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Preparation of gamma cyclodextrin stabilized solid lipid nanoparticles (SLNS) using stearic acid–γ-cyclodextrin inclusion complex

  • Jeetendra Singh NegiEmail author
  • Pronobesh Chattopadhyay
  • Ashok Kumar Sharma
  • Veerma Ram
Original Article

Abstract

The inclusion complexation behaviour of higher chain fatty acid, stearic acid (SA) with gamma cyclodextrin has been investigated. The inclusion complex was characterized by FT-IR, 1H NMR, 2D NMR, XRD and DSC techniques. The results showed that the SA molecule was entrapped inside the gamma cyclodextrin cavity. Further, inclusion complex was treated with lopinavir at 85 °C and emulsified with hot water at 85 °C. The resulted nanoemulsion was cooled down to form solid lipid nanoparticles (SLNs) stabilized with gamma cyclodextrin. Prepared SLNs were having average particle size of 212.5 ± 4.8 nm, zeta potential of −19.7 ± 0.66 mV and drug loading of 57.54 ± 0.62 %. The surface characteristics of SLNs were also observed with transmission electron microscopy and atomic force microscopy. Results indicate that inclusion complex of SA and gamma cyclodextrin can be used for SLNs preparation.

Keywords

Solid lipid nanoparticles (SLNs) Stearic acid–γ-cyclodextrin inclusion complex Gamma cyclodextrin 

Notes

Acknowledgments

Authors are grateful to AIIMS Dehli for providing TEM facility, Wadia Institute of himalayan geology, Dehradun for XRD facility, Sophisticated Analytical Instrumentation Facilities (SAIF), Panjab Univeristy for providing NMR facilities and SMITA lab, IIT Dehli for providing particle size, AFM and DSC facilities. Authors also would like to acknowledge Uttarakhand technical University, Dehradun for their kind support.

Supplementary material

10847_2014_415_MOESM1_ESM.docx (79 kb)
Supplementary material 1 (DOCX 78 kb)

