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Nanopartikel als Drug-Delivery-Systeme für die Ophthalmologie

Nanoparticles as drug delivery systems in ophthalmology

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Zusammenfassung

Nanopartikel sind aufgrund ihrer geringen Größe und der Vielseitigkeit der verwendeten Materialien hervorragend geeignet, um als Drug-Delivery-Systeme eingesetzt zu werden. Sie sind in der Lage, biologische Barrieren zu durchdringen, Medikamente zielgerichtet an ihren Wirkort zu bringen und dort verzögert freizusetzen. In der Onkologie schon lange im Einsatz, wird das Potenzial von Nanopartikeln zum Medikamententransport im letzten Jahrzehnt auch vermehrt in der Ophthalmologie erforscht. Damit ließen sich Hindernisse wie die schlechte Wirkstoffaufnahme bei der Gabe von Augentropfen und das Nebenwirkungsprofil bei der Anwendung von invasiven Methoden wie dem Einsetzen von Medikamentendepots in Form von Implantaten überwinden. Zu den wichtigsten untersuchten Strukturen zählen polymere Nanopartikel, Mizellen, Liposomen, „solid lipid nanoparticles“, Dendrimere und Cyclodextrine. Zusätzlich zur Zusammensetzung der eigentlichen Nanopartikel selbst können ihre Effektivität und Stabilität durch Beschichtungen verbessert werden. Die größten Herausforderungen liegen v. a. in der Langzeitstabilität, der Standardisierung bei der Herstellung und der Toxizität. Die bisherigen präklinischen und zum Teil auch klinischen Ergebnisse lassen darauf hoffen, dass ein baldiger Einsatz von Nanopartikeln zur Optimierung der okulären Wirkstoffaufnahme möglich ist.

Abstract

Nanoparticles are perfectly suited as drug delivery systems due to their size and the diversity of materials used. They are able to penetrate biological barriers, can directly deliver drugs to the target site and provide a sustained release profile. Having long been established in oncology, in the last decade research has started to take a closer look at the potential of nanoparticles for ocular drug delivery. Obstacles, such as poor delivery of drugs via eye drops and the side effects of invasive methods, such as placing implants as drug depots could be overcome. Among the most relevant investigated structures are polymeric nanoparticles, micelles, liposomes, solid lipid nanoparticles, dendrimers and cyclodextrins. Besides the composition of the nanoparticle itself, its efficacy and stability can be optimized through coatings; however, long-term stability, standardization of production and toxicity remain the major challenges. The preclinical and partly clinical results obtained so far will hopefully give impulse to the idea of applying nanoparticles for optimized ocular drug delivery in the near future.

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Literatur

  1. Wilczewska AZ et al (2012) Nanoparticles as drug delivery systems. Pharmacol Rep 64(5):1020–1037

    Article  CAS  PubMed  Google Scholar 

  2. Zhang W, Prausnitz MR, Edwards A (2004) Model of transient drug diffusion across cornea. J Control Release 99(2):241–258

    Article  CAS  PubMed  Google Scholar 

  3. Weissig V, Pettinger TK, Murdock N (2014) Nanopharmaceuticals (part I): products on the market. Int J Nanomedicine 9:4357–4373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hoffman AS (2008) The origins and evolution of „controlled“ drug delivery systems. J Control Release 132(3):153–163

    Article  CAS  PubMed  Google Scholar 

  5. Suri SS, Fenniri H, Singh B (2007) Nanotechnology-based drug delivery systems. J Occup Med Toxicol 2:16–16

    Article  PubMed  PubMed Central  Google Scholar 

  6. Nagarwal RC et al (2009) Polymeric nanoparticulate system: a potential approach for ocular drug delivery. J Control Release 136(1):2–13

    Article  CAS  PubMed  Google Scholar 

  7. Herrero-Vanrell R et al (2005) Self-assembled particles of an elastin-like polymer as vehicles for controlled drug release. J Control Release 102(1):113–122

    Article  CAS  PubMed  Google Scholar 

  8. Vauthier C et al (2003) Drug delivery to resistant tumors: the potential of poly(alkyl cyanoacrylate) nanoparticles. J Control Release 93(2):151–160

    Article  CAS  PubMed  Google Scholar 

  9. Kapoor DN et al (2015) PLGA: a unique polymer for drug delivery. Ther Deliv 6(1):41–58

    Article  CAS  PubMed  Google Scholar 

  10. Becker R et al (2012) The cost offsets and cost-effectiveness associated with pegylated drugs: a review of the literature. Expert Rev Pharmacoecon Outcomes Res 12(6):775–793

    Article  PubMed  Google Scholar 

  11. cited 2017; Available from: http://kalarx.com/pipeline/. Zugegriffen: 25.07.2017

  12. Yang H et al (2012) Hybrid dendrimer hydrogel/PLGA nanoparticle platform sustains drug delivery for one week and antiglaucoma effects for four days following one-time topical administration. ACS Nano 6(9):7595–7606

    Article  CAS  PubMed  Google Scholar 

  13. Liu S et al (2016) Prolonged ocular retention of mucoadhesive nanoparticle eye drop formulation enables treatment of eye diseases using significantly reduced dosage. Mol Pharm 13(9):2897–2905

    Article  CAS  PubMed  Google Scholar 

  14. De Campos AM, Sanchez A, Alonso MJ (2001) Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to cyclosporin A. Int J Pharm 224(1–2):159–168

