Rasagiline mesylate is an irreversible MAO-B inhibitor which requires daily oral administration for treatment of Parkinson’s disease due to its short half-life. Patients with Parkinson’s disease also develop dysphagia, i.e., difficulty in swallowing. Encapsulating rasagiline in polycaprolactone microspheres can alleviate the problem of daily oral administration by prolonging drug release from polymeric microspheres for 1 month by single subcutaneous administration. Polycaprolactone shows absence of any acidic environment generation during its degradation in body which is its advantage over poly (lactic-co-glycolic) acid. Exploiting pH-based solubility of rasagiline mesylate pH changes during microencapsulation process was performed to fabricate rasagiline mesylate–loaded polycaprolactone microspheres. Particle size analysis of microspheres showed mean particle size range of 24.18–47.87 μm. Scanning electron micrographs revealed spherical non-porous particles with small pits and depressions on the surface. In vitro release studies of formulations were performed to get an idea about in vivo behavior of prepared formulations. Stereotaxic rotenone model was used to study in vivo efficacy of formulation in rats. Selected formulation significantly (p < 0.05) improved various behavioral (locomotor activity, grip strength, etc.) and biochemical (lipid peroxidation, reduced glutathione, etc.) changes. Polymeric microspheres showed robust effect on all outcomes assessed with non-significant difference between daily administration of rasagiline mesylate solution and drug-loaded polymeric microspheres administered once in a month. With prepared controlled release injectable once a month, administration is required making it an interesting and convenient approach in treatment of Parkinson’s disease with dysphagia. Patient compliant system can be achieved by exploiting this approach for future use.
Polycaprolactone (PCL) Microencapsulation Scanning electron microscopy (SEM) Stereotaxic rotenone model Oxidative stress
This is a preview of subscription content, log in to check access.
The authors are thankful to Dr. Reddy’s Laboratories, India, for providing rasagiline mesylate samples ex-gratis.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The animal activity was previously approved by the Institutional Animal Ethics Committee (IAEC, UIPS, Panjab University, Chandigarh). All ethical guidelines as per CPCSEA guidelines (Committee for Prevention, Control, and Supervision of Animal Experiments) were followed during the animal activity.
DeMaagd G, Philip A. Parkinson’s disease and its management part 1: disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis. Pharmacol Ther. 2015;40(8):504–10 532.Google Scholar
Zhou C, Huang Y, Przedborski S. Oxidative stress in Parkinson’s disease: a mechanism of pathogenic and therapeutic significance. Ann N Y Acad Sci. 2008;1147:93–104.CrossRefPubMedPubMedCentralGoogle Scholar
Fernández M, Barcia E, Fernández-Carballido A, Garcia L, Slowing K, Negro S. Controlled release of rasagiline mesylate promotes neuroprotection in a rotenone-induced advanced model of Parkinson’s disease. Int J Pharm. 2012;438(1–2):266–78.CrossRefPubMedGoogle Scholar
Chen JJ, Swope DM. Clinical pharmacology of rasagiline: a novel, second-generation propargylamine for the treatment of Parkinson disease. J Clin Pharmacol. 2005;45(8):878–94.CrossRefPubMedGoogle Scholar
Kaur M, Sharma S, Sinha VR. Polymer based microspheres of aceclofenac as sustained release parenterals for prolonged anti-inflammatory effect. Mater Sci Eng C. 2017;72:492–500.CrossRefGoogle Scholar
