Advertisement

Emulsion-core and polyelectrolyte-shell nanocapsules: biocompatibility and neuroprotection against SH-SY5Y cells

  • Marek Piotrowski
  • Krzysztof Szczepanowicz
  • Danuta Jantas
  • Monika Leśkiewicz
  • Władysław Lasoń
  • Piotr Warszyński
Research Paper

Abstract

The emulsion-core and polyelectrolyte-coated nanocapsules, designed as water-insoluble neuroprotective drug delivery system, were synthesized using layer-by-layer saturation method. The isopropyl myristate was used as oil phase and docusate sodium salt as emulsifier. For the polyelectrolyte shell preparation, synthetic polyelectrolytes, cationic (PDADMAC, PAH, and PLL) and anionic (PGA) were used. The particle size and zeta potential of nanocapsules were characterized by the dynamic light scattering. The average size of synthesized nanocapsules ranged from ~80 to ~100 nm. Zeta potential values ranged from less than approximately −30 mV for the polyanion layers to greater than approximately +30 mV for the polycation layers. Biocompatibilities of the synthesized nanocarriers were evaluated against SH-SY5Y human neuroblastoma cells using various biochemical assays. The results obtained show that synthesized nanocapsules coated with PLL and PGA were nontoxic to SH-SY5Y cells, and they were used as nanocarriers for model neuroprotective drug (a calpain inhibitor MDL 28170). The neuroprotective action of the encapsulated MDL 28170 against hydrogen peroxide-induced oxidative stress cytotoxicity was evaluated in the same cell line. The results showed that nanoencapsulated form of MDL 28170 were biocompatible and protected SH-SY5Y cells against the H2O2 (0.5 mM/24 h)-induced damage in 20–40 times lower concentrations than those of the same drug added directly to the culture medium. These data suggest that the nanoscale carriers of neuroprotective drugs might serve as novel promising therapeutic agents for oxidative stress-related neurodegenerative processes.

Keywords

Nanoencapsulation Layer-by-layer Polyelectrolytes Cytotoxicity Calpain inhibitor-MDL 28170 Oxidative stress 

Notes

Acknowledgments

This study was co-financed by the Interdisciplinary PhD Studies: “Molecular sciences for medicine” (co-financed by the European Social Fund within the Human Capital Operational Programme); the Polish National Science Centre, grant no. DEC-2011/03/N/ST5/04808; and the Marian Smoluchowski Krakow Research Consortium, a leading National Research Centre KNOW, supported by the Ministry of Science and Higher Education.

Conflict of interest

The author reports no conflicts of interest in this work.

