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Novel surface modified polymer–lipid hybrid nanoparticles as intranasal carriers for ropinirole hydrochloride: in vitro, ex vivo and in vivo pharmacodynamic evaluation

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Abstract

Here we report fabrication and evaluation of novel surface modified polymer–lipid hybrid nanoparticles (PLN) as robust carriers for intranasal delivery of ropinirole hydrochloride (ROPI HCl). Sustained release, avoidance of hepatic first pass metabolism, and improved therapeutic efficacy are the major objectives of this experiment. PLN were fabricated by emulsification-solvent diffusion technique and evaluated for physicochemical parameters, in vitro mucoadhesion, in vitro diffusion, ex vivo permeation, mucosal toxicity and stability studies. Box-Behnken experimental design approach has been employed to assess the influence of two independent variables, viz. surfactant (Pluronic F-68) and charge modifier (stearylamine) concentration on particle size, ζ-potential and entrapment efficiency of prepared PLN. Numerical optimization techniques were used for selecting optimized formulation sample, further confirmed by three dimensional response surface plots and regression equations. Results of ANOVA demonstrated the significance of suggested models. DSC and SEM analysis revealed the encapsulation of amorphous form of drug into PLN system, and spherical shape. PLN formulation had shown good retention with no severe signs of damage on integrity of nasal mucosa. Release pattern of drug-loaded sample was best fitted to zero order kinetic model with non-Fickian super case II diffusion mechanism. In vivo pharmacodynamic studies were executed to compare therapeutic efficacy of prepared nasal PLN formulation against marketed oral formulation of same drug. In summary, the PLN could be potentially used as safe and stable carrier for intranasal delivery of ROPI HCl, especially in treatment of Parkinson’s disease.

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Abbreviations

PD:

Parkinson’s disease

DA:

Dopamine

PLN:

Polymer–lipid hybrid nanoparticles

ROPI HCl:

Ropinirole hydrochloride

CNS:

Central nervous system

DSC:

Differential Scanning Calorimetry

SEM:

Scanning Electron Microscopy

CPZ:

Chlorpromazine

PDI:

Polydispersity index

EE:

Entrapment efficiency

NSES:

Nasal simulated electrolyte solution

ANOVA:

Analysis of variance

IV:

Intravenous

s.c.:

Subcutaneous

PBS:

Phosphate buffer solution

SD:

Standard deviation

SEM:

Standard error of mean

MW:

Molecular weight

References

  1. Malavolta L, Cabral FR. Peptides: important tools for the treatment of central nervous system disorders. Neuropeptides. 2011;45:309–16.

    Article  CAS  Google Scholar 

  2. Parkinson’s Disease Foundation. Available online at: http://www.pdf.org/en/parkinson_statistics. Accessed 2 Sept 2012.

  3. Fang X, Sugiyama K, Akamine S, Namba H. The stepping test and its learning process in different degrees of unilateral striatal lesions by 6-hydroxydopamine in rats. Neurosci Res. 2006;55:403–9.

    Article  CAS  Google Scholar 

  4. Salawu F, Olokoba A, Damburam A. Current management of Parkinson’s disease. Ann Afr Med. 2010;9:55–61.

    Article  CAS  Google Scholar 

  5. Hurley MJ, Jenner P. What has been learnt from study of dopamine receptors in Parkinson’s disease? Pharmacol Ther. 2006;111:715–28.

    Article  CAS  Google Scholar 

  6. Fukuzaki K, Kamenosono T, Nagata R. Effects of ropinirole on various parkinsonian models in mice, rats, and cynomolgus monkeys. Pharmacol Biochem Behav. 2000;65:503–8.

    Article  CAS  Google Scholar 

  7. Azeem A, Talegaonkar S, Negi LM, Ahmed FJ, Khar RK, Iqbal Z. Oil based nanocarrier system for transdermal delivery of ropinirole: a mechanistic, pharmacokinetic and biochemical investigation. Int J Pharm. 2012;422:436–44.

    Article  CAS  Google Scholar 

  8. De Caro V, Giandalia G, Siragusa MG, Sutera FM, Gianolla LI. New prospective in treatment of Parkinson’s disease: studies on permeation of ropinirole through buccal mucosa. Int J Pharm. 2012;429:78–83.

    Article  Google Scholar 

  9. Pardeshi CV, Belgamwar VS. 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;10:1–16.

    Google Scholar 

  10. Mistry A, Stolnik S, Illum L. Nanoparticles for direct nose-to-brain delivery of drugs. Int J Pharm. 2009;379:146–57.

    Article  CAS  Google Scholar 

  11. Pardeshi C, Rajput P, Belgamwar V, Tekade A, Patil G, Chaudhary K, Sonje A. Solid lipid based nanocarriers: an overview. Acta Pharm. 2012;62:433–72.

    Article  CAS  Google Scholar 

  12. Zhang L, Chan JM, Gu FX, Rhee JW, Wang AZ, Radovic-Moreno AF, Alexis F, Langer R, Farokhzad OC. Self-assembled lipid polymer hybrid nanoparticles: a robust drug delivery platform. ACS Nano. 2008;8:1696–702.

    Article  Google Scholar 

  13. Wong HL, Rauth AM, Bendayan R, Wu XY. In vivo evaluation of a new polymer-lipid hybrid nanoparticle (PLN) formulation of doxorubicin in a murine solid tumor model. Eur J Pharm Sci. 2007;65:300–8.

    CAS  Google Scholar 

  14. Varshosaz J, Tabbakhian M, Mohammadi MY. Formulation and optimization of solid lipid nanoparticles of buspirone HCl for enhancement of its oral bioavailability. J Liposome Res. 2010;20:286–96.

