Volume : 09, Issue : 05, May – 2022
Title:
28.FORMULATION, DEVELOPMENT AND BIOLOGICAL EVALUATION OF RIVASTIGMINE LOADED LIPOSOMES FOR THE TREATMENT OF ALZHEIMER’S DISEASE
Authors :
Akansha Thakur, Deepika Sahu, Girish Sahu, Kushagra Nagori, Ayushmaan Roy, Ruchi Khare Shrivastava, Kartik T. Nakhate, Mukesh Sharma*
Abstract :
Alzheimer’s disease is a chronic neurodegenerative disorder associated with progressive destruction of cholinergic neurons. Currently, there is no therapy which can reverse the progression of Alzheimer’s disease. However, some drugs like memantine, donepzil, rivastigmine etc. are used to improve the quality of life of patients with Alzheimer’s disease. Practically, it is desired to achieve and maintain high therapeutic level of anti-Alzheimer’s drug in the brain; nevertheless, it is difficult to do so due to blood brain barrier. This problem could be overcome by formulating liposomes of anti-Alzheimer’s drugs. In this background, the present investigation was aimed at formulating rivastigmine liposomes by stationary phase interdiffusion method to improve its penetration and distribution in brain. The prepared formulation showed encapsulation efficiency of about 70%. The in vivo and in vitro release profile showed sustained release of rivastigmine from the liposomes. Moreover, a significantly higher level of rivastigmine was found in the brain with liposomes as compared to its solution. Finally, the effect of rivastigmine liposomes on scopolamine-induced memory deficits was assessed by novel object recognition test. Rivastigmine liposomes showed procognitive effect for the prolonged duration (48 hr) as compared to its solution (24 hr). The results of the present study suggest that delivering rivastigmine in the brain through liposomes could be a much better approach for the management of Alzheimer’s and other neuropsychiatric diseases.
Key Words: Alzheimer’s disease, rivastigmine, liposomes, cholinergic neurons, procognitive effect
Cite This Article:
Please cite this article in press Mukesh Kumar Sharma et al, Formulation, Development And Biological Evaluation Of Rivastigmine Loaded Liposomes For The Treatment Of Alzheimer’s Disease., Indo Am. J. P. Sci, 2022; 09(5).,
Number of Downloads : 10
References:
1. Agrawal M, Ajazuddin, Tripathi DK, Saraf S, Alexandar A, Udenaes MH. Recent advancement in liposomes targeting strategies to cross blood –brain barrier (BBB) for the treatment of Alzheimer’s disease. J of Controlled Release 2017; 260.
2. Helaly El SN, Elbary AA, Kaseem MA, and Nabarawi El MA. Electrosteric stealth rivastigmine loaded liposomes for brain targeting: preparation, characterization, ex vivo, bio-distribution and in vivo pharmacokinetics studies. Drug delivery. 2017; 24(1): 692-700.
3. Bejar C, wang RH, Weinstock M. Effect of rivastigmine on scopolamine –induced memory impairement in rats. European J of pharmacology. 1999; 383.
4. Grayson B, Leger M, Piercy C, Adamson L, Harte M, Neill CJ. Assessment of disease related cognitive impairments using the novel object recognition (NOR) task in rodents. J Behavioural Brain Research. 2015; 285.
5. Alzheimer Society of Canada (2016). The risk factor of Alzheimer’s Disease (Web Page). Toronto: Alzheimer Society Canada. www.alzheimer.ca/en/About-dementia/Alzheimer-s-disease [Accessed: 2017]
6. Huang X, Cuajungco MP, Atwood CS. Cu (II) potentiation of alzheimerabeta neurotoxicity. Correlation with cell-free hydro¬gen peroxide production and metal reduction. J Biol Chem. 1999; 274 (52):37111–37116.
7. Oesterling BM, Gulati A, Joshi MD. Nanocarrier-based approaches for treatment and detection of Alzheimer’s disease. J NanosciNano¬technol. 2014; 14 (1):137–156.
8. Phapal SM, Has C, Sunthar P. Spontaneous formation of single component liposomes from a solution. Chem. Phys, lipid. 2017; 205.
9. Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010; 362 (4):329–344.
10. Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev. 2001; 81 (2):741–766.
11. www.alzaids.com/complications-associated-with-alzheimers-disease.
12. Xia P, Chen HS, Zhang D, Lipton SA. Memantine preferentially blocks extrasynaptic over synaptic NMDA receptor currents in hippocampal autapses. J Neurosci. 2010;30(33):11246–11250.
13. Yang ZZ, Zhang YQ, Wang ZZ, Wu K, Lou JN, Qi XR. Enhanced brain distribution and pharmacodynamics of rivastigmine by liposomes following intranasal administration. Int J Pharm. 2013; 452 (1-2):344-54.
14. Zhang R, Xue G, Wang S, Zhang L, Shi C, Xin X. Novel Object Recognition as a Facile Behavior Test for Evaluating Drug Effects in AβPP/PS1 Alzheimer’s Disease Mouse Model. J of Alzheimer’s Disease. 2012; 31.
15. Huang H.C, Jiang Z.C. Accumulated amyloid-beta peptide and hyperphosphorylated tau protein: relationship and links in Alzheimer’s disease, J. Alzheimers Disease. (2009) 15–27.
16. Patel MM, Goyal BR, Bhadada SV, Bhatt JS, Amin AF. Getting into the brain: approaches to enhance brain drug delivery. CNS Drugs. 2009; 23 (1):35–58.
17. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science. 2002; 297 (5580):353–356.
18. Has C, Phapal SM, Sunthar P. Rapid single-step formation of liposomes by flow assisted stationary phase interdiffusion 2018; 212:144-151.