Skip to main content
SpringerLink
Log in

Intranasal Drug Delivery of Olanzapine-Loaded Chitosan Nanoparticles

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The aim of this study was to investigate olanzapine (OZ) systemic absolute bioavailability after intranasal (i.n.) administration in vivo to conscious rabbits. Furthermore, the study investigated the potential use of chitosan nanoparticles as a delivery system to enhance the systemic bioavailability of olanzapine following intranasal administration. Olanzapine-loaded chitosan nanoparticles were prepared through ionotropic gelation of chitosan with tripolyphosphate anions and studied in terms of their size, drug loading, and in vitro release. The OZ nanoparticles were administered i.n. to rabbits, and OZ plasma concentration at predetermined time points was compared to i.n. administration of OZ in solution. The concentrations of OZ in plasma were analyzed by ultra performance liquid chromatography mass spectroscopy (UPLC/MS). OZ-loaded chitosan nanoparticles significantly (p < 0.05) enhanced systemic absorption with 51 ± 11.2% absolute bioavailability as compared to 28 ± 6.7% after i.n. administration of OZ solution. The results of the present study suggest that intranasal administration of OZ-loaded chitosan nanoparticles formulation could be an attractive modality for delivery of OZ systemically.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

REFERENCES

  1. Tollefson GD, Taylor CC. Olanzapine: preclinical and clinical profiles of a novel antipsychotic agent. CNS Drug Rev. 2000;6:303–63.

    Article  CAS  Google Scholar 

  2. Bhana N, Perry CM. Olanzapine—a review of its use in the treatment of bipolar I disorder. CNS Drugs. 2001;15:871–904.

    Article  CAS  PubMed  Google Scholar 

  3. Keck PE, McElroy SL. Clinical pharmacodynamics and pharmacokinetics of antimanic and mood-stabilizing medications. J Clin Psychiatry. 2002;63:3–11.

    CAS  PubMed  Google Scholar 

  4. Montgomery W, Treuer T, Karagianis J, Ascher-Svanum H, Harrison G. Orally disintegrating olanzapine review: effectiveness, patient preference, adherence, and other properties. Patient Prefer Adherence. 2012;6:109–25.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Seager H. Drug-delivery products and the Zydis fast-dissolving dosage form. J Pharm Pharmacol. 1998;50:375–82.

    Article  CAS  PubMed  Google Scholar 

  6. Wilson JD, Enoch MD. Estimation of drug rejection by schizophrenic in-patients with analysis of clinical factors. Br J Psychiatry. 1967;113:209–11.

    Article  CAS  PubMed  Google Scholar 

  7. Owen RR, Fischer EP, Booth BM, Cuffel BJ. Medication noncompliance and substance abuse among patients with schizophrenia. Psychiatr Serv. 1996;47:853–8.

    CAS  PubMed  Google Scholar 

  8. Vanputten T. Drug refusal in schizophrenia—causes and prescribing hints. Hosp Community Psychiatry. 1978;29:110–2.

    CAS  Google Scholar 

  9. Thomas P, Alptekin K, Gheorghe M, Mauri M, Olivares JM, Riedel M. Management of patients presenting with acute psychotic episodes of schizophrenia. CNS Drugs. 2009;23:193–212.

    Article  CAS  PubMed  Google Scholar 

  10. Bloch Y, Mendlovic S, Strupinsky S, Altshuler A, Fennig S, Ratzoni G. Injections of depot antipsychotic medications in patients suffering from schizophrenia: do they hurt? J Clin Psychiatry. 2001;62:855–9.

    Article  CAS  PubMed  Google Scholar 

  11. de Leon J, Diaz FJ, Josiassen RC, Cooper TB, Simpson GM. Weight gain during a double-blind multiclosage clozapine study. J Clin Psychopharmacol. 2007;27:22–7.

    Article  PubMed  Google Scholar 

  12. Nemeroff CB. Dosing the antipsychotic medication olanzapine. J Clin Psychiatry. 1997;58:45–9.

    Article  CAS  PubMed  Google Scholar 

  13. Kurzthaler I, Fleischhacker WW. The clinical implications of weight gain in schizophrenia. J Clin Psychiatry. 2001;62:32–7.

