Nose to Brain Delivery of Galantamine Loaded Nanoparticles: In-vivo Pharmacodynamic and Biochemical Study in Mice

Author(s): Sunena, Shailendra Kumar Singh*, Dina Nath Mishra.

Journal Name: Current Drug Delivery

Volume 16 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Presence of blood brain barrier is one of the major hurdle in drug delivery to brain for the treatment of neurological diseases. Alternative and more effective drug delivery approaches have been investigated for the drug targeting to brain in therapeutic range.

Objective: The present investigation was carried out to improve the galantamine bioavailability in brain by intranasal drug delivery through thiolated chitosan nanoparticles and compared to nasal and oral delivery of its solution using pharmacodynamic activity as well as biochemical estimation.

Methods: Thiolated chitosan (modified) nanoparticles were fabricated using modified ionic gelation method and intranasal delivery is evaluated by reversal of scopolamine induced amnesia and biochemical estimation of acetylcholinesterase activity in Swiss albino mice brain. Scopolamine (0.4 mg/kg, i.p.) was used to induce amnesia. Piracetam (400mg/kg, i.p.) was used as positive control. Mice were treated with galantamine solution (4mg/kg) by oral and nasal route and formulated galantamine nanoparticles (equivalent to 4mg/kg) by intranasal administration for 7 successive days and the results were compared statistically.

Results: Intranasal delivery of galantamine loaded thiolated chitosan nanoparticles was found significant (p<0.05) as compared to oral and nasal administration of its solution, by pharmacodynamic study and biochemical estimation of acetylcholinesterase activity in Swiss albino mice brain.

Conclusion: Significant recovery in amnesia induced mice model by intranasal administration of galantamine loaded thiolated chitosan nanoparticles established the relevance of nose to brain delivery over the conventional oral therapies for the treatment of Alzheimer’s disease.

Keywords: Galantamine, nanoparticles, thiolated chitosan, acetylcholinesterase, amnesia, Alzheimer's disease (AD).

[1]
Scott, L.J.; Goa, K.L. Galantamine: A review of its use in Alzheimer’s disease. Drugs, 2000, 60, 1095-1122.
[2]
Ago, Y.; Koda, K.; Takuma, K.; Matsuda, T. Pharmacological aspects of the acetylcholinesterase inhibitor galantamine. J. Pharmacol. Sci., 2011, 116, 6-17.
[3]
Marco, L.; do Carmo Carreiras, M. Galanthamine, a natural product for the treatment of Alzheimer’s disease. Recent Pat CNS Drug Discov., 2006, 1(1), 105-111.
[4]
Farlow, M.R. Pharmacokinetic profiles of current therapies for Alzheimer’s disease: Implications for switching to galantamine. Clin. Ther., 2001, 23(1), 13-24.
[5]
Mistry, A.; Stolnik, S.; Illum, L. Nanoparticles for direct nose-to-brain delivery of drugs. Int. J. Pharm., 2009, 379, 146-157.
[6]
Girotra, P.; Singh, S.K. Chitosan: An emanating polymeric carrier for drug delivery. In: ; Thakur, V.K.; Thakur, M.K., Eds.; Handbook of Polymers for Pharmaceutical Technologies. Wiley: Scrivener Publishing LLC, 2015; pp. 33-60.
[7]
Smith, J.; Wood, E.; Dornish, M. Effect of chitosan on epithelial cell tight junctions. Pharm. Res., 2004, 21, 43-49.
[8]
Kawashima, Y.; Yamamoto, H.; Takeuchi, H.; Kuno, Y. Mucoadhesive DL- lactide/ glycolide copolymer nanospheres coated with chitosan to improve oral delivery of elcatonin. Pharm. Dev. Technol., 2000, 5, 77-85.
[9]
Bernkop-Schnurch, A.; Schwarz, V.; Steininger, S. Polymers with thiol groups: A new generation of mucoadhesive polymers. Pharm. Res., 1999, 16, 876-881.
[10]
Bernkop-Schnurch, A.; Hornof, M.D.; Guggi, D. Thiolated chitosans. Eur. J. Pharm. Biopharm., 2004, 57, 9-17.
[11]
Bernkop-Schnurch, A.; Heinrich, G.A. Development of a novel method for the preparation of submicron particles based on thiolated chitosan. Eur. J. Pharm. Biopharm., 2006, 63, 166-172.
[12]
Prabaharan, M.; Mano, J.F. Chitosan-based particles as controlled drug delivery systems. Drug Deliv., 2005, 12, 41-57.
[13]
Sunena, Mishra D.N.; Singh, S.K.; Kumar, A. Formulation and optimization of mucoadhesive galantamine loaded nanoparticles. Der. Pharm. Lett, 2016, 8(10), 206-212.
[14]
Sunena, Mishra D.N.; Singh, S.K.; Kumar, A. Comparative study of the permeation enhancing effects of chitosan and thiolated chitosan nanoparticles of galantamine through the nasal epthithelium. Inven. Rapid: Pharm. Tech, 2016, 4, 1-3.
[15]
Thirawong, N.; Nunthanid, J.; Puttipipatkhachorn, S.; Sriamornsak, P. Mucoadhesive properties of various pectins on gastrointestinal mucosa: An in vitro evaluation using texture analyser. Eur. J. Pharm. Biopharm., 2007, 67, 132-140.
[16]
Morris, R. Developments of a water maze procedure for studying spatial learning in rat. J. Neurosci. Methods, 1984, 11, 47-60.
[17]
Caine, E.D.; Weingartner, H.; Ludlow, C.L.; Cudahy, E.A.; Wehry, S. Qualitative analysis of scopolamine-induced amnesia. Psychopharmacology (Berl.), 1981, 74(1), 74-80.
[18]
Winblad, B. Piracetam: A review of pharmacological properties and clinical uses. CNS Drug Rev., 2005, 11(2), 169-182.
[19]
Ojha, R.; Sahu, A.N.; Muruganandam, A.V.; Singh, G.K.; Krishnamurthy, S. Asparagus recemosus enhances memory and protects against amnesia in rodent models. Brain Cogn., 2010, 74, 1-9.
[20]
Nagpal, K.; Singh, S.K.; Mishra, D.N. Nanoparticle mediated brain targeted delivery of gallic acid: In-vivo behavioral and biochemical studies for improved antioxidant and antidepressant-like activity. Drug Deliv., 2012, 19(8), 378-391.
[21]
Heise, G.A. Behavioral methods for measuring effects of drugs on learning and memory in animals. Med. Res. Rev., 1984, 4, 535-538.
[22]
Bartus, R.T. Evidence for direct cholinergic involvement in the scopolamine-induced amnesia in monkeys: Effects of concurrent administration of physostigmine and methylphenidate with scopolamine. Pharmacol. Biochem. Behav., 1978, 9, 833-836.
[23]
Taffe, M.A.; Weed, M.R.; Gold, L.H. Scopolamine alters rhesus monkey performance on a novel neuropsychological test battery. Brain Res. Cogn. Brain Res., 1999, 8, 203-212.
[24]
Ebert, U.; Kirch, W. Scopolamine models of dementia: Electroencephalogram findings and cognitive performance. Eur. J. Clin. Invest., 1998, 28, 944-949.
[25]
Mistry, A.; Stolnik, S.; Illum, L. Nanoparticles for direct nose-to-brain delivery of drugs. Int. J. Pharm., 2009, 379, 146-157.


Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 16
ISSUE: 1
Year: 2019
Page: [51 - 58]
Pages: 8
DOI: 10.2174/1567201815666181004094707
Price: $58

Article Metrics

PDF: 25
HTML: 5
EPUB: 2