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PHARMASPIRE - Volume 11, Issue 1, January-March, 2019

Pages: 1-9
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Novel frontiers in intranasal drug delivery of nanocarriers for Parkinson’s treatment: A recent update

Author: Manoj Kumar Katual, Gurfateh Singh, S. L. Harikumar

Category: Pharmaceutics


The role of nanotechnology has emerged as novel and effective tool for the treatment of various neurobehavioral dysfunctions which were sought to be incurable in an earlier time. The overprotective nature of BBB of the human central nervous system (CNS) has made the API agents unreachable to the actual site of action in its periphery. Parkinson’s disease (PD) is 2nd most neurodegenerative disorder of the CNS, affecting 7–10 million people of worldwide as the report of WHO 2014. It occurs due to the death of dopamine-generating cells in the Substantia-nigra, a region of the midbrain. It is characterized by tremor, rigidity, bradykinesia, dementia, depression, and falls or emerges with the progression of the disease. Ropinirole HCl is a low molecular weight, highly water-soluble drug. It is rapidly absorbed from the G.I.T and mean peak plasma concentrations have been achieved within 1.5 h after oral doses. The oral bioavailability of ropinirole HCl is 50% due to extensive first-pass metabolism by the liver. Its mean plasma half-life is 5–6 h. The present study tries to enlighten the prior art related to Parkinson’s treatment and to prepare Ropinirole HCl loaded nanostructured lipid carriers (NLC) that may overcome the problem of bioavailability and bypass the blood-brain barrier by preparing the intranasal drug delivery targeted to the brain thereby decreasing the dosing frequency and increasing patient compliance. The promising results of NLC of Ropinirole formulation suggested in this review work provides a futuristic approach for achieving better therapeutic efficacy by being able to target CNS.

Keywords: Bioavailability, nanostructured lipid carriers, nano-technology, Parkinson’s disease


1. Aarsland D, Litvan I, Salmon D, Galasko D, Wentzel-Larsen T, Larsen JP. Performance on the dementia rating scale in Parkinson’s disease with dementia and dementia with Lewy bodies: Comparison with progressive supranuclear palsy and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2013;74:1215-20.

2. Willis AW, Evanoff B, Lian M, Criswell A, Racette B. Geographic and ethnic variation in Parkinson disease: A population-based study of US medicare beneficiaries. Neuroepidemiology 2010;34:143-151.

3. Esposito E. Solid lipid nanoparticles as delivery systems for bromocriptine. Pharm Res 2018;25:1521-30.

4. Bhosale V, Nilesh R. Formulation and evaluation of transdermal patches of ropinirole HCL. Res J Pharm Biol Chem Sci 2017;2:138-48.

5. Misra A, Ganesh S, Shahiwala A. Drug delivery to the central nervous system: A review. J Pharm Pharm Sci 2013;6:252-73.

6. Ferrari C. Cabergoline in the long-term therapy of hyperprolactinemic disorders. Acta Endocrinol 2012;126:489-494.

7. Forno LS, Sternberger LA, Sternberger NH. Reaction of lewy bodies with antibodies to phosphorylated and nonphosphorylated neurofilaments. Neurosci Lett 2016;64:253-8.

8. Pardeshi CV, Belgamwar VS, Tekade AR, Surana SJ. Novel surface modified polymer lipid hybrid nanoparticles as intranasal carriers for Ropinirole hydrochloride: In-vitro ex-vivo and in-vivo pharmaco-dynamic evaluation. J Mater Sci 2013;24:2101-15.

9. De la Fuente-Fernandez R, Calne DB. Evidence for environmental causation of Parkinson’s disease. Parkinsonism Relat Disord 2016;8:235-41.

10. Filloux F, Townsend J. Pre-and post-synaptic neurotoxic effects of dopamine demonstrated by intrastriatal injection. Exp Neurol 2013;119:79-88.

11. Aarsland D, Larsen JP, Tandberg E, Laake K. Predictors of nursing home placement in Parkinson’s disease: A population-based, prospective study. J Am Geriatr Soc 2010;48:938-42.

12. Dawson VL. Neurobiology of flies and mice. Science 2015;4:631-2.

13. Fornstedt B, Pileblad E, Carlsson A. In vivo autoxidation of dopamine in guinea pig striatum increases with age. J Neurochem 2010;55:655-9. 14. Fritsch T, Smyth K, Wallendal M, Hyde T, Leo G, Geldmacher D. Parkinson disease: Research update and clinical management. South Med Assoc 2012;105:650-6.

15. Garbayo E, Ansorena E, Blanco-Prieto MJ. Drug development in Parkinson’s disease: From emerging molecules to innovative drug delivery systems. Maturitas 2013;76:272-8.

16. Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 2012;119:493-501.

17. Giasson BI, Uryu K, Trojanowski JQ. Mutant and wild type human alphasynucleins assemble into elongated filaments with distinct morphologies in vitro. J Biol Chem 2012;274:7619-22.

18. Bhatt D, Ajmeri N, Mandal S, Rajesh KS. Nanoparticle: Design, characterization and evaluation for oral delivery of ropinirole hydrochloride. Elixir Pharm 2017;8:4687-4689.

