Development and Characterization of Nasal Delivery of Selegiline Hydrochloride Loaded Nanolipid Carriers for the Management of Parkinson’s Disease

Author(s): Neeraj Mishra*, Sawarni Sharma, Rahul Deshmukh, Anoop Kumar, Ruchika Sharma.

Journal Name: Central Nervous System Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Central Nervous System Agents)

Volume 19 , Issue 1 , 2019

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Graphical Abstract:


Abstract:

Introduction: Parkinson’s Disease (PD) is one of the most common age-related neurodegenerative disorders which is marked with the loss of dopaminergic neurons. The present study performed on the nose to brain delivery of selegiline hydrochloride loaded nano lipid carrier, suggests that the nasal route is a good mean of targeting the drug directly into the brain.

Methods and Materials: Nanostructured lipid carriers were prepared by using hot homogenization. Selegiline hydrochloride loaded NLCs and rotenone treatment were given at a dose of 10 mg/kg administered from 14th day to 28th day. Behavioral parameters were determined at 7th, 14th, 21st and 28th day. On the 28th day, animals were sacrificed for biochemical estimation.

Results: The optimized drug loaded NLC formulation has shown 93±5.25% entrapment efficiency and 51.96% loading capacity. Optimized NLCs formulation has shown 70% release within 10 hours and after that, the release of the drug is sustained up to 22 hours (97%). Pharmacological action of the drug was found to restore the behavioral parameters in rotenone-induced rats.

Conclusion: Nano Lipid Carrier (NLCs) therapeutics has emerged as a prominent method for the treatment of Parkinson’s Disease (PD) as it offers targeted delivery and enhances the therapeutic efficacy of neurotherapeutics. It is concluded from the studies that, Selegiline HCl loaded nano lipid carrier which was administered through nasal route has the potential to be used in the management therapy of Parkinson’s disease.

Keywords: Nasal delivery, parkinson's disease, rotenone, selegiline HCl, stearylamine, Nano Lipid Carrier (NLC).