References

  1. 1.
    Loftsson, T., Duchene, D.: Cyclodextrins and their pharmaceutical applications. Int. J. Pharm. 329, 1–11 (2007)CrossRefGoogle Scholar
  2. 2.
    Rowe, R.C., Sheskey, P.J., Weller, P.J., Quinn, M.E.: Handbook of Pharmaceutical Excipients, 6th edn. The Pharmaceutical Press, London (2009)Google Scholar
  3. 3.
    Sun, T., Li, Y., Zhang, H., Li, J., Xin, F., Kong, L., Hao, A.: pH-reversible vesicles based on the “supramolecular amphiphilies” formed by cyclodextrin and anthraquinone derivate. Colloid Surf. A 375, 87–96 (2011)CrossRefGoogle Scholar
  4. 4.
    Messner, M., Kukov, S.V., Brewster, M.E., Jansook, P., Loftsson, T.: Self-assembly of cyclodextrin complexes: aggregation of hydrocortisone/cyclodextrin complexes. Int. J. Pharm. 407, 174–183 (2011)CrossRefGoogle Scholar
  5. 5.
    Paliwal, R., Rai, S., Vaidya, B., Khatri, K., Goyal, A.K., Mishra, N., Mehta, A., Vyas, S.P.: Effect of lipid core material on characteristics of solid lipid nanoparticles designed for oral lymphatic delivery. Nanomed. Nanotechnol. 5, 184–191 (2009)CrossRefGoogle Scholar
  6. 6.
    Noriega-Pelaez, E.K., Mendoza-Munoz, N., Ganem-Quintanar, A., Quintanar-Guerrero, D.: Optimization of the emulsification and solvent displacement method for the preparation of solid lipid nanoparticles. Drug Dev. Ind. Pharm. 37, 160–166 (2011)CrossRefGoogle Scholar
  7. 7.
    Agarwal, S., Pal, D., Mitra, A.K.: Both P-gp and MRP2 mediate transport of Lopinavir, a protease inhibitor. Int. J. Pharm. 339, 139–147 (2007)CrossRefGoogle Scholar
  8. 8.
    Alex, M.R.A., Chacko, A.J., Josea, S., Souto, E.B.: Lopinavir loaded solid lipid nanoparticles (SLN) for intestinal lymphatic targeting. Eur. J. Pharm. Sci. 42, 11–18 (2011)CrossRefGoogle Scholar
  9. 9.
    Negi, J.S., Chattopadhyay, P., Sharma, A.K., Ram, V.: Development of solid lipid nanoparticles (SLNs) of lopinavir using hot self nano-emulsification (SNE) technique. Eur. J. Pharm. Sci. 48, 231–239 (2013)CrossRefGoogle Scholar
  10. 10.
    Miecznik, P., Kaczmarek, M.: Ultrasonic investigations of inclusion complexation of cyclodextrin by iodide ions in pseudo-binary aqueous system. J. Mol. Liq. 133, 120–124 (2007)CrossRefGoogle Scholar
  11. 11.
    Chen, W., Yang, L., Ma, S., Yang, X., Fan, B., Lin, J.: Crassicauline A/β-cyclodextrin host-guest system: preparation, characterization, inclusion mode solubilisation and stability. Carbohyd. Polym. 84, 1321–1328 (2011)CrossRefGoogle Scholar
  12. 12.
    Trott, O., Olson, A.J.: AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. J. Comput. Chem. 31, 455–461 (2010)Google Scholar
  13. 13.
    Srinivasan, K., Stalin, T., Sivakumar, K.: Spectral and electrochemical study of host–guest inclusion complex between 2,4-dinitrophenol and β-cyclodextrin. Spectrochim. Acta A 94, 89–100 (2012)CrossRefGoogle Scholar
  14. 14.
    Varshosaz, J., Ghaffari, S., Khoshayand, M.R., Atyabi, F., Dehkordi, A.J., Kobafard, F.: Optimization of freeze-drying condition of amikacin solid lipid nanoparticles using D-optimal experimental design. Pharm. Dev. Technol. 17, 187–194 (2012)CrossRefGoogle Scholar
  15. 15.
    Kang, J.H., Oh, D.H., Oh, Y., Yong, C.S., Choi, H.: Effects of solid carriers on the crystalline properties, dissolution and bioavailability of flurbiprofen in solid self-nanoemulsifying drug delivery system (solid SNEDDS). Eur. J. Pharm. Biopharm. 80, 289–297 (2012)CrossRefGoogle Scholar
  16. 16.
    Souza, L.G., Silva, E.J., Martins, A.L.L., Mota, M.F., Braga, R.C., Lima, E.M., Valadares, M.C., Taveira, S.F., Marreto, R.N.: Development of topotecan loaded lipid nanoparticles for chemical stabilization and prolonged release. Eur. J. Pharm. Biopharm. 79, 189–196 (2011)CrossRefGoogle Scholar
  17. 17.
    Donato, E.M., Dias, C.L., Rossi, R.C., Valente, R.S., Froehlich, P.E., Bergold, A.M.: LC method for studies on the stability of lopinavir and ritonavir in soft gelatin capsules. Chromatographia 63, 437–443 (2006)CrossRefGoogle Scholar
  18. 18.
    Chen, H., Chang, X., Du, D., Liu, W., Liu, J., Weng, T., Yang, Y., Xu, H., Yang, X.: Podophyllotoxin loaded solid lipid nanoparticles for epidermal targeting. J. Control Release 110, 296–306 (2006)CrossRefGoogle Scholar