    CAS  PubMed  Google Scholar 

  14. Fuller MA, Shermock KM, Secic M, Grogg AL. Comparative study of the development of diabetes mellitus in patients taking risperidone and olanzapine. Pharmacotherapy. 2003;23:1037–43.

    Article  CAS  PubMed  Google Scholar 

  15. Yood MU, DeLorenze GN, Quesenberry CP, Jr., Oliveria SA, Tsai A-L, Kim E, et al. Association between second-generation antipsychotics and newly diagnosed treated diabetes mellitus: does the effect differ by dose? Bmc Psychiatry. 2011; 11: 197.

  16. Simon V, van Winkel R, De Hert M. Are weight gain and metabolic side effects of atypical antipsychotics dose dependent? A literature review. J Clin Psychiatry. 2009;70:1041–50.

    Article  CAS  PubMed  Google Scholar 

  17. Al-Ghananeem AM, Traboulsi AA, Dittert LW, Hussain AA. Targeted brain delivery of 17b-estradiol via nasally administered water soluble prodrugs. AAPS PharmSciTech. 2002;3:E5.

    Article  PubMed  Google Scholar 

  18. Hussain AA. Intranasal drug delivery. Adv Drug Deliv Rev. 1998;29:39–49.

    Article  CAS  PubMed  Google Scholar 

  19. Turker S, Onur E, Ozer Y. Nasal route and drug delivery systems. Pharm World Sci. 2004;26:137–42.

    Article  PubMed  Google Scholar 

  20. Sonia TA, Sharma CP. Chitosan and its derivatives for drug delivery perspective. In: Jayakumar R, Prabaharan M, Muzzarelli RAA, editors. Chitosan for biomaterials I. Advances in polymer science. 243. Berlin: Springer-Verlag Berlin; 2011. p. 23–53.

  21. Sinswat P, Tengamnuay P. Enhancing effect of chitosan on nasal absorption of salmon calcitonin in rats: comparison with hydroxypropyl- and dimethyl-beta-cyclodextrins. Int J Pharm. 2003;257:15–22.

    Article  CAS  PubMed  Google Scholar 

  22. Dyer AM, Hinchcliffe M, Watts P, Castile J, Jabbal-Gill I, Nankervis R, et al. Nasal delivery of insulin using novel chitosan based formulations: a comparative study in two animal models between simple chitosan formulations and chitosan nanoparticles. Pharm Res. 2002;19:998–1008.

    Article  CAS  PubMed  Google Scholar 

  23. Yu SY, Zhao Y, Wu FL, Zhang X, Lu WL, Zhang H, et al. Nasal insulin delivery in the chitosan solution: in vitro and in vivo studies. Int J Pharm. 2004;281:11–23.

    Article  CAS  PubMed  Google Scholar 

  24. Al-Ghananeem AM, Saeed H, Florence R, Yokel RA, Malkawi AH. Intranasal drug delivery of didanosine-loaded chitosan nanoparticles for brain targeting; an attractive route against infections caused by aids viruses. J Drug Target. 2010;18:381–8.

    Article  CAS  PubMed  Google Scholar 

  25. Al-Ghananeem AM, Malkawi AH, Crooks PA. Bioavailability of Delta(9)-tetrahydrocannabinol following intranasal administration of a mucoadhesive gel spray delivery system in conscious rabbits. Drug Dev Ind Pharm. 2011;37:329–34.

    Article  CAS  PubMed  Google Scholar 

  26. Hinchcliffe M, Jabbal-Gill I, Smith A. Effect of chitosan on the intranasal absorption of salmon calcitonin in sheep. J Pharm Pharmacol. 2005;57:681–7.

    Article  CAS  PubMed  Google Scholar 

  27. Patil S, Babbar A, Mathur R, Mishra A, Sawant K. Mucoadhesive chitosan microspheres of carvedilol for nasal administration. J Drug Target. 2010;18:321–31.

    Article  CAS  PubMed  Google Scholar 

  28. England RJA, Homer JJ, Knight LC, Ell SR. Nasal pH measurement: a reliable and repeatable parameter. Clin Otolaryngol. 1999;24:67–8.

