nanostructures 2015; 2(5): 137-44.
[51]
Qazvini NT, Zinatloo S. Synthesis and characterization of gelatin nanoparticles using CDI/NHS as a non-toxic cross-linking system. J Mater Sci Mater Med 2011; 22(1): 63-9.
[http://dx.doi.org/10.1007/s10856-010-4178-2] [PMID: 21052793]
[52]
Zinatloo-Ajabshir Z, Zinatloo-Ajabshir S. Preparation, and characterization of curcumin niosomal nanoparticles via a simple and eco-friendly route. J Nanostructures 2019; 9(4): 784-90.
[53]
Nair KGS, Ramaiyan V, Sukumaran SK. Enhancement of drug permeability across blood brain barrier using nanoparticles in meningitis. Inflammopharmacology 2018; 26(3): 675-84.
[http://dx.doi.org/10.1007/s10787-018-0468-y] [PMID: 29582240]
[54]
Muniswamy VJ, Raval N, Gondaliya P, Tambe V, Kalia K, Tekade RK. ‘Dendrimer-Cationized-Albumin’ encrusted polymeric nanoparticle improves BBB penetration and anticancer activity of doxorubicin. Int J Pharm 2019; 555: 77-99.
[http://dx.doi.org/10.1016/j.ijpharm.2018.11.035] [PMID: 30448308]
[55]
Musumeci T, Bonaccorso A, Puglisi G. Epilepsy disease and nose-to-brain delivery of polymeric nanoparticles: An overview. Pharmaceutics 2019; 11(3): 118.
[http://dx.doi.org/10.3390/pharmaceutics11030118] [PMID: 30871237]
[56]
Costa C, Moreira JN, Amaral MH, Sousa Lobo JM, Silva AC. Nose-to-brain delivery of lipid-based nanosystems for epileptic seizures and anxiety crisis. J Control Release 2019; 295: 187-200.
[http://dx.doi.org/10.1016/j.jconrel.2018.12.049] [PMID: 30610952]
[57]
Singh AP, Saraf SK, Saraf SA. SLN approach for nose-to-brain delivery of alprazolam. Drug Deliv Transl Res 2012; 2(6): 498-507.
[http://dx.doi.org/10.1007/s13346-012-0110-2] [PMID: 25787328]
[58]
Gangurde PK, Ajitkumar BN, Kumar L. Lamotrigine lipid nanoparticles for effective treatment of epilepsy: A focus on brain targeting via Nasal Route. J Pharm Innov 2019; 14(2): 91-111.
[http://dx.doi.org/10.1007/s12247-018-9343-z]
[59]
Eskandari S, Varshosaz J, Minaiyan M, Tabbakhian M. Brain delivery of valproic acid via intranasal administration of nanostructured lipid carriers: In vivo pharmacodynamic studies using rat electroshock model. Int J Nanomedicine 2011; 6: 363-71.
[PMID: 21499426]
[60]
Scioli Montoto S, Sbaraglini ML, Talevi A, et al. Carbamazepine-loaded solid lipid nanoparticles and nanostructured lipid carriers: Physicochemical characterization and in vitro/in vivo evaluation. Colloids Surf B Biointerfaces 2018; 167: 73-81.
[http://dx.doi.org/10.1016/j.colsurfb.2018.03.052] [PMID: 29627680]
[61]
Abbas H, Refai H, El Sayed N. Superparamagnetic iron oxide-loaded lipid nanocarriers incorporated in thermosensitive in situ gel for magnetic brain targeting of clonazepam. J Pharm Sci 2018; 107(8): 2119-27.
[http://dx.doi.org/10.1016/j.xphs.2018.04.007] [PMID: 29665379]
[62]
Sonvico F, Cagnani A, Rossi A, et al. Formation of self-organized nanoparticles by lecithin/chitosan ionic interaction. Int J Pharm 2006; 324(1): 67-73.
[http://dx.doi.org/10.1016/j.ijpharm.2006.06.036] [PMID: 16973314]
[63]
Yousfan A, Rubio N, Natouf AH, et al. Preparation and characterisation of PHT-loaded chitosan lecithin nanoparticles for intranasal drug delivery to the brain. RSC Advances 2020; 10(48): 28992-9009.
[http://dx.doi.org/10.1039/D0RA04890A]
[64]
Ahmad N, Ahmad R, Alrasheed RA, et al. Quantification and evaluations of catechin hydrate polymeric nanoparticles used in brain targeting for the treatment of epilepsy. Pharmaceutics 2020; 12(3): 203.
