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Current Drug Discovery Technologies

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ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

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General Research Article

Biopharmaceutical Potential of Selegiline Loaded Chitosan Nanoparticles in the Management of Parkinson's Disease

Author(s): Rajalakshmi Rukmangathen*, Indira Muzib Yallamalli and Prasanna Raju Yalavarthi

Volume 16, Issue 4, 2019

Page: [417 - 425] Pages: 9

DOI: 10.2174/1570163815666180418144019

Price: $65

Abstract

Background: Selegiline hydrochloride, a hydrophilic anti-Parkinson’ moiety, undergoes extensive first-pass metabolism and has low bioavailability. A process to obtain of selegiline (SH) loaded chitosan nanoparticles was attempted to circumvent the above problem, through intranasal delivery.

Methods: SH loaded polymeric nanoparticles were prepared by ionic gelation of chitosan with tripolyphosphate, and stabilized by tween 80/ poloxamer 188. The resulting nanoparticles (NPs) were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, entrapment efficiency, particle size, zeta potential and surface morphology by scanning electron microscopy. Further, they were schematically evaluated for mucoadhesive strength, in-vitro drug release, release kinetics, pharmacokinetics, catalepsy, akinesia, in-vivo lipid peroxidation, nitrite levels, glutathione, catalase enzyme levels in brain and physicochemical stability parameters.

Results: Selegiline nanoparticles (SP18) produced were in size of 63.1 nm, polydispersity index of 0.201, zeta potential of +35.2 mV, mucoadhesion of 65.4% and entrapment efficiency of 74.77%. Selegiline showed biphasic release from nanoparticles, over a period of 36 h, with Fickian diffusion controlled release profile. Maximum concentration of SH in plasma was recognized as 52.71 ng/ml at 2 h for SP18, 20.09 ng/ml at 1 h for marketed formulation, and 21.69 ng/ ml for drug solution. SH loaded NPs showed a reversive effect in catalepsy and akinesia behaviour. This effect was especially pronounced in rats receiving SH loaded CS-NPs. Significant decrease in lipid peroxidation and nitrite concentration; increase in reduced glutathione and catalase enzyme levels were obtained due to antioxidant characteristics of SH, which turned to be useful to treat Parkinson’s disease.

Conclusion: Selegiline loaded chitosan nanoparticles form an effective non-invasive drug delivery system of direct nose to brain targeting in Parkinson’s disease.

Keywords: Akinesia, catalepsy, chitosan, glutathione, ionotropic-gelation, porcine-mucin.