References

  1. Adamczak M, Hoel HJ, Gaudernack G, Barbasz J, Szczepanowicz K, Warszyński P (2012) Polyelectrolyte multilayer capsules with quantum dots for biomedical applications. Colloids Surf B Biointerfaces 90:211–216CrossRefGoogle Scholar
  2. Bazylińska U, Skrzela R, Piotrowski M, Szczepanowicz K, Warszyński P, Wilk KA (2012) Influence of dicephalic ionic surfactant interactions with oppositely charged polyelectrolyte upon the in vitro dye release from oil core nanocapsules. Bioelectrochemistry 87:147–153CrossRefGoogle Scholar
  3. Begley DJ (2004) Delivery of therapeutic agents to the central nervous system: the problems and the possibilities. Pharmacol Ther 104:29–45CrossRefGoogle Scholar
  4. Boridy S, Takahashi H, Akiyoshi K, Maysinger D (2009) The binding of pullulan modified cholesteryl nanogels to Abeta oligomers and their suppression of cytotoxicity. Biomaterials 30:5583–5591CrossRefGoogle Scholar
  5. Boulmedais F, Frisch B, Etienne O, Lavalle P, Picart C, Ogier J, Voegel J, Schaaf P, Egles C (2004) Polyelectrolyte multilayer films with pegylated polypeptides as a new type of anti-microbial protection for biomaterials. Biomaterials 25:2003–2011CrossRefGoogle Scholar
  6. Brambilla D, Le Droumaguet B, Nicolas J, Hashemi SH, Wu L, Moghimi SM, Couvreur P, Andrieux K (2011) Nanotechnologies for Alzheimer’s disease: diagnosis, therapy, and safety issues. Nanomedicine 7:521–540CrossRefGoogle Scholar
  7. Caruso F, Spasova M, Susha A, Giersig M, Caruso RA (2001) Magnetic nanocomposite particles and hollow spheres constructed by a sequential layering approach. Chem Mater 13:109–116CrossRefGoogle Scholar
  8. Czogalla A, Sikorski AF (2005) Spectrin and calpain: a ‘target’ and a ‘sniper’ in the pathology of neuronal cells. Cell Mol Life Sci 62:1913–1924CrossRefGoogle Scholar
  9. Decher G (1997) Fuzzy nanoassemblies: toward layered polymeric multicomposites. Science 277:1232–1237CrossRefGoogle Scholar
  10. Jain KK (2011) The handbook of neuroprotection. Springer, New YorkCrossRefGoogle Scholar
  11. Jantas D, Lorenc-Koci E, Kubera M, Lason W (2011) Neuroprotective effects of MAPK/ERK1/2 and calpain inhibitors on lactacystin-induced cell damage in primary cortical neurons. Neurotoxicology 32:845–856CrossRefGoogle Scholar
  12. Johnson DE (2000) Noncaspase proteases in apoptosis. Leukemia 14:1695–1703CrossRefGoogle Scholar
  13. Jokerst JV, Lobovkina T, Zare RN, Gambhir SS (2011) Nanoparticle PEGylation for imaging and therapy. Nanomedicine 6:715–728CrossRefGoogle Scholar
  14. Joshi SA, Chavhan SS, Sawant KK (2010) Rivastigmine-loaded PLGA and PBCA nanoparticles: preparation, optimization, characterization, in vitro and pharmacodynamic studies. Eur J Pharm Biopharm 76:189–199CrossRefGoogle Scholar
  15. Kabanov AV, Gendelman HE (2007) Nanomedicine in the diagnosis and therapy of neurodegenerative disorders. Prog Polym Sci 32:1054–1082CrossRefGoogle Scholar
  16. Kanwar JR, Sun X, Punj V, Sriramoju B, Mohan RR, Zhou S, Chauhan A, Kanwar RK (2012) Nanoparticles in the treatment and diagnosis of neurological disorders: untamed dragon with fire power to heal. Nanomedicine 8:399–414CrossRefGoogle Scholar
  17. Karatas H, Aktas Y, Gursoy-Ozdemir Y, Bodur E, Yemisci M, Caban S, Vural A, Pinarbasli O, Capan Y, Fernandez-Megia E, Novoa-Carballal R, Riguera R, Andrieux K, Couvreur P, Dalkara T (2009) A nanomedicine transports a peptide caspase-3 inhibitor across the blood-brain barrier and provides neuroprotection. J Neurosci 29:13761–13769CrossRefGoogle Scholar
  18. Kumar KNA, Ray SB, Nagaraja V, Raichur AM (2009) Encapsulation and release of rifampicin using poly(vinyl pyrrolidone)-poly(methacrylic acid) polyelectrolyte capsules. Mater Sci Eng C 29:2508–2513CrossRefGoogle Scholar
  19. Kwon S, Hong S, Kim J, Jung Y, Kim S, Kim H, Lee S, Jang C (2011a) The neuroprotective effects of Lonicera japonica THUNB. against hydrogen peroxide-induced apoptosis via phosphorylation of MAPKs and PI3 K/Akt in SH-SY5Y cells. Food Chem Toxicol 49:1011–1019CrossRefGoogle Scholar
  20. Kwon S, Kim J, Hong S, Jung Y, Kim H, Lee S, Jang C (2011b) Loganin protects against hydrogen peroxide-induced apoptosis by inhibiting phosphorylation of JNK, p38, and ERK 1/2 MAPKs in SH-SY5Y cells. Neurochem Int 58:533–541CrossRefGoogle Scholar