[1]
Reichmann, H. View point: Etiology in Parkinson’s disease. Dual hit or spreading intoxication. J. Neurol. Sci., 2011, 310(1-2), 9-11.
[2]
Davie, C.A. A review of Parkinson’s disease. Br. Med. Bull., 2008, 86, 109-127.
[3]
Rajput, A.; Dickson, D.W.; Robinson, C.A.; Ross, O.A.; Dächsel, J.C.; Lincoln, S.J.; Cobb, S.A.; Rajput, M.L.; Farrer, M.J. Parkinsonism, Lrrk2 G2019S, and tau neuropathology. Neurology, 2006, 67(8), 1506-1508.
[4]
Dauer, W.; Przedborski, S. Parkinson’s disease: Mechanisms and models. Neuron, 2003, 39(6), 889-909.
[5]
Brennan, K.A.; Genever, R.W. Managing parkinson’s disease during surgery. BMJ, 2010, 341, 990-993.
[6]
DeMaagd, G.; Philip, A. Parkinson’s disease and its management. P&T, 2015, 40(8), 504-510.
[7]
Velázquez-Paniagua, M.; Vázquez-Álvarez, A.M.; Valverde-Aguilar, G.; Vergara-Aragón, P. Current treatments in Parkinson’s including the proposal of an innovative dopamine microimplant. Rev. Med. Hosp. Gen. (Mex.), 2016, 79, 79-87.
[8]
Rosales-Martínez, P.; García-Pinilla, S.; Arroyo-Maya, I.J.; Hernández-Sánchez, H.; Cornejo-Mazón, M. Optimization of the conditions for the elaboration of chitosan nanoparticles charged with alpha lipoic acid, ascorbic acid and alpha-tocopherol. Rev. Mex. Ing. Quim., 2017, 16(1), 321-337.
[9]
Lee, K.C.; Chen, J.J. Transdermal selegiline for the treatment of major depressive disorder. Neuropsychiatr. Dis. Treat., 2007, 3(5), 527-537.
[10]
Wecker, L.; James, S.; Copeland, N.; Pacheco, M.A. Transdermal selegiline: Targeted effects on monoamine oxidases in the brain. Biol. Psychiatry, 2003, 54, 1099-1104.
[11]
Ali, J.; Ali, M.; Baboota, S.; Sahni, J.K.; Ramassamy, C.; Dao, L. Potential of nanoparticulate drug delivery systems by intranasal administration. Curr. Pharm. Des., 2010, 16, 1644-1653.
[12]
Dahlin, M.; Jansson, B.; Björk, E. Levels of dopamine in blood and brain following nasal administration to rats. Eur. J. Pharm. Sci., 2001, 14, 75-80.
[13]
Pardeshi, C.V.; Belgamwar, V.S. Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood-brain barrier: An excellent platform for brain targeting. Expert Opin. Drug Deliv., 2013, 10, 957-972.
[14]
Carvalho, F.C.; Campos, M.L.; Peccinini, R.G.; Gremião, M.P. Nasal administration of liquid crystal precursor mucoadhesive vehicle as an alternative antiretroviral therapy. Eur. J. Pharm. Biopharm., 2013, 84, 219-227.
[15]
Singh, D.; Rashid, M.; Hallan, S.S.; Mehra, N.K.; Prakash, A.; Mishra, N. Pharmacological evaluation of nasal delivery of selegiline hydrochloride-loaded thiolated chitosan nanoparticles for the treatment of depression. Artif. Cells Nanomed. Biotechnol., 2016, 44, 865-877.
[16]
Mistry, A.; Stolnik, S.; Illum, L. Nanoparticles for direct nose-to-brain delivery of drugs. Int. J. Pharm., 2009, 379, 146-157.
[17]
Talegaonkar, S.; Mishra, P.R. Intranasal delivery: An approach to bypass the blood brain barrier. Indian J. Pharmacol., 2004, 36(3), 140-147.
[18]
Misra, A.; Ganesh, S.; Shahiwala, A.; Shah, S.P. Drug delivery to the central nervous system: A review. J. Pharm. Pharm. Sci., 2003, 6, 252-273.
[19]
Sharma, D.; Singh, M.; Kumar, P.; Vikram, V.; Mishra, N. Development and characterization of morin hydrate loaded microemulsion for the management of Alzheimer’s disease. Artif. Cells Nanomed. Biotechnol., 2017, 45, 1620-1630.
[20]
Loo, C.H.; Basri, M.; Ismail, R.; Lau, H.L.; Tejo, B.A.; Kanthimathi, M.S.; Hassan, H.A.; Choo, Y.M. Effect of compositions in nanostructured lipid carriers (NLC) on skin hydration and occlusion. Int. J. Nanomedicine, 2013, 8(1), 13-22.
[21]
Karunakar, G.; Patel, N.P.; Kamal, S.S. Nano structured lipid carrier based drug delivery system. J. Chem. Educ., 2016, 8, 627-643.
[22]
Thatipamula, R.P.; Palem, C.R.; Gannu, R.; Mudragada, S.; Yamsani, M.R. Formulation and in vitro characterization of domperidone loaded solid lipid nanoparticles and nanostructured lipid carriers. Daru, 2011, 19(1), 23-32.
[23]
Havanoor, S.M.; Manjunath, K.; Bhagawati, S.T.; Veerapur, V.P. Isradipine loaded solid lipid nanoparticles for better treatment of hypertension-preparation, characterization and in vivo evaluation. Int. J. Biopharm., 2014, 5, 218-224.
[24]
Luong, T.N.; Carlisle, H.J.; Southwell, A.; Patterson, P.H. Assessment of motor balance and coordination in mice using the balance beam. J. Vis. Exp., 2011, 10(49), 2376.
[25]
Singh, M.; Thakur, V.; Deshmukh, R.; Sharma, A.; Rathore, M.S.; Kumar, A.; Mishra, M. Development and characterization of Morin hydrate loaded micellar nanocarriers for the effective management of Alzheimer’s disease. J. Microencapsul., 2018, 35(2), 137-148.
[26]
Kulkarni, A.D.; Vanjari, Y.H.; Karan, H.; Sancheti, K.H.; Belgamwar, V.S.; Surana, S.J.; Pardeshi, C.V. Nanotechnology-mediated nose to brain drug delivery for Parkinson’s disease: A mini review. J. Drug Target., 2015, 23(9), 775-788.
[27]
Tanaka, S.; Jared, W.; Halberstadt, A.L.; Virginia, L.M.; Mark, A.; Geyer, M.A. Four factors underlying mouse behavior in an open field. Behav. Brain Res., 2012, 233(1), 1-17.
[28]
Tipple, T.E.; Rogers, L.K. Methods for the determination of plasma or tissue glutathione levels. Methods Mol. Biol., 2012, 889, 315-324.
[29]
Siddique, Y.H.; Ara, G.; Afzal, M. Estimation of lipid peroxidation induced by hydrogen peroxide in cultured human lymphocytes. Dose Response, 2012, 10(1), 1-10.
[30]
Shukla, R.; Rajani, M.; Srivastava, N.; Barthwal, M.K.; Dikshit, M. Nitrite and malondialdehyde content in cerebrospinal fluid of patients with Parkinson’s disease. Int. J. Neurosci., 2006, 116(12), 1391-1402.
[31]
Lowry, O.H.; Rosebrough, N.J.; Farr, A.L.; Randall, R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem., 1951, 193, 265-275.
[32]
Abdel Moneim, A.E. The neuroprotective effects of purslane (Portulaca oleracea) on rotenone-induced biochemical changes and apoptosis in brain of rat. CNS Neurol. Disord. Drug Targets, 2013, 12(6), 830-841.
[33]
Ahmed, E.; Abdel Moneim, A.; Mohamed, A. Dkhil.; Saleh Al-Quraishy. The potential role of Portulaca oleracea as a neuroprotective agent in rotenone-induced neurotoxicity and apoptosis in the brain of rats. Pestic. Biochem. Physiol., 2013, 105, 203-212.


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Article Details

VOLUME: 19
ISSUE: 1
Year: 2019
Page: [46 - 56]
Pages: 11
DOI: 10.2174/1871524919666181126124846
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