[http://dx.doi.org/10.3390/pharmaceutics12030203] [PMID: 32120778]
[65]
Kaur S, Manhas P, Swami A, et al. Bioengineered PLGA-chitosan nanoparticles for brain targeted intranasal delivery of antiepileptic TRH analogues. Chem Eng J 2018; 346: 630-9.
[http://dx.doi.org/10.1016/j.cej.2018.03.176]
[66]
Lopalco A, Ali H, Denora N, Rytting E. Oxcarbazepine-loaded polymeric nanoparticles: development and permeability studies across in vitro models of the blood-brain barrier and human placental trophoblast. Int J Nanomedicine 2015; 10: 1985-96.
[PMID: 25792832]
[67]
Bonferoni MC, Rossi S, Sandri G, et al. Nanoemulsions for “nose-to-brain” drug delivery. Pharmaceutics 2019; 11(2): 1-17.
[http://dx.doi.org/10.3390/pharmaceutics11020084] [PMID: 30781585]
[68]
Chatterjee B, Gorain B, Mohananaidu K, Sengupta P, Mandal UK, Choudhury H. Targeted drug delivery to the brain via intranasal nanoemulsion: Available proof of concept and existing challenges. Int J Pharm 2019; 565: 258-68.
[http://dx.doi.org/10.1016/j.ijpharm.2019.05.032] [PMID: 31095983]
[69]
Patel RJ, Parikh RH. Intranasal delivery of topiramate nanoemulsion: Pharmacodynamic, pharmacokinetic and brain uptake studies. Int J Pharm 2020; 585: 119486.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119486] [PMID: 32502686]
[70]
Jain N, Akhter S, Jain GK, Khan ZI, Khar RK, Ahmad FJ. Antiepileptic intranasal Amiloride loaded mucoadhesive nanoemulsion: Development and safety assessment. J Biomed Nanotechnol 2011; 7(1): 142-3.
[http://dx.doi.org/10.1166/jbn.2011.1240] [PMID: 21485842]
[71]
Iqbal R, Ahmed S, Jain GK, Vohora D. Design and development of letrozole nanoemulsion: A comparative evaluation of brain targeted nanoemulsion with free letrozole against status epilepticus and neurodegeneration in mice. Int J Pharm 2019; 565: 20-32.
[http://dx.doi.org/10.1016/j.ijpharm.2019.04.076] [PMID: 31051232]
[72]
Choudhury H, Gorain B, Pandey M, et al. Recent update on nanoemulgel as topical drug delivery system. J Pharm Sci 2017; 106(7): 1736-51.
[http://dx.doi.org/10.1016/j.xphs.2017.03.042] [PMID: 28412398]
[73]
Pires PC, Santos LT, Rodrigues M, Alves G, Santos AO. Intranasal fosphenytoin: The promise of phosphate esters in nose-to-brain delivery of poorly soluble drugs. Int J Pharm 2021; 592: 120040.
[http://dx.doi.org/10.1016/j.ijpharm.2020.120040] [PMID: 33157214]
[74]
Pires PC, Peixoto D, Teixeira I, Rodrigues M, Alves G, Santos AO. Nanoemulsions and thermosensitive nanoemulgels of phenytoin and fosphenytoin for intranasal administration: Formulation development and in vitro characterization. Eur J Pharm Sci 2020; 141: 105099.
[http://dx.doi.org/10.1016/j.ejps.2019.105099] [PMID: 31672614]
[75]
El-Zaafarany GM, Soliman ME, Mansour S, et al. A tailored thermosensitive PLGA-PEG-PLGA/emulsomes composite for enhanced oxcarbazepine brain delivery via the nasal route. Pharmaceutics 2018; 10(4): 217.
[http://dx.doi.org/10.3390/pharmaceutics10040217] [PMID: 30400577]
[76]
Samia O, Hanan R, Kamal T. Carbamazepine mucoadhesive nanoemulgel (MNEG) as brain targeting delivery system via the olfactory mucosa. Drug Deliv 2012; 19(1): 58-67.
[http://dx.doi.org/10.3109/10717544.2011.644349] [PMID: 22191715]

Rights & Permissions Print Cite
Article Metrics
22
2
Wayfinder Image
Open Access Journals Promotions
© 2024 Bentham Science Publishers | Privacy Policy