  21. Mulik RS, Monkkonen J, Juvonen RO, Mahadik KR, Paradkar AR (2012) ApoE3 mediated polymeric nanoparticles containing curcumin: apoptosis induced in vitro anticancer activity against neuroblastoma cells. Int J Pharm 437:29–41CrossRefGoogle Scholar
  22. Pardridge WM (2003) Blood-brain barrier drug targeting: the future of brain drug development. Mol Interv 3(90–105):51Google Scholar
  23. Pinto Reis C, Neufeld RJ, Ribeiro, Antonio J, Veiga F (2006) Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles. Nanomedicine 2:8–21CrossRefGoogle Scholar
  24. Ray SK, Fidan M, Nowak MW, Wilford GG, Hogan EL, Banik NL (2000) Oxidative stress and Ca2+ influx upregulate calpain and induce apoptosis in PC12 cells. Brain Res 852:326–334CrossRefGoogle Scholar
  25. Reddy M, Wu L, Kou W, Ghorpade A, Labhasetwar V (2008) Superoxide dismutase-loaded PLGA nanoparticles protect cultured human neurons under oxidative stress. Appl Biochem Biotechnol 151:565–577CrossRefGoogle Scholar
  26. Silva GA (2007) Nanotechnology approaches for drug and small molecule delivery across the blood brain barrier. Surg Neurol 67:113–116CrossRefGoogle Scholar
  27. Sukhorukov GB, Donath E, Lichtenfeld H, Knippel E, Knippel M, Budde A, Mohwald H (1998) Layer-by-layer self assembly of polyelectrolytes on colloidal particles. Colloids Surf Physicochem Eng Aspects 137:253–266CrossRefGoogle Scholar
  28. Szczepanowicz K, Dronka-Gora D, Para G, Warszynski P (2010a) Encapsulation of liquid cores by layer-by-layer adsorption of polyelectrolytes. J Microencapsul 27:198–204CrossRefGoogle Scholar
  29. Szczepanowicz K, Hoel HJ, Szyk-Warszynska L, Bielanska E, Bouzga AM, Gaudernack G, Simon C, Warszynski P (2010b) Formation of biocompatible nanocapsules with emulsion core and pegylated shell by polyelectrolyte multilayer adsorption. Langmuir 26:12592–12597CrossRefGoogle Scholar
  30. Szczepanowicz K, Podgórna K, Szyk-Warszyńska L, Warszyński P (2013) Formation of oil filled nanocapsules with silica shells modified by sequential adsorption of polyelectrolytes. Colloids Surf Physicochem Eng Aspects. doi: 10.1016/j.colsurfa.2013.01.011
  31. Thompson SN, Carrico KM, Mustafa AG, Bains M, Hall ED (2010) A pharmacological analysis of the neuroprotective efficacy of the brain- and cell-permeable calpain inhibitor MDL-28170 in the mouse controlled cortical impact traumatic brain injury model. J Neurotrauma 27:2233–2243CrossRefGoogle Scholar
  32. Williams SR, Lepene BS, Thatcher CD, Long TE (2009) Synthesis and characterization of poly(ethylene glycol)-glutathione conjugate self-assembled nanoparticles for antioxidant delivery. Biomacromolecules 10:155–161CrossRefGoogle Scholar
  33. Wilson B, Samanta MK, Santhi K, Kumar KP, Paramakrishnan N, Suresh B (2008a) Targeted delivery of tacrine into the brain with polysorbate 80-coated poly(n-butylcyanoacrylate) nanoparticles. Eur J Pharm Biopharm 70:75–84CrossRefGoogle Scholar
  34. Wilson B, Samanta MK, Santhi K, Kumar KPS, Paramakrishnan N, Suresh B (2008b) Poly(n-butylcyanoacrylate) nanoparticles coated with polysorbate 80 for the targeted delivery of rivastigmine into the brain to treat Alzheimer’s disease. Brain Res 1200:159–168CrossRefGoogle Scholar
  35. Wilson B, Samanta MK, Santhi K, Kumar KP, Ramasamy M, Suresh B (2010) Chitosan nanoparticles as a new delivery system for the anti-Alzheimer drug tacrine. Nanomedicine 6:144–152CrossRefGoogle Scholar
  36. Wischke C, Schwendeman SP (2008) Principles of encapsulating hydrophobic drugs in PLA/PLGA microparticles. Int J Pharm 364:298–327CrossRefGoogle Scholar
  37. Wong HL, Wu XY, Bendayan R (2012) Nanotechnological advances for the delivery of CNS therapeutics. Adv Drug Deliv Rev 64:686–700CrossRefGoogle Scholar
  38. Xie HR, Hu LS, Li GY (2010) SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson’s disease. Chin Med J 123:1086–1092Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Marek Piotrowski
    • 1
  • Krzysztof Szczepanowicz
    • 1
  • Danuta Jantas
    • 2
  • Monika Leśkiewicz
    • 2
  • Władysław Lasoń
    • 2
  • Piotr Warszyński
    • 1
  1. 1.Jerzy Haber Institute of Catalysis and Surface ChemistryPolish Academy of SciencesKrakówPoland
  2. 2.Institute of PharmacologyPolish Academy of SciencesKrakówPoland

Personalised recommendations