Srivastava S, Sinha VR. Development and evaluation of stavudine loaded injectable polymeric particulate systems. Curr Drug Deliv. 2011;8:436–47.CrossRefPubMedGoogle Scholar
Xiong N, Huang J, Zhang Z, Zhaowen, Xiong J, Liu X, et al. Stereotaxical infusion of rotenone: a reliable rodent model for Parkinson’s disease. PloS One. 2009;4(11):e7878.CrossRefPubMedPubMedCentralGoogle Scholar
Kumar P, Paddi SS, Naidu PS, Kumar A. Cyclooxygenase inhibition attenuates 3-nitropropionic acid-induced neurotoxicity in rats: possible antioxidant mechanisms. Fundam Clin Pharmacol. 2007;21:297–306.CrossRefPubMedGoogle Scholar
Datta S, Jamwal S, Deshmukh R, Kumar P. Beneficial effects of lycopene against haloperidol induced orofacial dyskinesia in rats: possible neurotransmitters and neuroinflammation modulation. Eur J Pharmacol. 2015.Google Scholar
Wahl F, Allix M, Plotkine M, Boulu RG. Neurological and behavioral outcomes of focal cerebral ischemia in rats. Stroke. 1992;23:267–72.CrossRefPubMedGoogle Scholar
Wills ED. Mechanisms of lipid peroxide formation in tissues. Role of metals and haematin proteins in the catalysis of the oxidation unsaturated fatty acids. Biochem Biophys Acta. 1965;98:238–51.CrossRefPubMedGoogle Scholar
Jollow DJ, Mitchell JR, Zampaglione N, Gillette JR. Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite. Pharmacology. 1974;11:151–69.CrossRefPubMedGoogle Scholar
Kono Y. Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys. 1978;186:189–95.CrossRefPubMedGoogle Scholar
Gornall AG, Bardawill CJ, David MM. Determination of serum proteins by means of the biuret reaction. J Biol Chem. 1949;177:751–66.PubMedGoogle Scholar
Mahboubian A, Seyyed KH, Moghadam S, Atyabi F, Dinarvand R. Preparation and in-vitro evaluation of controlled release PLGA microparticles containing triptoreline. Iran J Pharm Res. 2010;9(4):369–78.PubMedPubMedCentralGoogle Scholar
Herrmann J, Bodmeier R, Imamura K, Hishikawa N, Sawada M, Nagatsu T. Biodegradable, somatostatin acetate containing microspheres prepared by various aqueous and non-aqueous solvent evaporation methods. Eur J Pharm Biopharm. 1998;45:75–82.CrossRefPubMedGoogle Scholar
Li M, Rouaud O, Poncelet D. Microencapsulation by solvent evaporation: state of the art for process engineering approaches. Int J Pharm. 2008;363:26–39.CrossRefPubMedGoogle Scholar
Kim BK, Hwang SJ, Park JB, Park HJ. Characteristics of felodipine loaded poly(E-caprolactone) microspheres. J Microencapsul. 2005;22:193–203.CrossRefPubMedGoogle Scholar
Cenci MA, Lundbland M. Utility of 6-hydroxydopamine lesioned rats in the preclinical screening of novel treatments for Parkinson’s disease. Animal models of movement disorders. 2005; 193–208. https://doi.org/10.1016/B978-012088382-0/50016-5.
Muller T. Pharmacokinetic/pharmacodynamic evaluation of rasagiline mesylate for Parkinson’s disease. Expert Opin Drug Metab Toxicol. 2014;10(10):1423–32.CrossRefPubMedGoogle Scholar
Speiser Z, Levy R, Cohen S. Effects of N-propargyl-1-(R)aminoindan (rasagiline) in models of motor and cognition disorders. J Neural Transm. 1998;52:287–300.Google Scholar
Huang W, Chen Y, Shohami E, Weinstock M. Neuroprotective effect of rasagiline, a selective monoamine oxidase-B inhibitor, against closed head injury in the mouse. Eur J Pharmacol. 1999;366(2–3):127–35.CrossRefPubMedGoogle Scholar
Varela A, Mavroidis M, Katsimpoulas M, Sfiroera I, Kappa N, Mesa A, et al. The neuroprotective agent rasagiline mesylate attenuates cardiac remodeling after experimental myocardial infarction. ESC Heart Fail. 2017;4:331–40.CrossRefPubMedPubMedCentralGoogle Scholar