19. Gibb WR. Accuracy in the clinical diagnosis of Parkinsonian syndromes. Postgrad Med J 2018;64:345-51.

20. Pardeshi CV, Rajput PV, Belgamwar VS, Tekade AR, Surana SJ. Novel surface modified solid lipid nanoparticles as intranasal carriers for ropinirole hydrochloride: Application of factorial design approach. Drug Deliv 2013;20:47-56.

21. Gjerstad MD, Wentzel-Larsen T, Aarsland D. Insomnia in Parkinson’s disease frequency and progression over time. J Neurol Neurosurg Psychiatry 2017;78:476-9.

22. Golbe LI, Langston JW. The etiology of Parkinson’s disease: New directions for research. In: Parkinson’s Disease and Movement Disorders. Baltimore, Maryland: Williams and Wilkins; 2013. p. 93-101.

23. Nasare L, Shrikant D, Shagufta A. Nasal drug delivery system: An emerging approach for brain targeting. World J Pharm Pharm Sci 2018;3:539-53.

24. Pardridge WM. Drug transport in brain via the cerebrospinal fluid. Fluids Barriers CNS 2017;8:1-7.

25. Parvas M, Parada C, Bueno D. A blood-CSF barrier function controls embryonic CSF protein composition and homeostasis during early CNS development. Dev Biol 2008;321:51-63.

26. Barbeau A. L-Dopa therapy in Parkinson’s disease. Can Med Assoc 1969;101:59-68. 27. Belluzi JD, Domino EF, May JM. A selective dopamineD2 receptor agonist, is efficacious in rat and monkey models of Parkinson’s disease. Mov Disord 2014;9:147-54.

28. Gorell JM. The risk of Parkinson’s disease with exposure to pesticides, farming, well water, and rural living. Neurology 1998;50:1346-50.

29. Shah H, Tanner CM, Bernstein AL, Fross RD, Leimpeter A, Bloch DA, et al. Formulation and comparative evaluation of transdermal patch and proniosomal gel of ropinirole. Int J Pharm Sci Nanotechnol 2016;9:3091-101.

30. Post B, Merkus MP, Haan RJ. Prognostic factors for the progression of Parkinson’s disease: A systematic review. Mov Disord 2017;22:1839-51.

31. Pursiainen V, Haapaniemi TH, Korpelainen JT. Sweating in Parkinsonian patients with wearing-off. Mov Disord 2017;828-32.

32. Hartley A, Stone JM, Heron C. Complex I inhibitors induce dose dependent apoptosis in PC12 cells relevance to Parkinson’s disease. J Neurochem 1994;63:1987-90.

33. Illum L. Nasal drug delivery: Possibilities, problems and solutions. J Control Release 2003;87:187-98.

34. Tetrud JW, Zigmond MJ. A novel formulation of selegiline for the treatment of Parkinson’sdisease. J Am Acad Neurol 2004;63:2-6.

35. Beitz JM. Parkinson’s disease: A review. Front Biosci 2014;S6:65-74.

36. Jorga KM, Ben-Sasson SA. The effect of tolcapone on the pharmacokinetics of benserazide. Eur J Neurol 2016;6:211-9.

37. Leroy E, Boyer R, Auburger G. The ubiquitin pathway in Parkinson’s disease. Nature 2018;395:451-2.

38. Katual MK, Harikumar SL. Drug delivery to CNS; various approaches for Parkinson’s disease management: An update. Int J Recent Sci Res 2016;7:9148-55.

39. Olanow CW, Tatton WG. Etiology and pathogenesis of Parkinson’s disease. Annu Rev Neurosci 1999;22:123-44.

40. Appasaheb PS. A review on intranasal drug delivery system. Int J Pharm 2013;3:333-44.

41. Goldman SM, Tanner CM. Etiology of Parkinson’s disease. Int J Pharm Sci Nanotechnol 2018;12:125-35.

42. Goldman JE, Yen SH, Chiu FC. Lewy bodies of Parkinson’s disease contain neurofilament antigens. Science 2013;221:1082-4.

43. Blasi P, Giovagnolia A, Schoubbena A, Pugliab C, Boninab F, Rossia C, et al. Lipidnanoparticles for brain targeting I. Formulation optimization. Int J Pharm 2011;419:287-95.

44. Khan RA, Mustafa G, Chuttani K, Baboota A, Sahni JK, Ali J. Bromocriptine loaded chitosan nanoparticles intended for direct nose to brain delivery: Pharmacodynamic, pharmacokinetic and scintigraphy study in mice model. Eur J Pharm Sci 2012;32:158-72.

45. Pu T, Li X, Sun Y, Ding X, Pan Y, Wang Q. Development of a prolonged-release pramipexole transdermal patch: In vitro and in vivo evaluation. Am Assoc Pharm Sci 2016;11:3254-361.

46. Huang Z, Zhai Y, Zhai G. Etiology of Parkinson’s disease. Can J Neurol Sci 2003;30:10-8.

47. Giladi N, McMahon D, Przedborski S. Motor blocks in Parkinson’s disease. Neurology 2012;42:333-9.