    Article  CAS  PubMed  Google Scholar 

  29. Dragan ES, Mihai M, Schwarz S. Complex nanoparticles based on chitosan and ionic/nonionic strong polyanions: formation, stability, and application. ACS Appl Mater Interfaces. 2009;1:1231–40.

    Article  CAS  PubMed  Google Scholar 

  30. Nielsen MKK, Johansen SS. Determination of olanzapine in whole blood using simple protein precipitation and liquid chromatography-tandem mass spectrometry. J Anal Toxicol. 2009;33:212–7.

    Article  CAS  PubMed  Google Scholar 

  31. Portero A, Remunan-Lopez C, Vila-Jato JL. Effect of chitosan and chitosan glutamate enhancing the dissolution properties of the poorly water soluble drug nifedipine. Int J Pharm. 1998;175:75–84.

    Article  CAS  Google Scholar 

  32. Illum L. Chitosan and its use as a pharmaceutical excipient. Pharm Res. 1998;15:1326–31.

    Article  CAS  PubMed  Google Scholar 

  33. Kumar M, Misra A, Mishra AK, Mishra P, Pathak K. Mucoadhesive nanoemulsion-based intranasal drug delivery system of olanzapine for brain targeting. J Drug Target. 2008;16:806–14.

    Article  CAS  PubMed  Google Scholar 

  34. He P, Davis SS, Illum L. In vitro evaluation of the mucoadhesive properties of chitosan microspheres. Int J Pharm. 1998;166:75–88.

    Article  CAS  Google Scholar 

  35. Illum L, Jabbal-Gill I, Hinchcliffe M, Fisher AN, Davis SS. Chitosan as a novel nasal delivery system for vaccines. Adv Drug Deliv Rev. 2001;51:81–96.

    Article  CAS  PubMed  Google Scholar 

  36. Markowitz JS, DeVane CL, Malcolm RJ, Gefroh HA, Wang JS, Zhu HF, et al. Pharmacokinetics of olanzapine after single-dose oral administration of standard tablet versus normal and sublingual administration of an orally disintegrating tablet in normal volunteers. J Clin Pharmacol. 2006;46:164–71.

    Article  CAS  PubMed  Google Scholar 

  37. Mayor SH, Illum L. Investigation of the effect of anaesthesia on nasal absorption of insulin in rats. Int J Pharm. 1997;149:123–9.

    Article  CAS  Google Scholar 

  38. Salama HA, Mahmoud AA, Kamel AO, Hady MA, Awad GAS. Brain delivery of olanzapine by intranasal administration of transfersomal vesicles. J Liposome Res. 2012;22:336–45.

    Article  CAS  PubMed  Google Scholar 

  39. Abdelbary GA, Tadros MI. Brain targeting of olanzapine via intranasal delivery of core-shell difunctional block copolymer mixed nanomicellar carriers: in vitro characterization, ex vivo estimation of nasal toxicity and in vivo biodistribution studies. Int J Pharm. 2013;452:300–10.

    Article  CAS  PubMed  Google Scholar 

  40. Gizurarson S. The relevance of nasal physiology to the design of drug absorption studies. Adv Drug Deliv Rev. 1993;11:329–47.

    Article  CAS  Google Scholar 

  41. Dondeti P, Zia HS, Needham TE. In-vivo evaluation of spray formulations of human insulin for nasal delivery. Int J Pharm. 1995;122:91–105.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Pharmacy, Sullivan University, 2100 Gardiner Lane, Louisville, Kentucky, 40205, USA

    Sarah Baltzley & Abeer M. Al-Ghananeem

  2. University of British Columbia, Vancouver, Canada

    Atiquzzaman Mohammad

  3. US WorldMeds, LLC, Louisville, Kentucky, USA

    Ahmad H. Malkawi

Authors
  1. Sarah Baltzley
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Atiquzzaman Mohammad
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmad H. Malkawi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abeer M. Al-Ghananeem
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abeer M. Al-Ghananeem.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Baltzley, S., Mohammad, A., Malkawi, A.H. et al. Intranasal Drug Delivery of Olanzapine-Loaded Chitosan Nanoparticles. AAPS PharmSciTech 15, 1598–1602 (2014). https://doi.org/10.1208/s12249-014-0189-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-014-0189-5

KEY WORDS

Search

Navigation