Graphical Abstract

[1]
George DeMaagd, Ashok Philip. Parkinson’s disease and its management. Pharm Therap 2015; 40(8): 504-32.
[2]
De Lau LM, Breteler MM. Epidemiology of Parkinson’s disease. Lancet Neurol 2006; 5: 525-35.
[3]
Dorsey ER, Constantinescu R, Thompson JP. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030 Neurol 2007; 68(3): 84-6.
[4]
Gao X, Chen H, Schwarzschild MA, Ascherio A. Use of ibuprofen and risk of Parkinson disease. Neurol 2011; 76(10): 863-9.
[5]
Howland RH. Transdermal selegiline: A novel MAOI formulation for depression. J Psychosoc Nurs Ment Health Serv 2006; 44: 9-12.
[6]
Nyholm D. Pharmacokinetic optimization in the treatment of Parkinson’s disease: an update. Clin Pharmacokinet 2006; 45: 109-36.
[7]
Lee KC, Chen JJ. Transdermal Selegiline for the treatment of major depressive disorder. Neuropsychiatr Dis Treat 2007; 3(5): 527-37.
[8]
BarbiMda S. Carvalho FC, Kiill CP, BarudHda S, Santagneli SH, Ribeiro SJ, Gremião MP. Preparation and characterization of chitosan nanoparticles for zidovudine nasal delivery. J Nanosci Nanotechnol 2015; 15(1): 865-74.
[9]
Fonseca-Santos B, Gremião MPD, Chorilli M. Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease. Int J Nanomedicine 2015; 10: 4981-5003.
[10]
Alam MI, Beg S, Samad A, et al. Strategy for effective brain drug delivery. Eur J Pharm Sci 2010; 40(5): 385-403.
[11]
Wilson B, Samanta M, Santhi K, Sampath Kumar K, Paramakrishnan N, Suresh B. Targeted delivery of tacrine into the brain with polysorbate 80-coated poly(n-butylcyanoacrylate) nanoparticles. Eur J Pharm Biopharm 2008; 70: 75-84.
[12]
HoLun Wong, Xiao Yu Wu, Reina Bendayan. Nanotechnological advances for the delivery of CNS therapeutics. Adv Drug Deliv Rev 2012; 64: 686-700.
[13]
Susana R, Ana M. Rosa da Costab, Ana Grenha. Chitosan/carrageenan nanoparticles: effect of cross-linking with tripolyphosphate and charge ratios. Carbohydr Polym 2012; 89: 282-9.
[14]
Haque S, Shadab MD, Fazil M, et al. Venlafaxine loaded chitosan NPs for brain targeting: Pharmacokinetic and pharmacodynamic evaluation. Carbohydr Polym 2012; 89: 72-9.
[15]
Fan W, Yan W, Xu Z, Ni H. Formation mechanism of monodisperse, low molecular weight chitosan nanoparticles by ionic gelation technique. Colloids Surf B Biointerfaces 2012; 90: 21-7.
[16]
Fazil M, Shadab M, Haque S, et al. Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting. Eur J Pharm Sci 2012; 47: 6-15.
[17]
Mittal D, Md S, Hasan Q, et al. Brain targeted nanoparticulate drug delivery system of rasagiline via intranasal route. Drug Deliv 2016; 23: 130-9.
[18]
Md S, Khan RA, Mustafa G, et al. Bromocriptine loaded chitosan nanoparticles intended for direct nose to brain delivery: pharmacodynamic, pharmacokinetic and scintigraphy study in mice model. Eur J Pharm Sci 2013; 48: 393-405.
[19]
Sonal S, Tushar M, Mohammad T, Razdan BK, Talegaonkar S. Appraisal of transdermal water-in-oil nanoemulgel of selegiline HCl for the effective management of Parkinson’s disease: pharmacodynamic, pharmacokinetic and biochemical investigations. AAPS PharmSciTech 2017; 1-17.
[20]
Danafar H, Schumacher U. Simple and sensitive high performance liquid chromatographic (HPLC) method for the determination of the selegiline in human plasma. Cogent Med 2016; 3(1): 1-10.
[http://dx.doi.org/10.1080/2331205]
[21]
Luthra PM, Barodia SK, Raghubir R. Antagonism of haloperidol-induced swim impairment in l-dopa and caffeine treated mice. A pre-clinical model to study Parkinson’s disease. J Neurosci Methods 2009; 178: 284-90.
[22]
Bais S, Gill NS, Kumar N. Neuroprotective effect of Juniperus communis on chlorpromazine induced Parkinson disease in animal model. Chin J Biol 2015; 1-7.
[http://dx.doi.org/10.1155/2015/542542]
[23]
Harini Chowdary V, Prasanna Raju Y, Basaveswara MVR, Jyotsna T, Vandana KR, Sundaresan CR. Potential of microemulsified entacapone drug delivery systems in the management of acute Parkinson’s disease. J Acu Diseas 2016; 5(4): 315-25.
[24]
Josephine J, Vijaya C, Wilson B. Albumin nanoparticles coated with polysorbate 80 as a novel drug carrier for the delivery of antiretroviral drug efavirenz. Int J Pharm Investig 2014; 4(3): 142-8.
[25]
Ekambaram P, Sathali AA. Formulation and evaluation of solid lipid nanoparticles of ramipril. J Young Pharm 2011; 3: 216-20.

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