  19. 19.
    Shah, M., Chuttani, K., Mishra, A.K., Pathak, K.: Oral solid compritol 888 ATO nanosuspension of simvastatin: optimization and biodistribution studies. Drug Dev. Ind. Pharm. 37, 526–537 (2011)CrossRefGoogle Scholar
  20. 20.
    Wu, H., Liang, H., Yuan, Q., Wang, T., Yan, X.: Preparation and stability investigation of the inclusion complex of sulforaphane with hydroxypropyl-β-cyclodextrin. Carbohyd. Polym. 82, 613–617 (2010)CrossRefGoogle Scholar
  21. 21.
    Yuan, C., Jin, Z., Xu, X.: Inclusion complex of astaxanthin with hydroxypropyl-β-cyclodextrin: UV, FTIR, 1H NMR and molecular modelling studies. Carbohyd. Polym. 89, 492–496 (2012)CrossRefGoogle Scholar
  22. 22.
    Ensikat, H.J., Boese, M., Mader, W., Barthlott, W., Koch, K.: Crystallinity of plant Epicuticular waxes: electron and X-ray diffraction studies. Chem. Phys. Lipids 144, 45–59 (2006)CrossRefGoogle Scholar
  23. 23.
    Hamdi, H., Abderrahim, R., Meganem, F.: Spectroscopic studies of inclusion complex of β-cyclodextrin and benzidine diammonium dipicrate. Spectrochim. Acta A 75, 32–36 (2010)CrossRefGoogle Scholar
  24. 24.
    1H NMR spectroscopy of fatty acids and their derivatives. http://lipidlibrary.aocs.org/nmr/1NMRsat/index.html/. Accessed 20 Sept 2013
  25. 25.
    Gonil, P., Sajomsang, W., Ruktanonchai, U.R., Pimpha, N., Sramala, I., Nuchuchua, O., Saesoo, S., Chaleawlert-umpon, S., Puttipipatkhachorn, S.: Novel quaternized chitosan containing β-cyclodextrin moiety: synthesis, characterization and antimicrobial activity. Carbohyd. Polym. 83, 905–913 (2011)CrossRefGoogle Scholar
  26. 26.
    Ruz, V., Froeyen, M., Busson, R., Gonzalex, M.M., Baudemprez, L., Mooter, G.V.D.: Characterization and molecular modelling of the inclusion complexes of 2-(2-nitrovinyl) furan (G-0) with cyclodextrines. Int. J. Pharm. 439, 275–285 (2012)CrossRefGoogle Scholar
  27. 27.
    Macedo, O.F.L., Andrade, G.R.S., Conegero, L.S., Barreto, L.S., Costa, N.B., Gimenez, I.F., Almeida, L.E., Kubota, D.: Physicochemical study and characterization of the trimethoprim/2-hydroxypropyl-γ-cyclodextrin inclusion complex. Spectrochim. Acta A 86, 101–106 (2012)CrossRefGoogle Scholar
  28. 28.
    Zhang, Z., Dallek, S., Vogt, R., Li, Y., Topping, T.D., Zhou, Y., Schoenung, J.M., Lavernia, J.: Degassing behavior of nanostructured Al and its composites. Metall. Mater. Trans. A 41, 532–541 (2010)CrossRefGoogle Scholar
  29. 29.
    Li, J., Yan, D., Jiang, X., Chen, Q.: Formation of the crystalline inclusion complex between γ-cyclodextrin and poly (N-acetylethylenimine). Polymer 43, 2625–2629 (2002)CrossRefGoogle Scholar
  30. 30.
    Klang, V., Matsko, N., Raupach, K., El-Hagin, N., Valenta, C.: Development of sucrose stearate-based nanoemulsions and optimisation through γ-cyclodextrin. Eur. J. Pharm. Biopharm. 79, 58–67 (2011)CrossRefGoogle Scholar
  31. 31.
    Das, S., Chaudhury, A.: Recent advances in lipid nanoparticles formulations with solid matrix for oral drug delivery. AAPS PharmSciTech. 12, 62–76 (2011)CrossRefGoogle Scholar
  32. 32.
    Awaad, A., Nakamura, M., Ishimura, K.: Imaging of size-dependent uptake and identification of novel pathways in mouse Peyer’s patches using fluorescent organosilica particles. Nanomed. Nanotechnol. 8, 627–636 (2012)CrossRefGoogle Scholar
  33. 33.
    Garg, A., Singh, S.: Enhancement of antifungal activity of eugenol in immunosuppressed rats through lipid nanocarriers. Colloid Surf. B 87, 280–288 (2011)CrossRefGoogle Scholar
  34. 34.
    Vitorino, C., Carvalho, F.A., Almeida, A.J., Sousa, J.J., Pais, A.A.C.C.: The size of solid lipid nanoparticles: an interpretation from experimental design. Colloids Surf. B 84, 117–130 (2011)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Jeetendra Singh Negi
    • 1
    Email author
  • Pronobesh Chattopadhyay
    • 2
  • Ashok Kumar Sharma
    • 3
  • Veerma Ram
    • 1
  1. 1.Department of Pharmaceutical SciencesS Bhagwan Singh PG Institute of Bio-medical Sciences and ResearchDehradunIndia
  2. 2.Division of Pharmaceutical TechnologyDefence Research LaboratoryTezpurIndia
  3. 3.Institute of PharmacyMinistry of HealthAsmaraGovernment of Eritrea

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