    Article  PubMed  Google Scholar 

  15. Seyfoddin A, Shaw J, Al-Kassas R (2010) Solid lipid nanoparticles for ocular drug delivery. Drug Deliv 17(7):467–489

    Article  CAS  PubMed  Google Scholar 

  16. Balguri SP, Adelli GR, Majumdar S (2016) Topical ophthalmic lipid nanoparticle formulations (SLN, NLC) of indomethacin for delivery to the posterior segment ocular tissues. Eur J Pharm Biopharm 109:224–235

    Article  CAS  PubMed  Google Scholar 

  17. Gökçe EH et al (2009) Cyclosporine A‑loaded solid lipid nanoparticles: ocular tolerance and in vivo drug release in rabbit eyes. Curr Eye Res 34(11):996–1003

    Article  PubMed  Google Scholar 

  18. Liu S, Jones L, Gu FX (2012) Nanomaterials for ocular drug delivery. Macromol Biosci 12(5):608–620

    Article  CAS  PubMed  Google Scholar 

  19. Allen TM, Cullis PR (2013) Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev 65(1):36–48

    Article  CAS  PubMed  Google Scholar 

  20. Honda M et al (2013) Liposomes and nanotechnology in drug development: focus on ocular targets. Int J Nanomedicine 8:495–503

    Article  PubMed  PubMed Central  Google Scholar 

  21. Chetoni P et al (2015) Liposomes as a potential ocular delivery system of distamycin A. Int J Pharm 492(1):120–126

    Article  CAS  PubMed  Google Scholar 

  22. Zhang R et al (2010) Treatment of experimental autoimmune uveoretinitis with intravitreal injection of Tacrolimus (FK506) encapsulated in liposomes. Invest Ophthalmol Vis Sci 51(7):3575–3582

    Article  PubMed  Google Scholar 

  23. Agarwal R et al (2016) Liposomes in topical ophthalmic drug delivery: an update. Drug Deliv 23(4):1075–1091

    CAS  PubMed  Google Scholar 

  24. Bochot A et al (2002) Intravitreal delivery of oligonucleotides by sterically stabilized liposomes. Invest Ophthalmol Vis Sci 43(1):253–259

    PubMed  Google Scholar 

  25. Mehanna MM, Elmaradny HA, Samaha MW (2010) Mucoadhesive liposomes as ocular delivery system: physical, microbiological, and in vivo assessment. Drug Dev Ind Pharm 36(1):108–118

    Article  CAS  PubMed  Google Scholar 

  26. Thassu D, Chader GJ (2012) Ocular drug delivery systems: barriers and application of nanoparticulate systems. CRC Press, Boca Raton

    Book  Google Scholar 

  27. Vandamme TF, Brobeck L (2005) Poly(amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide. J Control Release 102(1):23–38

    Article  CAS  PubMed  Google Scholar 

  28. Marano RJ et al (2005) Dendrimer delivery of an anti-VEGF oligonucleotide into the eye: a long-term study into inhibition of laser-induced CNV, distribution, uptake and toxicity. Gene Ther 12(21):1544–1550

    Article  CAS  PubMed  Google Scholar 

  29. Durairaj C et al (2010) Nanosized dendritic polyguanidilyated translocators for enhanced solubility, permeability, and delivery of gatifloxacin. Invest Ophthalmol Vis Sci 51(11):5804–5816

    Article  PubMed  Google Scholar 

  30. Freudenberg K, Cramer F (1948) Die Konstitution der Schardinger-Dextrine α, β und γ. Z Naturforsch B 3b:464

    CAS  Google Scholar 

  31. Franz G, Alban S (1999) Cyclodextrine, in Pharmakognosie-Phytopharmazie. Springer, Berlin, S 337–339

    Google Scholar 

  32. Ohira A et al (2015) Topical dexamethasone gamma-cyclodextrin nanoparticle eye drops increase visual acuity and decrease macular thickness in diabetic macular oedema. Acta Ophthalmol 93(7):610–615

    Article  CAS  PubMed  Google Scholar 

  33. Herrmann A et al (2015) Means and methods for ocular drug delivery. Google Patents

  34. Gu F, Jones LJW, Liu S (2015) Mucoadhesive nanoparticle delivery system. Google Patents

  35. Jesudian GGJ, Shastri VK (2015) Nanoparticles of polymer and lipid mixture core for targeted drug delivery. Google Patents

  36. Mousa SA (2017) Ocular nanoformulation and method of use in angiogenesis-mediated disorders. Google Patents

  37. Bejjani RA et al (2005) Nanoparticles for gene delivery to retinal pigment epithelial cells. Mol Vis 11:124–132

    CAS  PubMed  Google Scholar 

  38. Adijanto J, Naash MI (2015) Nanoparticle-based Technologies for Retinal Gene Therapy. Eur J Pharm Biopharm 95(0 0):353–367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Universitäts-Augenklinik Tübingen, Elfriede-Aulhorn-Str. 7, 72076, Tübingen, Deutschland

    M. Löscher, J. Hurst, L. Strudel, M. S. Spitzer &  S. Schnichels

  2. Augenklinik des Universitätsklinikums Hamburg-Eppendorf, Hamburg, Deutschland

    M. S. Spitzer

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  1. M. Löscher
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  2. J. Hurst
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  3. L. Strudel
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  4. M. S. Spitzer
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  5. S. Schnichels
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Correspondence to S. Schnichels.

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Interessenkonflikt

M.S. Spitzer und S. Schnichels sind Miterfinder der unter [33] genannten Technologie. M. Löscher, J. Hurst und L. Strudel geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Löscher, M., Hurst, J., Strudel, L. et al. Nanopartikel als Drug-Delivery-Systeme für die Ophthalmologie. Ophthalmologe 115, 184–189 (2018). https://doi.org/10.1007/s00347-017-0596-6

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  • DOI: https://doi.org/10.1007/s00347-017-0596-6

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