    Article  CAS  Google Scholar 

  15. Trotta M, Debernardi F, Caputo O. Preparation of solid lipid nanoparticles by a solvent emulsification–diffusion technique. Int J Pharm. 2003;257:153–60.

    Article  CAS  Google Scholar 

  16. Tan SW, Billa N, Roberts CR, Berley JC. Surfactant effects on the physical characteristics of Amphotericin B-containing nanostructured lipid carriers. Colloids Surf A. 2010;372:73–9.

    Article  CAS  Google Scholar 

  17. 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.

    Article  CAS  Google Scholar 

  18. Abdelwahed W, Degobert G, Stainmesse S, Fessi H. Freeze-drying of nanoparticles: formulation, process and storage considerations. Adv Drug Deliv Rev. 2006;58:1688–713.

    Article  CAS  Google Scholar 

  19. Pardeshi CV, Rajput PV, Belgamwar VS, Tekade AR. Formulation, optimization and evaluation of spray-dried mucoadhesive microspheres as intranasal carriers for Valsartan. J Microencapsul. 2011;29:103–14.

    Article  Google Scholar 

  20. Chalikwar SS, Mene BS, Pardeshi CV, Belgamwar VS, Surana SJ. Self-assembled, chitosan grafted PLGA nanoparticles for intranasal delivery: design, development and ex vivo characterisation. Polym Plast Technol Eng. 2013;52:368–80.

    Article  CAS  Google Scholar 

  21. Jain SA, Chauk DS, Mahajan HS, Tekade AR, Gattani SG. Formulation and evaluation of nasal mucoadhesive microspheres of Sumatriptan succinate. J Microencapsul. 2009;26:711–21.

    Article  CAS  Google Scholar 

  22. Chalikwar SS, Belgamwar VS, Talele VR, Surana SJ, Patil MU. Formulation and evaluation of Nimodipine-loaded solid lipid nanoparticles delivered via lymphatic transport system. Colloids Surf B. 2012;97:109–16.

    Article  CAS  Google Scholar 

  23. Vogel HG. Psychotropic and neurotropic activity. Drug discovery and evaluation: pharmacological assays. 2nd ed. New York: Springer; 2002. p. 577–81.

  24. Li Y, Wong HL, Shuhendlar AJ, Rauth AM, Wu XY. Molecular interactions, internal structure and drug release kinetics of rationally developed polymer-lipid hybrid nanoparticles. J Control Release. 2008;128:60–70.

    Article  CAS  Google Scholar 

  25. Heurtault B, Saulnier P, Pech B, Proust JE, Benoit JP. Physico-chemical stability of colloidal lipid particles. Biomaterials. 2003;24:4283–300.

    Article  CAS  Google Scholar 

  26. Venkateswarlu V, Manjunath K. Preparation, characterization and in vitro release kinetics of clozapine solid lipid nanoparticles. J Control Release. 2004;95:627–38.

    Article  CAS  Google Scholar 

  27. Venishetty VK, Chede R, Komuravelli R, Adepu L, Sistla R, Diwan PV. Design and evaluation of polymer coated carvedilol loaded solid lipid nanoparticles to improve the oral bioavailability: a novel strategy to avoid intraduodenal administration. Colloids Surf B. 2012;95:1–9.

    Article  CAS  Google Scholar 

  28. Mehnert W, Mader K. Solid lipid nanoparticles Production, characterization and applications. Adv Drug Deliv Rev. 2001;47:165–96.

    Article  CAS  Google Scholar 

  29. Paliwal R, Rai S, Vaidya B, Khatri K, Goyal AK, Mishra N, Mehta A, Vyas SP. Effect of lipid core material on characteristics of solid lipid nanoparticles designed for oral lymphatic delivery. Nanomedicine. 2009;5:184–91.

    Article  CAS  Google Scholar 

  30. Wang Q, Gong T, Sun X, Zhang Z. Structural characterization of novel phospholipid lipid nanoparticles for controlled drug delivery. Colloids Surf B. 2011;84:406–12.

    Article  CAS  Google Scholar 

  31. Mahajan HS, Tyagi VK, Patil RR, Dusunge SB. Thiolated xyloglucan: synthesis, characterization and evaluation as mucoadhesive in situ gelling agent. Carbohydr Polym. 2013;91:618–25.

    Article  CAS  Google Scholar 

  32. Lee PI. Kinetics of drug release from hydrogel matrices. J Control Release. 1985;2:277–88.

    Article  CAS  Google Scholar 

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Acknowledgments

Authors duly acknowledge the financial support from All India Council for Technical Education (AICTE) New Delhi, India, under Research Promotion Scheme (8023/BOR/RID/RPS-132/2009-10). The authors are also grateful to Lipoid GmbH (Ludwigshafen, Germany) for providing gratis sample of PHOSPHOLIPON ® 90G.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for content and writing of this article.

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Authors and Affiliations

  1. Department of Pharmaceutics, R. C. Patel Institute of Pharmaceutical Education and Research, Karwand Naka, Shirpur, Dhule, 425405, Maharashtra, India

    Chandrakantsing V. Pardeshi, Veena S. Belgamwar, Avinash R. Tekade & Sanjay J. Surana

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  1. Chandrakantsing V. Pardeshi
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  2. Veena S. Belgamwar
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  3. Avinash R. Tekade
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  4. Sanjay J. Surana
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Correspondence to Chandrakantsing V. Pardeshi.

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Pardeshi, C.V., Belgamwar, V.S., Tekade, A.R. et al. Novel surface modified polymer–lipid hybrid nanoparticles as intranasal carriers for ropinirole hydrochloride: in vitro, ex vivo and in vivo pharmacodynamic evaluation. J Mater Sci: Mater Med 24, 2101–2115 (2013). https://doi.org/10.1007/s10856-013-4965-7

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